Dexamethasone Compared With Prednisone During Induction Therapy and Methotrexate With or Without Leucovorin During Maintenance Therapy in Treating Patients With Newly Diagnosed High-Risk Acute Lymphoblastic Leukemia
Sponsor
Children's Oncology Group (Other)
Overall Status
Completed
CT.gov ID
NCT00075725
Collaborator
National Cancer Institute (NCI) (NIH)
3,154
234
4
207
13.5
0.1
Study Details
Study Description
Brief Summary
This randomized phase III trial is studying dexamethasone to see how well it works compared to prednisone during induction therapy. This trial is also studying methotrexate and leucovorin calcium to see how well they work compared to methotrexate alone during maintenance therapy in treating patients with newly diagnosed acute lymphoblastic leukemia (ALL). Drugs used in chemotherapy, such as dexamethasone, prednisone, methotrexate, and leucovorin calcium, work in different ways to stop cancer cells from dividing so they stop growing or die. Giving more than one drug may kill more cancer cells. It is not yet known which combination chemotherapy regimen is more effective in treating acute lymphoblastic leukemia.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 3 |
Detailed Description
OBJECTIVES:
-
Improve the outcome of children with high-risk acute lymphoblastic leukemia treated with 2 different chemotherapy regimens.
-
Determine the relative safety and efficacy of dexamethasone given for 14 days vs prednisone given for 28 days during induction.
-
Determine the relative safety and efficacy of high-dose methotrexate (5gm/m^2) with leucovorin rescue compared to escalating methotrexate without leucovorin rescue (Capizzi I) during interim maintenance I.
-
Correlate Day 29 minimal residual disease (MRD) with event-free survival (EFS) and overall survival (OS).
-
Correlate early marrow response status with day-29 MRD status. VI. Improve outcome by identifying additional high risk patients by Day 29 MRD for treatment with fully augmented Berlin-Frankfurt-Munster (BFM).
OUTLINE: This is a randomized, multicenter study. Patients are stratified according to early response (slow early response [SER] vs rapid early response [RER]). Induction therapy: Patients are randomized to 1 of 4 treatment arms.
ARM I: Patients receive cytarabine intrathecally (IT) on day 1, vincristine intravenously (IV) and daunorubicin IV on days 1, 8, 15, and 22, dexamethasone orally (PO) or IV twice daily (BID) on days 1-14, methotrexate (MTX) IT on days 8 and 29* and pegaspargase intramuscularly (IM) once on day 4, 5, or 6.
NOTE: *Patients with CNS3 disease (WBC > 5/mL in cerebrospinal fluid and positive for blasts on cytospin) also receive MTX IT on days 15 and 22.
ARM II: Patients receive induction therapy as in Arm I.
ARM III: Patients receive cytarabine, vincristine, daunorubicin, and pegaspargase as in Arm
- Patients also receive prednisone PO or IV BID on days 1-28 and MTX IT on days 8 and 29.
ARM IV: Patients receive induction therapy as in Arm III.
Patients in all arms are evaluated at day 29 of induction therapy. Patients with M3 disease are removed from study. Patients with M1 disease and less than 1% minimal residual disease (MRD) proceed to consolidation therapy beginning on day 36. Patients with M2 disease OR with MI disease and at least 1% MRD receive extended induction therapy for 2 additional weeks. Patients with SER disease and MLL rearrangements are removed from the study but may be eligible for treatment on protocol COG-AALL0031.
Extended induction therapy: Patients continue to receive therapy on the arm to which they were originally randomized.
ARMS I and II: Patients receive dexamethasone PO or IV BID on days 1-14, vincristine IV on days 1 and 8, daunorubicin IV on day 1 and pegaspargase IM on day 4, 5, or 6 and are then reevaluated.
ARMS III and IV: Patients receive prednisone PO or IV BID on days 1-14, and vincristine, daunorubicin, and pegaspargase as in Arms I and II and are then reevaluated.
Patients on all arms who have M1 disease and less than 1% MRD after extended induction proceed to consolidation therapy and continue as SER patients. All other patients are removed from study.
Consolidation therapy: All patients receive cyclophosphamide IV over 30 minutes on days 1 and 29, cytarabine IV or subcutaneously (SC) on days 1-4, 8-11, 29-32, and 36-39, mercaptopurine (MP) PO on days 1-14 and 29-42, vincristine IV on days 15, 22, 43, and 50; pegaspargase IM on days 15 and 43 and MTX* IT on days 1, 8, 15, and 22. Patients with testicular disease also receive radiotherapy to the testes.
NOTE: *Patients with CNS3 disease receive MTX on days 1 and 8 only.
Interim maintenance therapy I: Patients continue to receive treatment on the arm to which they were originally randomized.
ARM I: (escalating-dose MTX) Patients receive vincristine IV and escalating-dose MTX IV on days 1, 11, 21, 31, and 41, pegaspargase IM on days 2 and 22 and MTX IT on days 1 and 21.
ARM II: (high-dose MTX) Patients receive vincristine IV and high-dose methotrexate IV over 24 hours on days 1, 15, 29, and 43, MP PO on days 1-56 and IT MTX on days 1 and 29. Patients also receive leucovorin calcium IV every 6 hours for at least 3 doses, beginning 42 hours after start of each MTX infusion.
ARM III: (escalating-dose MTX) Patients receive interim maintenance I therapy as in Arm I.
ARM IV: (high-dose MTX) Patients receive interim maintenance I therapy as in Arm II.
DELAYED INTENSIFICATION THERAPY I: All patients receive vincristine IV on days 1, 8, 15, 43, and 50, dexamethasone PO or IV BID on days 1 to 21 for patients age 1 to 12 OR on days 1-7 and 15-21 for patients age 13 and over, doxorubicin IV on days 1, 8, and 15, pegaspargase IM on day 4, 5, or 6 AND day 43, cyclophosphamide IV over 30 minutes on day 29, cytarabine IV or SC on days 30-33 and 37-40, thioguanine PO on days 29-42 and MTX IT on days 1, 29, and 36.After delayed intensification I, SER patients proceed to interim maintenance II and delayed intensification II. RER patients proceed directly to maintenance.
INTERIM MAINTENANCE THERAPY II: All patients receive vincristine IV and MTX IV on days 1, 11, 21, 31, and 41, pegaspargase IM on days 2 and 22; and MTX IT on days 1 and 21. Patients then proceed to delayed intensification II.
DELAYED INTENSIFICATION THERAPY II: All patients receive therapy as in delayed intensification I, arm I. CNS3 patients also receive radiotherapy for 3-10 days, beginning on day 29. All other SER patients, patients with MLL rearrangements, and some patients pretreated with steroids (> 48 hours within the week prior to diagnosis) receive prophylactic cranial radiotherapy (CRT) for 8 days, beginning on day 29. Patients then proceed to maintenance therapy.
MAINTENANCE THERAPY: All patients receive vincristine IV on days 1, 29, and 57, dexamethasone PO BID on days 1-5, 29-33, and 57-61, MP PO on days 1-84, MTX IT on day 1*; and MTX PO on days 1, 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, and 78.
NOTE: *RER (who did not undergo CRT) patients also receive MTX IT on day 29 for maintenance courses 1-4.
In all arms, maintenance therapy repeats every 12 weeks until total duration of therapy is 2 years from the start of interim maintenance I for female patients and 3 years from the start of interim maintenance I for male patients. Patients with testicular disease may receive testicular radiotherapy for 8 days during one of the first 3 courses of maintenance therapy. Patients are followed monthly for 1 year, every 2 months for 1 year, every 3 months for 1 year, every 6 months for 1 year, and then annually thereafter.
Study Design
Study Type:
Interventional
Actual Enrollment
:
3154 participants
Allocation:
Randomized
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
High Risk B-Precursor Acute Lymphoblastic Leukemia (ALL)
Actual Study Start Date
:
Dec 29, 2003
Actual Primary Completion Date
:
Dec 31, 2010
Actual Study Completion Date
:
Mar 31, 2021
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Active Comparator: Arm I Patients in arm I receive intrathecal cytarabine in week 1; infusions of vincristine and daunorubicin once a week in weeks 1-4; dexamethasone by mouth or infusion twice a day in weeks 1 and 2; intrathecal methotrexate in weeks 2 and 5 or 2-5; and an injection of pegaspargase in week 1. |
Drug: Cyclophosphamide
Given IV
Other Names:
Drug: Cytarabine
Given IT, SC, or IV
Other Names:
Drug: Daunorubicin Hydrochloride
Given IV
Other Names:
Drug: Dexamethasone
Given PO or IV
Other Names:
Drug: Doxorubicin Hydrochloride
Given IV
Other Names:
Drug: Mercaptopurine
Given PO
Other Names:
Drug: Methotrexate
Given IT or IV
Other Names:
Drug: Pegaspargase
Given IM
Other Names:
Radiation: Radiation Therapy
Undergo radiation therapy
Other Names:
Drug: Thioguanine
Given PO
Other Names:
Drug: Vincristine Sulfate
Given IV
Other Names:
|
| Active Comparator: Arm II Patients in arm II will receive intrathecal cytarabine in week 1; infusions of vincristine and daunorubicin once a week in weeks 1-4; dexamethasone by mouth or infusion twice a day in weeks 1 and 2; intrathecal methotrexate in weeks 2 and 5 or 2-5; and an injection of pegaspargase in week 1. |
Drug: Cyclophosphamide
Given IV
Other Names:
Drug: Cytarabine
Given IT, SC, or IV
Other Names:
Drug: Daunorubicin Hydrochloride
Given IV
Other Names:
Drug: Dexamethasone
Given PO or IV
Other Names:
Drug: Doxorubicin Hydrochloride
Given IV
Other Names:
Drug: Leucovorin Calcium
Given IV
Other Names:
Drug: Mercaptopurine
Given PO
Other Names:
Drug: Methotrexate
Given IT or IV
Other Names:
Drug: Pegaspargase
Given IM
Other Names:
Radiation: Radiation Therapy
Undergo radiation therapy
Other Names:
Drug: Thioguanine
Given PO
Other Names:
Drug: Vincristine Sulfate
Given IV
Other Names:
|
| Experimental: Arm III Patients in arm III will receive cytarabine, vincristine, daunorubicin, and pegaspargase as in groups one and two. They will also receive prednisone by mouth or infusion twice a day in weeks 1-4 and intrathecal methotrexate in weeks 2 and 5. Some patients in all groups may receive induction therapy for 2 additional weeks. Beginning in week 6 or 7, patients may receive combination chemotherapy by infusion, injection, intrathecally, and by mouth for up to 8 weeks. |
Drug: Cyclophosphamide
Given IV
Other Names:
Drug: Cytarabine
Given IT, SC, or IV
Other Names:
Drug: Daunorubicin Hydrochloride
Given IV
Other Names:
Drug: Dexamethasone
Given PO or IV
Other Names:
Drug: Doxorubicin Hydrochloride
Given IV
Other Names:
Drug: Mercaptopurine
Given PO
Other Names:
Drug: Methotrexate
Given IT or IV
Other Names:
Drug: Pegaspargase
Given IM
Other Names:
Drug: Prednisone
Given PO or IV
Other Names:
Radiation: Radiation Therapy
Undergo radiation therapy
Other Names:
Drug: Thioguanine
Given PO
Other Names:
Drug: Vincristine Sulfate
Given IV
Other Names:
|
| Experimental: Arm IV Patients in arm IV will receive cytarabine, vincristine, daunorubicin, and pegaspargase as in groups one and two. They will also receive prednisone by mouth or infusion twice a day in weeks 1-4 and intrathecal methotrexate in weeks 2 and 5. Some patients in all groups may receive induction therapy for 2 additional weeks. Beginning in week 6 or 7, patients may receive combination chemotherapy by infusion, injection, intrathecally, and by mouth for up to 8 weeks. |
Drug: Cyclophosphamide
Given IV
Other Names:
Drug: Cytarabine
Given IT, SC, or IV
Other Names:
Drug: Daunorubicin Hydrochloride
Given IV
Other Names:
Drug: Dexamethasone
Given PO or IV
Other Names:
Drug: Doxorubicin Hydrochloride
Given IV
Other Names:
Drug: Leucovorin Calcium
Given IV
Other Names:
Drug: Mercaptopurine
Given PO
Other Names:
Drug: Methotrexate
Given IT or IV
Other Names:
Drug: Pegaspargase
Given IM
Other Names:
Drug: Prednisone
Given PO or IV
Other Names:
Radiation: Radiation Therapy
Undergo radiation therapy
Other Names:
Drug: Thioguanine
Given PO
Other Names:
Drug: Vincristine Sulfate
Given IV
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Comparison of the Increase in Cure Rate of High Risk ALL Without Causing More Serious Side Effects Between Interventions [5 years]
Event Free Probability.
Secondary Outcome Measures
- Correlation of Minimal Residual Disease (MRD) Positive With Overall Survival (OS) [5 Years]
Bone marrow MRD status is defined as positive with >= 0.1 detectable leukemia cells, and negative with < 0.1 detectable leukemia cells.
- Correlation of Minimal Residual Disease (MRD) Negative With Overall Survival (OS). [5 years]
Bone marrow MRD status is defined as negative with < .01 detectable leukemia cells.
- Correlation of Early Marrow Response Status With MRD Positive. [Day 29]
Bone marrow status is defined as: M1: < 5% lymphoblasts; M2: 5-25% lymphoblasts; M3: > 25% lymphoblasts. Bone marrow MRD status is defined as positive with >= 0.1 detectable leukemia cells, and negative with < 0.1 detectable leukemia cells.
- Correlation of Early Marrow Response Status With MRD Negative. [Day 29]
Bone marrow status is defined as: M1: < 5% lymphoblasts; M2: 5-25% lymphoblasts; M3: > 25% lymphoblasts. Bone marrow MRD status is defined as positive with >= 0.1 detectable leukemia cells, and negative with < 0.1 detectable leukemia cells.
- Correlation of Minimal Residual Disease (MRD) Positive With Event Free Survival (EFS) [5 years]
Bone marrow MRD status is defined as positive with >= 0.1 detectable leukemia cells.
- Correlation of Minimal Residual Disease (MRD) Negative With Event Free Survival (EFS). [5 years]
Bone marrow MRD status is defined as negative with < 0.1 detectable leukemia cells.
Eligibility Criteria
Criteria
Ages Eligible for Study:
1 Year
to 30 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
-
Must be eligible for and enrolled on classification study COG-AALL03B1
-
Newly diagnosed B-precursor acute lymphoblastic leukemia
-
WBC > 50,000/mm^3 for patients age 1 to 9
-
Any WBC for patients age 10 to 30 OR patients who have received prior steroid therapy OR patients with testicular disease
-
Whit blood cell (WBC) criteria:
-
Age 1 - 9 years: WBC >= 50,000/uL
-
Age 10 - 30 years: any WBC
-
Prior steroid therapy: any WBC
-
Testicular disease: any WBC
-
Patients shall have had no other prior cytotoxic chemotherapy with the exception of steroids and intrathecal cytarabine
-
Patients receiving prior steroid therapy (as described in AALL03B1) are eligible for study; the dose and duration of previous steroid therapy should be carefully documented
-
All patients and/or their parents or legal guardians must sign a written informed consent
-
All institutional, Food and Drug Administration (FDA), and National Cancer Institute (NCI) requirements for human studies must be met
Exclusion Criteria:
- Patients with Down syndrome are ineligible to enroll onto this study
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Children's Hospital of Alabama | Birmingham | Alabama | United States | 35233 |
| 2 | University of Alabama at Birmingham Cancer Center | Birmingham | Alabama | United States | 35233 |
| 3 | USA Health Strada Patient Care Center | Mobile | Alabama | United States | 36604 |
| 4 | Banner Children's at Desert | Mesa | Arizona | United States | 85202 |
| 5 | Phoenix Childrens Hospital | Phoenix | Arizona | United States | 85016 |
| 6 | Banner University Medical Center - Tucson | Tucson | Arizona | United States | 85719 |
| 7 | Arkansas Children's Hospital | Little Rock | Arkansas | United States | 72202-3591 |
| 8 | University of Arkansas for Medical Sciences | Little Rock | Arkansas | United States | 72205 |
| 9 | Kaiser Permanente Downey Medical Center | Downey | California | United States | 90242 |
| 10 | City of Hope Comprehensive Cancer Center | Duarte | California | United States | 91010 |
| 11 | Loma Linda University Medical Center | Loma Linda | California | United States | 92354 |
| 12 | Miller Children's and Women's Hospital Long Beach | Long Beach | California | United States | 90806 |
| 13 | Children's Hospital Los Angeles | Los Angeles | California | United States | 90027 |
| 14 | Cedars Sinai Medical Center | Los Angeles | California | United States | 90048 |
| 15 | Mattel Children's Hospital UCLA | Los Angeles | California | United States | 90095 |
| 16 | UCLA / Jonsson Comprehensive Cancer Center | Los Angeles | California | United States | 90095 |
| 17 | Valley Children's Hospital | Madera | California | United States | 93636 |
| 18 | UCSF Benioff Children's Hospital Oakland | Oakland | California | United States | 94609 |
| 19 | Kaiser Permanente-Oakland | Oakland | California | United States | 94611 |
| 20 | Children's Hospital of Orange County | Orange | California | United States | 92868 |
| 21 | Lucile Packard Children's Hospital Stanford University | Palo Alto | California | United States | 94304 |
| 22 | Sutter Medical Center Sacramento | Sacramento | California | United States | 95816 |
| 23 | University of California Davis Comprehensive Cancer Center | Sacramento | California | United States | 95817 |
| 24 | Rady Children's Hospital - San Diego | San Diego | California | United States | 92123 |
| 25 | UCSF Medical Center-Parnassus | San Francisco | California | United States | 94143 |
| 26 | Santa Barbara Cottage Hospital | Santa Barbara | California | United States | 93102 |
| 27 | Children's Hospital Colorado | Aurora | Colorado | United States | 80045 |
| 28 | Presbyterian - Saint Lukes Medical Center - Health One | Denver | Colorado | United States | 80218 |
| 29 | Rocky Mountain Hospital for Children-Presbyterian Saint Luke's Medical Center | Denver | Colorado | United States | 80218 |
| 30 | University of Connecticut | Farmington | Connecticut | United States | 06030 |
| 31 | Connecticut Children's Medical Center | Hartford | Connecticut | United States | 06106 |
| 32 | Yale University | New Haven | Connecticut | United States | 06520 |
| 33 | Alfred I duPont Hospital for Children | Wilmington | Delaware | United States | 19803 |
| 34 | MedStar Georgetown University Hospital | Washington | District of Columbia | United States | 20007 |
| 35 | Children's National Medical Center | Washington | District of Columbia | United States | 20010 |
| 36 | Broward Health Medical Center | Fort Lauderdale | Florida | United States | 33316 |
| 37 | Lee Memorial Health System | Fort Myers | Florida | United States | 33901 |
| 38 | Golisano Children's Hospital of Southwest Florida | Fort Myers | Florida | United States | 33908 |
| 39 | University of Florida Health Science Center - Gainesville | Gainesville | Florida | United States | 32610 |
| 40 | Memorial Regional Hospital/Joe DiMaggio Children's Hospital | Hollywood | Florida | United States | 33021 |
| 41 | Nemours Children's Clinic-Jacksonville | Jacksonville | Florida | United States | 32207 |
| 42 | University of Miami Miller School of Medicine-Sylvester Cancer Center | Miami | Florida | United States | 33136 |
| 43 | Nicklaus Children's Hospital | Miami | Florida | United States | 33155 |
| 44 | Miami Cancer Institute | Miami | Florida | United States | 33176 |
| 45 | AdventHealth Orlando | Orlando | Florida | United States | 32803 |
| 46 | Nemours Children's Clinic - Orlando | Orlando | Florida | United States | 32806 |
| 47 | Orlando Health Cancer Institute | Orlando | Florida | United States | 32806 |
| 48 | Nemours Children's Hospital | Orlando | Florida | United States | 32827 |
| 49 | Nemours Children's Clinic - Pensacola | Pensacola | Florida | United States | 32504 |
| 50 | Sacred Heart Hospital | Pensacola | Florida | United States | 32504 |
| 51 | Johns Hopkins All Children's Hospital | Saint Petersburg | Florida | United States | 33701 |
| 52 | Saint Joseph's Hospital/Children's Hospital-Tampa | Tampa | Florida | United States | 33607 |
| 53 | Saint Mary's Hospital | West Palm Beach | Florida | United States | 33407 |
| 54 | Children's Healthcare of Atlanta - Egleston | Atlanta | Georgia | United States | 30322 |
| 55 | Emory University Hospital/Winship Cancer Institute | Atlanta | Georgia | United States | 30322 |
| 56 | Augusta University Medical Center | Augusta | Georgia | United States | 30912 |
| 57 | Memorial Health University Medical Center | Savannah | Georgia | United States | 31404 |
| 58 | University of Hawaii Cancer Center | Honolulu | Hawaii | United States | 96813 |
| 59 | Tripler Army Medical Center | Honolulu | Hawaii | United States | 96859 |
| 60 | Saint Luke's Cancer Institute - Boise | Boise | Idaho | United States | 83712 |
| 61 | Lurie Children's Hospital-Chicago | Chicago | Illinois | United States | 60611 |
| 62 | Rush University Medical Center | Chicago | Illinois | United States | 60612 |
| 63 | University of Illinois | Chicago | Illinois | United States | 60612 |
| 64 | University of Chicago Comprehensive Cancer Center | Chicago | Illinois | United States | 60637 |
| 65 | Loyola University Medical Center | Maywood | Illinois | United States | 60153 |
| 66 | Advocate Children's Hospital-Oak Lawn | Oak Lawn | Illinois | United States | 60453 |
| 67 | Advocate Lutheran General Hospital | Park Ridge | Illinois | United States | 60068 |
| 68 | Southern Illinois University School of Medicine | Springfield | Illinois | United States | 62702 |
| 69 | Indiana University/Melvin and Bren Simon Cancer Center | Indianapolis | Indiana | United States | 46202 |
| 70 | Riley Hospital for Children | Indianapolis | Indiana | United States | 46202 |
| 71 | Saint Vincent Hospital and Health Care Center | Indianapolis | Indiana | United States | 46260 |
| 72 | Blank Children's Hospital | Des Moines | Iowa | United States | 50309 |
| 73 | University of Iowa/Holden Comprehensive Cancer Center | Iowa City | Iowa | United States | 52242 |
| 74 | University of Kansas Cancer Center | Kansas City | Kansas | United States | 66160 |
| 75 | University of Kentucky/Markey Cancer Center | Lexington | Kentucky | United States | 40536 |
| 76 | Norton Children's Hospital | Louisville | Kentucky | United States | 40202 |
| 77 | Tulane University Health Sciences Center | New Orleans | Louisiana | United States | 70112 |
| 78 | Children's Hospital New Orleans | New Orleans | Louisiana | United States | 70118 |
| 79 | Eastern Maine Medical Center | Bangor | Maine | United States | 04401 |
| 80 | Maine Children's Cancer Program | Scarborough | Maine | United States | 04074 |
| 81 | University of Maryland/Greenebaum Cancer Center | Baltimore | Maryland | United States | 21201 |
| 82 | Sinai Hospital of Baltimore | Baltimore | Maryland | United States | 21215 |
| 83 | Johns Hopkins University/Sidney Kimmel Cancer Center | Baltimore | Maryland | United States | 21287 |
| 84 | Walter Reed National Military Medical Center | Bethesda | Maryland | United States | 20889-5600 |
| 85 | Tufts Children's Hospital | Boston | Massachusetts | United States | 02111 |
| 86 | Massachusetts General Hospital Cancer Center | Boston | Massachusetts | United States | 02114 |
| 87 | Baystate Medical Center | Springfield | Massachusetts | United States | 01199 |
| 88 | UMass Memorial Medical Center - University Campus | Worcester | Massachusetts | United States | 01655 |
| 89 | C S Mott Children's Hospital | Ann Arbor | Michigan | United States | 48109 |
| 90 | Wayne State University/Karmanos Cancer Institute | Detroit | Michigan | United States | 48201 |
| 91 | Ascension Saint John Hospital | Detroit | Michigan | United States | 48236 |
| 92 | Michigan State University Clinical Center | East Lansing | Michigan | United States | 48824-7016 |
| 93 | Hurley Medical Center | Flint | Michigan | United States | 48503 |
| 94 | Helen DeVos Children's Hospital at Spectrum Health | Grand Rapids | Michigan | United States | 49503 |
| 95 | Spectrum Health at Butterworth Campus | Grand Rapids | Michigan | United States | 49503 |
| 96 | Bronson Methodist Hospital | Kalamazoo | Michigan | United States | 49007 |
| 97 | Kalamazoo Center for Medical Studies | Kalamazoo | Michigan | United States | 49008 |
| 98 | Beaumont Children's Hospital-Royal Oak | Royal Oak | Michigan | United States | 48073 |
| 99 | William Beaumont Hospital-Royal Oak | Royal Oak | Michigan | United States | 48073 |
| 100 | Children's Hospitals and Clinics of Minnesota - Minneapolis | Minneapolis | Minnesota | United States | 55404 |
| 101 | University of Minnesota/Masonic Cancer Center | Minneapolis | Minnesota | United States | 55455 |
| 102 | Mayo Clinic in Rochester | Rochester | Minnesota | United States | 55905 |
| 103 | Children's Hospital and Clinic-Saint Paul | Saint Paul | Minnesota | United States | 55102 |
| 104 | University of Mississippi Medical Center | Jackson | Mississippi | United States | 39216 |
| 105 | Columbia Regional | Columbia | Missouri | United States | 65201 |
| 106 | University of Missouri - Ellis Fischel | Columbia | Missouri | United States | 65212 |
| 107 | Children's Mercy Hospitals and Clinics | Kansas City | Missouri | United States | 64108 |
| 108 | Cardinal Glennon Children's Medical Center | Saint Louis | Missouri | United States | 63104 |
| 109 | Washington University School of Medicine | Saint Louis | Missouri | United States | 63110 |
| 110 | Children's Hospital and Medical Center of Omaha | Omaha | Nebraska | United States | 68114 |
| 111 | University of Nebraska Medical Center | Omaha | Nebraska | United States | 68198 |
| 112 | Nevada Cancer Research Foundation NCORP | Las Vegas | Nevada | United States | 89169 |
| 113 | Dartmouth Hitchcock Medical Center | Lebanon | New Hampshire | United States | 03756 |
| 114 | Hackensack University Medical Center | Hackensack | New Jersey | United States | 07601 |
| 115 | Saint Barnabas Medical Center | Livingston | New Jersey | United States | 07039 |
| 116 | Morristown Medical Center | Morristown | New Jersey | United States | 07960 |
| 117 | Saint Peter's University Hospital | New Brunswick | New Jersey | United States | 08901 |
| 118 | Rutgers Cancer Institute of New Jersey-Robert Wood Johnson University Hospital | New Brunswick | New Jersey | United States | 08903 |
| 119 | Newark Beth Israel Medical Center | Newark | New Jersey | United States | 07112 |
| 120 | Saint Joseph's Regional Medical Center | Paterson | New Jersey | United States | 07503 |
| 121 | Overlook Hospital | Summit | New Jersey | United States | 07902 |
| 122 | University of New Mexico Cancer Center | Albuquerque | New Mexico | United States | 87102 |
| 123 | Albany Medical Center | Albany | New York | United States | 12208 |
| 124 | Montefiore Medical Center - Moses Campus | Bronx | New York | United States | 10467 |
| 125 | Brooklyn Hospital Center | Brooklyn | New York | United States | 11201 |
| 126 | Brookdale Hospital Medical Center | Brooklyn | New York | United States | 11212 |
| 127 | Maimonides Medical Center | Brooklyn | New York | United States | 11219 |
| 128 | Roswell Park Cancer Institute | Buffalo | New York | United States | 14263 |
| 129 | NYU Winthrop Hospital | Mineola | New York | United States | 11501 |
| 130 | The Steven and Alexandra Cohen Children's Medical Center of New York | New Hyde Park | New York | United States | 11040 |
| 131 | Laura and Isaac Perlmutter Cancer Center at NYU Langone | New York | New York | United States | 10016 |
| 132 | Mount Sinai Hospital | New York | New York | United States | 10029 |
| 133 | NYP/Weill Cornell Medical Center | New York | New York | United States | 10065 |
| 134 | Stony Brook University Medical Center | Stony Brook | New York | United States | 11794 |
| 135 | State University of New York Upstate Medical University | Syracuse | New York | United States | 13210 |
| 136 | New York Medical College | Valhalla | New York | United States | 10595 |
| 137 | Mission Hospital | Asheville | North Carolina | United States | 28801 |
| 138 | UNC Lineberger Comprehensive Cancer Center | Chapel Hill | North Carolina | United States | 27599 |
| 139 | Carolinas Medical Center/Levine Cancer Institute | Charlotte | North Carolina | United States | 28203 |
| 140 | Novant Health Presbyterian Medical Center | Charlotte | North Carolina | United States | 28204 |
| 141 | Duke University Medical Center | Durham | North Carolina | United States | 27710 |
| 142 | East Carolina University | Greenville | North Carolina | United States | 27834 |
| 143 | Wake Forest University Health Sciences | Winston-Salem | North Carolina | United States | 27157 |
| 144 | Sanford Broadway Medical Center | Fargo | North Dakota | United States | 58122 |
| 145 | Children's Hospital Medical Center of Akron | Akron | Ohio | United States | 44308 |
| 146 | Cincinnati Children's Hospital Medical Center | Cincinnati | Ohio | United States | 45229 |
| 147 | Rainbow Babies and Childrens Hospital | Cleveland | Ohio | United States | 44106 |
| 148 | Cleveland Clinic Foundation | Cleveland | Ohio | United States | 44195 |
| 149 | Nationwide Children's Hospital | Columbus | Ohio | United States | 43205 |
| 150 | Dayton Children's Hospital | Dayton | Ohio | United States | 45404 |
| 151 | ProMedica Toledo Hospital/Russell J Ebeid Children's Hospital | Toledo | Ohio | United States | 43606 |
| 152 | Mercy Children's Hospital | Toledo | Ohio | United States | 43608 |
| 153 | University of Toledo | Toledo | Ohio | United States | 43614 |
| 154 | Tod Children's Hospital - Forum Health | Youngstown | Ohio | United States | 44501 |
| 155 | University of Oklahoma Health Sciences Center | Oklahoma City | Oklahoma | United States | 73104 |
| 156 | Natalie Warren Bryant Cancer Center at Saint Francis | Tulsa | Oklahoma | United States | 74136 |
| 157 | Legacy Emanuel Children's Hospital | Portland | Oregon | United States | 97227 |
| 158 | Legacy Emanuel Hospital and Health Center | Portland | Oregon | United States | 97227 |
| 159 | Oregon Health and Science University | Portland | Oregon | United States | 97239 |
| 160 | Lehigh Valley Hospital - Muhlenberg | Bethlehem | Pennsylvania | United States | 18017 |
| 161 | Geisinger Medical Center | Danville | Pennsylvania | United States | 17822 |
| 162 | Penn State Milton S Hershey Medical Center | Hershey | Pennsylvania | United States | 17033-0850 |
| 163 | Penn State Children's Hospital | Hershey | Pennsylvania | United States | 17033 |
| 164 | Children's Hospital of Philadelphia | Philadelphia | Pennsylvania | United States | 19104 |
| 165 | Children's Oncology Group | Philadelphia | Pennsylvania | United States | 19104 |
| 166 | Saint Christopher's Hospital for Children | Philadelphia | Pennsylvania | United States | 19134 |
| 167 | Children's Hospital of Pittsburgh of UPMC | Pittsburgh | Pennsylvania | United States | 15224 |
| 168 | Rhode Island Hospital | Providence | Rhode Island | United States | 02903 |
| 169 | Medical University of South Carolina | Charleston | South Carolina | United States | 29425 |
| 170 | Prisma Health Richland Hospital | Columbia | South Carolina | United States | 29203 |
| 171 | BI-LO Charities Children's Cancer Center | Greenville | South Carolina | United States | 29605 |
| 172 | Greenville Cancer Treatment Center | Greenville | South Carolina | United States | 29605 |
| 173 | Sanford USD Medical Center - Sioux Falls | Sioux Falls | South Dakota | United States | 57117-5134 |
| 174 | T C Thompson Children's Hospital | Chattanooga | Tennessee | United States | 37403 |
| 175 | East Tennessee Childrens Hospital | Knoxville | Tennessee | United States | 37916 |
| 176 | Vanderbilt University/Ingram Cancer Center | Nashville | Tennessee | United States | 37232 |
| 177 | Texas Tech University Health Sciences Center-Amarillo | Amarillo | Texas | United States | 79106 |
| 178 | Dell Children's Medical Center of Central Texas | Austin | Texas | United States | 78723 |
| 179 | Driscoll Children's Hospital | Corpus Christi | Texas | United States | 78411 |
| 180 | Medical City Dallas Hospital | Dallas | Texas | United States | 75230 |
| 181 | UT Southwestern/Simmons Cancer Center-Dallas | Dallas | Texas | United States | 75390 |
| 182 | Cook Children's Medical Center | Fort Worth | Texas | United States | 76104 |
| 183 | University of Texas Medical Branch | Galveston | Texas | United States | 77555-0565 |
| 184 | Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center | Houston | Texas | United States | 77030 |
| 185 | M D Anderson Cancer Center | Houston | Texas | United States | 77030 |
| 186 | Covenant Children's Hospital | Lubbock | Texas | United States | 79410 |
| 187 | Methodist Children's Hospital of South Texas | San Antonio | Texas | United States | 78229 |
| 188 | University of Texas Health Science Center at San Antonio | San Antonio | Texas | United States | 78229 |
| 189 | Scott and White Memorial Hospital | Temple | Texas | United States | 76508 |
| 190 | Primary Children's Hospital | Salt Lake City | Utah | United States | 84113 |
| 191 | University of Vermont and State Agricultural College | Burlington | Vermont | United States | 05405 |
| 192 | University of Virginia Cancer Center | Charlottesville | Virginia | United States | 22908 |
| 193 | Inova Fairfax Hospital | Falls Church | Virginia | United States | 22042 |
| 194 | Children's Hospital of The King's Daughters | Norfolk | Virginia | United States | 23507 |
| 195 | Naval Medical Center - Portsmouth | Portsmouth | Virginia | United States | 23708-2197 |
| 196 | Virginia Commonwealth University/Massey Cancer Center | Richmond | Virginia | United States | 23298 |
| 197 | Carilion Children's | Roanoke | Virginia | United States | 24014 |
| 198 | Seattle Children's Hospital | Seattle | Washington | United States | 98105 |
| 199 | Providence Sacred Heart Medical Center and Children's Hospital | Spokane | Washington | United States | 99204 |
| 200 | Mary Bridge Children's Hospital and Health Center | Tacoma | Washington | United States | 98405 |
| 201 | Madigan Army Medical Center | Tacoma | Washington | United States | 98431 |
| 202 | West Virginia University Charleston Division | Charleston | West Virginia | United States | 25304 |
| 203 | West Virginia University Healthcare | Morgantown | West Virginia | United States | 26506 |
| 204 | Saint Vincent Hospital Cancer Center Green Bay | Green Bay | Wisconsin | United States | 54301 |
| 205 | Gundersen Lutheran Medical Center | La Crosse | Wisconsin | United States | 54601 |
| 206 | University of Wisconsin Hospital and Clinics | Madison | Wisconsin | United States | 53792 |
| 207 | Marshfield Medical Center-Marshfield | Marshfield | Wisconsin | United States | 54449 |
| 208 | Children's Hospital of Wisconsin | Milwaukee | Wisconsin | United States | 53226 |
| 209 | Royal Brisbane and Women's Hospital | Herston | Queensland | Australia | 4029 |
| 210 | Royal Children's Hospital-Brisbane | Herston | Queensland | Australia | 4029 |
| 211 | Women's and Children's Hospital-Adelaide | North Adelaide | South Australia | Australia | 5006 |
| 212 | Royal Children's Hospital | Parkville | Victoria | Australia | 3052 |
| 213 | Princess Margaret Hospital for Children | Perth | Western Australia | Australia | 6008 |
| 214 | Alberta Children's Hospital | Calgary | Alberta | Canada | T3B 6A8 |
| 215 | University of Alberta Hospital | Edmonton | Alberta | Canada | T6G 2B7 |
| 216 | British Columbia Children's Hospital | Vancouver | British Columbia | Canada | V6H 3V4 |
| 217 | CancerCare Manitoba | Winnipeg | Manitoba | Canada | R3E 0V9 |
| 218 | Janeway Child Health Centre | Saint John's | Newfoundland and Labrador | Canada | A1B 3V6 |
| 219 | IWK Health Centre | Halifax | Nova Scotia | Canada | B3K 6R8 |
| 220 | Kingston Health Sciences Centre | Kingston | Ontario | Canada | K7L 2V7 |
| 221 | Children's Hospital | London | Ontario | Canada | N6A 5W9 |
| 222 | Victoria Hospital | London | Ontario | Canada | N6K 1C2 |
| 223 | Children's Hospital of Eastern Ontario | Ottawa | Ontario | Canada | K1H 8L1 |
| 224 | Hospital for Sick Children | Toronto | Ontario | Canada | M5G 1X8 |
| 225 | The Montreal Children's Hospital of the MUHC | Montreal | Quebec | Canada | H3H 1P3 |
| 226 | Centre Hospitalier Universitaire de Sherbrooke-Fleurimont | Sherbrooke | Quebec | Canada | J1H 5N4 |
| 227 | Allan Blair Cancer Centre | Regina | Saskatchewan | Canada | S4T 7T1 |
| 228 | Saskatoon Cancer Centre | Saskatoon | Saskatchewan | Canada | S7N 4H4 |
| 229 | Starship Children's Hospital | Grafton | Auckland | New Zealand | 1145 |
| 230 | Christchurch Hospital | Christchurch | New Zealand | 8011 | |
| 231 | Wellington Children's Hospital | Wellington | New Zealand | 6002 | |
| 232 | Swiss Pediatric Oncology Group - Bern | Bern | Switzerland | 3010 | |
| 233 | Swiss Pediatric Oncology Group - Geneva | Geneva | Switzerland | 1205 | |
| 234 | Swiss Pediatric Oncology Group - Lausanne | Lausanne | Switzerland | 1011 |
Sponsors and Collaborators
- Children's Oncology Group
- National Cancer Institute (NCI)
Investigators
- Principal Investigator: Eric C Larsen, Children's Oncology Group
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.Responsible Party:
Children's Oncology Group
ClinicalTrials.gov Identifier:
NCT00075725
Other Study ID Numbers:
- AALL0232
- NCI-2009-00301
- COG-AALL0232
- CDR0000349182
- 11723
- AALL0232
- AALL0232
- U10CA098543
First Posted:
Jan 13, 2004
Last Update Posted:
Apr 27, 2021
Last Verified:
Apr 1, 2021
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | Dexamethasone and Capizzi Methotrexate Patients < 10 Years | Dexamethasone, High Dose Methotrexate (Non Randomly Assigned) | Dexamethasone & Capizzi Methotrexate Patients => 10 Years Old | Dexamethasone, High Dose Methotrexate (IM) < 10 Years | Prednisone, Capizzi Methotrexate <10 Years | Prednisone, Capezzi Methotrexate >= 10 Years | Prednisone and High Dose Methotrexate < 10 Yrs Old | Prednisone and High Dose Methotrexate >=10 Years | Dexamethasone, High Dose Methotrexate (IM) >= 10 Years | Prednisone, Capezzi Methotrexate (Down's Syndrome) | Dexamethasone, Capizzi Methotrexate Down Syndrome (Non Random) | Prednisone and High Dose Methotrexate (Non Randomly Assigned) |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Patients receive intrathecal cytarabine (Age-based dosing: Age (yrs) Dose 1 - 1.99 30 mg 2 - 2.99 50 mg ≥ 3 70 mg) on day 1; infusions of vincristine sulfate 1.5 mg/m2/dose (maximum dose of 2 mg) on Days 1, 8, 15 and 22 and daunorubicin hydrochloride (25 mg/m2/dose on Days 1, 8, 15 and 22. Dexamethasone (5 mg/m2/dose on Days 1-14 by mouth or infusion twice a day in weeks 1 and 2; intrathecal methotrexate (Aged based dosing: Age (yrs) Dose 1 - 1.99 8 mg 2 - 2.99 10 mg 3 - 8.99 12 mg ≥ 9 15 mg) on days 8 and 29 (CNS3 also on days 15 & 22) and an injection of pegaspargase (2500 International units/m2 x 1 dose on Day 4, 5 or 6). | Patients non-randomly assigned to the DH (High Dose) regimen based on one (or more) of the following characteristics: (1) CNS3 status at entry, (2) testicular leukemic involvement at entry, or (3) extensive pre-treatment with steroids prior to entry. Patients receive intrathecal cytarabine (Age-based dosing: Age (yrs) Dose 1 - 1.99 30 mg 2 - 2.99 50 mg ≥ 3 70 mg) on day 1; infusions of vincristine sulfate 1.5 mg/m2/dose (maximum dose of 2 mg) on Days 1, 8, 15 and 22 and daunorubicin hydrochloride (25 mg/m2/dose on Days 1, 8, 15 and 22. Dexamethasone (5 mg/m2/dose on Days 1-14 by mouth or infusion twice a day in weeks 1 and 2; intrathecal methotrexate (Aged based dosing: Age (yrs) Dose 1 - 1.99 8 mg 2 - 2.99 10 mg 3 - 8.99 12 mg ≥ 9 15 mg) on days 8 and 29 (CNS3 also on days 15 & 22) and an injection of pegaspargase (2500 International units/m2 x 1 dose on Day 4, 5 or 6). | Patients receive intrathecal cytarabine (Age-based dosing: Age (yrs) Dose 1 - 1.99 30 mg 2 - 2.99 50 mg ≥ 3 70 mg) on day 1; infusions of vincristine sulfate 1.5 mg/m2/dose (maximum dose of 2 mg) on Days 1, 8, 15 and 22 and daunorubicin hydrochloride (25 mg/m2/dose on Days 1, 8, 15 and 22. Dexamethasone (5 mg/m2/dose on Days 1-14 by mouth or infusion twice a day in weeks 1 and 2; intrathecal methotrexate (Aged based dosing: Age (yrs) Dose 1 - 1.99 8 mg 2 - 2.99 10 mg 3 - 8.99 12 mg ≥ 9 15 mg) on days 8 and 29 (CNS3 also on days 15 & 22) and an injection of pegaspargase (2500 International units/m2 x 1 dose on Day 4, 5 or 6). | Patients randomly assigned to the DH regimen based on one (or more) of the following characteristics: (1) No CNS3 status at entry, (2) no testicular leukemic involvement at entry, or (3) no extensive pre-treatment with steroids prior to entry. Patients receive intrathecal cytarabine (Age-based dosing: Age (yrs) Dose 1 - 1.99 30 mg 2 - 2.99 50 mg ≥ 3 70 mg) on day 1; infusions of vincristine sulfate 1.5 mg/m2/dose (maximum dose of 2 mg) on Days 1, 8, 15 and 22 and daunorubicin hydrochloride (25 mg/m2/dose on Days 1, 8, 15 and 22. Dexamethasone (5 mg/m2/dose on Days 1-14 by mouth or infusion twice a day in weeks 1 and 2; intrathecal methotrexate (Aged based dosing: Age (yrs) Dose 1 - 1.99 8 mg 2 - 2.99 10 mg 3 - 8.99 12 mg ≥ 9 15 mg) on days 8 and 29 (CNS3 also on days 15 & 22) and an injection of pegaspargase (2500 International units/m2 x 1 dose on Day 4, 5 or 6). | Patients in regimen PC (Prednisone, Capizzi) will receive cytarabine, vincristine sulfate, daunorubicin hydrochloride, and pegaspargase. They will also receive prednisone by mouth or infusion twice a day in weeks 1-4 and intrathecal methotrexate in weeks 2 and 5. Some patients in all groups may receive induction therapy for 2 additional weeks. Beginning in week 6 or 7, patients may receive combination chemotherapy (vincristine sulfate, dexamethasone, doxorubicin hydrochloride, pegaspargase, cyclophosphamide, mercaptopurine, cytarabine, thioguanine) by infusion, injection, intrathecally, and by mouth for up to 8 weeks. | Patients in regimen PC will receive cytarabine, vincristine sulfate, daunorubicin hydrochloride, and pegaspargase. They will also receive prednisone by mouth or infusion twice a day in weeks 1-4 and intrathecal methotrexate in weeks 2 and 5. Some patients in all groups may receive induction therapy for 2 additional weeks. Beginning in week 6 or 7, patients may receive combination chemotherapy (vincristine sulfate, dexamethasone, doxorubicin hydrochloride, pegaspargase, cyclophosphamide, mercaptopurine, cytarabine, thioguanine) by infusion, injection, intrathecally, and by mouth for up to 8 weeks. | Patients randomly assigned to the PH (Prednisone, High Dose MTX) regimen receive intrathecal cytarabine (Age-based dosing: Age (yrs) Dose 1 - 1.99 30 mg 2 - 2.99 50 mg ≥ 3 70 mg) on day 1; infusions of vincristine sulfate 1.5 mg/m2/dose (maximum dose of 2 mg) on Days 1, 8, 15 and 22 and daunorubicin hydrochloride (25 mg/m2/dose on Days 1, 8, 15 and 22. They will also receive prednisone by mouth or infusion twice a day in weeks 1-4 and intrathecal methotrexate in weeks 2 and 5. Some patients in all groups may receive induction therapy for 2 additional weeks. Beginning in week 6 or 7, patients may receive combination chemotherapy (vincristine sulfate, dexamethasone, doxorubicin hydrochloride, pegaspargase, cyclophosphamide, mercaptopurine, cytarabine, thioguanine) by infusion, injection, intrathecally, and by mouth for up to 8 weeks. | Patients randomly assigned to the PH regimen receive intrathecal cytarabine (Age-based dosing: Age (yrs) Dose 1 - 1.99 30 mg 2 - 2.99 50 mg ≥ 3 70 mg) on day 1; infusions of vincristine sulfate 1.5 mg/m2/dose (maximum dose of 2 mg) on Days 1, 8, 15 and 22 and daunorubicin hydrochloride (25 mg/m2/dose on Days 1, 8, 15 and 22. They will also receive prednisone by mouth or infusion twice a day in weeks 1-4 and intrathecal methotrexate in weeks 2 and 5. Some patients in all groups may receive induction therapy for 2 additional weeks. Beginning in week 6 or 7, patients may receive combination chemotherapy (vincristine sulfate, dexamethasone, doxorubicin hydrochloride, pegaspargase, cyclophosphamide, mercaptopurine, cytarabine, thioguanine) by infusion, injection, intrathecally, and by mouth for up to 8 weeks. | Patients randomly assigned to the DH regimen based on one (or more) of the following characteristics: (1) No CNS3 status at entry, (2) no testicular leukemic involvement at entry, or (3) no extensive pre-treatment with steroids prior to entry. Patients receive intrathecal cytarabine (Age-based dosing: Age (yrs) Dose 1 - 1.99 30 mg 2 - 2.99 50 mg ≥ 3 70 mg) on day 1; infusions of vincristine sulfate 1.5 mg/m2/dose (maximum dose of 2 mg) on Days 1, 8, 15 and 22 and daunorubicin hydrochloride (25 mg/m2/dose on Days 1, 8, 15 and 22. Dexamethasone (5 mg/m2/dose on Days 1-14 by mouth or infusion twice a day in weeks 1 and 2; intrathecal methotrexate (Aged based dosing: Age (yrs) Dose 1 - 1.99 8 mg 2 - 2.99 10 mg 3 - 8.99 12 mg ≥ 9 15 mg) on days 8 and 29 (CNS3 also on days 15 & 22) and an injection of pegaspargase (2500 International units/m2 x 1 dose on Day 4, 5 or 6). | Patients in regimen PC will receive cytarabine, vincristine sulfate, daunorubicin hydrochloride, and pegaspargase. They will also receive prednisone by mouth or infusion twice a day in weeks 1-4 and intrathecal methotrexate in weeks 2 and 5. Some patients in all groups may receive induction therapy for 2 additional weeks. Beginning in week 6 or 7, patients may receive combination chemotherapy (vincristine sulfate, dexamethasone, doxorubicin hydrochloride, pegaspargase, cyclophosphamide, mercaptopurine, cytarabine, thioguanine) by infusion, injection, intrathecally, and by mouth for up to 8 weeks. | Patients receive intrathecal cytarabine (Age-based dosing: Age (yrs) Dose 1 - 1.99 30 mg 2 - 2.99 50 mg ≥ 3 70 mg) on day 1; infusions of vincristine sulfate 1.5 mg/m2/dose (maximum dose of 2 mg) on Days 1, 8, 15 and 22 and daunorubicin hydrochloride (25 mg/m2/dose on Days 1, 8, 15 and 22. Dexamethasone (5 mg/m2/dose on Days 1-14 by mouth or infusion twice a day in weeks 1 and 2; intrathecal methotrexate (Aged based dosing: Age (yrs) Dose 1 - 1.99 8 mg 2 - 2.99 10 mg 3 - 8.99 12 mg ≥ 9 15 mg) on days 8 and 29 (CNS3 also on days 15 & 22) and an injection of pegaspargase (2500 International units/m2 x 1 dose on Day 4, 5 or 6). | Patients non-randomly assigned to the PH regimen based on one (or more) of the following: (1) CNS3 status at entry, (2) testicular leukemic involvement at entry, or (3) extensive pre-treatment with steroids prior to entry. Patients receive intrathecal cytarabine (Age-based dosing: Age (yrs) Dose 1 - 1.99 30 mg 2 - 2.99 50 mg ≥ 3 70 mg) on day 1; infusions of vincristine sulfate 1.5 mg/m2/dose (maximum dose of 2 mg) on Days 1, 8, 15 and 22 and daunorubicin hydrochloride (25 mg/m2/dose on Days 1, 8, 15 and 22. They will also receive prednisone by mouth or infusion twice a day in weeks 1-4 and intrathecal MTX in weeks 2 and 5. Some patients in all groups may receive induction therapy for 2 additional weeks. Beginning in week 6 or 7, patients may receive combination chemotherapy (vincristine sulfate, dexamethasone, doxorubicin hydrochloride, pegaspargase, cyclophosphamide, mercaptopurine, cytarabine, thioguanine) by infusion, injection, intrathecally, and by mouth for up to 8 weeks. |
| Period Title: Overall Study | ||||||||||||
| STARTED | 246 | 106 | 296 | 246 | 232 | 710 | 246 | 696 | 302 | 34 | 12 | 28 |
| COMPLETED | 172 | 57 | 175 | 168 | 166 | 397 | 171 | 401 | 185 | 16 | 3 | 10 |
| NOT COMPLETED | 74 | 49 | 121 | 78 | 66 | 313 | 75 | 295 | 117 | 18 | 9 | 18 |
Baseline Characteristics
| Arm/Group Title | Dexamethasone and Capizzi Methotrexate Patients < 10 Years | Dexamethasone, High Dose Methotrexate (Non Randomly Assigned) | Dexamethasone & Capizzi Methotrexate Patients => 10 Years Old | Dexamethasone, High Dose Methotrexate (IM) < 10 Years | Prednisone, Capizzi Methotrexate <10 Years | Prednisone, Capezzi Methotrexate >= 10 Years | Prednisone and High Dose Methotrexate < 10 Yrs Old | Prednisone and High Dose Methotrexate >=10 Years | Dexamethasone, High Dose Methotrexate (IM) >= 10 Years | Prednisone, Capezzi Methotrexate (Down's Syndrome) | Dexamethasone, Capizzi Methotrexate Down Syndrome | Prednisone and High Dose Methotrexate (Non Randomly Assigned) | Total |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Patients receive intrathecal cytarabine (Age-based dosing: Age (yrs) Dose 1 - 1.99 30 mg 2 - 2.99 50 mg ≥ 3 70 mg) on day 1; infusions of vincristine sulfate 1.5 mg/m2/dose (maximum dose of 2 mg) on Days 1, 8, 15 and 22 and daunorubicin hydrochloride (25 mg/m2/dose on Days 1, 8, 15 and 22. Dexamethasone (5 mg/m2/dose on Days 1-14 by mouth or infusion twice a day in weeks 1 and 2; intrathecal methotrexate (Aged based dosing: Age (yrs) Dose 1 - 1.99 8 mg 2 - 2.99 10 mg 3 - 8.99 12 mg ≥ 9 15 mg) on days 8 and 29 (CNS3 also on days 15 & 22) and an injection of pegaspargase (2500 International units/m2 x 1 dose on Day 4, 5 or 6). | Patients non-randomly assigned to the DH regimen based on one (or more) of the following characteristics: (1) CNS3 status at entry, (2) testicular leukemic involvement at entry, or (3) extensive pre-treatment with steroids prior to entry. Patients receive intrathecal cytarabine (Age-based dosing: Age (yrs) Dose 1 - 1.99 30 mg 2 - 2.99 50 mg ≥ 3 70 mg) on day 1; infusions of vincristine sulfate 1.5 mg/m2/dose (maximum dose of 2 mg) on Days 1, 8, 15 and 22 and daunorubicin hydrochloride (25 mg/m2/dose on Days 1, 8, 15 and 22. Dexamethasone (5 mg/m2/dose on Days 1-14 by mouth or infusion twice a day in weeks 1 and 2; intrathecal methotrexate (Aged based dosing: Age (yrs) Dose 1 - 1.99 8 mg 2 - 2.99 10 mg 3 - 8.99 12 mg ≥ 9 15 mg) on days 8 and 29 (CNS3 also on days 15 & 22) and an injection of pegaspargase (2500 International units/m2 x 1 dose on Day 4, 5 or 6). | Patients receive intrathecal cytarabine (Age-based dosing: Age (yrs) Dose 1 - 1.99 30 mg 2 - 2.99 50 mg ≥ 3 70 mg) on day 1; infusions of vincristine sulfate 1.5 mg/m2/dose (maximum dose of 2 mg) on Days 1, 8, 15 and 22 and daunorubicin hydrochloride (25 mg/m2/dose on Days 1, 8, 15 and 22. Dexamethasone (5 mg/m2/dose on Days 1-14 by mouth or infusion twice a day in weeks 1 and 2; intrathecal methotrexate (Aged based dosing: Age (yrs) Dose 1 - 1.99 8 mg 2 - 2.99 10 mg 3 - 8.99 12 mg ≥ 9 15 mg) on days 8 and 29 (CNS3 also on days 15 & 22) and an injection of pegaspargase (2500 International units/m2 x 1 dose on Day 4, 5 or 6). | Patients randomly assigned to the DH regimen based on one (or more) of the following characteristics: (1) No CNS3 status at entry, (2) no testicular leukemic involvement at entry, or (3) no extensive pre-treatment with steroids prior to entry. Patients receive intrathecal cytarabine (Age-based dosing: Age (yrs) Dose 1 - 1.99 30 mg 2 - 2.99 50 mg ≥ 3 70 mg) on day 1; infusions of vincristine sulfate 1.5 mg/m2/dose (maximum dose of 2 mg) on Days 1, 8, 15 and 22 and daunorubicin hydrochloride (25 mg/m2/dose on Days 1, 8, 15 and 22. Dexamethasone (5 mg/m2/dose on Days 1-14 by mouth or infusion twice a day in weeks 1 and 2; intrathecal methotrexate (Aged based dosing: Age (yrs) Dose 1 - 1.99 8 mg 2 - 2.99 10 mg 3 - 8.99 12 mg ≥ 9 15 mg) on days 8 and 29 (CNS3 also on days 15 & 22) and an injection of pegaspargase (2500 International units/m2 x 1 dose on Day 4, 5 or 6). | Patients in regimen PC will receive cytarabine, vincristine sulfate, daunorubicin hydrochloride, and pegaspargase. They will also receive prednisone by mouth or infusion twice a day in weeks 1-4 and intrathecal methotrexate in weeks 2 and 5. Some patients in all groups may receive induction therapy for 2 additional weeks. Beginning in week 6 or 7, patients may receive combination chemotherapy (vincristine sulfate, dexamethasone, doxorubicin hydrochloride, pegaspargase, cyclophosphamide, mercaptopurine, cytarabine, thioguanine) by infusion, injection, intrathecally, and by mouth for up to 8 weeks. | Patients in regimen PC will receive cytarabine, vincristine sulfate, daunorubicin hydrochloride, and pegaspargase. They will also receive prednisone by mouth or infusion twice a day in weeks 1-4 and intrathecal methotrexate in weeks 2 and 5. Some patients in all groups may receive induction therapy for 2 additional weeks. Beginning in week 6 or 7, patients may receive combination chemotherapy (vincristine sulfate, dexamethasone, doxorubicin hydrochloride, pegaspargase, cyclophosphamide, mercaptopurine, cytarabine, thioguanine) by infusion, injection, intrathecally, and by mouth for up to 8 weeks. | Patients randomly assigned to the PH regimen receive intrathecal cytarabine (Age-based dosing: Age (yrs) Dose 1 - 1.99 30 mg 2 - 2.99 50 mg ≥ 3 70 mg) on day 1; infusions of vincristine sulfate 1.5 mg/m2/dose (maximum dose of 2 mg) on Days 1, 8, 15 and 22 and daunorubicin hydrochloride (25 mg/m2/dose on Days 1, 8, 15 and 22. They will also receive prednisone by mouth or infusion twice a day in weeks 1-4 and intrathecal methotrexate in weeks 2 and 5. Some patients in all groups may receive induction therapy for 2 additional weeks. Beginning in week 6 or 7, patients may receive combination chemotherapy (vincristine sulfate, dexamethasone, doxorubicin hydrochloride, pegaspargase, cyclophosphamide, mercaptopurine, cytarabine, thioguanine) by infusion, injection, intrathecally, and by mouth for up to 8 weeks. | Patients randomly assigned to the PH regimen receive intrathecal cytarabine (Age-based dosing: Age (yrs) Dose 1 - 1.99 30 mg 2 - 2.99 50 mg ≥ 3 70 mg) on day 1; infusions of vincristine sulfate 1.5 mg/m2/dose (maximum dose of 2 mg) on Days 1, 8, 15 and 22 and daunorubicin hydrochloride (25 mg/m2/dose on Days 1, 8, 15 and 22. They will also receive prednisone by mouth or infusion twice a day in weeks 1-4 and intrathecal methotrexate in weeks 2 and 5. Some patients in all groups may receive induction therapy for 2 additional weeks. Beginning in week 6 or 7, patients may receive combination chemotherapy (vincristine sulfate, dexamethasone, doxorubicin hydrochloride, pegaspargase, cyclophosphamide, mercaptopurine, cytarabine, thioguanine) by infusion, injection, intrathecally, and by mouth for up to 8 weeks. | Patients randomly assigned to the DH regimen based on one (or more) of the following characteristics: (1) No CNS3 status at entry, (2) no testicular leukemic involvement at entry, or (3) no extensive pre-treatment with steroids prior to entry. Patients receive intrathecal cytarabine (Age-based dosing: Age (yrs) Dose 1 - 1.99 30 mg 2 - 2.99 50 mg ≥ 3 70 mg) on day 1; infusions of vincristine sulfate 1.5 mg/m2/dose (maximum dose of 2 mg) on Days 1, 8, 15 and 22 and daunorubicin hydrochloride (25 mg/m2/dose on Days 1, 8, 15 and 22. Dexamethasone (5 mg/m2/dose on Days 1-14 by mouth or infusion twice a day in weeks 1 and 2; intrathecal methotrexate (Aged based dosing: Age (yrs) Dose 1 - 1.99 8 mg 2 - 2.99 10 mg 3 - 8.99 12 mg ≥ 9 15 mg) on days 8 and 29 (CNS3 also on days 15 & 22) and an injection of pegaspargase (2500 International units/m2 x 1 dose on Day 4, 5 or 6). | Patients in regimen PC will receive cytarabine, vincristine sulfate, daunorubicin hydrochloride, and pegaspargase. They will also receive prednisone by mouth or infusion twice a day in weeks 1-4 and intrathecal methotrexate in weeks 2 and 5. Some patients in all groups may receive induction therapy for 2 additional weeks. Beginning in week 6 or 7, patients may receive combination chemotherapy (vincristine sulfate, dexamethasone, doxorubicin hydrochloride, pegaspargase, cyclophosphamide, mercaptopurine, cytarabine, thioguanine) by infusion, injection, intrathecally, and by mouth for up to 8 weeks. | Patients receive intrathecal cytarabine (Age-based dosing: Age (yrs) Dose 1 - 1.99 30 mg 2 - 2.99 50 mg ≥ 3 70 mg) on day 1; infusions of vincristine sulfate 1.5 mg/m2/dose (maximum dose of 2 mg) on Days 1, 8, 15 and 22 and daunorubicin hydrochloride (25 mg/m2/dose on Days 1, 8, 15 and 22. Dexamethasone (5 mg/m2/dose on Days 1-14 by mouth or infusion twice a day in weeks 1 and 2; intrathecal methotrexate (Aged based dosing: Age (yrs) Dose 1 - 1.99 8 mg 2 - 2.99 10 mg 3 - 8.99 12 mg ≥ 9 15 mg) on days 8 and 29 (CNS3 also on days 15 & 22) and an injection of pegaspargase (2500 International units/m2 x 1 dose on Day 4, 5 or 6). | Patients non-randomly assigned to the PH regimen based on one (or more) of the following characteristics: (1) CNS3 status at entry, (2) testicular leukemic involvement at entry, or (3) extensive pre-treatment with steroids prior to entry. Patients receive intrathecal cytarabine (Age-based dosing: Age (yrs) Dose 1 - 1.99 30 mg 2 - 2.99 50 mg ≥ 3 70 mg) on day 1; infusions of vincristine sulfate 1.5 mg/m2/dose (maximum dose of 2 mg) on Days 1, 8, 15 and 22 and daunorubicin hydrochloride (25 mg/m2/dose on Days 1, 8, 15 and 22. They will also receive prednisone by mouth or infusion twice a day in weeks 1-4 and intrathecal methotrexate in weeks 2 and 5. Some patients in all groups may receive induction therapy for 2 additional weeks. Beginning in week 6 or 7, patients may receive combination chemotherapy (vincristine sulfate, dexamethasone, doxorubicin hydrochloride, pegaspargase, cyclophosphamide, mercaptopurine, cytarabine, thioguanine) by infusion, injection, intrathecally, and by mouth | Total of all reporting groups |
| Overall Participants | 246 | 106 | 296 | 246 | 232 | 710 | 246 | 696 | 302 | 34 | 12 | 28 | 3154 |
| Age (Count of Participants) | |||||||||||||
| <=18 years |
246
100%
|
96
90.6%
|
275
92.9%
|
246
100%
|
232
100%
|
641
90.3%
|
246
100%
|
610
87.6%
|
266
88.1%
|
30
88.2%
|
10
83.3%
|
26
92.9%
|
2924
92.7%
|
| Between 18 and 65 years |
0
0%
|
10
9.4%
|
21
7.1%
|
0
0%
|
0
0%
|
69
9.7%
|
0
0%
|
86
12.4%
|
36
11.9%
|
4
11.8%
|
2
16.7%
|
2
7.1%
|
230
7.3%
|
| >=65 years |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Age (years) [Mean (Standard Deviation) ] | |||||||||||||
| Mean (Standard Deviation) [years] |
4.0
(2.3)
|
9.3
(6.0)
|
14.1
(2.8)
|
4.1
(2.2)
|
4.2
(2.2)
|
14.7
(3.3)
|
4.2
(2.2)
|
14.5
(3.2)
|
14.6
(2.9)
|
10.5
(5.7)
|
12.3
(6.6)
|
14.4
(2.9)
|
10.8
(5.7)
|
| Sex: Female, Male (Count of Participants) | |||||||||||||
| Female |
129
52.4%
|
31
29.2%
|
135
45.6%
|
117
47.6%
|
106
45.7%
|
321
45.2%
|
108
43.9%
|
288
41.4%
|
128
42.4%
|
18
52.9%
|
7
58.3%
|
11
39.3%
|
1399
44.4%
|
| Male |
117
47.6%
|
75
70.8%
|
161
54.4%
|
129
52.4%
|
126
54.3%
|
389
54.8%
|
138
56.1%
|
408
58.6%
|
174
57.6%
|
16
47.1%
|
5
41.7%
|
17
60.7%
|
1755
55.6%
|
| Ethnicity (NIH/OMB) (Count of Participants) | |||||||||||||
| Hispanic or Latino |
54
22%
|
22
20.8%
|
62
20.9%
|
55
22.4%
|
62
26.7%
|
167
23.5%
|
61
24.8%
|
168
24.1%
|
69
22.8%
|
6
17.6%
|
0
0%
|
7
25%
|
733
23.2%
|
| Not Hispanic or Latino |
179
72.8%
|
81
76.4%
|
217
73.3%
|
182
74%
|
165
71.1%
|
516
72.7%
|
179
72.8%
|
504
72.4%
|
219
72.5%
|
27
79.4%
|
10
83.3%
|
20
71.4%
|
2299
72.9%
|
| Unknown or Not Reported |
13
5.3%
|
3
2.8%
|
17
5.7%
|
9
3.7%
|
5
2.2%
|
27
3.8%
|
6
2.4%
|
24
3.4%
|
14
4.6%
|
1
2.9%
|
2
16.7%
|
1
3.6%
|
122
3.9%
|
| Race (NIH/OMB) (Count of Participants) | |||||||||||||
| American Indian or Alaska Native |
0
0%
|
0
0%
|
0
0%
|
1
0.4%
|
0
0%
|
4
0.6%
|
1
0.4%
|
7
1%
|
2
0.7%
|
1
2.9%
|
2
16.7%
|
0
0%
|
18
0.6%
|
| Asian |
8
3.3%
|
6
5.7%
|
11
3.7%
|
9
3.7%
|
7
3%
|
21
3%
|
8
3.3%
|
27
3.9%
|
18
6%
|
2
5.9%
|
0
0%
|
0
0%
|
117
3.7%
|
| Native Hawaiian or Other Pacific Islander |
2
0.8%
|
1
0.9%
|
1
0.3%
|
2
0.8%
|
1
0.4%
|
5
0.7%
|
5
2%
|
6
0.9%
|
2
0.7%
|
0
0%
|
0
0%
|
0
0%
|
25
0.8%
|
| Black or African American |
12
4.9%
|
14
13.2%
|
24
8.1%
|
12
4.9%
|
15
6.5%
|
55
7.7%
|
14
5.7%
|
51
7.3%
|
19
6.3%
|
2
5.9%
|
0
0%
|
1
3.6%
|
219
6.9%
|
| White |
196
79.7%
|
76
71.7%
|
235
79.4%
|
187
76%
|
175
75.4%
|
534
75.2%
|
187
76%
|
519
74.6%
|
227
75.2%
|
26
76.5%
|
9
75%
|
24
85.7%
|
2395
75.9%
|
| More than one race |
3
1.2%
|
3
2.8%
|
1
0.3%
|
8
3.3%
|
5
2.2%
|
8
1.1%
|
5
2%
|
4
0.6%
|
3
1%
|
0
0%
|
0
0%
|
0
0%
|
40
1.3%
|
| Unknown or Not Reported |
25
10.2%
|
6
5.7%
|
24
8.1%
|
27
11%
|
29
12.5%
|
83
11.7%
|
26
10.6%
|
82
11.8%
|
31
10.3%
|
3
8.8%
|
1
8.3%
|
3
10.7%
|
340
10.8%
|
Outcome Measures
| Title | Comparison of the Increase in Cure Rate of High Risk ALL Without Causing More Serious Side Effects Between Interventions |
|---|---|
| Description | Event Free Probability. |
| Time Frame | 5 years |
Outcome Measure Data
| Analysis Population Description |
|---|
| Group "Prednisone and High Dose MTX (non-random)" who either had EFS events occur before 5 years or did not have minimum 5 years of follow-up. |
| Arm/Group Title | Dexamethasone and Capizzi Methotrexate Patients < 10 Years | Dexamethasone, High Dose Methotrexate (Non Randomly Assigned) | Dexamethasone & Capizzi Methotrexate Patients => 10 Years Old | Dexamethasone, High Dose Methotrexate (IM) < 10 Years | Prednisone, Capizzi Methotrexate <10 Years | Prednisone, Capezzi Methotrexate >= 10 Years | Predisone and High Dose Methotrexate < 10 Yrs Old | Prenisone and High Dose Methotrexate >=10 Years | Dexamethasone, High Dose Methotrexate (IM) >= 10 Years | Prenisone, Capezzi Methotrexate (Down's Syndrome) | Dexamethasone, Capizzi Methotrexate Down Syndrome (Non Random) |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Patients receive intrathecal cytarabine (Age-based dosing: Age (yrs) Dose 1 - 1.99 30 mg 2 - 2.99 50 mg ≥ 3 70 mg) on day 1; infusions of vincristine sulfate 1.5 mg/m2/dose (maximum dose of 2 mg) on Days 1, 8, 15 and 22 and daunorubicin hydrochloride (25 mg/m2/dose on Days 1, 8, 15 and 22. Dexamethasone (5 mg/m2/dose on Days 1-14 by mouth or infusion twice a day in weeks 1 and 2; intrathecal methotrexate (Aged based dosing: Age (yrs) Dose 1 - 1.99 8 mg 2 - 2.99 10 mg 3 - 8.99 12 mg ≥ 9 15 mg) on days 8 and 29 (CNS3 also on days 15 & 22) and an injection of pegaspargase (2500 International units/m2 x 1 dose on Day 4, 5 or 6). | Patients non-randomly assigned to the DH regimen based on one (or more) of the following characteristics: (1) CNS3 status at entry, (2) testicular leukemic involvement at entry, or (3) extensive pre-treatment with steroids prior to entry. Patients receive intrathecal cytarabine (Age-based dosing: Age (yrs) Dose 1 - 1.99 30 mg 2 - 2.99 50 mg ≥ 3 70 mg) on day 1; infusions of vincristine sulfate 1.5 mg/m2/dose (maximum dose of 2 mg) on Days 1, 8, 15 and 22 and daunorubicin hydrochloride (25 mg/m2/dose on Days 1, 8, 15 and 22. Dexamethasone (5 mg/m2/dose on Days 1-14 by mouth or infusion twice a day in weeks 1 and 2; intrathecal methotrexate (Aged based dosing: Age (yrs) Dose 1 - 1.99 8 mg 2 - 2.99 10 mg 3 - 8.99 12 mg ≥ 9 15 mg) on days 8 and 29 (CNS3 also on days 15 & 22) and an injection of pegaspargase (2500 International units/m2 x 1 dose on Day 4, 5 or 6). | Patients receive intrathecal cytarabine (Age-based dosing: Age (yrs) Dose 1 - 1.99 30 mg 2 - 2.99 50 mg ≥ 3 70 mg) on day 1; infusions of vincristine sulfate 1.5 mg/m2/dose (maximum dose of 2 mg) on Days 1, 8, 15 and 22 and daunorubicin hydrochloride (25 mg/m2/dose on Days 1, 8, 15 and 22. Dexamethasone (5 mg/m2/dose on Days 1-14 by mouth or infusion twice a day in weeks 1 and 2; intrathecal methotrexate (Aged based dosing: Age (yrs) Dose 1 - 1.99 8 mg 2 - 2.99 10 mg 3 - 8.99 12 mg ≥ 9 15 mg) on days 8 and 29 (CNS3 also on days 15 & 22) and an injection of pegaspargase (2500 International units/m2 x 1 dose on Day 4, 5 or 6). | Patients randomly assigned to the DH regimen based on one (or more) of the following characteristics: (1) No CNS3 status at entry, (2) no testicular leukemic involvement at entry, or (3) no extensive pre-treatment with steroids prior to entry. Patients receive intrathecal cytarabine (Age-based dosing: Age (yrs) Dose 1 - 1.99 30 mg 2 - 2.99 50 mg ≥ 3 70 mg) on day 1; infusions of vincristine sulfate 1.5 mg/m2/dose (maximum dose of 2 mg) on Days 1, 8, 15 and 22 and daunorubicin hydrochloride (25 mg/m2/dose on Days 1, 8, 15 and 22. Dexamethasone (5 mg/m2/dose on Days 1-14 by mouth or infusion twice a day in weeks 1 and 2; intrathecal methotrexate (Aged based dosing: Age (yrs) Dose 1 - 1.99 8 mg 2 - 2.99 10 mg 3 - 8.99 12 mg ≥ 9 15 mg) on days 8 and 29 (CNS3 also on days 15 & 22) and an injection of pegaspargase (2500 International units/m2 x 1 dose on Day 4, 5 or 6). | Patients in regimen PC will receive cytarabine, vincristine sulfate, daunorubicin hydrochloride, and pegaspargase. They will also receive prednisone by mouth or infusion twice a day in weeks 1-4 and intrathecal methotrexate in weeks 2 and 5. Some patients in all groups may receive induction therapy for 2 additional weeks. Beginning in week 6 or 7, patients may receive combination chemotherapy (vincristine sulfate, dexamethasone, doxorubicin hydrochloride, pegaspargase, cyclophosphamide, mercaptopurine, cytarabine, thioguanine) by infusion, injection, intrathecally, and by mouth for up to 8 weeks. | Patients in regimen PC will receive cytarabine, vincristine sulfate, daunorubicin hydrochloride, and pegaspargase. They will also receive prednisone by mouth or infusion twice a day in weeks 1-4 and intrathecal methotrexate in weeks 2 and 5. Some patients in all groups may receive induction therapy for 2 additional weeks. Beginning in week 6 or 7, patients may receive combination chemotherapy (vincristine sulfate, dexamethasone, doxorubicin hydrochloride, pegaspargase, cyclophosphamide, mercaptopurine, cytarabine, thioguanine) by infusion, injection, intrathecally, and by mouth for up to 8 weeks. | Patients randomly assigned to the PH regimen receive intrathecal cytarabine (Age-based dosing: Age (yrs) Dose 1 - 1.99 30 mg 2 - 2.99 50 mg ≥ 3 70 mg) on day 1; infusions of vincristine sulfate 1.5 mg/m2/dose (maximum dose of 2 mg) on Days 1, 8, 15 and 22 and daunorubicin hydrochloride (25 mg/m2/dose on Days 1, 8, 15 and 22. They will also receive prednisone by mouth or infusion twice a day in weeks 1-4 and intrathecal methotrexate in weeks 2 and 5. Some patients in all groups may receive induction therapy for 2 additional weeks. Beginning in week 6 or 7, patients may receive combination chemotherapy (vincristine sulfate, dexamethasone, doxorubicin hydrochloride, pegaspargase, cyclophosphamide, mercaptopurine, cytarabine, thioguanine) by infusion, injection, intrathecally, and by mouth for up to 8 weeks. | Patients randomly assigned to the PH regimen receive intrathecal cytarabine (Age-based dosing: Age (yrs) Dose 1 - 1.99 30 mg 2 - 2.99 50 mg ≥ 3 70 mg) on day 1; infusions of vincristine sulfate 1.5 mg/m2/dose (maximum dose of 2 mg) on Days 1, 8, 15 and 22 and daunorubicin hydrochloride (25 mg/m2/dose on Days 1, 8, 15 and 22. They will also receive prednisone by mouth or infusion twice a day in weeks 1-4 and intrathecal methotrexate in weeks 2 and 5. Some patients in all groups may receive induction therapy for 2 additional weeks. Beginning in week 6 or 7, patients may receive combination chemotherapy (vincristine sulfate, dexamethasone, doxorubicin hydrochloride, pegaspargase, cyclophosphamide, mercaptopurine, cytarabine, thioguanine) by infusion, injection, intrathecally, and by mouth for up to 8 weeks. | Patients randomly assigned to the DH regimen based on one (or more) of the following characteristics: (1) No CNS3 status at entry, (2) no testicular leukemic involvement at entry, or (3) no extensive pre-treatment with steroids prior to entry. Patients receive intrathecal cytarabine (Age-based dosing: Age (yrs) Dose 1 - 1.99 30 mg 2 - 2.99 50 mg ≥ 3 70 mg) on day 1; infusions of vincristine sulfate 1.5 mg/m2/dose (maximum dose of 2 mg) on Days 1, 8, 15 and 22 and daunorubicin hydrochloride (25 mg/m2/dose on Days 1, 8, 15 and 22. Dexamethasone (5 mg/m2/dose on Days 1-14 by mouth or infusion twice a day in weeks 1 and 2; intrathecal methotrexate (Aged based dosing: Age (yrs) Dose 1 - 1.99 8 mg 2 - 2.99 10 mg 3 - 8.99 12 mg ≥ 9 15 mg) on days 8 and 29 (CNS3 also on days 15 & 22) and an injection of pegaspargase (2500 International units/m2 x 1 dose on Day 4, 5 or 6). | Patients in regimen PC will receive cytarabine, vincristine sulfate, daunorubicin hydrochloride, and pegaspargase. They will also receive prednisone by mouth or infusion twice a day in weeks 1-4 and intrathecal methotrexate in weeks 2 and 5. Some patients in all groups may receive induction therapy for 2 additional weeks. Beginning in week 6 or 7, patients may receive combination chemotherapy (vincristine sulfate, dexamethasone, doxorubicin hydrochloride, pegaspargase, cyclophosphamide, mercaptopurine, cytarabine, thioguanine) by infusion, injection, intrathecally, and by mouth for up to 8 weeks. | Patients receive intrathecal cytarabine (Age-based dosing: Age (yrs) Dose 1 - 1.99 30 mg 2 - 2.99 50 mg ≥ 3 70 mg) on day 1; infusions of vincristine sulfate 1.5 mg/m2/dose (maximum dose of 2 mg) on Days 1, 8, 15 and 22 and daunorubicin hydrochloride (25 mg/m2/dose on Days 1, 8, 15 and 22. Dexamethasone (5 mg/m2/dose on Days 1-14 by mouth or infusion twice a day in weeks 1 and 2; intrathecal methotrexate (Aged based dosing: Age (yrs) Dose 1 - 1.99 8 mg 2 - 2.99 10 mg 3 - 8.99 12 mg ≥ 9 15 mg) on days 8 and 29 (CNS3 also on days 15 & 22) and an injection of pegaspargase (2500 International units/m2 x 1 dose on Day 4, 5 or 6). |
| Measure Participants | 218 | 90 | 261 | 206 | 214 | 598 | 213 | 601 | 262 | 30 | 9 |
| Number (95% Confidence Interval) [percentage of participants] |
83.2
33.8%
|
81.6
77%
|
69.1
23.3%
|
91.2
37.1%
|
82.1
35.4%
|
73.5
10.4%
|
80.8
32.8%
|
75.8
10.9%
|
77.0
25.5%
|
61.8
181.8%
|
44.4
370%
|
| Title | Correlation of Minimal Residual Disease (MRD) Positive With Overall Survival (OS) |
|---|---|
| Description | Bone marrow MRD status is defined as positive with >= 0.1 detectable leukemia cells, and negative with < 0.1 detectable leukemia cells. |
| Time Frame | 5 Years |
Outcome Measure Data
| Analysis Population Description |
|---|
| Groups "Prednisone Capizzi MTX (Down's Syndrome)", "Dexamethasone, Capizzi MTX (non-random)" & "Prednisone and High Dose MTX (non-random) are not included in this OM as no patients survived the 5 year window for analysis. Cohort of MRD Positive patients who either had EFS/OS events occur before 5 years or did not have minimum 5 years of follow-up. |
| Arm/Group Title | Dexamethasone and Capizzi Methotrexate Patients < 10 Years | Dexamethasone, High Dose Methotrexate (Non Randomly Assigned) | Dexamethasone & Capizzi Methotrexate Patients => 10 Years Old | Dexamethasone, High Dose Methotrexate (IM) < 10 Years | Prednisone, Capizzi Methotrexate <10 Years | Prednisone, Capizzi Methotrexate >= 10 Years | Predisone and High Dose Methotrexate < 10 Yrs Old | Prednisone and High Dose Methotrexate >=10 Years | Dexamethasone, High Dose Methotrexate (IM) >= 10 Years |
|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Patients receive intrathecal cytarabine (Age-based dosing: Age (yrs) Dose 1 - 1.99 30 mg 2 - 2.99 50 mg ≥ 3 70 mg) on day 1; infusions of vincristine sulfate 1.5 mg/m2/dose (maximum dose of 2 mg) on Days 1, 8, 15 and 22 and daunorubicin hydrochloride (25 mg/m2/dose on Days 1, 8, 15 and 22. Dexamethasone (5 mg/m2/dose on Days 1-14 by mouth or infusion twice a day in weeks 1 and 2; intrathecal methotrexate (Aged based dosing: Age (yrs) Dose 1 - 1.99 8 mg 2 - 2.99 10 mg 3 - 8.99 12 mg ≥ 9 15 mg) on days 8 and 29 (CNS3 also on days 15 & 22) and an injection of pegaspargase (2500 International units/m2 x 1 dose on Day 4, 5 or 6). | Patients non-randomly assigned to the DH regimen based on one (or more) of the following characteristics: (1) CNS3 status at entry, (2) testicular leukemic involvement at entry, or (3) extensive pre-treatment with steroids prior to entry. Patients receive intrathecal cytarabine (Age-based dosing: Age (yrs) Dose 1 - 1.99 30 mg 2 - 2.99 50 mg ≥ 3 70 mg) on day 1; infusions of vincristine sulfate 1.5 mg/m2/dose (maximum dose of 2 mg) on Days 1, 8, 15 and 22 and daunorubicin hydrochloride (25 mg/m2/dose on Days 1, 8, 15 and 22. Dexamethasone (5 mg/m2/dose on Days 1-14 by mouth or infusion twice a day in weeks 1 and 2; intrathecal methotrexate (Aged based dosing: Age (yrs) Dose 1 - 1.99 8 mg 2 - 2.99 10 mg 3 - 8.99 12 mg ≥ 9 15 mg) on days 8 and 29 (CNS3 also on days 15 & 22) and an injection of pegaspargase (2500 International units/m2 x 1 dose on Day 4, 5 or 6). | Patients receive intrathecal cytarabine (Age-based dosing: Age (yrs) Dose 1 - 1.99 30 mg 2 - 2.99 50 mg ≥ 3 70 mg) on day 1; infusions of vincristine sulfate 1.5 mg/m2/dose (maximum dose of 2 mg) on Days 1, 8, 15 and 22 and daunorubicin hydrochloride (25 mg/m2/dose on Days 1, 8, 15 and 22. Dexamethasone (5 mg/m2/dose on Days 1-14 by mouth or infusion twice a day in weeks 1 and 2; intrathecal methotrexate (Aged based dosing: Age (yrs) Dose 1 - 1.99 8 mg 2 - 2.99 10 mg 3 - 8.99 12 mg ≥ 9 15 mg) on days 8 and 29 (CNS3 also on days 15 & 22) and an injection of pegaspargase (2500 International units/m2 x 1 dose on Day 4, 5 or 6). | Patients randomly assigned to the DH regimen based on one (or more) of the following characteristics: (1) No CNS3 status at entry, (2) no testicular leukemic involvement at entry, or (3) no extensive pre-treatment with steroids prior to entry. Patients receive intrathecal cytarabine (Age-based dosing: Age (yrs) Dose 1 - 1.99 30 mg 2 - 2.99 50 mg ≥ 3 70 mg) on day 1; infusions of vincristine sulfate 1.5 mg/m2/dose (maximum dose of 2 mg) on Days 1, 8, 15 and 22 and daunorubicin hydrochloride (25 mg/m2/dose on Days 1, 8, 15 and 22. Dexamethasone (5 mg/m2/dose on Days 1-14 by mouth or infusion twice a day in weeks 1 and 2; intrathecal methotrexate (Aged based dosing: Age (yrs) Dose 1 - 1.99 8 mg 2 - 2.99 10 mg 3 - 8.99 12 mg ≥ 9 15 mg) on days 8 and 29 (CNS3 also on days 15 & 22) and an injection of pegaspargase (2500 International units/m2 x 1 dose on Day 4, 5 or 6). | Patients in regimen PC will receive cytarabine, vincristine sulfate, daunorubicin hydrochloride, and pegaspargase. They will also receive prednisone by mouth or infusion twice a day in weeks 1-4 and intrathecal methotrexate in weeks 2 and 5. Some patients in all groups may receive induction therapy for 2 additional weeks. Beginning in week 6 or 7, patients may receive combination chemotherapy (vincristine sulfate, dexamethasone, doxorubicin hydrochloride, pegaspargase, cyclophosphamide, mercaptopurine, cytarabine, thioguanine) by infusion, injection, intrathecally, and by mouth for up to 8 weeks. | Patients in regimen PC will receive cytarabine, vincristine sulfate, daunorubicin hydrochloride, and pegaspargase. They will also receive prednisone by mouth or infusion twice a day in weeks 1-4 and intrathecal methotrexate in weeks 2 and 5. Some patients in all groups may receive induction therapy for 2 additional weeks. Beginning in week 6 or 7, patients may receive combination chemotherapy (vincristine sulfate, dexamethasone, doxorubicin hydrochloride, pegaspargase, cyclophosphamide, mercaptopurine, cytarabine, thioguanine) by infusion, injection, intrathecally, and by mouth for up to 8 weeks. | Patients randomly assigned to the PH regimen receive intrathecal cytarabine (Age-based dosing: Age (yrs) Dose 1 - 1.99 30 mg 2 - 2.99 50 mg ≥ 3 70 mg) on day 1; infusions of vincristine sulfate 1.5 mg/m2/dose (maximum dose of 2 mg) on Days 1, 8, 15 and 22 and daunorubicin hydrochloride (25 mg/m2/dose on Days 1, 8, 15 and 22. They will also receive prednisone by mouth or infusion twice a day in weeks 1-4 and intrathecal methotrexate in weeks 2 and 5. Some patients in all groups may receive induction therapy for 2 additional weeks. Beginning in week 6 or 7, patients may receive combination chemotherapy (vincristine sulfate, dexamethasone, doxorubicin hydrochloride, pegaspargase, cyclophosphamide, mercaptopurine, cytarabine, thioguanine) by infusion, injection, intrathecally, and by mouth for up to 8 weeks. | Patients randomly assigned to the PH regimen receive intrathecal cytarabine (Age-based dosing: Age (yrs) Dose 1 - 1.99 30 mg 2 - 2.99 50 mg ≥ 3 70 mg) on day 1; infusions of vincristine sulfate 1.5 mg/m2/dose (maximum dose of 2 mg) on Days 1, 8, 15 and 22 and daunorubicin hydrochloride (25 mg/m2/dose on Days 1, 8, 15 and 22. They will also receive prednisone by mouth or infusion twice a day in weeks 1-4 and intrathecal methotrexate in weeks 2 and 5. Some patients in all groups may receive induction therapy for 2 additional weeks. Beginning in week 6 or 7, patients may receive combination chemotherapy (vincristine sulfate, dexamethasone, doxorubicin hydrochloride, pegaspargase, cyclophosphamide, mercaptopurine, cytarabine, thioguanine) by infusion, injection, intrathecally, and by mouth for up to 8 weeks. | Patients randomly assigned to the DH regimen based on one (or more) of the following characteristics: (1) No CNS3 status at entry, (2) no testicular leukemic involvement at entry, or (3) no extensive pre-treatment with steroids prior to entry. Patients receive intrathecal cytarabine (Age-based dosing: Age (yrs) Dose 1 - 1.99 30 mg 2 - 2.99 50 mg ≥ 3 70 mg) on day 1; infusions of vincristine sulfate 1.5 mg/m2/dose (maximum dose of 2 mg) on Days 1, 8, 15 and 22 and daunorubicin hydrochloride (25 mg/m2/dose on Days 1, 8, 15 and 22. Dexamethasone (5 mg/m2/dose on Days 1-14 by mouth or infusion twice a day in weeks 1 and 2; intrathecal methotrexate (Aged based dosing: Age (yrs) Dose 1 - 1.99 8 mg 2 - 2.99 10 mg 3 - 8.99 12 mg ≥ 9 15 mg) on days 8 and 29 (CNS3 also on days 15 & 22) and an injection of pegaspargase (2500 International units/m2 x 1 dose on Day 4, 5 or 6). |
| Measure Participants | 28 | 13 | 53 | 15 | 17 | 116 | 20 | 112 | 44 |
| Number (95% Confidence Interval) [percentage of participants] |
79.2
32.2%
|
69.9
65.9%
|
65.6
22.2%
|
86.2
35%
|
93.8
40.4%
|
63.1
8.9%
|
84.2
34.2%
|
73.6
10.6%
|
74.6
24.7%
|
| Title | Correlation of Minimal Residual Disease (MRD) Negative With Overall Survival (OS). |
|---|---|
| Description | Bone marrow MRD status is defined as negative with < .01 detectable leukemia cells. |
| Time Frame | 5 years |
Outcome Measure Data
| Analysis Population Description |
|---|
| Patients on Arm/Group "Prednisone and High Dose Methotrexate (non randomly assigned)" are not included in the OM as there were no survivors for the 5 year duration. Cohort of MRD Negative patients some of whom have had EFS/OS events after 5 years or have minimum 5 years of follow-up. |
| Arm/Group Title | Dexamethasone and Capizzi Methotrexate Patients < 10 Years | Dexamethasone, High Dose Methotrexate (Non Randomly Assigned) | Dexamethasone & Capizzi Methotrexate Patients => 10 Years Old | Dexamethasone, High Dose Methotrexate (IM) < 10 Years | Prednisone, Capizzi Methotrexate <10 Years | Prednisone, Capizzi Methotrexate >= 10 Years | Prednisone and High Dose Methotrexate < 10 Yrs Old | Prednisone and High Dose Methotrexate >=10 Years | Dexamethasone, High Dose Methotrexate (IM) >= 10 Years | Prednisone, Capizzi Methotrexate (Down's Syndrome) | Dexamethasone, Capizzi Methotrexate Down Syndrome (Non Random) |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Patients receive intrathecal cytarabine (Age-based dosing: Age (yrs) Dose 1 - 1.99 30 mg 2 - 2.99 50 mg ≥ 3 70 mg) on day 1; infusions of vincristine sulfate 1.5 mg/m2/dose (maximum dose of 2 mg) on Days 1, 8, 15 and 22 and daunorubicin hydrochloride (25 mg/m2/dose on Days 1, 8, 15 and 22. Dexamethasone (5 mg/m2/dose on Days 1-14 by mouth or infusion twice a day in weeks 1 and 2; intrathecal methotrexate (Aged based dosing: Age (yrs) Dose 1 - 1.99 8 mg 2 - 2.99 10 mg 3 - 8.99 12 mg ≥ 9 15 mg) on days 8 and 29 (CNS3 also on days 15 & 22) and an injection of pegaspargase (2500 International units/m2 x 1 dose on Day 4, 5 or 6). | Patients non-randomly assigned to the DH regimen based on one (or more) of the following characteristics: (1) CNS3 status at entry, (2) testicular leukemic involvement at entry, or (3) extensive pre-treatment with steroids prior to entry. Patients receive intrathecal cytarabine (Age-based dosing: Age (yrs) Dose 1 - 1.99 30 mg 2 - 2.99 50 mg ≥ 3 70 mg) on day 1; infusions of vincristine sulfate 1.5 mg/m2/dose (maximum dose of 2 mg) on Days 1, 8, 15 and 22 and daunorubicin hydrochloride (25 mg/m2/dose on Days 1, 8, 15 and 22. Dexamethasone (5 mg/m2/dose on Days 1-14 by mouth or infusion twice a day in weeks 1 and 2; intrathecal methotrexate (Aged based dosing: Age (yrs) Dose 1 - 1.99 8 mg 2 - 2.99 10 mg 3 - 8.99 12 mg ≥ 9 15 mg) on days 8 and 29 (CNS3 also on days 15 & 22) and an injection of pegaspargase (2500 International units/m2 x 1 dose on Day 4, 5 or 6). | Patients receive intrathecal cytarabine (Age-based dosing: Age (yrs) Dose 1 - 1.99 30 mg 2 - 2.99 50 mg ≥ 3 70 mg) on day 1; infusions of vincristine sulfate 1.5 mg/m2/dose (maximum dose of 2 mg) on Days 1, 8, 15 and 22 and daunorubicin hydrochloride (25 mg/m2/dose on Days 1, 8, 15 and 22. Dexamethasone (5 mg/m2/dose on Days 1-14 by mouth or infusion twice a day in weeks 1 and 2; intrathecal methotrexate (Aged based dosing: Age (yrs) Dose 1 - 1.99 8 mg 2 - 2.99 10 mg 3 - 8.99 12 mg ≥ 9 15 mg) on days 8 and 29 (CNS3 also on days 15 & 22) and an injection of pegaspargase (2500 International units/m2 x 1 dose on Day 4, 5 or 6). | Patients randomly assigned to the DH regimen based on one (or more) of the following characteristics: (1) No CNS3 status at entry, (2) no testicular leukemic involvement at entry, or (3) no extensive pre-treatment with steroids prior to entry. Patients receive intrathecal cytarabine (Age-based dosing: Age (yrs) Dose 1 - 1.99 30 mg 2 - 2.99 50 mg ≥ 3 70 mg) on day 1; infusions of vincristine sulfate 1.5 mg/m2/dose (maximum dose of 2 mg) on Days 1, 8, 15 and 22 and daunorubicin hydrochloride (25 mg/m2/dose on Days 1, 8, 15 and 22. Dexamethasone (5 mg/m2/dose on Days 1-14 by mouth or infusion twice a day in weeks 1 and 2; intrathecal methotrexate (Aged based dosing: Age (yrs) Dose 1 - 1.99 8 mg 2 - 2.99 10 mg 3 - 8.99 12 mg ≥ 9 15 mg) on days 8 and 29 (CNS3 also on days 15 & 22) and an injection of pegaspargase (2500 International units/m2 x 1 dose on Day 4, 5 or 6). | Patients in regimen PC will receive cytarabine, vincristine sulfate, daunorubicin hydrochloride, and pegaspargase. They will also receive prednisone by mouth or infusion twice a day in weeks 1-4 and intrathecal methotrexate in weeks 2 and 5. Some patients in all groups may receive induction therapy for 2 additional weeks. Beginning in week 6 or 7, patients may receive combination chemotherapy (vincristine sulfate, dexamethasone, doxorubicin hydrochloride, pegaspargase, cyclophosphamide, mercaptopurine, cytarabine, thioguanine) by infusion, injection, intrathecally, and by mouth for up to 8 weeks. | Patients in regimen PC will receive cytarabine, vincristine sulfate, daunorubicin hydrochloride, and pegaspargase. They will also receive prednisone by mouth or infusion twice a day in weeks 1-4 and intrathecal methotrexate in weeks 2 and 5. Some patients in all groups may receive induction therapy for 2 additional weeks. Beginning in week 6 or 7, patients may receive combination chemotherapy (vincristine sulfate, dexamethasone, doxorubicin hydrochloride, pegaspargase, cyclophosphamide, mercaptopurine, cytarabine, thioguanine) by infusion, injection, intrathecally, and by mouth for up to 8 weeks. | Patients randomly assigned to the PH regimen receive intrathecal cytarabine (Age-based dosing: Age (yrs) Dose 1 - 1.99 30 mg 2 - 2.99 50 mg ≥ 3 70 mg) on day 1; infusions of vincristine sulfate 1.5 mg/m2/dose (maximum dose of 2 mg) on Days 1, 8, 15 and 22 and daunorubicin hydrochloride (25 mg/m2/dose on Days 1, 8, 15 and 22. They will also receive prednisone by mouth or infusion twice a day in weeks 1-4 and intrathecal methotrexate in weeks 2 and 5. Some patients in all groups may receive induction therapy for 2 additional weeks. Beginning in week 6 or 7, patients may receive combination chemotherapy (vincristine sulfate, dexamethasone, doxorubicin hydrochloride, pegaspargase, cyclophosphamide, mercaptopurine, cytarabine, thioguanine) by infusion, injection, intrathecally, and by mouth for up to 8 weeks. | Patients randomly assigned to the PH regimen receive intrathecal cytarabine (Age-based dosing: Age (yrs) Dose 1 - 1.99 30 mg 2 - 2.99 50 mg ≥ 3 70 mg) on day 1; infusions of vincristine sulfate 1.5 mg/m2/dose (maximum dose of 2 mg) on Days 1, 8, 15 and 22 and daunorubicin hydrochloride (25 mg/m2/dose on Days 1, 8, 15 and 22. They will also receive prednisone by mouth or infusion twice a day in weeks 1-4 and intrathecal methotrexate in weeks 2 and 5. Some patients in all groups may receive induction therapy for 2 additional weeks. Beginning in week 6 or 7, patients may receive combination chemotherapy (vincristine sulfate, dexamethasone, doxorubicin hydrochloride, pegaspargase, cyclophosphamide, mercaptopurine, cytarabine, thioguanine) by infusion, injection, intrathecally, and by mouth for up to 8 weeks. | Patients randomly assigned to the DH regimen based on one (or more) of the following characteristics: (1) No CNS3 status at entry, (2) no testicular leukemic involvement at entry, or (3) no extensive pre-treatment with steroids prior to entry. Patients receive intrathecal cytarabine (Age-based dosing: Age (yrs) Dose 1 - 1.99 30 mg 2 - 2.99 50 mg ≥ 3 70 mg) on day 1; infusions of vincristine sulfate 1.5 mg/m2/dose (maximum dose of 2 mg) on Days 1, 8, 15 and 22 and daunorubicin hydrochloride (25 mg/m2/dose on Days 1, 8, 15 and 22. Dexamethasone (5 mg/m2/dose on Days 1-14 by mouth or infusion twice a day in weeks 1 and 2; intrathecal methotrexate (Aged based dosing: Age (yrs) Dose 1 - 1.99 8 mg 2 - 2.99 10 mg 3 - 8.99 12 mg ≥ 9 15 mg) on days 8 and 29 (CNS3 also on days 15 & 22) and an injection of pegaspargase (2500 International units/m2 x 1 dose on Day 4, 5 or 6). | Patients in regimen PC will receive cytarabine, vincristine sulfate, daunorubicin hydrochloride, and pegaspargase. They will also receive prednisone by mouth or infusion twice a day in weeks 1-4 and intrathecal methotrexate in weeks 2 and 5. Some patients in all groups may receive induction therapy for 2 additional weeks. Beginning in week 6 or 7, patients may receive combination chemotherapy (vincristine sulfate, dexamethasone, doxorubicin hydrochloride, pegaspargase, cyclophosphamide, mercaptopurine, cytarabine, thioguanine) by infusion, injection, intrathecally, and by mouth for up to 8 weeks. | Patients receive intrathecal cytarabine (Age-based dosing: Age (yrs) Dose 1 - 1.99 30 mg 2 - 2.99 50 mg ≥ 3 70 mg) on day 1; infusions of vincristine sulfate 1.5 mg/m2/dose (maximum dose of 2 mg) on Days 1, 8, 15 and 22 and daunorubicin hydrochloride (25 mg/m2/dose on Days 1, 8, 15 and 22. Dexamethasone (5 mg/m2/dose on Days 1-14 by mouth or infusion twice a day in weeks 1 and 2; intrathecal methotrexate (Aged based dosing: Age (yrs) Dose 1 - 1.99 8 mg 2 - 2.99 10 mg 3 - 8.99 12 mg ≥ 9 15 mg) on days 8 and 29 (CNS3 also on days 15 & 22) and an injection of pegaspargase (2500 International units/m2 x 1 dose on Day 4, 5 or 6). |
| Measure Participants | 185 | 73 | 198 | 189 | 195 | 472 | 191 | 480 | 209 | 25 | 4 |
| Number (95% Confidence Interval) [percentage of participants] |
95.4
38.8%
|
92.9
87.6%
|
87.4
29.5%
|
98.1
39.9%
|
93.3
40.2%
|
90.2
12.7%
|
94.5
38.4%
|
90.5
13%
|
91.6
30.3%
|
78.3
230.3%
|
25.0
208.3%
|
| Title | Correlation of Early Marrow Response Status With MRD Positive. |
|---|---|
| Description | Bone marrow status is defined as: M1: < 5% lymphoblasts; M2: 5-25% lymphoblasts; M3: > 25% lymphoblasts. Bone marrow MRD status is defined as positive with >= 0.1 detectable leukemia cells, and negative with < 0.1 detectable leukemia cells. |
| Time Frame | Day 29 |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Dexamethasone and Capizzi Methotrexate Patients < 10 Years | Dexamethasone, High Dose Methotrexate (Non Randomly Assigned) | Dexamethasone & Capizzi Methotrexate Patients => 10 Years Old | Dexamethasone, High Dose Methotrexate (IM) < 10 Years | Prednisone, Capizzi Methotrexate <10 Years | Prednisone, Capezzi Methotrexate >= 10 Years | Prednisone and High Dose Methotrexate < 10 Yrs Old | Prednisone and High Dose Methotrexate >=10 Years | Dexamethasone, High Dose Methotrexate (IM) >= 10 Years | Prednisone, Capezzi Methotrexate (Down's Syndrome) | Dexamethasone, Capizzi Methotrexate Down Syndrome (Non Random) | Prednisone and High Dose Methotrexate (Non Randomly Assigned) |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Patients receive intrathecal cytarabine (Age-based dosing: Age (yrs) Dose 1 - 1.99 30 mg 2 - 2.99 50 mg ≥ 3 70 mg) on day 1; infusions of vincristine sulfate 1.5 mg/m2/dose (maximum dose of 2 mg) on Days 1, 8, 15 and 22 and daunorubicin hydrochloride (25 mg/m2/dose on Days 1, 8, 15 and 22. Dexamethasone (5 mg/m2/dose on Days 1-14 by mouth or infusion twice a day in weeks 1 and 2; intrathecal methotrexate (Aged based dosing: Age (yrs) Dose 1 - 1.99 8 mg 2 - 2.99 10 mg 3 - 8.99 12 mg ≥ 9 15 mg) on days 8 and 29 (CNS3 also on days 15 & 22) and an injection of pegaspargase (2500 International units/m2 x 1 dose on Day 4, 5 or 6). | Patients non-randomly assigned to the DH regimen based on one (or more) of the following characteristics: (1) CNS3 status at entry, (2) testicular leukemic involvement at entry, or (3) extensive pre-treatment with steroids prior to entry. Patients receive intrathecal cytarabine (Age-based dosing: Age (yrs) Dose 1 - 1.99 30 mg 2 - 2.99 50 mg ≥ 3 70 mg) on day 1; infusions of vincristine sulfate 1.5 mg/m2/dose (maximum dose of 2 mg) on Days 1, 8, 15 and 22 and daunorubicin hydrochloride (25 mg/m2/dose on Days 1, 8, 15 and 22. Dexamethasone (5 mg/m2/dose on Days 1-14 by mouth or infusion twice a day in weeks 1 and 2; intrathecal methotrexate (Aged based dosing: Age (yrs) Dose 1 - 1.99 8 mg 2 - 2.99 10 mg 3 - 8.99 12 mg ≥ 9 15 mg) on days 8 and 29 (CNS3 also on days 15 & 22) and an injection of pegaspargase (2500 International units/m2 x 1 dose on Day 4, 5 or 6). | Patients receive intrathecal cytarabine (Age-based dosing: Age (yrs) Dose 1 - 1.99 30 mg 2 - 2.99 50 mg ≥ 3 70 mg) on day 1; infusions of vincristine sulfate 1.5 mg/m2/dose (maximum dose of 2 mg) on Days 1, 8, 15 and 22 and daunorubicin hydrochloride (25 mg/m2/dose on Days 1, 8, 15 and 22. Dexamethasone (5 mg/m2/dose on Days 1-14 by mouth or infusion twice a day in weeks 1 and 2; intrathecal methotrexate (Aged based dosing: Age (yrs) Dose 1 - 1.99 8 mg 2 - 2.99 10 mg 3 - 8.99 12 mg ≥ 9 15 mg) on days 8 and 29 (CNS3 also on days 15 & 22) and an injection of pegaspargase (2500 International units/m2 x 1 dose on Day 4, 5 or 6). | Patients randomly assigned to the DH regimen based on one (or more) of the following characteristics: (1) No CNS3 status at entry, (2) no testicular leukemic involvement at entry, or (3) no extensive pre-treatment with steroids prior to entry. Patients receive intrathecal cytarabine (Age-based dosing: Age (yrs) Dose 1 - 1.99 30 mg 2 - 2.99 50 mg ≥ 3 70 mg) on day 1; infusions of vincristine sulfate 1.5 mg/m2/dose (maximum dose of 2 mg) on Days 1, 8, 15 and 22 and daunorubicin hydrochloride (25 mg/m2/dose on Days 1, 8, 15 and 22. Dexamethasone (5 mg/m2/dose on Days 1-14 by mouth or infusion twice a day in weeks 1 and 2; intrathecal methotrexate (Aged based dosing: Age (yrs) Dose 1 - 1.99 8 mg 2 - 2.99 10 mg 3 - 8.99 12 mg ≥ 9 15 mg) on days 8 and 29 (CNS3 also on days 15 & 22) and an injection of pegaspargase (2500 International units/m2 x 1 dose on Day 4, 5 or 6). | Patients in regimen PC will receive cytarabine, vincristine sulfate, daunorubicin hydrochloride, and pegaspargase. They will also receive prednisone by mouth or infusion twice a day in weeks 1-4 and intrathecal methotrexate in weeks 2 and 5. Some patients in all groups may receive induction therapy for 2 additional weeks. Beginning in week 6 or 7, patients may receive combination chemotherapy (vincristine sulfate, dexamethasone, doxorubicin hydrochloride, pegaspargase, cyclophosphamide, mercaptopurine, cytarabine, thioguanine) by infusion, injection, intrathecally, and by mouth for up to 8 weeks. | Patients in regimen PC will receive cytarabine, vincristine sulfate, daunorubicin hydrochloride, and pegaspargase. They will also receive prednisone by mouth or infusion twice a day in weeks 1-4 and intrathecal methotrexate in weeks 2 and 5. Some patients in all groups may receive induction therapy for 2 additional weeks. Beginning in week 6 or 7, patients may receive combination chemotherapy (vincristine sulfate, dexamethasone, doxorubicin hydrochloride, pegaspargase, cyclophosphamide, mercaptopurine, cytarabine, thioguanine) by infusion, injection, intrathecally, and by mouth for up to 8 weeks. | Patients randomly assigned to the PH regimen receive intrathecal cytarabine (Age-based dosing: Age (yrs) Dose 1 - 1.99 30 mg 2 - 2.99 50 mg ≥ 3 70 mg) on day 1; infusions of vincristine sulfate 1.5 mg/m2/dose (maximum dose of 2 mg) on Days 1, 8, 15 and 22 and daunorubicin hydrochloride (25 mg/m2/dose on Days 1, 8, 15 and 22. They will also receive prednisone by mouth or infusion twice a day in weeks 1-4 and intrathecal methotrexate in weeks 2 and 5. Some patients in all groups may receive induction therapy for 2 additional weeks. Beginning in week 6 or 7, patients may receive combination chemotherapy (vincristine sulfate, dexamethasone, doxorubicin hydrochloride, pegaspargase, cyclophosphamide, mercaptopurine, cytarabine, thioguanine) by infusion, injection, intrathecally, and by mouth for up to 8 weeks. | Patients randomly assigned to the PH regimen receive intrathecal cytarabine (Age-based dosing: Age (yrs) Dose 1 - 1.99 30 mg 2 - 2.99 50 mg ≥ 3 70 mg) on day 1; infusions of vincristine sulfate 1.5 mg/m2/dose (maximum dose of 2 mg) on Days 1, 8, 15 and 22 and daunorubicin hydrochloride (25 mg/m2/dose on Days 1, 8, 15 and 22. They will also receive prednisone by mouth or infusion twice a day in weeks 1-4 and intrathecal methotrexate in weeks 2 and 5. Some patients in all groups may receive induction therapy for 2 additional weeks. Beginning in week 6 or 7, patients may receive combination chemotherapy (vincristine sulfate, dexamethasone, doxorubicin hydrochloride, pegaspargase, cyclophosphamide, mercaptopurine, cytarabine, thioguanine) by infusion, injection, intrathecally, and by mouth for up to 8 weeks. | Patients randomly assigned to the DH regimen based on one (or more) of the following characteristics: (1) No CNS3 status at entry, (2) no testicular leukemic involvement at entry, or (3) no extensive pre-treatment with steroids prior to entry. Patients receive intrathecal cytarabine (Age-based dosing: Age (yrs) Dose 1 - 1.99 30 mg 2 - 2.99 50 mg ≥ 3 70 mg) on day 1; infusions of vincristine sulfate 1.5 mg/m2/dose (maximum dose of 2 mg) on Days 1, 8, 15 and 22 and daunorubicin hydrochloride (25 mg/m2/dose on Days 1, 8, 15 and 22. Dexamethasone (5 mg/m2/dose on Days 1-14 by mouth or infusion twice a day in weeks 1 and 2; intrathecal methotrexate (Aged based dosing: Age (yrs) Dose 1 - 1.99 8 mg 2 - 2.99 10 mg 3 - 8.99 12 mg ≥ 9 15 mg) on days 8 and 29 (CNS3 also on days 15 & 22) and an injection of pegaspargase (2500 International units/m2 x 1 dose on Day 4, 5 or 6). | Patients in regimen PC will receive cytarabine, vincristine sulfate, daunorubicin hydrochloride, and pegaspargase. They will also receive prednisone by mouth or infusion twice a day in weeks 1-4 and intrathecal methotrexate in weeks 2 and 5. Some patients in all groups may receive induction therapy for 2 additional weeks. Beginning in week 6 or 7, patients may receive combination chemotherapy (vincristine sulfate, dexamethasone, doxorubicin hydrochloride, pegaspargase, cyclophosphamide, mercaptopurine, cytarabine, thioguanine) by infusion, injection, intrathecally, and by mouth for up to 8 weeks. | Patients receive intrathecal cytarabine (Age-based dosing: Age (yrs) Dose 1 - 1.99 30 mg 2 - 2.99 50 mg ≥ 3 70 mg) on day 1; infusions of vincristine sulfate 1.5 mg/m2/dose (maximum dose of 2 mg) on Days 1, 8, 15 and 22 and daunorubicin hydrochloride (25 mg/m2/dose on Days 1, 8, 15 and 22. Dexamethasone (5 mg/m2/dose on Days 1-14 by mouth or infusion twice a day in weeks 1 and 2; intrathecal methotrexate (Aged based dosing: Age (yrs) Dose 1 - 1.99 8 mg 2 - 2.99 10 mg 3 - 8.99 12 mg ≥ 9 15 mg) on days 8 and 29 (CNS3 also on days 15 & 22) and an injection of pegaspargase (2500 International units/m2 x 1 dose on Day 4, 5 or 6). | Patients non-randomly assigned to the PH regimen based on one (or more) of the following: (1) CNS3 status at entry, (2) testicular leukemic involvement at entry, or (3) extensive pre-treatment with steroids prior to entry. Patients receive intrathecal cytarabine (Age-based dosing: Age (yrs) Dose 1 - 1.99 30 mg 2 - 2.99 50 mg ≥ 3 70 mg) on day 1; infusions of vincristine sulfate 1.5 mg/m2/dose (maximum dose of 2 mg) on Days 1, 8, 15 and 22 and daunorubicin hydrochloride (25 mg/m2/dose on Days 1, 8, 15 and 22. They will also receive prednisone by mouth or infusion twice a day in weeks 1-4 and intrathecal MTX in weeks 2 and 5. Some patients in all groups may receive induction therapy for 2 additional weeks. Beginning in week 6 or 7, patients may receive combination chemotherapy (vincristine sulfate, dexamethasone, doxorubicin hydrochloride, pegaspargase, cyclophosphamide, mercaptopurine, cytarabine, thioguanine) by infusion, injection, intrathecally, and by mouth for up to 8 weeks. |
| Measure Participants | 28 | 13 | 53 | 15 | 17 | 116 | 20 | 112 | 44 | 3 | 3 | 5 |
| Number [participants] |
26
10.6%
|
12
11.3%
|
43
14.5%
|
14
5.7%
|
16
6.9%
|
95
13.4%
|
17
6.9%
|
98
14.1%
|
39
12.9%
|
3
8.8%
|
3
25%
|
3
10.7%
|
| Title | Correlation of Early Marrow Response Status With MRD Negative. |
|---|---|
| Description | Bone marrow status is defined as: M1: < 5% lymphoblasts; M2: 5-25% lymphoblasts; M3: > 25% lymphoblasts. Bone marrow MRD status is defined as positive with >= 0.1 detectable leukemia cells, and negative with < 0.1 detectable leukemia cells. |
| Time Frame | Day 29 |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Dexamethasone and Capizzi Methotrexate Patients < 10 Years | Dexamethasone, High Dose Methotrexate (Non Randomly Assigned) | Dexamethasone & Capizzi Methotrexate Patients => 10 Years Old | Dexamethasone, High Dose Methotrexate (IM) < 10 Years | Prednisone, Capizzi Methotrexate <10 Years | Prednisone, Capezzi Methotrexate >= 10 Years | Prednisone and High Dose Methotrexate < 10 Yrs Old | Prednisone and High Dose Methotrexate >=10 Years | Dexamethasone, High Dose Methotrexate (IM) >= 10 Years | Prednisone, Capezzi Methotrexate (Down's Syndrome) | Dexamethasone, Capizzi Methotrexate Down Syndrome (Non Random) | Prednisone and High Dose Methotrexate (Non Randomly Assigned) |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Patients receive intrathecal cytarabine (Age-based dosing: Age (yrs) Dose 1 - 1.99 30 mg 2 - 2.99 50 mg ≥ 3 70 mg) on day 1; infusions of vincristine sulfate 1.5 mg/m2/dose (maximum dose of 2 mg) on Days 1, 8, 15 and 22 and daunorubicin hydrochloride (25 mg/m2/dose on Days 1, 8, 15 and 22. Dexamethasone (5 mg/m2/dose on Days 1-14 by mouth or infusion twice a day in weeks 1 and 2; intrathecal methotrexate (Aged based dosing: Age (yrs) Dose 1 - 1.99 8 mg 2 - 2.99 10 mg 3 - 8.99 12 mg ≥ 9 15 mg) on days 8 and 29 (CNS3 also on days 15 & 22) and an injection of pegaspargase (2500 International units/m2 x 1 dose on Day 4, 5 or 6). | Patients non-randomly assigned to the DH regimen based on one (or more) of the following characteristics: (1) CNS3 status at entry, (2) testicular leukemic involvement at entry, or (3) extensive pre-treatment with steroids prior to entry. Patients receive intrathecal cytarabine (Age-based dosing: Age (yrs) Dose 1 - 1.99 30 mg 2 - 2.99 50 mg ≥ 3 70 mg) on day 1; infusions of vincristine sulfate 1.5 mg/m2/dose (maximum dose of 2 mg) on Days 1, 8, 15 and 22 and daunorubicin hydrochloride (25 mg/m2/dose on Days 1, 8, 15 and 22. Dexamethasone (5 mg/m2/dose on Days 1-14 by mouth or infusion twice a day in weeks 1 and 2; intrathecal methotrexate (Aged based dosing: Age (yrs) Dose 1 - 1.99 8 mg 2 - 2.99 10 mg 3 - 8.99 12 mg ≥ 9 15 mg) on days 8 and 29 (CNS3 also on days 15 & 22) and an injection of pegaspargase (2500 International units/m2 x 1 dose on Day 4, 5 or 6). | Patients receive intrathecal cytarabine (Age-based dosing: Age (yrs) Dose 1 - 1.99 30 mg 2 - 2.99 50 mg ≥ 3 70 mg) on day 1; infusions of vincristine sulfate 1.5 mg/m2/dose (maximum dose of 2 mg) on Days 1, 8, 15 and 22 and daunorubicin hydrochloride (25 mg/m2/dose on Days 1, 8, 15 and 22. Dexamethasone (5 mg/m2/dose on Days 1-14 by mouth or infusion twice a day in weeks 1 and 2; intrathecal methotrexate (Aged based dosing: Age (yrs) Dose 1 - 1.99 8 mg 2 - 2.99 10 mg 3 - 8.99 12 mg ≥ 9 15 mg) on days 8 and 29 (CNS3 also on days 15 & 22) and an injection of pegaspargase (2500 International units/m2 x 1 dose on Day 4, 5 or 6). | Patients randomly assigned to the DH regimen based on one (or more) of the following characteristics: (1) No CNS3 status at entry, (2) no testicular leukemic involvement at entry, or (3) no extensive pre-treatment with steroids prior to entry. Patients receive intrathecal cytarabine (Age-based dosing: Age (yrs) Dose 1 - 1.99 30 mg 2 - 2.99 50 mg ≥ 3 70 mg) on day 1; infusions of vincristine sulfate 1.5 mg/m2/dose (maximum dose of 2 mg) on Days 1, 8, 15 and 22 and daunorubicin hydrochloride (25 mg/m2/dose on Days 1, 8, 15 and 22. Dexamethasone (5 mg/m2/dose on Days 1-14 by mouth or infusion twice a day in weeks 1 and 2; intrathecal methotrexate (Aged based dosing: Age (yrs) Dose 1 - 1.99 8 mg 2 - 2.99 10 mg 3 - 8.99 12 mg ≥ 9 15 mg) on days 8 and 29 (CNS3 also on days 15 & 22) and an injection of pegaspargase (2500 International units/m2 x 1 dose on Day 4, 5 or 6). | Patients in regimen PC will receive cytarabine, vincristine sulfate, daunorubicin hydrochloride, and pegaspargase. They will also receive prednisone by mouth or infusion twice a day in weeks 1-4 and intrathecal methotrexate in weeks 2 and 5. Some patients in all groups may receive induction therapy for 2 additional weeks. Beginning in week 6 or 7, patients may receive combination chemotherapy (vincristine sulfate, dexamethasone, doxorubicin hydrochloride, pegaspargase, cyclophosphamide, mercaptopurine, cytarabine, thioguanine) by infusion, injection, intrathecally, and by mouth for up to 8 weeks. | Patients in regimen PC will receive cytarabine, vincristine sulfate, daunorubicin hydrochloride, and pegaspargase. They will also receive prednisone by mouth or infusion twice a day in weeks 1-4 and intrathecal methotrexate in weeks 2 and 5. Some patients in all groups may receive induction therapy for 2 additional weeks. Beginning in week 6 or 7, patients may receive combination chemotherapy (vincristine sulfate, dexamethasone, doxorubicin hydrochloride, pegaspargase, cyclophosphamide, mercaptopurine, cytarabine, thioguanine) by infusion, injection, intrathecally, and by mouth for up to 8 weeks. | Patients randomly assigned to the PH regimen receive intrathecal cytarabine (Age-based dosing: Age (yrs) Dose 1 - 1.99 30 mg 2 - 2.99 50 mg ≥ 3 70 mg) on day 1; infusions of vincristine sulfate 1.5 mg/m2/dose (maximum dose of 2 mg) on Days 1, 8, 15 and 22 and daunorubicin hydrochloride (25 mg/m2/dose on Days 1, 8, 15 and 22. They will also receive prednisone by mouth or infusion twice a day in weeks 1-4 and intrathecal methotrexate in weeks 2 and 5. Some patients in all groups may receive induction therapy for 2 additional weeks. Beginning in week 6 or 7, patients may receive combination chemotherapy (vincristine sulfate, dexamethasone, doxorubicin hydrochloride, pegaspargase, cyclophosphamide, mercaptopurine, cytarabine, thioguanine) by infusion, injection, intrathecally, and by mouth for up to 8 weeks. | Patients randomly assigned to the PH regimen receive intrathecal cytarabine (Age-based dosing: Age (yrs) Dose 1 - 1.99 30 mg 2 - 2.99 50 mg ≥ 3 70 mg) on day 1; infusions of vincristine sulfate 1.5 mg/m2/dose (maximum dose of 2 mg) on Days 1, 8, 15 and 22 and daunorubicin hydrochloride (25 mg/m2/dose on Days 1, 8, 15 and 22. They will also receive prednisone by mouth or infusion twice a day in weeks 1-4 and intrathecal methotrexate in weeks 2 and 5. Some patients in all groups may receive induction therapy for 2 additional weeks. Beginning in week 6 or 7, patients may receive combination chemotherapy (vincristine sulfate, dexamethasone, doxorubicin hydrochloride, pegaspargase, cyclophosphamide, mercaptopurine, cytarabine, thioguanine) by infusion, injection, intrathecally, and by mouth for up to 8 weeks. | Patients randomly assigned to the DH regimen based on one (or more) of the following characteristics: (1) No CNS3 status at entry, (2) no testicular leukemic involvement at entry, or (3) no extensive pre-treatment with steroids prior to entry. Patients receive intrathecal cytarabine (Age-based dosing: Age (yrs) Dose 1 - 1.99 30 mg 2 - 2.99 50 mg ≥ 3 70 mg) on day 1; infusions of vincristine sulfate 1.5 mg/m2/dose (maximum dose of 2 mg) on Days 1, 8, 15 and 22 and daunorubicin hydrochloride (25 mg/m2/dose on Days 1, 8, 15 and 22. Dexamethasone (5 mg/m2/dose on Days 1-14 by mouth or infusion twice a day in weeks 1 and 2; intrathecal methotrexate (Aged based dosing: Age (yrs) Dose 1 - 1.99 8 mg 2 - 2.99 10 mg 3 - 8.99 12 mg ≥ 9 15 mg) on days 8 and 29 (CNS3 also on days 15 & 22) and an injection of pegaspargase (2500 International units/m2 x 1 dose on Day 4, 5 or 6). | Patients in regimen PC will receive cytarabine, vincristine sulfate, daunorubicin hydrochloride, and pegaspargase. They will also receive prednisone by mouth or infusion twice a day in weeks 1-4 and intrathecal methotrexate in weeks 2 and 5. Some patients in all groups may receive induction therapy for 2 additional weeks. Beginning in week 6 or 7, patients may receive combination chemotherapy (vincristine sulfate, dexamethasone, doxorubicin hydrochloride, pegaspargase, cyclophosphamide, mercaptopurine, cytarabine, thioguanine) by infusion, injection, intrathecally, and by mouth for up to 8 weeks. | Patients receive intrathecal cytarabine (Age-based dosing: Age (yrs) Dose 1 - 1.99 30 mg 2 - 2.99 50 mg ≥ 3 70 mg) on day 1; infusions of vincristine sulfate 1.5 mg/m2/dose (maximum dose of 2 mg) on Days 1, 8, 15 and 22 and daunorubicin hydrochloride (25 mg/m2/dose on Days 1, 8, 15 and 22. Dexamethasone (5 mg/m2/dose on Days 1-14 by mouth or infusion twice a day in weeks 1 and 2; intrathecal methotrexate (Aged based dosing: Age (yrs) Dose 1 - 1.99 8 mg 2 - 2.99 10 mg 3 - 8.99 12 mg ≥ 9 15 mg) on days 8 and 29 (CNS3 also on days 15 & 22) and an injection of pegaspargase (2500 International units/m2 x 1 dose on Day 4, 5 or 6). | Patients non-randomly assigned to the PH regimen based on one (or more) of the following: (1) CNS3 status at entry, (2) testicular leukemic involvement at entry, or (3) extensive pre-treatment with steroids prior to entry. Patients receive intrathecal cytarabine (Age-based dosing: Age (yrs) Dose 1 - 1.99 30 mg 2 - 2.99 50 mg ≥ 3 70 mg) on day 1; infusions of vincristine sulfate 1.5 mg/m2/dose (maximum dose of 2 mg) on Days 1, 8, 15 and 22 and daunorubicin hydrochloride (25 mg/m2/dose on Days 1, 8, 15 and 22. They will also receive prednisone by mouth or infusion twice a day in weeks 1-4 and intrathecal MTX in weeks 2 and 5. Some patients in all groups may receive induction therapy for 2 additional weeks. Beginning in week 6 or 7, patients may receive combination chemotherapy (vincristine sulfate, dexamethasone, doxorubicin hydrochloride, pegaspargase, cyclophosphamide, mercaptopurine, cytarabine, thioguanine) by infusion, injection, intrathecally, and by mouth for up to 8 weeks. |
| Measure Participants | 185 | 73 | 198 | 189 | 195 | 472 | 191 | 480 | 209 | 25 | 4 | 18 |
| Number [participants] |
182
74%
|
72
67.9%
|
198
66.9%
|
188
76.4%
|
195
84.1%
|
471
66.3%
|
190
77.2%
|
479
68.8%
|
208
68.9%
|
25
73.5%
|
3
25%
|
18
64.3%
|
| Title | Correlation of Minimal Residual Disease (MRD) Positive With Event Free Survival (EFS) |
|---|---|
| Description | Bone marrow MRD status is defined as positive with >= 0.1 detectable leukemia cells. |
| Time Frame | 5 years |
Outcome Measure Data
| Analysis Population Description |
|---|
| Groups "Prednisone Capizzi MTX (Down's Syndrome)", "Dexamethasone, Capizzi MTX (non-random)" & "Prednisone and High Dose MTX (non-random) are not included in this OM as no patients survived the 5 year window for analysis. Cohort of MRD Positive patients who either had EFS/OS events occur before 5 years or did not have minimum 5 years of follow-up. |
| Arm/Group Title | Dexamethasone and Capizzi Methotrexate Patients < 10 Years | Dexamethasone, High Dose Methotrexate (Non Randomly Assigned) | Dexamethasone & Capizzi Methotrexate Patients => 10 Years Old | Dexamethasone, High Dose Methotrexate (IM) < 10 Years | Prednisone, Capizzi Methotrexate <10 Years | Prednisone, Capizzi Methotrexate >= 10 Years | Prednisone and High Dose Methotrexate < 10 Yrs Old | Prednisone and High Dose Methotrexate >=10 Years | Dexamethasone, High Dose Methotrexate (IM) >= 10 Years |
|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Patients receive intrathecal cytarabine (Age-based dosing: Age (yrs) Dose 1 - 1.99 30 mg 2 - 2.99 50 mg ≥ 3 70 mg) on day 1; infusions of vincristine sulfate 1.5 mg/m2/dose (maximum dose of 2 mg) on Days 1, 8, 15 and 22 and daunorubicin hydrochloride (25 mg/m2/dose on Days 1, 8, 15 and 22. Dexamethasone (5 mg/m2/dose on Days 1-14 by mouth or infusion twice a day in weeks 1 and 2; intrathecal methotrexate (Aged based dosing: Age (yrs) Dose 1 - 1.99 8 mg 2 - 2.99 10 mg 3 - 8.99 12 mg ≥ 9 15 mg) on days 8 and 29 (CNS3 also on days 15 & 22) and an injection of pegaspargase (2500 International units/m2 x 1 dose on Day 4, 5 or 6). | Patients non-randomly assigned to the DH regimen based on one (or more) of the following characteristics: (1) CNS3 status at entry, (2) testicular leukemic involvement at entry, or (3) extensive pre-treatment with steroids prior to entry. Patients receive intrathecal cytarabine (Age-based dosing: Age (yrs) Dose 1 - 1.99 30 mg 2 - 2.99 50 mg ≥ 3 70 mg) on day 1; infusions of vincristine sulfate 1.5 mg/m2/dose (maximum dose of 2 mg) on Days 1, 8, 15 and 22 and daunorubicin hydrochloride (25 mg/m2/dose on Days 1, 8, 15 and 22. Dexamethasone (5 mg/m2/dose on Days 1-14 by mouth or infusion twice a day in weeks 1 and 2; intrathecal methotrexate (Aged based dosing: Age (yrs) Dose 1 - 1.99 8 mg 2 - 2.99 10 mg 3 - 8.99 12 mg ≥ 9 15 mg) on days 8 and 29 (CNS3 also on days 15 & 22) and an injection of pegaspargase (2500 International units/m2 x 1 dose on Day 4, 5 or 6). | Patients receive intrathecal cytarabine (Age-based dosing: Age (yrs) Dose 1 - 1.99 30 mg 2 - 2.99 50 mg ≥ 3 70 mg) on day 1; infusions of vincristine sulfate 1.5 mg/m2/dose (maximum dose of 2 mg) on Days 1, 8, 15 and 22 and daunorubicin hydrochloride (25 mg/m2/dose on Days 1, 8, 15 and 22. Dexamethasone (5 mg/m2/dose on Days 1-14 by mouth or infusion twice a day in weeks 1 and 2; intrathecal methotrexate (Aged based dosing: Age (yrs) Dose 1 - 1.99 8 mg 2 - 2.99 10 mg 3 - 8.99 12 mg ≥ 9 15 mg) on days 8 and 29 (CNS3 also on days 15 & 22) and an injection of pegaspargase (2500 International units/m2 x 1 dose on Day 4, 5 or 6). | Patients randomly assigned to the DH regimen based on one (or more) of the following characteristics: (1) No CNS3 status at entry, (2) no testicular leukemic involvement at entry, or (3) no extensive pre-treatment with steroids prior to entry. Patients receive intrathecal cytarabine (Age-based dosing: Age (yrs) Dose 1 - 1.99 30 mg 2 - 2.99 50 mg ≥ 3 70 mg) on day 1; infusions of vincristine sulfate 1.5 mg/m2/dose (maximum dose of 2 mg) on Days 1, 8, 15 and 22 and daunorubicin hydrochloride (25 mg/m2/dose on Days 1, 8, 15 and 22. Dexamethasone (5 mg/m2/dose on Days 1-14 by mouth or infusion twice a day in weeks 1 and 2; intrathecal methotrexate (Aged based dosing: Age (yrs) Dose 1 - 1.99 8 mg 2 - 2.99 10 mg 3 - 8.99 12 mg ≥ 9 15 mg) on days 8 and 29 (CNS3 also on days 15 & 22) and an injection of pegaspargase (2500 International units/m2 x 1 dose on Day 4, 5 or 6). | Patients in regimen PC will receive cytarabine, vincristine sulfate, daunorubicin hydrochloride, and pegaspargase. They will also receive prednisone by mouth or infusion twice a day in weeks 1-4 and intrathecal methotrexate in weeks 2 and 5. Some patients in all groups may receive induction therapy for 2 additional weeks. Beginning in week 6 or 7, patients may receive combination chemotherapy (vincristine sulfate, dexamethasone, doxorubicin hydrochloride, pegaspargase, cyclophosphamide, mercaptopurine, cytarabine, thioguanine) by infusion, injection, intrathecally, and by mouth for up to 8 weeks. | Patients in regimen PC will receive cytarabine, vincristine sulfate, daunorubicin hydrochloride, and pegaspargase. They will also receive prednisone by mouth or infusion twice a day in weeks 1-4 and intrathecal methotrexate in weeks 2 and 5. Some patients in all groups may receive induction therapy for 2 additional weeks. Beginning in week 6 or 7, patients may receive combination chemotherapy (vincristine sulfate, dexamethasone, doxorubicin hydrochloride, pegaspargase, cyclophosphamide, mercaptopurine, cytarabine, thioguanine) by infusion, injection, intrathecally, and by mouth for up to 8 weeks. | Patients randomly assigned to the PH regimen receive intrathecal cytarabine (Age-based dosing: Age (yrs) Dose 1 - 1.99 30 mg 2 - 2.99 50 mg ≥ 3 70 mg) on day 1; infusions of vincristine sulfate 1.5 mg/m2/dose (maximum dose of 2 mg) on Days 1, 8, 15 and 22 and daunorubicin hydrochloride (25 mg/m2/dose on Days 1, 8, 15 and 22. They will also receive prednisone by mouth or infusion twice a day in weeks 1-4 and intrathecal methotrexate in weeks 2 and 5. Some patients in all groups may receive induction therapy for 2 additional weeks. Beginning in week 6 or 7, patients may receive combination chemotherapy (vincristine sulfate, dexamethasone, doxorubicin hydrochloride, pegaspargase, cyclophosphamide, mercaptopurine, cytarabine, thioguanine) by infusion, injection, intrathecally, and by mouth for up to 8 weeks. | Patients randomly assigned to the PH regimen receive intrathecal cytarabine (Age-based dosing: Age (yrs) Dose 1 - 1.99 30 mg 2 - 2.99 50 mg ≥ 3 70 mg) on day 1; infusions of vincristine sulfate 1.5 mg/m2/dose (maximum dose of 2 mg) on Days 1, 8, 15 and 22 and daunorubicin hydrochloride (25 mg/m2/dose on Days 1, 8, 15 and 22. They will also receive prednisone by mouth or infusion twice a day in weeks 1-4 and intrathecal methotrexate in weeks 2 and 5. Some patients in all groups may receive induction therapy for 2 additional weeks. Beginning in week 6 or 7, patients may receive combination chemotherapy (vincristine sulfate, dexamethasone, doxorubicin hydrochloride, pegaspargase, cyclophosphamide, mercaptopurine, cytarabine, thioguanine) by infusion, injection, intrathecally, and by mouth for up to 8 weeks. | Patients randomly assigned to the DH regimen based on one (or more) of the following characteristics: (1) No CNS3 status at entry, (2) no testicular leukemic involvement at entry, or (3) no extensive pre-treatment with steroids prior to entry. Patients receive intrathecal cytarabine (Age-based dosing: Age (yrs) Dose 1 - 1.99 30 mg 2 - 2.99 50 mg ≥ 3 70 mg) on day 1; infusions of vincristine sulfate 1.5 mg/m2/dose (maximum dose of 2 mg) on Days 1, 8, 15 and 22 and daunorubicin hydrochloride (25 mg/m2/dose on Days 1, 8, 15 and 22. Dexamethasone (5 mg/m2/dose on Days 1-14 by mouth or infusion twice a day in weeks 1 and 2; intrathecal methotrexate (Aged based dosing: Age (yrs) Dose 1 - 1.99 8 mg 2 - 2.99 10 mg 3 - 8.99 12 mg ≥ 9 15 mg) on days 8 and 29 (CNS3 also on days 15 & 22) and an injection of pegaspargase (2500 International units/m2 x 1 dose on Day 4, 5 or 6). |
| Measure Participants | 28 | 13 | 53 | 15 | 17 | 116 | 20 | 112 | 44 |
| Number (95% Confidence Interval) [percentage of participants] |
66.5
27%
|
43.3
40.8%
|
35.4
12%
|
80
32.5%
|
34.7
15%
|
39
5.5%
|
55
22.4%
|
47.8
6.9%
|
49.4
16.4%
|
| Title | Correlation of Minimal Residual Disease (MRD) Negative With Event Free Survival (EFS). |
|---|---|
| Description | Bone marrow MRD status is defined as negative with < 0.1 detectable leukemia cells. |
| Time Frame | 5 years |
Outcome Measure Data
| Analysis Population Description |
|---|
| Group "Prednisone and High Dose MTX (non-random)" who either had EFS/OS events occur before 5 years or did not have minimum 5 years of follow-up. |
| Arm/Group Title | Dexamethasone and Capizzi Methotrexate Patients < 10 Years | Dexamethasone, High Dose Methotrexate (Non Randomly Assigned) | Dexamethasone & Capizzi Methotrexate Patients => 10 Years Old | Dexamethasone, High Dose Methotrexate (IM) < 10 Years | Prednisone, Capizzi Methotrexate <10 Years | Prednisone, Capezzi Methotrexate >= 10 Years | Prednisone and High Dose Methotrexate < 10 Yrs Old | Prednisone and High Dose Methotrexate >=10 Years | Dexamethasone, High Dose Methotrexate (IM) >= 10 Years | Prednisone, Capezzi Methotrexate (Down's Syndrome) | Dexamethasone, Capizzi Methotrexate Down Syndrome (Non Random) |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Patients receive intrathecal cytarabine (Age-based dosing: Age (yrs) Dose 1 - 1.99 30 mg 2 - 2.99 50 mg ≥ 3 70 mg) on day 1; infusions of vincristine sulfate 1.5 mg/m2/dose (maximum dose of 2 mg) on Days 1, 8, 15 and 22 and daunorubicin hydrochloride (25 mg/m2/dose on Days 1, 8, 15 and 22. Dexamethasone (5 mg/m2/dose on Days 1-14 by mouth or infusion twice a day in weeks 1 and 2; intrathecal methotrexate (Aged based dosing: Age (yrs) Dose 1 - 1.99 8 mg 2 - 2.99 10 mg 3 - 8.99 12 mg ≥ 9 15 mg) on days 8 and 29 (CNS3 also on days 15 & 22) and an injection of pegaspargase (2500 International units/m2 x 1 dose on Day 4, 5 or 6). | Patients non-randomly assigned to the DH regimen based on one (or more) of the following characteristics: (1) CNS3 status at entry, (2) testicular leukemic involvement at entry, or (3) extensive pre-treatment with steroids prior to entry. Patients receive intrathecal cytarabine (Age-based dosing: Age (yrs) Dose 1 - 1.99 30 mg 2 - 2.99 50 mg ≥ 3 70 mg) on day 1; infusions of vincristine sulfate 1.5 mg/m2/dose (maximum dose of 2 mg) on Days 1, 8, 15 and 22 and daunorubicin hydrochloride (25 mg/m2/dose on Days 1, 8, 15 and 22. Dexamethasone (5 mg/m2/dose on Days 1-14 by mouth or infusion twice a day in weeks 1 and 2; intrathecal methotrexate (Aged based dosing: Age (yrs) Dose 1 - 1.99 8 mg 2 - 2.99 10 mg 3 - 8.99 12 mg ≥ 9 15 mg) on days 8 and 29 (CNS3 also on days 15 & 22) and an injection of pegaspargase (2500 International units/m2 x 1 dose on Day 4, 5 or 6). | Patients receive intrathecal cytarabine (Age-based dosing: Age (yrs) Dose 1 - 1.99 30 mg 2 - 2.99 50 mg ≥ 3 70 mg) on day 1; infusions of vincristine sulfate 1.5 mg/m2/dose (maximum dose of 2 mg) on Days 1, 8, 15 and 22 and daunorubicin hydrochloride (25 mg/m2/dose on Days 1, 8, 15 and 22. Dexamethasone (5 mg/m2/dose on Days 1-14 by mouth or infusion twice a day in weeks 1 and 2; intrathecal methotrexate (Aged based dosing: Age (yrs) Dose 1 - 1.99 8 mg 2 - 2.99 10 mg 3 - 8.99 12 mg ≥ 9 15 mg) on days 8 and 29 (CNS3 also on days 15 & 22) and an injection of pegaspargase (2500 International units/m2 x 1 dose on Day 4, 5 or 6). | Patients randomly assigned to the DH regimen based on one (or more) of the following characteristics: (1) No CNS3 status at entry, (2) no testicular leukemic involvement at entry, or (3) no extensive pre-treatment with steroids prior to entry. Patients receive intrathecal cytarabine (Age-based dosing: Age (yrs) Dose 1 - 1.99 30 mg 2 - 2.99 50 mg ≥ 3 70 mg) on day 1; infusions of vincristine sulfate 1.5 mg/m2/dose (maximum dose of 2 mg) on Days 1, 8, 15 and 22 and daunorubicin hydrochloride (25 mg/m2/dose on Days 1, 8, 15 and 22. Dexamethasone (5 mg/m2/dose on Days 1-14 by mouth or infusion twice a day in weeks 1 and 2; intrathecal methotrexate (Aged based dosing: Age (yrs) Dose 1 - 1.99 8 mg 2 - 2.99 10 mg 3 - 8.99 12 mg ≥ 9 15 mg) on days 8 and 29 (CNS3 also on days 15 & 22) and an injection of pegaspargase (2500 International units/m2 x 1 dose on Day 4, 5 or 6). | Patients in regimen PC will receive cytarabine, vincristine sulfate, daunorubicin hydrochloride, and pegaspargase. They will also receive prednisone by mouth or infusion twice a day in weeks 1-4 and intrathecal methotrexate in weeks 2 and 5. Some patients in all groups may receive induction therapy for 2 additional weeks. Beginning in week 6 or 7, patients may receive combination chemotherapy (vincristine sulfate, dexamethasone, doxorubicin hydrochloride, pegaspargase, cyclophosphamide, mercaptopurine, cytarabine, thioguanine) by infusion, injection, intrathecally, and by mouth for up to 8 weeks. | Patients in regimen PC will receive cytarabine, vincristine sulfate, daunorubicin hydrochloride, and pegaspargase. They will also receive prednisone by mouth or infusion twice a day in weeks 1-4 and intrathecal methotrexate in weeks 2 and 5. Some patients in all groups may receive induction therapy for 2 additional weeks. Beginning in week 6 or 7, patients may receive combination chemotherapy (vincristine sulfate, dexamethasone, doxorubicin hydrochloride, pegaspargase, cyclophosphamide, mercaptopurine, cytarabine, thioguanine) by infusion, injection, intrathecally, and by mouth for up to 8 weeks. | Patients randomly assigned to the PH regimen receive intrathecal cytarabine (Age-based dosing: Age (yrs) Dose 1 - 1.99 30 mg 2 - 2.99 50 mg ≥ 3 70 mg) on day 1; infusions of vincristine sulfate 1.5 mg/m2/dose (maximum dose of 2 mg) on Days 1, 8, 15 and 22 and daunorubicin hydrochloride (25 mg/m2/dose on Days 1, 8, 15 and 22. They will also receive prednisone by mouth or infusion twice a day in weeks 1-4 and intrathecal methotrexate in weeks 2 and 5. Some patients in all groups may receive induction therapy for 2 additional weeks. Beginning in week 6 or 7, patients may receive combination chemotherapy (vincristine sulfate, dexamethasone, doxorubicin hydrochloride, pegaspargase, cyclophosphamide, mercaptopurine, cytarabine, thioguanine) by infusion, injection, intrathecally, and by mouth for up to 8 weeks. | Patients randomly assigned to the PH regimen receive intrathecal cytarabine (Age-based dosing: Age (yrs) Dose 1 - 1.99 30 mg 2 - 2.99 50 mg ≥ 3 70 mg) on day 1; infusions of vincristine sulfate 1.5 mg/m2/dose (maximum dose of 2 mg) on Days 1, 8, 15 and 22 and daunorubicin hydrochloride (25 mg/m2/dose on Days 1, 8, 15 and 22. They will also receive prednisone by mouth or infusion twice a day in weeks 1-4 and intrathecal methotrexate in weeks 2 and 5. Some patients in all groups may receive induction therapy for 2 additional weeks. Beginning in week 6 or 7, patients may receive combination chemotherapy (vincristine sulfate, dexamethasone, doxorubicin hydrochloride, pegaspargase, cyclophosphamide, mercaptopurine, cytarabine, thioguanine) by infusion, injection, intrathecally, and by mouth for up to 8 weeks. | Patients randomly assigned to the DH regimen based on one (or more) of the following characteristics: (1) No CNS3 status at entry, (2) no testicular leukemic involvement at entry, or (3) no extensive pre-treatment with steroids prior to entry. Patients receive intrathecal cytarabine (Age-based dosing: Age (yrs) Dose 1 - 1.99 30 mg 2 - 2.99 50 mg ≥ 3 70 mg) on day 1; infusions of vincristine sulfate 1.5 mg/m2/dose (maximum dose of 2 mg) on Days 1, 8, 15 and 22 and daunorubicin hydrochloride (25 mg/m2/dose on Days 1, 8, 15 and 22. Dexamethasone (5 mg/m2/dose on Days 1-14 by mouth or infusion twice a day in weeks 1 and 2; intrathecal methotrexate (Aged based dosing: Age (yrs) Dose 1 - 1.99 8 mg 2 - 2.99 10 mg 3 - 8.99 12 mg ≥ 9 15 mg) on days 8 and 29 (CNS3 also on days 15 & 22) and an injection of pegaspargase (2500 International units/m2 x 1 dose on Day 4, 5 or 6). | Patients in regimen PC will receive cytarabine, vincristine sulfate, daunorubicin hydrochloride, and pegaspargase. They will also receive prednisone by mouth or infusion twice a day in weeks 1-4 and intrathecal methotrexate in weeks 2 and 5. Some patients in all groups may receive induction therapy for 2 additional weeks. Beginning in week 6 or 7, patients may receive combination chemotherapy (vincristine sulfate, dexamethasone, doxorubicin hydrochloride, pegaspargase, cyclophosphamide, mercaptopurine, cytarabine, thioguanine) by infusion, injection, intrathecally, and by mouth for up to 8 weeks. | Patients receive intrathecal cytarabine (Age-based dosing: Age (yrs) Dose 1 - 1.99 30 mg 2 - 2.99 50 mg ≥ 3 70 mg) on day 1; infusions of vincristine sulfate 1.5 mg/m2/dose (maximum dose of 2 mg) on Days 1, 8, 15 and 22 and daunorubicin hydrochloride (25 mg/m2/dose on Days 1, 8, 15 and 22. Dexamethasone (5 mg/m2/dose on Days 1-14 by mouth or infusion twice a day in weeks 1 and 2; intrathecal methotrexate (Aged based dosing: Age (yrs) Dose 1 - 1.99 8 mg 2 - 2.99 10 mg 3 - 8.99 12 mg ≥ 9 15 mg) on days 8 and 29 (CNS3 also on days 15 & 22) and an injection of pegaspargase (2500 International units/m2 x 1 dose on Day 4, 5 or 6). |
| Measure Participants | 185 | 73 | 198 | 189 | 195 | 472 | 191 | 480 | 209 | 25 | 4 |
| Number (95% Confidence Interval) [percentage of participants] |
86.4
35.1%
|
93.6
88.3%
|
80.5
27.2%
|
93.1
37.8%
|
86.5
37.3%
|
83.4
11.7%
|
84.2
34.2%
|
83.9
12.1%
|
85.3
28.2%
|
74.4
218.8%
|
25
208.3%
|
Adverse Events
| Time Frame | ||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs. | |||||||||||||||||||||||
| Arm/Group Title | Dexamethasone and Capizzi Methotrexate Patients < 10 Years | Dexamethasone, High Dose Methotrexate (Non Randomly Assigned) | Dexamethasone & Capizzi Methotrexate Patients => 10 Years Old | Dexamethasone, High Dose Methotrexate (IM) < 10 Years | Prednisone, Capizzi Methotrexate <10 Years | Prednisone, Capezzi Methotrexate >= 10 Years | Prednisone and High Dose Methotrexate < 10 Yrs Old | Prednisone and High Dose Methotrexate >=10 Years | Dexamethasone, High Dose Methotrexate (IM) >= 10 Years | Prednisone, Capezzi Methotrexate (Down's Syndrome) | Dexamethasone, Capizzi Methotrexate Down Syndrome (Non Random) | Prednisone and High Dose Methotrexate (Non Randomly Assigned) | ||||||||||||
| Arm/Group Description | Patients receive intrathecal cytarabine (Age-based dosing: Age (yrs) Dose 1 - 1.99 30 mg 2 - 2.99 50 mg ≥ 3 70 mg) on day 1; infusions of vincristine sulfate 1.5 mg/m2/dose (maximum dose of 2 mg) on Days 1, 8, 15 and 22 and daunorubicin hydrochloride (25 mg/m2/dose on Days 1, 8, 15 and 22. Dexamethasone (5 mg/m2/dose on Days 1-14 by mouth or infusion twice a day in weeks 1 and 2; intrathecal methotrexate (Aged based dosing: Age (yrs) Dose 1 - 1.99 8 mg 2 - 2.99 10 mg 3 - 8.99 12 mg ≥ 9 15 mg) on days 8 and 29 (CNS3 also on days 15 & 22) and an injection of pegaspargase (2500 International units/m2 x 1 dose on Day 4, 5 or 6). | Patients non-randomly assigned to the DH regimen based on one (or more) of the following characteristics: (1) CNS3 status at entry, (2) testicular leukemic involvement at entry, or (3) extensive pre-treatment with steroids prior to entry. Patients receive intrathecal cytarabine (Age-based dosing: Age (yrs) Dose 1 - 1.99 30 mg 2 - 2.99 50 mg ≥ 3 70 mg) on day 1; infusions of vincristine sulfate 1.5 mg/m2/dose (maximum dose of 2 mg) on Days 1, 8, 15 and 22 and daunorubicin hydrochloride (25 mg/m2/dose on Days 1, 8, 15 and 22. Dexamethasone (5 mg/m2/dose on Days 1-14 by mouth or infusion twice a day in weeks 1 and 2; intrathecal methotrexate (Aged based dosing: Age (yrs) Dose 1 - 1.99 8 mg 2 - 2.99 10 mg 3 - 8.99 12 mg ≥ 9 15 mg) on days 8 and 29 (CNS3 also on days 15 & 22) and an injection of pegaspargase (2500 International units/m2 x 1 dose on Day 4, 5 or 6). | Patients receive intrathecal cytarabine (Age-based dosing: Age (yrs) Dose 1 - 1.99 30 mg 2 - 2.99 50 mg ≥ 3 70 mg) on day 1; infusions of vincristine sulfate 1.5 mg/m2/dose (maximum dose of 2 mg) on Days 1, 8, 15 and 22 and daunorubicin hydrochloride (25 mg/m2/dose on Days 1, 8, 15 and 22. Dexamethasone (5 mg/m2/dose on Days 1-14 by mouth or infusion twice a day in weeks 1 and 2; intrathecal methotrexate (Aged based dosing: Age (yrs) Dose 1 - 1.99 8 mg 2 - 2.99 10 mg 3 - 8.99 12 mg ≥ 9 15 mg) on days 8 and 29 (CNS3 also on days 15 & 22) and an injection of pegaspargase (2500 International units/m2 x 1 dose on Day 4, 5 or 6). | Patients randomly assigned to the DH regimen based on one (or more) of the following characteristics: (1) No CNS3 status at entry, (2) no testicular leukemic involvement at entry, or (3) no extensive pre-treatment with steroids prior to entry. Patients receive intrathecal cytarabine (Age-based dosing: Age (yrs) Dose 1 - 1.99 30 mg 2 - 2.99 50 mg ≥ 3 70 mg) on day 1; infusions of vincristine sulfate 1.5 mg/m2/dose (maximum dose of 2 mg) on Days 1, 8, 15 and 22 and daunorubicin hydrochloride (25 mg/m2/dose on Days 1, 8, 15 and 22. Dexamethasone (5 mg/m2/dose on Days 1-14 by mouth or infusion twice a day in weeks 1 and 2; intrathecal methotrexate (Aged based dosing: Age (yrs) Dose 1 - 1.99 8 mg 2 - 2.99 10 mg 3 - 8.99 12 mg ≥ 9 15 mg) on days 8 and 29 (CNS3 also on days 15 & 22) and an injection of pegaspargase (2500 International units/m2 x 1 dose on Day 4, 5 or 6). | Patients in regimen PC will receive cytarabine, vincristine sulfate, daunorubicin hydrochloride, and pegaspargase. They will also receive prednisone by mouth or infusion twice a day in weeks 1-4 and intrathecal methotrexate in weeks 2 and 5. Some patients in all groups may receive induction therapy for 2 additional weeks. Beginning in week 6 or 7, patients may receive combination chemotherapy (vincristine sulfate, dexamethasone, doxorubicin hydrochloride, pegaspargase, cyclophosphamide, mercaptopurine, cytarabine, thioguanine) by infusion, injection, intrathecally, and by mouth for up to 8 weeks. | Patients in regimen PC will receive cytarabine, vincristine sulfate, daunorubicin hydrochloride, and pegaspargase. They will also receive prednisone by mouth or infusion twice a day in weeks 1-4 and intrathecal methotrexate in weeks 2 and 5. Some patients in all groups may receive induction therapy for 2 additional weeks. Beginning in week 6 or 7, patients may receive combination chemotherapy (vincristine sulfate, dexamethasone, doxorubicin hydrochloride, pegaspargase, cyclophosphamide, mercaptopurine, cytarabine, thioguanine) by infusion, injection, intrathecally, and by mouth for up to 8 weeks. | Patients randomly assigned to the PH regimen receive intrathecal cytarabine (Age-based dosing: Age (yrs) Dose 1 - 1.99 30 mg 2 - 2.99 50 mg ≥ 3 70 mg) on day 1; infusions of vincristine sulfate 1.5 mg/m2/dose (maximum dose of 2 mg) on Days 1, 8, 15 and 22 and daunorubicin hydrochloride (25 mg/m2/dose on Days 1, 8, 15 and 22. They will also receive prednisone by mouth or infusion twice a day in weeks 1-4 and intrathecal methotrexate in weeks 2 and 5. Some patients in all groups may receive induction therapy for 2 additional weeks. Beginning in week 6 or 7, patients may receive combination chemotherapy (vincristine sulfate, dexamethasone, doxorubicin hydrochloride, pegaspargase, cyclophosphamide, mercaptopurine, cytarabine, thioguanine) by infusion, injection, intrathecally, and by mouth for up to 8 weeks. | Patients randomly assigned to the PH regimen receive intrathecal cytarabine (Age-based dosing: Age (yrs) Dose 1 - 1.99 30 mg 2 - 2.99 50 mg ≥ 3 70 mg) on day 1; infusions of vincristine sulfate 1.5 mg/m2/dose (maximum dose of 2 mg) on Days 1, 8, 15 and 22 and daunorubicin hydrochloride (25 mg/m2/dose on Days 1, 8, 15 and 22. They will also receive prednisone by mouth or infusion twice a day in weeks 1-4 and intrathecal methotrexate in weeks 2 and 5. Some patients in all groups may receive induction therapy for 2 additional weeks. Beginning in week 6 or 7, patients may receive combination chemotherapy (vincristine sulfate, dexamethasone, doxorubicin hydrochloride, pegaspargase, cyclophosphamide, mercaptopurine, cytarabine, thioguanine) by infusion, injection, intrathecally, and by mouth for up to 8 weeks. | Patients randomly assigned to the DH regimen based on one (or more) of the following characteristics: (1) No CNS3 status at entry, (2) no testicular leukemic involvement at entry, or (3) no extensive pre-treatment with steroids prior to entry. Patients receive intrathecal cytarabine (Age-based dosing: Age (yrs) Dose 1 - 1.99 30 mg 2 - 2.99 50 mg ≥ 3 70 mg) on day 1; infusions of vincristine sulfate 1.5 mg/m2/dose (maximum dose of 2 mg) on Days 1, 8, 15 and 22 and daunorubicin hydrochloride (25 mg/m2/dose on Days 1, 8, 15 and 22. Dexamethasone (5 mg/m2/dose on Days 1-14 by mouth or infusion twice a day in weeks 1 and 2; intrathecal methotrexate (Aged based dosing: Age (yrs) Dose 1 - 1.99 8 mg 2 - 2.99 10 mg 3 - 8.99 12 mg ≥ 9 15 mg) on days 8 and 29 (CNS3 also on days 15 & 22) and an injection of pegaspargase (2500 International units/m2 x 1 dose on Day 4, 5 or 6). | Patients in regimen PC will receive cytarabine, vincristine sulfate, daunorubicin hydrochloride, and pegaspargase. They will also receive prednisone by mouth or infusion twice a day in weeks 1-4 and intrathecal methotrexate in weeks 2 and 5. Some patients in all groups may receive induction therapy for 2 additional weeks. Beginning in week 6 or 7, patients may receive combination chemotherapy (vincristine sulfate, dexamethasone, doxorubicin hydrochloride, pegaspargase, cyclophosphamide, mercaptopurine, cytarabine, thioguanine) by infusion, injection, intrathecally, and by mouth for up to 8 weeks. | Patients receive intrathecal cytarabine (Age-based dosing: Age (yrs) Dose 1 - 1.99 30 mg 2 - 2.99 50 mg ≥ 3 70 mg) on day 1; infusions of vincristine sulfate 1.5 mg/m2/dose (maximum dose of 2 mg) on Days 1, 8, 15 and 22 and daunorubicin hydrochloride (25 mg/m2/dose on Days 1, 8, 15 and 22. Dexamethasone (5 mg/m2/dose on Days 1-14 by mouth or infusion twice a day in weeks 1 and 2; intrathecal methotrexate (Aged based dosing: Age (yrs) Dose 1 - 1.99 8 mg 2 - 2.99 10 mg 3 - 8.99 12 mg ≥ 9 15 mg) on days 8 and 29 (CNS3 also on days 15 & 22) and an injection of pegaspargase (2500 International units/m2 x 1 dose on Day 4, 5 or 6). | Patients non-randomly assigned to the PH regimen based on one (or more) of the following: (1) CNS3 status at entry, (2) testicular leukemic involvement at entry, or (3) extensive pre-treatment with steroids prior to entry. Patients receive intrathecal cytarabine (Age-based dosing: Age (yrs) Dose 1 - 1.99 30 mg 2 - 2.99 50 mg ≥ 3 70 mg) on day 1; infusions of vincristine sulfate 1.5 mg/m2/dose (maximum dose of 2 mg) on Days 1, 8, 15 and 22 and daunorubicin hydrochloride (25 mg/m2/dose on Days 1, 8, 15 and 22. They will also receive prednisone by mouth or infusion twice a day in weeks 1-4 and intrathecal MTX in weeks 2 and 5. Some patients in all groups may receive induction therapy for 2 additional weeks. Beginning in week 6 or 7, patients may receive combination chemotherapy (vincristine sulfate, dexamethasone, doxorubicin hydrochloride, pegaspargase, cyclophosphamide, mercaptopurine, cytarabine, thioguanine) by infusion, injection, intrathecally, and by mouth for up to 8 weeks. | ||||||||||||
All Cause Mortality |
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| Dexamethasone and Capizzi Methotrexate Patients < 10 Years | Dexamethasone, High Dose Methotrexate (Non Randomly Assigned) | Dexamethasone & Capizzi Methotrexate Patients => 10 Years Old | Dexamethasone, High Dose Methotrexate (IM) < 10 Years | Prednisone, Capizzi Methotrexate <10 Years | Prednisone, Capezzi Methotrexate >= 10 Years | Prednisone and High Dose Methotrexate < 10 Yrs Old | Prednisone and High Dose Methotrexate >=10 Years | Dexamethasone, High Dose Methotrexate (IM) >= 10 Years | Prednisone, Capezzi Methotrexate (Down's Syndrome) | Dexamethasone, Capizzi Methotrexate Down Syndrome (Non Random) | Prednisone and High Dose Methotrexate (Non Randomly Assigned) | |||||||||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | / (NaN) | / (NaN) | / (NaN) | / (NaN) | / (NaN) | / (NaN) | / (NaN) | / (NaN) | / (NaN) | / (NaN) | / (NaN) | / (NaN) | ||||||||||||
Serious Adverse Events |
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| Dexamethasone and Capizzi Methotrexate Patients < 10 Years | Dexamethasone, High Dose Methotrexate (Non Randomly Assigned) | Dexamethasone & Capizzi Methotrexate Patients => 10 Years Old | Dexamethasone, High Dose Methotrexate (IM) < 10 Years | Prednisone, Capizzi Methotrexate <10 Years | Prednisone, Capezzi Methotrexate >= 10 Years | Prednisone and High Dose Methotrexate < 10 Yrs Old | Prednisone and High Dose Methotrexate >=10 Years | Dexamethasone, High Dose Methotrexate (IM) >= 10 Years | Prednisone, Capezzi Methotrexate (Down's Syndrome) | Dexamethasone, Capizzi Methotrexate Down Syndrome (Non Random) | Prednisone and High Dose Methotrexate (Non Randomly Assigned) | |||||||||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 16/218 (7.3%) | 17/90 (18.9%) | 42/261 (16.1%) | 25/206 (12.1%) | 20/214 (9.3%) | 64/598 (10.7%) | 16/213 (7.5%) | 67/601 (11.1%) | 27/262 (10.3%) | 3/30 (10%) | 3/9 (33.3%) | 1/23 (4.3%) | ||||||||||||
| Blood and lymphatic system disorders | ||||||||||||||||||||||||
| Anemia | 1/218 (0.5%) | 1 | 0/90 (0%) | 0 | 2/261 (0.8%) | 2 | 4/206 (1.9%) | 5 | 1/214 (0.5%) | 1 | 4/598 (0.7%) | 4 | 0/213 (0%) | 0 | 2/601 (0.3%) | 2 | 1/262 (0.4%) | 1 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Blood and lymphatic system disorders - Other, specify | 0/218 (0%) | 0 | 0/90 (0%) | 0 | 0/261 (0%) | 0 | 1/206 (0.5%) | 2 | 0/214 (0%) | 0 | 1/598 (0.2%) | 1 | 0/213 (0%) | 0 | 0/601 (0%) | 0 | 0/262 (0%) | 0 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Bone marrow hypocellular | 0/218 (0%) | 0 | 0/90 (0%) | 0 | 0/261 (0%) | 0 | 0/206 (0%) | 0 | 0/214 (0%) | 0 | 1/598 (0.2%) | 1 | 0/213 (0%) | 0 | 0/601 (0%) | 0 | 0/262 (0%) | 0 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Disseminated intravascular coagulation | 0/218 (0%) | 0 | 2/90 (2.2%) | 2 | 1/261 (0.4%) | 1 | 0/206 (0%) | 0 | 0/214 (0%) | 0 | 0/598 (0%) | 0 | 0/213 (0%) | 0 | 3/601 (0.5%) | 3 | 1/262 (0.4%) | 1 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Febrile neutropenia | 4/218 (1.8%) | 7 | 0/90 (0%) | 0 | 2/261 (0.8%) | 2 | 2/206 (1%) | 3 | 2/214 (0.9%) | 2 | 4/598 (0.7%) | 4 | 0/213 (0%) | 0 | 1/601 (0.2%) | 1 | 3/262 (1.1%) | 3 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Hemolysis | 0/218 (0%) | 0 | 0/90 (0%) | 0 | 0/261 (0%) | 0 | 0/206 (0%) | 0 | 0/214 (0%) | 0 | 1/598 (0.2%) | 1 | 0/213 (0%) | 0 | 1/601 (0.2%) | 1 | 0/262 (0%) | 0 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Cardiac disorders | ||||||||||||||||||||||||
| Cardiac arrest | 0/218 (0%) | 0 | 1/90 (1.1%) | 1 | 0/261 (0%) | 0 | 0/206 (0%) | 0 | 0/214 (0%) | 0 | 0/598 (0%) | 0 | 0/213 (0%) | 0 | 1/601 (0.2%) | 1 | 0/262 (0%) | 0 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Cardiac disorders - Other, specify | 0/218 (0%) | 0 | 0/90 (0%) | 0 | 0/261 (0%) | 0 | 0/206 (0%) | 0 | 0/214 (0%) | 0 | 0/598 (0%) | 0 | 0/213 (0%) | 0 | 0/601 (0%) | 0 | 1/262 (0.4%) | 1 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Left ventricular systolic dysfunction | 0/218 (0%) | 0 | 0/90 (0%) | 0 | 0/261 (0%) | 0 | 0/206 (0%) | 0 | 0/214 (0%) | 0 | 0/598 (0%) | 0 | 0/213 (0%) | 0 | 0/601 (0%) | 0 | 0/262 (0%) | 0 | 0/30 (0%) | 0 | 1/9 (11.1%) | 1 | 0/23 (0%) | 0 |
| Myocardial infarction | 0/218 (0%) | 0 | 0/90 (0%) | 0 | 0/261 (0%) | 0 | 0/206 (0%) | 0 | 0/214 (0%) | 0 | 0/598 (0%) | 0 | 0/213 (0%) | 0 | 1/601 (0.2%) | 1 | 0/262 (0%) | 0 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Sinus tachycardia | 0/218 (0%) | 0 | 0/90 (0%) | 0 | 0/261 (0%) | 0 | 0/206 (0%) | 0 | 0/214 (0%) | 0 | 1/598 (0.2%) | 1 | 0/213 (0%) | 0 | 0/601 (0%) | 0 | 0/262 (0%) | 0 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Ventricular tachycardia | 0/218 (0%) | 0 | 0/90 (0%) | 0 | 0/261 (0%) | 0 | 0/206 (0%) | 0 | 0/214 (0%) | 0 | 0/598 (0%) | 0 | 0/213 (0%) | 0 | 1/601 (0.2%) | 1 | 0/262 (0%) | 0 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Endocrine disorders | ||||||||||||||||||||||||
| Adrenal insufficiency | 0/218 (0%) | 0 | 0/90 (0%) | 0 | 0/261 (0%) | 0 | 0/206 (0%) | 0 | 0/214 (0%) | 0 | 0/598 (0%) | 0 | 0/213 (0%) | 0 | 0/601 (0%) | 0 | 1/262 (0.4%) | 1 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Eye disorders | ||||||||||||||||||||||||
| Eye disorders - Other, specify | 0/218 (0%) | 0 | 0/90 (0%) | 0 | 0/261 (0%) | 0 | 0/206 (0%) | 0 | 0/214 (0%) | 0 | 0/598 (0%) | 0 | 0/213 (0%) | 0 | 1/601 (0.2%) | 1 | 0/262 (0%) | 0 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Gastrointestinal disorders | ||||||||||||||||||||||||
| Abdominal distension | 0/218 (0%) | 0 | 0/90 (0%) | 0 | 0/261 (0%) | 0 | 0/206 (0%) | 0 | 0/214 (0%) | 0 | 0/598 (0%) | 0 | 0/213 (0%) | 0 | 1/601 (0.2%) | 1 | 0/262 (0%) | 0 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Abdominal pain | 0/218 (0%) | 0 | 0/90 (0%) | 0 | 1/261 (0.4%) | 1 | 1/206 (0.5%) | 1 | 0/214 (0%) | 0 | 0/598 (0%) | 0 | 0/213 (0%) | 0 | 0/601 (0%) | 0 | 0/262 (0%) | 0 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Ascites | 0/218 (0%) | 0 | 0/90 (0%) | 0 | 0/261 (0%) | 0 | 2/206 (1%) | 2 | 0/214 (0%) | 0 | 0/598 (0%) | 0 | 0/213 (0%) | 0 | 0/601 (0%) | 0 | 0/262 (0%) | 0 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Colitis | 0/218 (0%) | 0 | 0/90 (0%) | 0 | 1/261 (0.4%) | 1 | 0/206 (0%) | 0 | 0/214 (0%) | 0 | 1/598 (0.2%) | 1 | 0/213 (0%) | 0 | 1/601 (0.2%) | 1 | 0/262 (0%) | 0 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Colonic perforation | 0/218 (0%) | 0 | 0/90 (0%) | 0 | 1/261 (0.4%) | 1 | 0/206 (0%) | 0 | 0/214 (0%) | 0 | 0/598 (0%) | 0 | 0/213 (0%) | 0 | 0/601 (0%) | 0 | 0/262 (0%) | 0 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Constipation | 0/218 (0%) | 0 | 0/90 (0%) | 0 | 1/261 (0.4%) | 1 | 0/206 (0%) | 0 | 0/214 (0%) | 0 | 0/598 (0%) | 0 | 0/213 (0%) | 0 | 0/601 (0%) | 0 | 1/262 (0.4%) | 1 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Diarrhea | 0/218 (0%) | 0 | 0/90 (0%) | 0 | 0/261 (0%) | 0 | 0/206 (0%) | 0 | 0/214 (0%) | 0 | 0/598 (0%) | 0 | 0/213 (0%) | 0 | 0/601 (0%) | 0 | 0/262 (0%) | 0 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 1/23 (4.3%) | 1 |
| Enterocolitis | 0/218 (0%) | 0 | 0/90 (0%) | 0 | 0/261 (0%) | 0 | 1/206 (0.5%) | 1 | 0/214 (0%) | 0 | 0/598 (0%) | 0 | 0/213 (0%) | 0 | 0/601 (0%) | 0 | 0/262 (0%) | 0 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Esophagitis | 0/218 (0%) | 0 | 0/90 (0%) | 0 | 0/261 (0%) | 0 | 0/206 (0%) | 0 | 0/214 (0%) | 0 | 0/598 (0%) | 0 | 0/213 (0%) | 0 | 1/601 (0.2%) | 1 | 0/262 (0%) | 0 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Ileal hemorrhage | 0/218 (0%) | 0 | 0/90 (0%) | 0 | 1/261 (0.4%) | 1 | 0/206 (0%) | 0 | 0/214 (0%) | 0 | 0/598 (0%) | 0 | 0/213 (0%) | 0 | 0/601 (0%) | 0 | 0/262 (0%) | 0 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Ileal perforation | 0/218 (0%) | 0 | 0/90 (0%) | 0 | 0/261 (0%) | 0 | 0/206 (0%) | 0 | 0/214 (0%) | 0 | 0/598 (0%) | 0 | 1/213 (0.5%) | 1 | 0/601 (0%) | 0 | 0/262 (0%) | 0 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Jejunal perforation | 0/218 (0%) | 0 | 0/90 (0%) | 0 | 0/261 (0%) | 0 | 0/206 (0%) | 0 | 0/214 (0%) | 0 | 0/598 (0%) | 0 | 0/213 (0%) | 0 | 1/601 (0.2%) | 1 | 0/262 (0%) | 0 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Lower gastrointestinal hemorrhage | 0/218 (0%) | 0 | 0/90 (0%) | 0 | 0/261 (0%) | 0 | 1/206 (0.5%) | 1 | 0/214 (0%) | 0 | 0/598 (0%) | 0 | 0/213 (0%) | 0 | 0/601 (0%) | 0 | 0/262 (0%) | 0 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Mucositis oral | 0/218 (0%) | 0 | 0/90 (0%) | 0 | 0/261 (0%) | 0 | 1/206 (0.5%) | 1 | 0/214 (0%) | 0 | 2/598 (0.3%) | 2 | 0/213 (0%) | 0 | 3/601 (0.5%) | 3 | 0/262 (0%) | 0 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Nausea | 0/218 (0%) | 0 | 0/90 (0%) | 0 | 1/261 (0.4%) | 1 | 0/206 (0%) | 0 | 0/214 (0%) | 0 | 1/598 (0.2%) | 1 | 0/213 (0%) | 0 | 0/601 (0%) | 0 | 0/262 (0%) | 0 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Oral pain | 0/218 (0%) | 0 | 0/90 (0%) | 0 | 0/261 (0%) | 0 | 0/206 (0%) | 0 | 0/214 (0%) | 0 | 1/598 (0.2%) | 1 | 0/213 (0%) | 0 | 0/601 (0%) | 0 | 0/262 (0%) | 0 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Pancreatitis | 0/218 (0%) | 0 | 0/90 (0%) | 0 | 0/261 (0%) | 0 | 0/206 (0%) | 0 | 1/214 (0.5%) | 1 | 1/598 (0.2%) | 1 | 1/213 (0.5%) | 1 | 1/601 (0.2%) | 1 | 0/262 (0%) | 0 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Rectal mucositis | 0/218 (0%) | 0 | 0/90 (0%) | 0 | 0/261 (0%) | 0 | 0/206 (0%) | 0 | 0/214 (0%) | 0 | 1/598 (0.2%) | 1 | 0/213 (0%) | 0 | 0/601 (0%) | 0 | 0/262 (0%) | 0 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Small intestinal perforation | 0/218 (0%) | 0 | 0/90 (0%) | 0 | 0/261 (0%) | 0 | 0/206 (0%) | 0 | 0/214 (0%) | 0 | 0/598 (0%) | 0 | 1/213 (0.5%) | 1 | 0/601 (0%) | 0 | 0/262 (0%) | 0 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Typhlitis | 0/218 (0%) | 0 | 0/90 (0%) | 0 | 2/261 (0.8%) | 2 | 0/206 (0%) | 0 | 0/214 (0%) | 0 | 1/598 (0.2%) | 1 | 1/213 (0.5%) | 1 | 0/601 (0%) | 0 | 1/262 (0.4%) | 1 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Vomiting | 0/218 (0%) | 0 | 1/90 (1.1%) | 1 | 0/261 (0%) | 0 | 0/206 (0%) | 0 | 1/214 (0.5%) | 1 | 1/598 (0.2%) | 1 | 0/213 (0%) | 0 | 3/601 (0.5%) | 3 | 0/262 (0%) | 0 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| General disorders | ||||||||||||||||||||||||
| Fever | 0/218 (0%) | 0 | 0/90 (0%) | 0 | 0/261 (0%) | 0 | 0/206 (0%) | 0 | 0/214 (0%) | 0 | 1/598 (0.2%) | 1 | 0/213 (0%) | 0 | 1/601 (0.2%) | 1 | 0/262 (0%) | 0 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| General disorders and administration site conditions - Other, specify | 0/218 (0%) | 0 | 0/90 (0%) | 0 | 0/261 (0%) | 0 | 0/206 (0%) | 0 | 1/214 (0.5%) | 1 | 0/598 (0%) | 0 | 0/213 (0%) | 0 | 0/601 (0%) | 0 | 0/262 (0%) | 0 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Multi-organ failure | 1/218 (0.5%) | 1 | 0/90 (0%) | 0 | 0/261 (0%) | 0 | 0/206 (0%) | 0 | 1/214 (0.5%) | 1 | 1/598 (0.2%) | 1 | 1/213 (0.5%) | 1 | 2/601 (0.3%) | 2 | 2/262 (0.8%) | 2 | 1/30 (3.3%) | 1 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Pain | 0/218 (0%) | 0 | 0/90 (0%) | 0 | 0/261 (0%) | 0 | 2/206 (1%) | 2 | 0/214 (0%) | 0 | 1/598 (0.2%) | 1 | 0/213 (0%) | 0 | 1/601 (0.2%) | 1 | 0/262 (0%) | 0 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Sudden death NOS | 0/218 (0%) | 0 | 0/90 (0%) | 0 | 0/261 (0%) | 0 | 0/206 (0%) | 0 | 1/214 (0.5%) | 1 | 1/598 (0.2%) | 1 | 0/213 (0%) | 0 | 1/601 (0.2%) | 1 | 0/262 (0%) | 0 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Hepatobiliary disorders | ||||||||||||||||||||||||
| Hepatic failure | 0/218 (0%) | 0 | 0/90 (0%) | 0 | 4/261 (1.5%) | 4 | 0/206 (0%) | 0 | 0/214 (0%) | 0 | 5/598 (0.8%) | 5 | 0/213 (0%) | 0 | 1/601 (0.2%) | 1 | 2/262 (0.8%) | 2 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Hepatic pain | 0/218 (0%) | 0 | 0/90 (0%) | 0 | 0/261 (0%) | 0 | 1/206 (0.5%) | 1 | 0/214 (0%) | 0 | 0/598 (0%) | 0 | 0/213 (0%) | 0 | 0/601 (0%) | 0 | 0/262 (0%) | 0 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Hepatobiliary disorders - Other, specify | 0/218 (0%) | 0 | 0/90 (0%) | 0 | 2/261 (0.8%) | 2 | 1/206 (0.5%) | 2 | 1/214 (0.5%) | 1 | 1/598 (0.2%) | 1 | 1/213 (0.5%) | 1 | 0/601 (0%) | 0 | 2/262 (0.8%) | 3 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Portal hypertension | 0/218 (0%) | 0 | 0/90 (0%) | 0 | 0/261 (0%) | 0 | 2/206 (1%) | 2 | 0/214 (0%) | 0 | 0/598 (0%) | 0 | 0/213 (0%) | 0 | 0/601 (0%) | 0 | 0/262 (0%) | 0 | 0/30 (0%) | 0 | 1/9 (11.1%) | 1 | 0/23 (0%) | 0 |
| Immune system disorders | ||||||||||||||||||||||||
| Allergic reaction | 1/218 (0.5%) | 1 | 0/90 (0%) | 0 | 1/261 (0.4%) | 1 | 0/206 (0%) | 0 | 0/214 (0%) | 0 | 1/598 (0.2%) | 1 | 0/213 (0%) | 0 | 0/601 (0%) | 0 | 0/262 (0%) | 0 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Anaphylaxis | 1/218 (0.5%) | 1 | 1/90 (1.1%) | 1 | 0/261 (0%) | 0 | 1/206 (0.5%) | 1 | 1/214 (0.5%) | 1 | 5/598 (0.8%) | 5 | 0/213 (0%) | 0 | 3/601 (0.5%) | 3 | 1/262 (0.4%) | 1 | 1/30 (3.3%) | 1 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Infections and infestations | ||||||||||||||||||||||||
| Appendicitis perforated | 0/218 (0%) | 0 | 0/90 (0%) | 0 | 0/261 (0%) | 0 | 0/206 (0%) | 0 | 0/214 (0%) | 0 | 1/598 (0.2%) | 1 | 0/213 (0%) | 0 | 0/601 (0%) | 0 | 0/262 (0%) | 0 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Bronchial infection | 0/218 (0%) | 0 | 0/90 (0%) | 0 | 0/261 (0%) | 0 | 0/206 (0%) | 0 | 0/214 (0%) | 0 | 1/598 (0.2%) | 1 | 0/213 (0%) | 0 | 0/601 (0%) | 0 | 0/262 (0%) | 0 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Enterocolitis infectious | 0/218 (0%) | 0 | 0/90 (0%) | 0 | 0/261 (0%) | 0 | 1/206 (0.5%) | 1 | 0/214 (0%) | 0 | 2/598 (0.3%) | 2 | 0/213 (0%) | 0 | 0/601 (0%) | 0 | 0/262 (0%) | 0 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Hepatitis viral | 0/218 (0%) | 0 | 0/90 (0%) | 0 | 0/261 (0%) | 0 | 0/206 (0%) | 0 | 0/214 (0%) | 0 | 1/598 (0.2%) | 1 | 0/213 (0%) | 0 | 0/601 (0%) | 0 | 0/262 (0%) | 0 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Infections and infestations - Other, specify | 3/218 (1.4%) | 7 | 6/90 (6.7%) | 6 | 11/261 (4.2%) | 13 | 2/206 (1%) | 2 | 2/214 (0.9%) | 2 | 13/598 (2.2%) | 17 | 4/213 (1.9%) | 4 | 12/601 (2%) | 17 | 5/262 (1.9%) | 8 | 1/30 (3.3%) | 1 | 2/9 (22.2%) | 2 | 0/23 (0%) | 0 |
| Lip infection | 0/218 (0%) | 0 | 0/90 (0%) | 0 | 0/261 (0%) | 0 | 0/206 (0%) | 0 | 1/214 (0.5%) | 1 | 0/598 (0%) | 0 | 0/213 (0%) | 0 | 0/601 (0%) | 0 | 0/262 (0%) | 0 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Lung infection | 0/218 (0%) | 0 | 0/90 (0%) | 0 | 0/261 (0%) | 0 | 0/206 (0%) | 0 | 0/214 (0%) | 0 | 2/598 (0.3%) | 2 | 1/213 (0.5%) | 1 | 0/601 (0%) | 0 | 0/262 (0%) | 0 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Otitis media | 0/218 (0%) | 0 | 0/90 (0%) | 0 | 0/261 (0%) | 0 | 0/206 (0%) | 0 | 1/214 (0.5%) | 1 | 0/598 (0%) | 0 | 0/213 (0%) | 0 | 0/601 (0%) | 0 | 0/262 (0%) | 0 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Pharyngitis | 0/218 (0%) | 0 | 0/90 (0%) | 0 | 0/261 (0%) | 0 | 1/206 (0.5%) | 1 | 0/214 (0%) | 0 | 0/598 (0%) | 0 | 0/213 (0%) | 0 | 0/601 (0%) | 0 | 0/262 (0%) | 0 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Sepsis | 0/218 (0%) | 0 | 0/90 (0%) | 0 | 1/261 (0.4%) | 1 | 0/206 (0%) | 0 | 0/214 (0%) | 0 | 2/598 (0.3%) | 2 | 0/213 (0%) | 0 | 2/601 (0.3%) | 2 | 1/262 (0.4%) | 1 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Skin infection | 0/218 (0%) | 0 | 0/90 (0%) | 0 | 0/261 (0%) | 0 | 0/206 (0%) | 0 | 1/214 (0.5%) | 2 | 0/598 (0%) | 0 | 0/213 (0%) | 0 | 0/601 (0%) | 0 | 0/262 (0%) | 0 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Soft tissue infection | 0/218 (0%) | 0 | 0/90 (0%) | 0 | 0/261 (0%) | 0 | 0/206 (0%) | 0 | 0/214 (0%) | 0 | 1/598 (0.2%) | 1 | 0/213 (0%) | 0 | 1/601 (0.2%) | 1 | 0/262 (0%) | 0 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Upper respiratory infection | 0/218 (0%) | 0 | 0/90 (0%) | 0 | 0/261 (0%) | 0 | 0/206 (0%) | 0 | 1/214 (0.5%) | 1 | 1/598 (0.2%) | 1 | 0/213 (0%) | 0 | 0/601 (0%) | 0 | 0/262 (0%) | 0 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Urinary tract infection | 0/218 (0%) | 0 | 0/90 (0%) | 0 | 0/261 (0%) | 0 | 0/206 (0%) | 0 | 0/214 (0%) | 0 | 0/598 (0%) | 0 | 0/213 (0%) | 0 | 0/601 (0%) | 0 | 1/262 (0.4%) | 1 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Injury, poisoning and procedural complications | ||||||||||||||||||||||||
| Vascular access complication | 1/218 (0.5%) | 1 | 0/90 (0%) | 0 | 0/261 (0%) | 0 | 0/206 (0%) | 0 | 0/214 (0%) | 0 | 0/598 (0%) | 0 | 0/213 (0%) | 0 | 0/601 (0%) | 0 | 1/262 (0.4%) | 1 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Investigations | ||||||||||||||||||||||||
| Activated partial thromboplastin time prolonged | 0/218 (0%) | 0 | 0/90 (0%) | 0 | 0/261 (0%) | 0 | 0/206 (0%) | 0 | 0/214 (0%) | 0 | 0/598 (0%) | 0 | 0/213 (0%) | 0 | 2/601 (0.3%) | 2 | 0/262 (0%) | 0 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Alanine aminotransferase increased | 1/218 (0.5%) | 3 | 0/90 (0%) | 0 | 2/261 (0.8%) | 2 | 4/206 (1.9%) | 4 | 1/214 (0.5%) | 1 | 6/598 (1%) | 6 | 3/213 (1.4%) | 3 | 3/601 (0.5%) | 3 | 1/262 (0.4%) | 1 | 1/30 (3.3%) | 1 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Aspartate aminotransferase increased | 1/218 (0.5%) | 1 | 1/90 (1.1%) | 1 | 2/261 (0.8%) | 2 | 4/206 (1.9%) | 5 | 0/214 (0%) | 0 | 4/598 (0.7%) | 4 | 1/213 (0.5%) | 1 | 4/601 (0.7%) | 4 | 2/262 (0.8%) | 2 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Blood bilirubin increased | 0/218 (0%) | 0 | 0/90 (0%) | 0 | 3/261 (1.1%) | 4 | 1/206 (0.5%) | 1 | 0/214 (0%) | 0 | 6/598 (1%) | 7 | 0/213 (0%) | 0 | 3/601 (0.5%) | 3 | 0/262 (0%) | 0 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Cholesterol high | 0/218 (0%) | 0 | 0/90 (0%) | 0 | 1/261 (0.4%) | 1 | 0/206 (0%) | 0 | 0/214 (0%) | 0 | 0/598 (0%) | 0 | 0/213 (0%) | 0 | 1/601 (0.2%) | 1 | 0/262 (0%) | 0 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Creatinine increased | 0/218 (0%) | 0 | 0/90 (0%) | 0 | 1/261 (0.4%) | 1 | 0/206 (0%) | 0 | 0/214 (0%) | 0 | 0/598 (0%) | 0 | 0/213 (0%) | 0 | 1/601 (0.2%) | 1 | 1/262 (0.4%) | 1 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| GGT increased | 0/218 (0%) | 0 | 0/90 (0%) | 0 | 0/261 (0%) | 0 | 1/206 (0.5%) | 1 | 0/214 (0%) | 0 | 2/598 (0.3%) | 2 | 0/213 (0%) | 0 | 0/601 (0%) | 0 | 0/262 (0%) | 0 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| INR increased | 0/218 (0%) | 0 | 0/90 (0%) | 0 | 0/261 (0%) | 0 | 0/206 (0%) | 0 | 0/214 (0%) | 0 | 1/598 (0.2%) | 1 | 0/213 (0%) | 0 | 0/601 (0%) | 0 | 0/262 (0%) | 0 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Investigations - Other, specify | 0/218 (0%) | 0 | 0/90 (0%) | 0 | 1/261 (0.4%) | 1 | 2/206 (1%) | 2 | 0/214 (0%) | 0 | 1/598 (0.2%) | 1 | 1/213 (0.5%) | 2 | 2/601 (0.3%) | 2 | 1/262 (0.4%) | 1 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Lipase increased | 0/218 (0%) | 0 | 0/90 (0%) | 0 | 0/261 (0%) | 0 | 0/206 (0%) | 0 | 0/214 (0%) | 0 | 0/598 (0%) | 0 | 1/213 (0.5%) | 1 | 2/601 (0.3%) | 2 | 0/262 (0%) | 0 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Lymphocyte count decreased | 0/218 (0%) | 0 | 0/90 (0%) | 0 | 0/261 (0%) | 0 | 2/206 (1%) | 2 | 0/214 (0%) | 0 | 0/598 (0%) | 0 | 0/213 (0%) | 0 | 0/601 (0%) | 0 | 0/262 (0%) | 0 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Neutrophil count decreased | 2/218 (0.9%) | 2 | 1/90 (1.1%) | 1 | 5/261 (1.9%) | 5 | 6/206 (2.9%) | 6 | 3/214 (1.4%) | 3 | 5/598 (0.8%) | 6 | 4/213 (1.9%) | 4 | 2/601 (0.3%) | 2 | 4/262 (1.5%) | 4 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Platelet count decreased | 0/218 (0%) | 0 | 0/90 (0%) | 0 | 4/261 (1.5%) | 4 | 1/206 (0.5%) | 2 | 1/214 (0.5%) | 1 | 4/598 (0.7%) | 4 | 0/213 (0%) | 0 | 2/601 (0.3%) | 2 | 3/262 (1.1%) | 3 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Serum amylase increased | 0/218 (0%) | 0 | 0/90 (0%) | 0 | 1/261 (0.4%) | 1 | 0/206 (0%) | 0 | 0/214 (0%) | 0 | 1/598 (0.2%) | 1 | 0/213 (0%) | 0 | 1/601 (0.2%) | 1 | 0/262 (0%) | 0 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Weight gain | 0/218 (0%) | 0 | 0/90 (0%) | 0 | 0/261 (0%) | 0 | 1/206 (0.5%) | 1 | 0/214 (0%) | 0 | 0/598 (0%) | 0 | 0/213 (0%) | 0 | 0/601 (0%) | 0 | 0/262 (0%) | 0 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Weight loss | 0/218 (0%) | 0 | 1/90 (1.1%) | 1 | 0/261 (0%) | 0 | 1/206 (0.5%) | 1 | 0/214 (0%) | 0 | 0/598 (0%) | 0 | 0/213 (0%) | 0 | 0/601 (0%) | 0 | 0/262 (0%) | 0 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| White blood cell decreased | 1/218 (0.5%) | 1 | 1/90 (1.1%) | 1 | 3/261 (1.1%) | 3 | 2/206 (1%) | 2 | 0/214 (0%) | 0 | 3/598 (0.5%) | 3 | 0/213 (0%) | 0 | 2/601 (0.3%) | 2 | 1/262 (0.4%) | 1 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Metabolism and nutrition disorders | ||||||||||||||||||||||||
| Acidosis | 0/218 (0%) | 0 | 0/90 (0%) | 0 | 0/261 (0%) | 0 | 0/206 (0%) | 0 | 0/214 (0%) | 0 | 1/598 (0.2%) | 1 | 0/213 (0%) | 0 | 2/601 (0.3%) | 3 | 3/262 (1.1%) | 3 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Alkalosis | 0/218 (0%) | 0 | 0/90 (0%) | 0 | 0/261 (0%) | 0 | 1/206 (0.5%) | 1 | 0/214 (0%) | 0 | 0/598 (0%) | 0 | 0/213 (0%) | 0 | 0/601 (0%) | 0 | 0/262 (0%) | 0 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Anorexia | 0/218 (0%) | 0 | 0/90 (0%) | 0 | 0/261 (0%) | 0 | 0/206 (0%) | 0 | 0/214 (0%) | 0 | 2/598 (0.3%) | 2 | 0/213 (0%) | 0 | 0/601 (0%) | 0 | 0/262 (0%) | 0 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Dehydration | 0/218 (0%) | 0 | 1/90 (1.1%) | 1 | 0/261 (0%) | 0 | 0/206 (0%) | 0 | 1/214 (0.5%) | 1 | 2/598 (0.3%) | 2 | 0/213 (0%) | 0 | 0/601 (0%) | 0 | 0/262 (0%) | 0 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Glucose intolerance | 0/218 (0%) | 0 | 1/90 (1.1%) | 1 | 0/261 (0%) | 0 | 0/206 (0%) | 0 | 0/214 (0%) | 0 | 0/598 (0%) | 0 | 0/213 (0%) | 0 | 0/601 (0%) | 0 | 0/262 (0%) | 0 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Hypercalcemia | 0/218 (0%) | 0 | 0/90 (0%) | 0 | 0/261 (0%) | 0 | 0/206 (0%) | 0 | 0/214 (0%) | 0 | 1/598 (0.2%) | 1 | 0/213 (0%) | 0 | 1/601 (0.2%) | 1 | 0/262 (0%) | 0 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Hyperglycemia | 0/218 (0%) | 0 | 0/90 (0%) | 0 | 2/261 (0.8%) | 2 | 0/206 (0%) | 0 | 0/214 (0%) | 0 | 5/598 (0.8%) | 5 | 0/213 (0%) | 0 | 3/601 (0.5%) | 3 | 0/262 (0%) | 0 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Hyperkalemia | 0/218 (0%) | 0 | 0/90 (0%) | 0 | 0/261 (0%) | 0 | 0/206 (0%) | 0 | 0/214 (0%) | 0 | 0/598 (0%) | 0 | 0/213 (0%) | 0 | 1/601 (0.2%) | 1 | 0/262 (0%) | 0 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Hypermagnesemia | 0/218 (0%) | 0 | 0/90 (0%) | 0 | 0/261 (0%) | 0 | 0/206 (0%) | 0 | 0/214 (0%) | 0 | 0/598 (0%) | 0 | 0/213 (0%) | 0 | 1/601 (0.2%) | 1 | 0/262 (0%) | 0 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Hypernatremia | 0/218 (0%) | 0 | 0/90 (0%) | 0 | 0/261 (0%) | 0 | 0/206 (0%) | 0 | 0/214 (0%) | 0 | 1/598 (0.2%) | 1 | 0/213 (0%) | 0 | 1/601 (0.2%) | 1 | 0/262 (0%) | 0 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Hypertriglyceridemia | 0/218 (0%) | 0 | 0/90 (0%) | 0 | 0/261 (0%) | 0 | 0/206 (0%) | 0 | 0/214 (0%) | 0 | 0/598 (0%) | 0 | 0/213 (0%) | 0 | 1/601 (0.2%) | 1 | 0/262 (0%) | 0 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Hyperuricemia | 0/218 (0%) | 0 | 0/90 (0%) | 0 | 0/261 (0%) | 0 | 0/206 (0%) | 0 | 0/214 (0%) | 0 | 0/598 (0%) | 0 | 0/213 (0%) | 0 | 1/601 (0.2%) | 1 | 0/262 (0%) | 0 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Hypoalbuminemia | 0/218 (0%) | 0 | 2/90 (2.2%) | 2 | 1/261 (0.4%) | 1 | 1/206 (0.5%) | 1 | 0/214 (0%) | 0 | 1/598 (0.2%) | 1 | 0/213 (0%) | 0 | 0/601 (0%) | 0 | 0/262 (0%) | 0 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Hypocalcemia | 0/218 (0%) | 0 | 0/90 (0%) | 0 | 1/261 (0.4%) | 1 | 0/206 (0%) | 0 | 0/214 (0%) | 0 | 2/598 (0.3%) | 2 | 0/213 (0%) | 0 | 1/601 (0.2%) | 1 | 1/262 (0.4%) | 1 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Hypoglycemia | 0/218 (0%) | 0 | 0/90 (0%) | 0 | 0/261 (0%) | 0 | 0/206 (0%) | 0 | 1/214 (0.5%) | 1 | 0/598 (0%) | 0 | 0/213 (0%) | 0 | 1/601 (0.2%) | 1 | 0/262 (0%) | 0 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Hypokalemia | 0/218 (0%) | 0 | 1/90 (1.1%) | 1 | 1/261 (0.4%) | 1 | 0/206 (0%) | 0 | 1/214 (0.5%) | 1 | 2/598 (0.3%) | 2 | 0/213 (0%) | 0 | 0/601 (0%) | 0 | 0/262 (0%) | 0 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Hyponatremia | 0/218 (0%) | 0 | 0/90 (0%) | 0 | 0/261 (0%) | 0 | 0/206 (0%) | 0 | 0/214 (0%) | 0 | 3/598 (0.5%) | 3 | 0/213 (0%) | 0 | 1/601 (0.2%) | 1 | 0/262 (0%) | 0 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Iron overload | 0/218 (0%) | 0 | 0/90 (0%) | 0 | 1/261 (0.4%) | 1 | 0/206 (0%) | 0 | 0/214 (0%) | 0 | 0/598 (0%) | 0 | 0/213 (0%) | 0 | 0/601 (0%) | 0 | 1/262 (0.4%) | 4 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Tumor lysis syndrome | 0/218 (0%) | 0 | 0/90 (0%) | 0 | 0/261 (0%) | 0 | 0/206 (0%) | 0 | 0/214 (0%) | 0 | 0/598 (0%) | 0 | 0/213 (0%) | 0 | 1/601 (0.2%) | 1 | 0/262 (0%) | 0 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Musculoskeletal and connective tissue disorders | ||||||||||||||||||||||||
| Abdominal soft tissue necrosis | 0/218 (0%) | 0 | 0/90 (0%) | 0 | 0/261 (0%) | 0 | 0/206 (0%) | 0 | 0/214 (0%) | 0 | 0/598 (0%) | 0 | 0/213 (0%) | 0 | 0/601 (0%) | 0 | 1/262 (0.4%) | 1 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Avascular necrosis | 0/218 (0%) | 0 | 0/90 (0%) | 0 | 0/261 (0%) | 0 | 0/206 (0%) | 0 | 1/214 (0.5%) | 1 | 1/598 (0.2%) | 2 | 0/213 (0%) | 0 | 1/601 (0.2%) | 1 | 1/262 (0.4%) | 1 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Back pain | 0/218 (0%) | 0 | 0/90 (0%) | 0 | 0/261 (0%) | 0 | 0/206 (0%) | 0 | 0/214 (0%) | 0 | 0/598 (0%) | 0 | 0/213 (0%) | 0 | 1/601 (0.2%) | 1 | 0/262 (0%) | 0 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Generalized muscle weakness | 0/218 (0%) | 0 | 0/90 (0%) | 0 | 1/261 (0.4%) | 1 | 0/206 (0%) | 0 | 0/214 (0%) | 0 | 0/598 (0%) | 0 | 0/213 (0%) | 0 | 0/601 (0%) | 0 | 0/262 (0%) | 0 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Muscle weakness lower limb | 0/218 (0%) | 0 | 0/90 (0%) | 0 | 0/261 (0%) | 0 | 0/206 (0%) | 0 | 0/214 (0%) | 0 | 0/598 (0%) | 0 | 0/213 (0%) | 0 | 1/601 (0.2%) | 1 | 0/262 (0%) | 0 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Osteoporosis | 0/218 (0%) | 0 | 0/90 (0%) | 0 | 0/261 (0%) | 0 | 0/206 (0%) | 0 | 0/214 (0%) | 0 | 0/598 (0%) | 0 | 0/213 (0%) | 0 | 1/601 (0.2%) | 1 | 0/262 (0%) | 0 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Pain in extremity | 0/218 (0%) | 0 | 0/90 (0%) | 0 | 0/261 (0%) | 0 | 0/206 (0%) | 0 | 0/214 (0%) | 0 | 0/598 (0%) | 0 | 0/213 (0%) | 0 | 0/601 (0%) | 0 | 1/262 (0.4%) | 1 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Pelvic soft tissue necrosis | 0/218 (0%) | 0 | 0/90 (0%) | 0 | 0/261 (0%) | 0 | 0/206 (0%) | 0 | 0/214 (0%) | 0 | 0/598 (0%) | 0 | 0/213 (0%) | 0 | 0/601 (0%) | 0 | 1/262 (0.4%) | 1 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Soft tissue necrosis lower limb | 0/218 (0%) | 0 | 1/90 (1.1%) | 1 | 0/261 (0%) | 0 | 0/206 (0%) | 0 | 0/214 (0%) | 0 | 0/598 (0%) | 0 | 0/213 (0%) | 0 | 0/601 (0%) | 0 | 0/262 (0%) | 0 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||||||||||||||||||||
| Leukemia secondary to oncology chemotherapy | 0/218 (0%) | 0 | 0/90 (0%) | 0 | 0/261 (0%) | 0 | 0/206 (0%) | 0 | 1/214 (0.5%) | 1 | 0/598 (0%) | 0 | 0/213 (0%) | 0 | 0/601 (0%) | 0 | 0/262 (0%) | 0 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Treatment related secondary malignancy | 0/218 (0%) | 0 | 0/90 (0%) | 0 | 0/261 (0%) | 0 | 0/206 (0%) | 0 | 0/214 (0%) | 0 | 0/598 (0%) | 0 | 0/213 (0%) | 0 | 1/601 (0.2%) | 1 | 0/262 (0%) | 0 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Nervous system disorders | ||||||||||||||||||||||||
| Amnesia | 0/218 (0%) | 0 | 0/90 (0%) | 0 | 0/261 (0%) | 0 | 0/206 (0%) | 0 | 0/214 (0%) | 0 | 0/598 (0%) | 0 | 0/213 (0%) | 0 | 1/601 (0.2%) | 1 | 0/262 (0%) | 0 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Cognitive disturbance | 0/218 (0%) | 0 | 0/90 (0%) | 0 | 0/261 (0%) | 0 | 0/206 (0%) | 0 | 0/214 (0%) | 0 | 0/598 (0%) | 0 | 0/213 (0%) | 0 | 2/601 (0.3%) | 2 | 1/262 (0.4%) | 1 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Depressed level of consciousness | 0/218 (0%) | 0 | 1/90 (1.1%) | 1 | 0/261 (0%) | 0 | 0/206 (0%) | 0 | 0/214 (0%) | 0 | 0/598 (0%) | 0 | 0/213 (0%) | 0 | 1/601 (0.2%) | 1 | 1/262 (0.4%) | 1 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Dizziness | 0/218 (0%) | 0 | 0/90 (0%) | 0 | 0/261 (0%) | 0 | 0/206 (0%) | 0 | 0/214 (0%) | 0 | 0/598 (0%) | 0 | 0/213 (0%) | 0 | 1/601 (0.2%) | 1 | 0/262 (0%) | 0 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Dysphasia | 0/218 (0%) | 0 | 0/90 (0%) | 0 | 1/261 (0.4%) | 1 | 0/206 (0%) | 0 | 0/214 (0%) | 0 | 0/598 (0%) | 0 | 0/213 (0%) | 0 | 1/601 (0.2%) | 1 | 0/262 (0%) | 0 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Encephalopathy | 1/218 (0.5%) | 1 | 0/90 (0%) | 0 | 0/261 (0%) | 0 | 0/206 (0%) | 0 | 0/214 (0%) | 0 | 1/598 (0.2%) | 1 | 0/213 (0%) | 0 | 1/601 (0.2%) | 1 | 3/262 (1.1%) | 3 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Facial nerve disorder | 0/218 (0%) | 0 | 0/90 (0%) | 0 | 0/261 (0%) | 0 | 0/206 (0%) | 0 | 0/214 (0%) | 0 | 0/598 (0%) | 0 | 0/213 (0%) | 0 | 1/601 (0.2%) | 1 | 1/262 (0.4%) | 1 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Headache | 0/218 (0%) | 0 | 0/90 (0%) | 0 | 1/261 (0.4%) | 1 | 0/206 (0%) | 0 | 0/214 (0%) | 0 | 0/598 (0%) | 0 | 0/213 (0%) | 0 | 0/601 (0%) | 0 | 0/262 (0%) | 0 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Intracranial hemorrhage | 0/218 (0%) | 0 | 0/90 (0%) | 0 | 1/261 (0.4%) | 1 | 0/206 (0%) | 0 | 0/214 (0%) | 0 | 0/598 (0%) | 0 | 0/213 (0%) | 0 | 1/601 (0.2%) | 1 | 0/262 (0%) | 0 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Leukoencephalopathy | 0/218 (0%) | 0 | 0/90 (0%) | 0 | 0/261 (0%) | 0 | 0/206 (0%) | 0 | 0/214 (0%) | 0 | 1/598 (0.2%) | 1 | 0/213 (0%) | 0 | 0/601 (0%) | 0 | 0/262 (0%) | 0 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Nervous system disorders - Other, specify | 0/218 (0%) | 0 | 0/90 (0%) | 0 | 2/261 (0.8%) | 2 | 1/206 (0.5%) | 1 | 0/214 (0%) | 0 | 2/598 (0.3%) | 2 | 1/213 (0.5%) | 1 | 6/601 (1%) | 7 | 2/262 (0.8%) | 2 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Peripheral motor neuropathy | 0/218 (0%) | 0 | 1/90 (1.1%) | 1 | 3/261 (1.1%) | 3 | 0/206 (0%) | 0 | 0/214 (0%) | 0 | 5/598 (0.8%) | 7 | 0/213 (0%) | 0 | 6/601 (1%) | 6 | 2/262 (0.8%) | 2 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Peripheral sensory neuropathy | 0/218 (0%) | 0 | 1/90 (1.1%) | 1 | 1/261 (0.4%) | 1 | 1/206 (0.5%) | 1 | 0/214 (0%) | 0 | 2/598 (0.3%) | 2 | 0/213 (0%) | 0 | 1/601 (0.2%) | 1 | 0/262 (0%) | 0 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Seizure | 0/218 (0%) | 0 | 0/90 (0%) | 0 | 1/261 (0.4%) | 1 | 0/206 (0%) | 0 | 0/214 (0%) | 0 | 2/598 (0.3%) | 2 | 0/213 (0%) | 0 | 2/601 (0.3%) | 2 | 3/262 (1.1%) | 3 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Stroke | 0/218 (0%) | 0 | 0/90 (0%) | 0 | 0/261 (0%) | 0 | 0/206 (0%) | 0 | 0/214 (0%) | 0 | 0/598 (0%) | 0 | 0/213 (0%) | 0 | 1/601 (0.2%) | 1 | 0/262 (0%) | 0 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Trigeminal nerve disorder | 0/218 (0%) | 0 | 0/90 (0%) | 0 | 0/261 (0%) | 0 | 0/206 (0%) | 0 | 0/214 (0%) | 0 | 1/598 (0.2%) | 1 | 0/213 (0%) | 0 | 0/601 (0%) | 0 | 0/262 (0%) | 0 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Vagus nerve disorder | 0/218 (0%) | 0 | 0/90 (0%) | 0 | 0/261 (0%) | 0 | 0/206 (0%) | 0 | 0/214 (0%) | 0 | 0/598 (0%) | 0 | 0/213 (0%) | 0 | 0/601 (0%) | 0 | 1/262 (0.4%) | 1 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Pregnancy, puerperium and perinatal conditions | ||||||||||||||||||||||||
| Pregnancy, puerperium and perinatal conditions - Other, specify | 0/218 (0%) | 0 | 0/90 (0%) | 0 | 0/261 (0%) | 0 | 0/206 (0%) | 0 | 0/214 (0%) | 0 | 0/598 (0%) | 0 | 0/213 (0%) | 0 | 1/601 (0.2%) | 1 | 0/262 (0%) | 0 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Psychiatric disorders | ||||||||||||||||||||||||
| Confusion | 0/218 (0%) | 0 | 0/90 (0%) | 0 | 0/261 (0%) | 0 | 0/206 (0%) | 0 | 0/214 (0%) | 0 | 0/598 (0%) | 0 | 0/213 (0%) | 0 | 2/601 (0.3%) | 2 | 0/262 (0%) | 0 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Personality change | 0/218 (0%) | 0 | 0/90 (0%) | 0 | 0/261 (0%) | 0 | 0/206 (0%) | 0 | 0/214 (0%) | 0 | 0/598 (0%) | 0 | 0/213 (0%) | 0 | 1/601 (0.2%) | 1 | 0/262 (0%) | 0 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Renal and urinary disorders | ||||||||||||||||||||||||
| Acute kidney injury | 0/218 (0%) | 0 | 0/90 (0%) | 0 | 3/261 (1.1%) | 3 | 0/206 (0%) | 0 | 0/214 (0%) | 0 | 3/598 (0.5%) | 3 | 0/213 (0%) | 0 | 2/601 (0.3%) | 3 | 1/262 (0.4%) | 1 | 0/30 (0%) | 0 | 1/9 (11.1%) | 1 | 0/23 (0%) | 0 |
| Cystitis noninfective | 0/218 (0%) | 0 | 0/90 (0%) | 0 | 0/261 (0%) | 0 | 1/206 (0.5%) | 1 | 1/214 (0.5%) | 1 | 0/598 (0%) | 0 | 0/213 (0%) | 0 | 0/601 (0%) | 0 | 0/262 (0%) | 0 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Hematuria | 0/218 (0%) | 0 | 0/90 (0%) | 0 | 0/261 (0%) | 0 | 1/206 (0.5%) | 1 | 0/214 (0%) | 0 | 0/598 (0%) | 0 | 0/213 (0%) | 0 | 0/601 (0%) | 0 | 0/262 (0%) | 0 | 1/30 (3.3%) | 1 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Renal and urinary disorders - Other, specify | 0/218 (0%) | 0 | 0/90 (0%) | 0 | 0/261 (0%) | 0 | 0/206 (0%) | 0 | 0/214 (0%) | 0 | 0/598 (0%) | 0 | 0/213 (0%) | 0 | 1/601 (0.2%) | 1 | 2/262 (0.8%) | 2 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Respiratory, thoracic and mediastinal disorders | ||||||||||||||||||||||||
| Adult respiratory distress syndrome | 0/218 (0%) | 0 | 0/90 (0%) | 0 | 1/261 (0.4%) | 1 | 0/206 (0%) | 0 | 0/214 (0%) | 0 | 1/598 (0.2%) | 1 | 0/213 (0%) | 0 | 5/601 (0.8%) | 5 | 1/262 (0.4%) | 1 | 0/30 (0%) | 0 | 1/9 (11.1%) | 1 | 0/23 (0%) | 0 |
| Aspiration | 0/218 (0%) | 0 | 0/90 (0%) | 0 | 0/261 (0%) | 0 | 0/206 (0%) | 0 | 0/214 (0%) | 0 | 0/598 (0%) | 0 | 0/213 (0%) | 0 | 0/601 (0%) | 0 | 0/262 (0%) | 0 | 0/30 (0%) | 0 | 1/9 (11.1%) | 1 | 0/23 (0%) | 0 |
| Bronchopulmonary hemorrhage | 0/218 (0%) | 0 | 0/90 (0%) | 0 | 0/261 (0%) | 0 | 0/206 (0%) | 0 | 0/214 (0%) | 0 | 0/598 (0%) | 0 | 0/213 (0%) | 0 | 1/601 (0.2%) | 1 | 0/262 (0%) | 0 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Dyspnea | 0/218 (0%) | 0 | 0/90 (0%) | 0 | 0/261 (0%) | 0 | 0/206 (0%) | 0 | 0/214 (0%) | 0 | 0/598 (0%) | 0 | 0/213 (0%) | 0 | 0/601 (0%) | 0 | 1/262 (0.4%) | 1 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Hypoxia | 0/218 (0%) | 0 | 0/90 (0%) | 0 | 2/261 (0.8%) | 2 | 1/206 (0.5%) | 1 | 0/214 (0%) | 0 | 1/598 (0.2%) | 1 | 0/213 (0%) | 0 | 3/601 (0.5%) | 4 | 0/262 (0%) | 0 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Pleural effusion | 0/218 (0%) | 0 | 0/90 (0%) | 0 | 1/261 (0.4%) | 1 | 0/206 (0%) | 0 | 0/214 (0%) | 0 | 0/598 (0%) | 0 | 0/213 (0%) | 0 | 0/601 (0%) | 0 | 0/262 (0%) | 0 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Pneumonitis | 0/218 (0%) | 0 | 0/90 (0%) | 0 | 1/261 (0.4%) | 1 | 0/206 (0%) | 0 | 0/214 (0%) | 0 | 0/598 (0%) | 0 | 0/213 (0%) | 0 | 0/601 (0%) | 0 | 0/262 (0%) | 0 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Respiratory, thoracic and mediastinal disorders - Other, specify | 0/218 (0%) | 0 | 0/90 (0%) | 0 | 0/261 (0%) | 0 | 0/206 (0%) | 0 | 0/214 (0%) | 0 | 0/598 (0%) | 0 | 0/213 (0%) | 0 | 1/601 (0.2%) | 1 | 2/262 (0.8%) | 2 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Sinus disorder | 0/218 (0%) | 0 | 0/90 (0%) | 0 | 0/261 (0%) | 0 | 0/206 (0%) | 0 | 0/214 (0%) | 0 | 0/598 (0%) | 0 | 0/213 (0%) | 0 | 1/601 (0.2%) | 1 | 0/262 (0%) | 0 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Tracheal mucositis | 0/218 (0%) | 0 | 0/90 (0%) | 0 | 0/261 (0%) | 0 | 0/206 (0%) | 0 | 0/214 (0%) | 0 | 1/598 (0.2%) | 1 | 0/213 (0%) | 0 | 0/601 (0%) | 0 | 0/262 (0%) | 0 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Skin and subcutaneous tissue disorders | ||||||||||||||||||||||||
| Erythema multiforme | 0/218 (0%) | 0 | 0/90 (0%) | 0 | 0/261 (0%) | 0 | 0/206 (0%) | 0 | 0/214 (0%) | 0 | 1/598 (0.2%) | 1 | 0/213 (0%) | 0 | 0/601 (0%) | 0 | 0/262 (0%) | 0 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Palmar-plantar erythrodysesthesia syndrome | 0/218 (0%) | 0 | 0/90 (0%) | 0 | 0/261 (0%) | 0 | 0/206 (0%) | 0 | 0/214 (0%) | 0 | 1/598 (0.2%) | 1 | 0/213 (0%) | 0 | 0/601 (0%) | 0 | 0/262 (0%) | 0 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Purpura | 0/218 (0%) | 0 | 0/90 (0%) | 0 | 0/261 (0%) | 0 | 0/206 (0%) | 0 | 0/214 (0%) | 0 | 1/598 (0.2%) | 1 | 0/213 (0%) | 0 | 0/601 (0%) | 0 | 0/262 (0%) | 0 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Rash maculo-papular | 0/218 (0%) | 0 | 0/90 (0%) | 0 | 0/261 (0%) | 0 | 0/206 (0%) | 0 | 0/214 (0%) | 0 | 1/598 (0.2%) | 1 | 0/213 (0%) | 0 | 1/601 (0.2%) | 1 | 0/262 (0%) | 0 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Skin ulceration | 0/218 (0%) | 0 | 0/90 (0%) | 0 | 0/261 (0%) | 0 | 0/206 (0%) | 0 | 0/214 (0%) | 0 | 0/598 (0%) | 0 | 0/213 (0%) | 0 | 0/601 (0%) | 0 | 1/262 (0.4%) | 1 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Stevens-Johnson syndrome | 0/218 (0%) | 0 | 0/90 (0%) | 0 | 0/261 (0%) | 0 | 0/206 (0%) | 0 | 0/214 (0%) | 0 | 0/598 (0%) | 0 | 0/213 (0%) | 0 | 0/601 (0%) | 0 | 1/262 (0.4%) | 1 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Urticaria | 0/218 (0%) | 0 | 0/90 (0%) | 0 | 0/261 (0%) | 0 | 1/206 (0.5%) | 1 | 0/214 (0%) | 0 | 0/598 (0%) | 0 | 0/213 (0%) | 0 | 1/601 (0.2%) | 1 | 0/262 (0%) | 0 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Vascular disorders | ||||||||||||||||||||||||
| Capillary leak syndrome | 0/218 (0%) | 0 | 0/90 (0%) | 0 | 0/261 (0%) | 0 | 0/206 (0%) | 0 | 0/214 (0%) | 0 | 0/598 (0%) | 0 | 0/213 (0%) | 0 | 0/601 (0%) | 0 | 0/262 (0%) | 0 | 0/30 (0%) | 0 | 1/9 (11.1%) | 1 | 0/23 (0%) | 0 |
| Hypertension | 1/218 (0.5%) | 1 | 0/90 (0%) | 0 | 1/261 (0.4%) | 1 | 0/206 (0%) | 0 | 0/214 (0%) | 0 | 0/598 (0%) | 0 | 0/213 (0%) | 0 | 0/601 (0%) | 0 | 0/262 (0%) | 0 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Hypotension | 0/218 (0%) | 0 | 0/90 (0%) | 0 | 2/261 (0.8%) | 2 | 1/206 (0.5%) | 1 | 0/214 (0%) | 0 | 1/598 (0.2%) | 1 | 0/213 (0%) | 0 | 4/601 (0.7%) | 5 | 4/262 (1.5%) | 4 | 0/30 (0%) | 0 | 1/9 (11.1%) | 1 | 0/23 (0%) | 0 |
| Thromboembolic event | 0/218 (0%) | 0 | 0/90 (0%) | 0 | 1/261 (0.4%) | 1 | 0/206 (0%) | 0 | 1/214 (0.5%) | 1 | 3/598 (0.5%) | 3 | 0/213 (0%) | 0 | 2/601 (0.3%) | 2 | 0/262 (0%) | 0 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Vascular disorders - Other, specify | 0/218 (0%) | 0 | 0/90 (0%) | 0 | 3/261 (1.1%) | 3 | 0/206 (0%) | 0 | 0/214 (0%) | 0 | 0/598 (0%) | 0 | 1/213 (0.5%) | 1 | 1/601 (0.2%) | 1 | 0/262 (0%) | 0 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
Other (Not Including Serious) Adverse Events |
||||||||||||||||||||||||
| Dexamethasone and Capizzi Methotrexate Patients < 10 Years | Dexamethasone, High Dose Methotrexate (Non Randomly Assigned) | Dexamethasone & Capizzi Methotrexate Patients => 10 Years Old | Dexamethasone, High Dose Methotrexate (IM) < 10 Years | Prednisone, Capizzi Methotrexate <10 Years | Prednisone, Capezzi Methotrexate >= 10 Years | Prednisone and High Dose Methotrexate < 10 Yrs Old | Prednisone and High Dose Methotrexate >=10 Years | Dexamethasone, High Dose Methotrexate (IM) >= 10 Years | Prednisone, Capezzi Methotrexate (Down's Syndrome) | Dexamethasone, Capizzi Methotrexate Down Syndrome (Non Random) | Prednisone and High Dose Methotrexate (Non Randomly Assigned) | |||||||||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 215/218 (98.6%) | 87/90 (96.7%) | 250/261 (95.8%) | 203/206 (98.5%) | 212/214 (99.1%) | 564/598 (94.3%) | 204/213 (95.8%) | 576/601 (95.8%) | 256/262 (97.7%) | 30/30 (100%) | 9/9 (100%) | 20/23 (87%) | ||||||||||||
| Blood and lymphatic system disorders | ||||||||||||||||||||||||
| Anemia | 71/218 (32.6%) | 147 | 33/90 (36.7%) | 71 | 70/261 (26.8%) | 128 | 68/206 (33%) | 134 | 63/214 (29.4%) | 123 | 179/598 (29.9%) | 317 | 68/213 (31.9%) | 122 | 167/601 (27.8%) | 280 | 88/262 (33.6%) | 169 | 13/30 (43.3%) | 27 | 4/9 (44.4%) | 5 | 5/23 (21.7%) | 8 |
| Blood and lymphatic system disorders - Other, specify | 3/218 (1.4%) | 7 | 1/90 (1.1%) | 1 | 3/261 (1.1%) | 3 | 3/206 (1.5%) | 3 | 7/214 (3.3%) | 9 | 5/598 (0.8%) | 5 | 4/213 (1.9%) | 8 | 6/601 (1%) | 6 | 3/262 (1.1%) | 5 | 2/30 (6.7%) | 2 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Bone marrow hypocellular | 0/218 (0%) | 0 | 1/90 (1.1%) | 1 | 2/261 (0.8%) | 3 | 0/206 (0%) | 0 | 1/214 (0.5%) | 1 | 1/598 (0.2%) | 1 | 0/213 (0%) | 0 | 0/601 (0%) | 0 | 0/262 (0%) | 0 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Disseminated intravascular coagulation | 0/218 (0%) | 0 | 1/90 (1.1%) | 1 | 4/261 (1.5%) | 4 | 3/206 (1.5%) | 3 | 0/214 (0%) | 0 | 7/598 (1.2%) | 8 | 0/213 (0%) | 0 | 2/601 (0.3%) | 2 | 3/262 (1.1%) | 3 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Febrile neutropenia | 164/218 (75.2%) | 387 | 52/90 (57.8%) | 124 | 141/261 (54%) | 279 | 134/206 (65%) | 318 | 140/214 (65.4%) | 314 | 278/598 (46.5%) | 504 | 140/213 (65.7%) | 318 | 283/601 (47.1%) | 514 | 139/262 (53.1%) | 268 | 22/30 (73.3%) | 49 | 4/9 (44.4%) | 6 | 12/23 (52.2%) | 16 |
| Hemolysis | 1/218 (0.5%) | 1 | 0/90 (0%) | 0 | 4/261 (1.5%) | 4 | 0/206 (0%) | 0 | 0/214 (0%) | 0 | 3/598 (0.5%) | 3 | 0/213 (0%) | 0 | 3/601 (0.5%) | 3 | 1/262 (0.4%) | 1 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Hemolytic uremic syndrome | 0/218 (0%) | 0 | 0/90 (0%) | 0 | 0/261 (0%) | 0 | 0/206 (0%) | 0 | 0/214 (0%) | 0 | 0/598 (0%) | 0 | 0/213 (0%) | 0 | 1/601 (0.2%) | 1 | 0/262 (0%) | 0 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Leukocytosis | 1/218 (0.5%) | 1 | 0/90 (0%) | 0 | 0/261 (0%) | 0 | 0/206 (0%) | 0 | 0/214 (0%) | 0 | 2/598 (0.3%) | 5 | 0/213 (0%) | 0 | 0/601 (0%) | 0 | 0/262 (0%) | 0 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Spleen disorder | 0/218 (0%) | 0 | 0/90 (0%) | 0 | 0/261 (0%) | 0 | 1/206 (0.5%) | 1 | 0/214 (0%) | 0 | 0/598 (0%) | 0 | 0/213 (0%) | 0 | 0/601 (0%) | 0 | 0/262 (0%) | 0 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Thrombotic thrombocytopenic purpura | 0/218 (0%) | 0 | 0/90 (0%) | 0 | 0/261 (0%) | 0 | 0/206 (0%) | 0 | 0/214 (0%) | 0 | 0/598 (0%) | 0 | 0/213 (0%) | 0 | 1/601 (0.2%) | 1 | 0/262 (0%) | 0 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Cardiac disorders | ||||||||||||||||||||||||
| Asystole | 0/218 (0%) | 0 | 0/90 (0%) | 0 | 0/261 (0%) | 0 | 1/206 (0.5%) | 1 | 0/214 (0%) | 0 | 0/598 (0%) | 0 | 0/213 (0%) | 0 | 0/601 (0%) | 0 | 0/262 (0%) | 0 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Atrial flutter | 0/218 (0%) | 0 | 0/90 (0%) | 0 | 0/261 (0%) | 0 | 0/206 (0%) | 0 | 0/214 (0%) | 0 | 1/598 (0.2%) | 1 | 0/213 (0%) | 0 | 0/601 (0%) | 0 | 0/262 (0%) | 0 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Cardiac arrest | 1/218 (0.5%) | 1 | 0/90 (0%) | 0 | 0/261 (0%) | 0 | 0/206 (0%) | 0 | 0/214 (0%) | 0 | 2/598 (0.3%) | 2 | 0/213 (0%) | 0 | 2/601 (0.3%) | 2 | 0/262 (0%) | 0 | 0/30 (0%) | 0 | 1/9 (11.1%) | 1 | 0/23 (0%) | 0 |
| Cardiac disorders - Other, specify | 0/218 (0%) | 0 | 1/90 (1.1%) | 1 | 0/261 (0%) | 0 | 2/206 (1%) | 2 | 1/214 (0.5%) | 1 | 0/598 (0%) | 0 | 1/213 (0.5%) | 1 | 5/601 (0.8%) | 5 | 1/262 (0.4%) | 1 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Left ventricular systolic dysfunction | 0/218 (0%) | 0 | 1/90 (1.1%) | 1 | 0/261 (0%) | 0 | 0/206 (0%) | 0 | 1/214 (0.5%) | 1 | 1/598 (0.2%) | 1 | 0/213 (0%) | 0 | 2/601 (0.3%) | 2 | 1/262 (0.4%) | 1 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Myocardial infarction | 0/218 (0%) | 0 | 0/90 (0%) | 0 | 0/261 (0%) | 0 | 0/206 (0%) | 0 | 0/214 (0%) | 0 | 1/598 (0.2%) | 1 | 0/213 (0%) | 0 | 0/601 (0%) | 0 | 0/262 (0%) | 0 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Paroxysmal atrial tachycardia | 0/218 (0%) | 0 | 0/90 (0%) | 0 | 0/261 (0%) | 0 | 0/206 (0%) | 0 | 0/214 (0%) | 0 | 1/598 (0.2%) | 1 | 0/213 (0%) | 0 | 0/601 (0%) | 0 | 0/262 (0%) | 0 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Pericardial effusion | 2/218 (0.9%) | 2 | 0/90 (0%) | 0 | 0/261 (0%) | 0 | 1/206 (0.5%) | 1 | 0/214 (0%) | 0 | 0/598 (0%) | 0 | 1/213 (0.5%) | 1 | 2/601 (0.3%) | 2 | 1/262 (0.4%) | 4 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Restrictive cardiomyopathy | 0/218 (0%) | 0 | 0/90 (0%) | 0 | 0/261 (0%) | 0 | 0/206 (0%) | 0 | 0/214 (0%) | 0 | 0/598 (0%) | 0 | 0/213 (0%) | 0 | 1/601 (0.2%) | 1 | 0/262 (0%) | 0 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Sinus bradycardia | 0/218 (0%) | 0 | 0/90 (0%) | 0 | 0/261 (0%) | 0 | 0/206 (0%) | 0 | 0/214 (0%) | 0 | 0/598 (0%) | 0 | 0/213 (0%) | 0 | 1/601 (0.2%) | 1 | 0/262 (0%) | 0 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Sinus tachycardia | 2/218 (0.9%) | 2 | 0/90 (0%) | 0 | 1/261 (0.4%) | 1 | 1/206 (0.5%) | 1 | 0/214 (0%) | 0 | 0/598 (0%) | 0 | 1/213 (0.5%) | 1 | 3/601 (0.5%) | 3 | 0/262 (0%) | 0 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Supraventricular tachycardia | 0/218 (0%) | 0 | 0/90 (0%) | 0 | 0/261 (0%) | 0 | 0/206 (0%) | 0 | 0/214 (0%) | 0 | 2/598 (0.3%) | 2 | 0/213 (0%) | 0 | 0/601 (0%) | 0 | 0/262 (0%) | 0 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Ventricular arrhythmia | 0/218 (0%) | 0 | 0/90 (0%) | 0 | 0/261 (0%) | 0 | 0/206 (0%) | 0 | 0/214 (0%) | 0 | 0/598 (0%) | 0 | 0/213 (0%) | 0 | 1/601 (0.2%) | 1 | 0/262 (0%) | 0 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Ventricular fibrillation | 0/218 (0%) | 0 | 0/90 (0%) | 0 | 0/261 (0%) | 0 | 0/206 (0%) | 0 | 0/214 (0%) | 0 | 0/598 (0%) | 0 | 0/213 (0%) | 0 | 1/601 (0.2%) | 1 | 0/262 (0%) | 0 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Ventricular tachycardia | 0/218 (0%) | 0 | 0/90 (0%) | 0 | 0/261 (0%) | 0 | 1/206 (0.5%) | 1 | 0/214 (0%) | 0 | 1/598 (0.2%) | 1 | 0/213 (0%) | 0 | 2/601 (0.3%) | 2 | 0/262 (0%) | 0 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Ear and labyrinth disorders | ||||||||||||||||||||||||
| Ear pain | 0/218 (0%) | 0 | 0/90 (0%) | 0 | 0/261 (0%) | 0 | 0/206 (0%) | 0 | 1/214 (0.5%) | 1 | 0/598 (0%) | 0 | 0/213 (0%) | 0 | 1/601 (0.2%) | 1 | 1/262 (0.4%) | 1 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| External ear inflammation | 0/218 (0%) | 0 | 0/90 (0%) | 0 | 1/261 (0.4%) | 3 | 0/206 (0%) | 0 | 0/214 (0%) | 0 | 0/598 (0%) | 0 | 1/213 (0.5%) | 1 | 0/601 (0%) | 0 | 0/262 (0%) | 0 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Hearing impaired | 0/218 (0%) | 0 | 0/90 (0%) | 0 | 0/261 (0%) | 0 | 0/206 (0%) | 0 | 0/214 (0%) | 0 | 0/598 (0%) | 0 | 0/213 (0%) | 0 | 0/601 (0%) | 0 | 1/262 (0.4%) | 1 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Middle ear inflammation | 2/218 (0.9%) | 2 | 1/90 (1.1%) | 2 | 1/261 (0.4%) | 1 | 3/206 (1.5%) | 3 | 2/214 (0.9%) | 2 | 1/598 (0.2%) | 1 | 0/213 (0%) | 0 | 0/601 (0%) | 0 | 0/262 (0%) | 0 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Endocrine disorders | ||||||||||||||||||||||||
| Adrenal insufficiency | 0/218 (0%) | 0 | 1/90 (1.1%) | 1 | 1/261 (0.4%) | 1 | 0/206 (0%) | 0 | 1/214 (0.5%) | 1 | 2/598 (0.3%) | 2 | 0/213 (0%) | 0 | 0/601 (0%) | 0 | 0/262 (0%) | 0 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Delayed puberty | 0/218 (0%) | 0 | 0/90 (0%) | 0 | 0/261 (0%) | 0 | 0/206 (0%) | 0 | 0/214 (0%) | 0 | 0/598 (0%) | 0 | 0/213 (0%) | 0 | 0/601 (0%) | 0 | 1/262 (0.4%) | 1 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Endocrine disorders - Other, specify | 1/218 (0.5%) | 1 | 0/90 (0%) | 0 | 0/261 (0%) | 0 | 0/206 (0%) | 0 | 0/214 (0%) | 0 | 0/598 (0%) | 0 | 0/213 (0%) | 0 | 0/601 (0%) | 0 | 0/262 (0%) | 0 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Eye disorders | ||||||||||||||||||||||||
| Blurred vision | 0/218 (0%) | 0 | 1/90 (1.1%) | 1 | 0/261 (0%) | 0 | 0/206 (0%) | 0 | 0/214 (0%) | 0 | 1/598 (0.2%) | 1 | 0/213 (0%) | 0 | 2/601 (0.3%) | 2 | 0/262 (0%) | 0 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Cataract | 0/218 (0%) | 0 | 1/90 (1.1%) | 1 | 1/261 (0.4%) | 1 | 0/206 (0%) | 0 | 0/214 (0%) | 0 | 0/598 (0%) | 0 | 0/213 (0%) | 0 | 0/601 (0%) | 0 | 0/262 (0%) | 0 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Extraocular muscle paresis | 0/218 (0%) | 0 | 0/90 (0%) | 0 | 1/261 (0.4%) | 1 | 0/206 (0%) | 0 | 0/214 (0%) | 0 | 1/598 (0.2%) | 1 | 0/213 (0%) | 0 | 0/601 (0%) | 0 | 0/262 (0%) | 0 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Eye disorders - Other, specify | 0/218 (0%) | 0 | 0/90 (0%) | 0 | 0/261 (0%) | 0 | 0/206 (0%) | 0 | 3/214 (1.4%) | 4 | 2/598 (0.3%) | 2 | 0/213 (0%) | 0 | 1/601 (0.2%) | 1 | 2/262 (0.8%) | 2 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Eye pain | 0/218 (0%) | 0 | 0/90 (0%) | 0 | 1/261 (0.4%) | 1 | 0/206 (0%) | 0 | 0/214 (0%) | 0 | 0/598 (0%) | 0 | 0/213 (0%) | 0 | 0/601 (0%) | 0 | 0/262 (0%) | 0 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Flashing lights | 0/218 (0%) | 0 | 0/90 (0%) | 0 | 0/261 (0%) | 0 | 0/206 (0%) | 0 | 0/214 (0%) | 0 | 1/598 (0.2%) | 1 | 0/213 (0%) | 0 | 1/601 (0.2%) | 1 | 0/262 (0%) | 0 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Optic nerve disorder | 0/218 (0%) | 0 | 0/90 (0%) | 0 | 1/261 (0.4%) | 1 | 0/206 (0%) | 0 | 1/214 (0.5%) | 1 | 1/598 (0.2%) | 1 | 0/213 (0%) | 0 | 0/601 (0%) | 0 | 0/262 (0%) | 0 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Papilledema | 0/218 (0%) | 0 | 0/90 (0%) | 0 | 0/261 (0%) | 0 | 0/206 (0%) | 0 | 1/214 (0.5%) | 1 | 0/598 (0%) | 0 | 0/213 (0%) | 0 | 0/601 (0%) | 0 | 0/262 (0%) | 0 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Photophobia | 0/218 (0%) | 0 | 1/90 (1.1%) | 1 | 0/261 (0%) | 0 | 0/206 (0%) | 0 | 0/214 (0%) | 0 | 1/598 (0.2%) | 1 | 0/213 (0%) | 0 | 1/601 (0.2%) | 1 | 0/262 (0%) | 0 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Retinal detachment | 0/218 (0%) | 0 | 0/90 (0%) | 0 | 0/261 (0%) | 0 | 0/206 (0%) | 0 | 0/214 (0%) | 0 | 1/598 (0.2%) | 2 | 0/213 (0%) | 0 | 0/601 (0%) | 0 | 0/262 (0%) | 0 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Vitreous hemorrhage | 0/218 (0%) | 0 | 0/90 (0%) | 0 | 1/261 (0.4%) | 1 | 0/206 (0%) | 0 | 0/214 (0%) | 0 | 0/598 (0%) | 0 | 0/213 (0%) | 0 | 0/601 (0%) | 0 | 0/262 (0%) | 0 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Gastrointestinal disorders | ||||||||||||||||||||||||
| Abdominal distension | 2/218 (0.9%) | 2 | 3/90 (3.3%) | 3 | 1/261 (0.4%) | 1 | 0/206 (0%) | 0 | 0/214 (0%) | 0 | 0/598 (0%) | 0 | 2/213 (0.9%) | 3 | 1/601 (0.2%) | 1 | 1/262 (0.4%) | 1 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Abdominal pain | 12/218 (5.5%) | 13 | 12/90 (13.3%) | 15 | 38/261 (14.6%) | 45 | 16/206 (7.8%) | 20 | 12/214 (5.6%) | 13 | 52/598 (8.7%) | 68 | 9/213 (4.2%) | 9 | 35/601 (5.8%) | 46 | 16/262 (6.1%) | 23 | 1/30 (3.3%) | 1 | 1/9 (11.1%) | 1 | 1/23 (4.3%) | 1 |
| Anal fistula | 0/218 (0%) | 0 | 0/90 (0%) | 0 | 0/261 (0%) | 0 | 0/206 (0%) | 0 | 0/214 (0%) | 0 | 0/598 (0%) | 0 | 0/213 (0%) | 0 | 1/601 (0.2%) | 1 | 0/262 (0%) | 0 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Anal mucositis | 1/218 (0.5%) | 1 | 0/90 (0%) | 0 | 6/261 (2.3%) | 6 | 1/206 (0.5%) | 1 | 0/214 (0%) | 0 | 3/598 (0.5%) | 3 | 1/213 (0.5%) | 1 | 2/601 (0.3%) | 2 | 0/262 (0%) | 0 | 1/30 (3.3%) | 1 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Anal necrosis | 0/218 (0%) | 0 | 0/90 (0%) | 0 | 0/261 (0%) | 0 | 0/206 (0%) | 0 | 0/214 (0%) | 0 | 0/598 (0%) | 0 | 0/213 (0%) | 0 | 0/601 (0%) | 0 | 1/262 (0.4%) | 2 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Anal pain | 1/218 (0.5%) | 1 | 1/90 (1.1%) | 1 | 2/261 (0.8%) | 2 | 1/206 (0.5%) | 1 | 0/214 (0%) | 0 | 3/598 (0.5%) | 3 | 0/213 (0%) | 0 | 1/601 (0.2%) | 1 | 0/262 (0%) | 0 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Ascites | 1/218 (0.5%) | 1 | 2/90 (2.2%) | 2 | 3/261 (1.1%) | 3 | 2/206 (1%) | 2 | 0/214 (0%) | 0 | 6/598 (1%) | 6 | 0/213 (0%) | 0 | 2/601 (0.3%) | 2 | 4/262 (1.5%) | 4 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Colitis | 6/218 (2.8%) | 7 | 2/90 (2.2%) | 3 | 9/261 (3.4%) | 9 | 6/206 (2.9%) | 6 | 2/214 (0.9%) | 2 | 9/598 (1.5%) | 9 | 1/213 (0.5%) | 1 | 7/601 (1.2%) | 10 | 3/262 (1.1%) | 4 | 2/30 (6.7%) | 2 | 1/9 (11.1%) | 1 | 0/23 (0%) | 0 |
| Colonic hemorrhage | 0/218 (0%) | 0 | 0/90 (0%) | 0 | 0/261 (0%) | 0 | 0/206 (0%) | 0 | 0/214 (0%) | 0 | 0/598 (0%) | 0 | 0/213 (0%) | 0 | 0/601 (0%) | 0 | 1/262 (0.4%) | 1 | 1/30 (3.3%) | 1 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Colonic perforation | 0/218 (0%) | 0 | 0/90 (0%) | 0 | 0/261 (0%) | 0 | 1/206 (0.5%) | 1 | 0/214 (0%) | 0 | 1/598 (0.2%) | 1 | 0/213 (0%) | 0 | 0/601 (0%) | 0 | 0/262 (0%) | 0 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Constipation | 5/218 (2.3%) | 5 | 2/90 (2.2%) | 2 | 1/261 (0.4%) | 2 | 4/206 (1.9%) | 5 | 1/214 (0.5%) | 1 | 8/598 (1.3%) | 9 | 6/213 (2.8%) | 6 | 17/601 (2.8%) | 20 | 7/262 (2.7%) | 7 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 1/23 (4.3%) | 1 |
| Dental caries | 0/218 (0%) | 0 | 0/90 (0%) | 0 | 1/261 (0.4%) | 1 | 0/206 (0%) | 0 | 0/214 (0%) | 0 | 0/598 (0%) | 0 | 0/213 (0%) | 0 | 1/601 (0.2%) | 1 | 0/262 (0%) | 0 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Diarrhea | 18/218 (8.3%) | 22 | 7/90 (7.8%) | 7 | 20/261 (7.7%) | 24 | 24/206 (11.7%) | 33 | 18/214 (8.4%) | 22 | 35/598 (5.9%) | 39 | 16/213 (7.5%) | 19 | 36/601 (6%) | 39 | 17/262 (6.5%) | 21 | 7/30 (23.3%) | 7 | 3/9 (33.3%) | 3 | 1/23 (4.3%) | 1 |
| Dry mouth | 0/218 (0%) | 0 | 0/90 (0%) | 0 | 1/261 (0.4%) | 1 | 0/206 (0%) | 0 | 0/214 (0%) | 0 | 0/598 (0%) | 0 | 1/213 (0.5%) | 1 | 0/601 (0%) | 0 | 1/262 (0.4%) | 1 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Duodenal hemorrhage | 0/218 (0%) | 0 | 0/90 (0%) | 0 | 0/261 (0%) | 0 | 0/206 (0%) | 0 | 1/214 (0.5%) | 1 | 0/598 (0%) | 0 | 0/213 (0%) | 0 | 0/601 (0%) | 0 | 0/262 (0%) | 0 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Duodenal obstruction | 0/218 (0%) | 0 | 0/90 (0%) | 0 | 1/261 (0.4%) | 1 | 0/206 (0%) | 0 | 0/214 (0%) | 0 | 0/598 (0%) | 0 | 0/213 (0%) | 0 | 0/601 (0%) | 0 | 0/262 (0%) | 0 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Duodenal ulcer | 0/218 (0%) | 0 | 0/90 (0%) | 0 | 1/261 (0.4%) | 1 | 0/206 (0%) | 0 | 1/214 (0.5%) | 1 | 0/598 (0%) | 0 | 0/213 (0%) | 0 | 0/601 (0%) | 0 | 0/262 (0%) | 0 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Dyspepsia | 0/218 (0%) | 0 | 0/90 (0%) | 0 | 1/261 (0.4%) | 1 | 0/206 (0%) | 0 | 0/214 (0%) | 0 | 0/598 (0%) | 0 | 0/213 (0%) | 0 | 2/601 (0.3%) | 2 | 2/262 (0.8%) | 2 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Dysphagia | 0/218 (0%) | 0 | 3/90 (3.3%) | 3 | 4/261 (1.5%) | 4 | 1/206 (0.5%) | 1 | 1/214 (0.5%) | 1 | 7/598 (1.2%) | 8 | 1/213 (0.5%) | 2 | 5/601 (0.8%) | 5 | 1/262 (0.4%) | 1 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 1/23 (4.3%) | 1 |
| Enterocolitis | 3/218 (1.4%) | 4 | 0/90 (0%) | 0 | 3/261 (1.1%) | 3 | 3/206 (1.5%) | 3 | 0/214 (0%) | 0 | 1/598 (0.2%) | 1 | 1/213 (0.5%) | 1 | 2/601 (0.3%) | 2 | 2/262 (0.8%) | 2 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Esophageal hemorrhage | 1/218 (0.5%) | 1 | 0/90 (0%) | 0 | 0/261 (0%) | 0 | 0/206 (0%) | 0 | 0/214 (0%) | 0 | 0/598 (0%) | 0 | 0/213 (0%) | 0 | 0/601 (0%) | 0 | 0/262 (0%) | 0 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Esophageal pain | 0/218 (0%) | 0 | 1/90 (1.1%) | 1 | 0/261 (0%) | 0 | 0/206 (0%) | 0 | 0/214 (0%) | 0 | 3/598 (0.5%) | 4 | 0/213 (0%) | 0 | 3/601 (0.5%) | 4 | 0/262 (0%) | 0 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Esophageal ulcer | 0/218 (0%) | 0 | 0/90 (0%) | 0 | 0/261 (0%) | 0 | 0/206 (0%) | 0 | 0/214 (0%) | 0 | 1/598 (0.2%) | 1 | 0/213 (0%) | 0 | 0/601 (0%) | 0 | 0/262 (0%) | 0 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Esophagitis | 1/218 (0.5%) | 1 | 3/90 (3.3%) | 3 | 9/261 (3.4%) | 9 | 2/206 (1%) | 2 | 1/214 (0.5%) | 1 | 15/598 (2.5%) | 18 | 1/213 (0.5%) | 1 | 11/601 (1.8%) | 11 | 9/262 (3.4%) | 10 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Fecal incontinence | 0/218 (0%) | 0 | 0/90 (0%) | 0 | 0/261 (0%) | 0 | 0/206 (0%) | 0 | 0/214 (0%) | 0 | 1/598 (0.2%) | 1 | 0/213 (0%) | 0 | 0/601 (0%) | 0 | 0/262 (0%) | 0 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Gastric ulcer | 0/218 (0%) | 0 | 0/90 (0%) | 0 | 1/261 (0.4%) | 1 | 0/206 (0%) | 0 | 1/214 (0.5%) | 1 | 0/598 (0%) | 0 | 0/213 (0%) | 0 | 0/601 (0%) | 0 | 0/262 (0%) | 0 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Gastritis | 1/218 (0.5%) | 1 | 2/90 (2.2%) | 2 | 2/261 (0.8%) | 2 | 1/206 (0.5%) | 1 | 3/214 (1.4%) | 3 | 15/598 (2.5%) | 15 | 2/213 (0.9%) | 2 | 7/601 (1.2%) | 7 | 6/262 (2.3%) | 7 | 0/30 (0%) | 0 | 1/9 (11.1%) | 1 | 1/23 (4.3%) | 1 |
| Gastrointestinal disorders - Other, specify | 5/218 (2.3%) | 5 | 2/90 (2.2%) | 2 | 3/261 (1.1%) | 3 | 3/206 (1.5%) | 3 | 3/214 (1.4%) | 3 | 6/598 (1%) | 6 | 1/213 (0.5%) | 1 | 4/601 (0.7%) | 7 | 5/262 (1.9%) | 6 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Gastroparesis | 0/218 (0%) | 0 | 1/90 (1.1%) | 1 | 0/261 (0%) | 0 | 0/206 (0%) | 0 | 0/214 (0%) | 0 | 0/598 (0%) | 0 | 0/213 (0%) | 0 | 0/601 (0%) | 0 | 0/262 (0%) | 0 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Gingival pain | 0/218 (0%) | 0 | 0/90 (0%) | 0 | 1/261 (0.4%) | 1 | 0/206 (0%) | 0 | 0/214 (0%) | 0 | 1/598 (0.2%) | 1 | 0/213 (0%) | 0 | 3/601 (0.5%) | 3 | 2/262 (0.8%) | 2 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Hemorrhoids | 0/218 (0%) | 0 | 0/90 (0%) | 0 | 0/261 (0%) | 0 | 0/206 (0%) | 0 | 0/214 (0%) | 0 | 2/598 (0.3%) | 2 | 0/213 (0%) | 0 | 0/601 (0%) | 0 | 0/262 (0%) | 0 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Ileal obstruction | 0/218 (0%) | 0 | 0/90 (0%) | 0 | 0/261 (0%) | 0 | 0/206 (0%) | 0 | 0/214 (0%) | 0 | 0/598 (0%) | 0 | 1/213 (0.5%) | 1 | 0/601 (0%) | 0 | 0/262 (0%) | 0 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Ileal perforation | 0/218 (0%) | 0 | 0/90 (0%) | 0 | 0/261 (0%) | 0 | 0/206 (0%) | 0 | 0/214 (0%) | 0 | 0/598 (0%) | 0 | 0/213 (0%) | 0 | 1/601 (0.2%) | 1 | 0/262 (0%) | 0 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Ileus | 2/218 (0.9%) | 2 | 5/90 (5.6%) | 5 | 8/261 (3.1%) | 8 | 4/206 (1.9%) | 4 | 1/214 (0.5%) | 1 | 8/598 (1.3%) | 8 | 3/213 (1.4%) | 3 | 7/601 (1.2%) | 13 | 2/262 (0.8%) | 2 | 0/30 (0%) | 0 | 1/9 (11.1%) | 1 | 0/23 (0%) | 0 |
| Intra-abdominal hemorrhage | 1/218 (0.5%) | 1 | 0/90 (0%) | 0 | 1/261 (0.4%) | 1 | 0/206 (0%) | 0 | 0/214 (0%) | 0 | 1/598 (0.2%) | 1 | 0/213 (0%) | 0 | 0/601 (0%) | 0 | 0/262 (0%) | 0 | 0/30 (0%) | 0 | 1/9 (11.1%) | 1 | 0/23 (0%) | 0 |
| Jejunal perforation | 0/218 (0%) | 0 | 0/90 (0%) | 0 | 1/261 (0.4%) | 1 | 0/206 (0%) | 0 | 0/214 (0%) | 0 | 0/598 (0%) | 0 | 0/213 (0%) | 0 | 2/601 (0.3%) | 2 | 0/262 (0%) | 0 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Lip pain | 0/218 (0%) | 0 | 0/90 (0%) | 0 | 0/261 (0%) | 0 | 0/206 (0%) | 0 | 0/214 (0%) | 0 | 1/598 (0.2%) | 1 | 0/213 (0%) | 0 | 1/601 (0.2%) | 1 | 0/262 (0%) | 0 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Lower gastrointestinal hemorrhage | 0/218 (0%) | 0 | 1/90 (1.1%) | 1 | 0/261 (0%) | 0 | 1/206 (0.5%) | 1 | 0/214 (0%) | 0 | 1/598 (0.2%) | 1 | 0/213 (0%) | 0 | 2/601 (0.3%) | 2 | 0/262 (0%) | 0 | 1/30 (3.3%) | 1 | 1/9 (11.1%) | 1 | 0/23 (0%) | 0 |
| Malabsorption | 1/218 (0.5%) | 1 | 1/90 (1.1%) | 1 | 0/261 (0%) | 0 | 0/206 (0%) | 0 | 0/214 (0%) | 0 | 2/598 (0.3%) | 2 | 0/213 (0%) | 0 | 1/601 (0.2%) | 1 | 0/262 (0%) | 0 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Mucositis oral | 22/218 (10.1%) | 28 | 19/90 (21.1%) | 24 | 57/261 (21.8%) | 63 | 27/206 (13.1%) | 32 | 13/214 (6.1%) | 13 | 134/598 (22.4%) | 155 | 31/213 (14.6%) | 38 | 99/601 (16.5%) | 113 | 48/262 (18.3%) | 61 | 11/30 (36.7%) | 14 | 4/9 (44.4%) | 5 | 3/23 (13%) | 3 |
| Nausea | 8/218 (3.7%) | 8 | 5/90 (5.6%) | 7 | 26/261 (10%) | 29 | 7/206 (3.4%) | 9 | 2/214 (0.9%) | 2 | 64/598 (10.7%) | 86 | 4/213 (1.9%) | 4 | 48/601 (8%) | 60 | 32/262 (12.2%) | 39 | 4/30 (13.3%) | 4 | 1/9 (11.1%) | 1 | 1/23 (4.3%) | 1 |
| Oral hemorrhage | 0/218 (0%) | 0 | 0/90 (0%) | 0 | 0/261 (0%) | 0 | 0/206 (0%) | 0 | 0/214 (0%) | 0 | 1/598 (0.2%) | 1 | 1/213 (0.5%) | 1 | 1/601 (0.2%) | 1 | 1/262 (0.4%) | 1 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Oral pain | 2/218 (0.9%) | 2 | 5/90 (5.6%) | 5 | 11/261 (4.2%) | 12 | 3/206 (1.5%) | 3 | 7/214 (3.3%) | 8 | 23/598 (3.8%) | 24 | 9/213 (4.2%) | 10 | 12/601 (2%) | 13 | 8/262 (3.1%) | 8 | 2/30 (6.7%) | 2 | 0/9 (0%) | 0 | 1/23 (4.3%) | 1 |
| Pancreatic hemorrhage | 0/218 (0%) | 0 | 0/90 (0%) | 0 | 0/261 (0%) | 0 | 0/206 (0%) | 0 | 0/214 (0%) | 0 | 1/598 (0.2%) | 1 | 0/213 (0%) | 0 | 0/601 (0%) | 0 | 0/262 (0%) | 0 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Pancreatic necrosis | 0/218 (0%) | 0 | 0/90 (0%) | 0 | 1/261 (0.4%) | 1 | 0/206 (0%) | 0 | 0/214 (0%) | 0 | 1/598 (0.2%) | 1 | 0/213 (0%) | 0 | 0/601 (0%) | 0 | 1/262 (0.4%) | 1 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Pancreatitis | 3/218 (1.4%) | 4 | 5/90 (5.6%) | 6 | 16/261 (6.1%) | 21 | 6/206 (2.9%) | 7 | 4/214 (1.9%) | 6 | 31/598 (5.2%) | 34 | 5/213 (2.3%) | 5 | 16/601 (2.7%) | 26 | 7/262 (2.7%) | 7 | 1/30 (3.3%) | 1 | 0/9 (0%) | 0 | 1/23 (4.3%) | 1 |
| Proctitis | 0/218 (0%) | 0 | 0/90 (0%) | 0 | 2/261 (0.8%) | 2 | 0/206 (0%) | 0 | 0/214 (0%) | 0 | 0/598 (0%) | 0 | 0/213 (0%) | 0 | 1/601 (0.2%) | 1 | 0/262 (0%) | 0 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Rectal hemorrhage | 0/218 (0%) | 0 | 0/90 (0%) | 0 | 0/261 (0%) | 0 | 0/206 (0%) | 0 | 0/214 (0%) | 0 | 3/598 (0.5%) | 3 | 0/213 (0%) | 0 | 1/601 (0.2%) | 1 | 0/262 (0%) | 0 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Rectal mucositis | 0/218 (0%) | 0 | 0/90 (0%) | 0 | 0/261 (0%) | 0 | 0/206 (0%) | 0 | 0/214 (0%) | 0 | 1/598 (0.2%) | 1 | 3/213 (1.4%) | 3 | 1/601 (0.2%) | 1 | 0/262 (0%) | 0 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Rectal pain | 0/218 (0%) | 0 | 0/90 (0%) | 0 | 2/261 (0.8%) | 2 | 2/206 (1%) | 2 | 0/214 (0%) | 0 | 1/598 (0.2%) | 1 | 0/213 (0%) | 0 | 4/601 (0.7%) | 4 | 0/262 (0%) | 0 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Rectal ulcer | 0/218 (0%) | 0 | 0/90 (0%) | 0 | 1/261 (0.4%) | 3 | 0/206 (0%) | 0 | 0/214 (0%) | 0 | 0/598 (0%) | 0 | 0/213 (0%) | 0 | 1/601 (0.2%) | 2 | 0/262 (0%) | 0 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Small intestinal mucositis | 0/218 (0%) | 0 | 0/90 (0%) | 0 | 0/261 (0%) | 0 | 1/206 (0.5%) | 1 | 0/214 (0%) | 0 | 2/598 (0.3%) | 2 | 0/213 (0%) | 0 | 0/601 (0%) | 0 | 0/262 (0%) | 0 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Small intestinal obstruction | 0/218 (0%) | 0 | 1/90 (1.1%) | 2 | 0/261 (0%) | 0 | 0/206 (0%) | 0 | 0/214 (0%) | 0 | 1/598 (0.2%) | 1 | 0/213 (0%) | 0 | 2/601 (0.3%) | 2 | 0/262 (0%) | 0 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Small intestinal perforation | 0/218 (0%) | 0 | 1/90 (1.1%) | 1 | 0/261 (0%) | 0 | 0/206 (0%) | 0 | 0/214 (0%) | 0 | 0/598 (0%) | 0 | 0/213 (0%) | 0 | 0/601 (0%) | 0 | 0/262 (0%) | 0 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Stomach pain | 0/218 (0%) | 0 | 1/90 (1.1%) | 1 | 3/261 (1.1%) | 3 | 2/206 (1%) | 2 | 0/214 (0%) | 0 | 4/598 (0.7%) | 4 | 0/213 (0%) | 0 | 2/601 (0.3%) | 2 | 2/262 (0.8%) | 2 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Toothache | 0/218 (0%) | 0 | 1/90 (1.1%) | 1 | 1/261 (0.4%) | 1 | 0/206 (0%) | 0 | 0/214 (0%) | 0 | 0/598 (0%) | 0 | 1/213 (0.5%) | 1 | 0/601 (0%) | 0 | 0/262 (0%) | 0 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Typhlitis | 5/218 (2.3%) | 5 | 5/90 (5.6%) | 5 | 10/261 (3.8%) | 11 | 7/206 (3.4%) | 7 | 1/214 (0.5%) | 1 | 13/598 (2.2%) | 15 | 3/213 (1.4%) | 3 | 12/601 (2%) | 12 | 6/262 (2.3%) | 6 | 0/30 (0%) | 0 | 1/9 (11.1%) | 1 | 1/23 (4.3%) | 1 |
| Upper gastrointestinal hemorrhage | 0/218 (0%) | 0 | 0/90 (0%) | 0 | 0/261 (0%) | 0 | 2/206 (1%) | 2 | 0/214 (0%) | 0 | 1/598 (0.2%) | 1 | 0/213 (0%) | 0 | 1/601 (0.2%) | 1 | 1/262 (0.4%) | 3 | 0/30 (0%) | 0 | 1/9 (11.1%) | 1 | 0/23 (0%) | 0 |
| Vomiting | 16/218 (7.3%) | 16 | 11/90 (12.2%) | 13 | 40/261 (15.3%) | 47 | 16/206 (7.8%) | 17 | 13/214 (6.1%) | 17 | 78/598 (13%) | 99 | 18/213 (8.5%) | 20 | 74/601 (12.3%) | 89 | 30/262 (11.5%) | 36 | 5/30 (16.7%) | 5 | 3/9 (33.3%) | 3 | 0/23 (0%) | 0 |
| General disorders | ||||||||||||||||||||||||
| Chills | 1/218 (0.5%) | 1 | 1/90 (1.1%) | 1 | 0/261 (0%) | 0 | 0/206 (0%) | 0 | 1/214 (0.5%) | 1 | 0/598 (0%) | 0 | 0/213 (0%) | 0 | 1/601 (0.2%) | 1 | 1/262 (0.4%) | 1 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Death NOS | 0/218 (0%) | 0 | 0/90 (0%) | 0 | 0/261 (0%) | 0 | 0/206 (0%) | 0 | 0/214 (0%) | 0 | 1/598 (0.2%) | 1 | 0/213 (0%) | 0 | 0/601 (0%) | 0 | 0/262 (0%) | 0 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Edema face | 0/218 (0%) | 0 | 2/90 (2.2%) | 2 | 0/261 (0%) | 0 | 0/206 (0%) | 0 | 0/214 (0%) | 0 | 0/598 (0%) | 0 | 0/213 (0%) | 0 | 1/601 (0.2%) | 1 | 0/262 (0%) | 0 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Edema limbs | 0/218 (0%) | 0 | 0/90 (0%) | 0 | 0/261 (0%) | 0 | 0/206 (0%) | 0 | 0/214 (0%) | 0 | 1/598 (0.2%) | 1 | 0/213 (0%) | 0 | 0/601 (0%) | 0 | 0/262 (0%) | 0 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Edema trunk | 0/218 (0%) | 0 | 0/90 (0%) | 0 | 0/261 (0%) | 0 | 0/206 (0%) | 0 | 0/214 (0%) | 0 | 0/598 (0%) | 0 | 0/213 (0%) | 0 | 0/601 (0%) | 0 | 0/262 (0%) | 0 | 0/30 (0%) | 0 | 1/9 (11.1%) | 1 | 0/23 (0%) | 0 |
| Facial pain | 0/218 (0%) | 0 | 0/90 (0%) | 0 | 0/261 (0%) | 0 | 0/206 (0%) | 0 | 0/214 (0%) | 0 | 1/598 (0.2%) | 1 | 1/213 (0.5%) | 1 | 2/601 (0.3%) | 2 | 1/262 (0.4%) | 1 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Fatigue | 0/218 (0%) | 0 | 4/90 (4.4%) | 5 | 7/261 (2.7%) | 9 | 3/206 (1.5%) | 3 | 5/214 (2.3%) | 5 | 13/598 (2.2%) | 17 | 2/213 (0.9%) | 2 | 17/601 (2.8%) | 18 | 6/262 (2.3%) | 6 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 2/23 (8.7%) | 2 |
| Fever | 26/218 (11.9%) | 34 | 3/90 (3.3%) | 4 | 16/261 (6.1%) | 17 | 15/206 (7.3%) | 19 | 20/214 (9.3%) | 26 | 26/598 (4.3%) | 36 | 19/213 (8.9%) | 23 | 27/601 (4.5%) | 34 | 9/262 (3.4%) | 10 | 3/30 (10%) | 3 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Flu like symptoms | 2/218 (0.9%) | 2 | 0/90 (0%) | 0 | 1/261 (0.4%) | 1 | 2/206 (1%) | 2 | 1/214 (0.5%) | 1 | 3/598 (0.5%) | 3 | 2/213 (0.9%) | 2 | 3/601 (0.5%) | 3 | 0/262 (0%) | 0 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Gait disturbance | 0/218 (0%) | 0 | 0/90 (0%) | 0 | 0/261 (0%) | 0 | 2/206 (1%) | 2 | 0/214 (0%) | 0 | 5/598 (0.8%) | 6 | 2/213 (0.9%) | 6 | 2/601 (0.3%) | 2 | 0/262 (0%) | 0 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| General disorders and administration site conditions - Other, specify | 3/218 (1.4%) | 3 | 2/90 (2.2%) | 5 | 0/261 (0%) | 0 | 0/206 (0%) | 0 | 0/214 (0%) | 0 | 2/598 (0.3%) | 2 | 1/213 (0.5%) | 1 | 4/601 (0.7%) | 4 | 6/262 (2.3%) | 6 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 1/23 (4.3%) | 1 |
| Hypothermia | 0/218 (0%) | 0 | 0/90 (0%) | 0 | 0/261 (0%) | 0 | 0/206 (0%) | 0 | 0/214 (0%) | 0 | 0/598 (0%) | 0 | 0/213 (0%) | 0 | 1/601 (0.2%) | 1 | 0/262 (0%) | 0 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Infusion related reaction | 0/218 (0%) | 0 | 0/90 (0%) | 0 | 0/261 (0%) | 0 | 0/206 (0%) | 0 | 1/214 (0.5%) | 1 | 2/598 (0.3%) | 2 | 0/213 (0%) | 0 | 0/601 (0%) | 0 | 0/262 (0%) | 0 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Injection site reaction | 0/218 (0%) | 0 | 0/90 (0%) | 0 | 0/261 (0%) | 0 | 0/206 (0%) | 0 | 0/214 (0%) | 0 | 1/598 (0.2%) | 1 | 0/213 (0%) | 0 | 0/601 (0%) | 0 | 0/262 (0%) | 0 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Irritability | 3/218 (1.4%) | 3 | 0/90 (0%) | 0 | 0/261 (0%) | 0 | 1/206 (0.5%) | 1 | 0/214 (0%) | 0 | 0/598 (0%) | 0 | 1/213 (0.5%) | 1 | 0/601 (0%) | 0 | 0/262 (0%) | 0 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Multi-organ failure | 0/218 (0%) | 0 | 0/90 (0%) | 0 | 0/261 (0%) | 0 | 0/206 (0%) | 0 | 0/214 (0%) | 0 | 2/598 (0.3%) | 2 | 0/213 (0%) | 0 | 0/601 (0%) | 0 | 0/262 (0%) | 0 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Non-cardiac chest pain | 1/218 (0.5%) | 1 | 1/90 (1.1%) | 1 | 4/261 (1.5%) | 4 | 0/206 (0%) | 0 | 1/214 (0.5%) | 1 | 8/598 (1.3%) | 9 | 0/213 (0%) | 0 | 5/601 (0.8%) | 5 | 5/262 (1.9%) | 5 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Pain | 2/218 (0.9%) | 2 | 6/90 (6.7%) | 7 | 10/261 (3.8%) | 11 | 4/206 (1.9%) | 4 | 3/214 (1.4%) | 3 | 25/598 (4.2%) | 31 | 3/213 (1.4%) | 3 | 30/601 (5%) | 31 | 7/262 (2.7%) | 8 | 1/30 (3.3%) | 1 | 0/9 (0%) | 0 | 2/23 (8.7%) | 2 |
| Hepatobiliary disorders | ||||||||||||||||||||||||
| Cholecystitis | 1/218 (0.5%) | 1 | 0/90 (0%) | 0 | 3/261 (1.1%) | 3 | 0/206 (0%) | 0 | 0/214 (0%) | 0 | 7/598 (1.2%) | 8 | 0/213 (0%) | 0 | 6/601 (1%) | 6 | 2/262 (0.8%) | 2 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Gallbladder obstruction | 0/218 (0%) | 0 | 0/90 (0%) | 0 | 0/261 (0%) | 0 | 0/206 (0%) | 0 | 0/214 (0%) | 0 | 1/598 (0.2%) | 2 | 0/213 (0%) | 0 | 0/601 (0%) | 0 | 0/262 (0%) | 0 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Gallbladder pain | 0/218 (0%) | 0 | 0/90 (0%) | 0 | 0/261 (0%) | 0 | 0/206 (0%) | 0 | 0/214 (0%) | 0 | 0/598 (0%) | 0 | 0/213 (0%) | 0 | 2/601 (0.3%) | 2 | 0/262 (0%) | 0 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Hepatic failure | 0/218 (0%) | 0 | 0/90 (0%) | 0 | 0/261 (0%) | 0 | 0/206 (0%) | 0 | 0/214 (0%) | 0 | 2/598 (0.3%) | 2 | 0/213 (0%) | 0 | 2/601 (0.3%) | 2 | 3/262 (1.1%) | 4 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Hepatic hemorrhage | 0/218 (0%) | 0 | 0/90 (0%) | 0 | 0/261 (0%) | 0 | 0/206 (0%) | 0 | 0/214 (0%) | 0 | 0/598 (0%) | 0 | 0/213 (0%) | 0 | 1/601 (0.2%) | 1 | 0/262 (0%) | 0 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Hepatic necrosis | 0/218 (0%) | 0 | 0/90 (0%) | 0 | 0/261 (0%) | 0 | 0/206 (0%) | 0 | 0/214 (0%) | 0 | 1/598 (0.2%) | 1 | 0/213 (0%) | 0 | 0/601 (0%) | 0 | 0/262 (0%) | 0 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Hepatic pain | 0/218 (0%) | 0 | 1/90 (1.1%) | 1 | 0/261 (0%) | 0 | 1/206 (0.5%) | 1 | 0/214 (0%) | 0 | 1/598 (0.2%) | 1 | 0/213 (0%) | 0 | 1/601 (0.2%) | 1 | 0/262 (0%) | 0 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Hepatobiliary disorders - Other, specify | 0/218 (0%) | 0 | 1/90 (1.1%) | 1 | 1/261 (0.4%) | 1 | 0/206 (0%) | 0 | 1/214 (0.5%) | 1 | 6/598 (1%) | 8 | 0/213 (0%) | 0 | 8/601 (1.3%) | 9 | 3/262 (1.1%) | 4 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 1/23 (4.3%) | 1 |
| Portal hypertension | 1/218 (0.5%) | 1 | 1/90 (1.1%) | 1 | 1/261 (0.4%) | 1 | 3/206 (1.5%) | 3 | 1/214 (0.5%) | 1 | 2/598 (0.3%) | 3 | 2/213 (0.9%) | 2 | 1/601 (0.2%) | 1 | 2/262 (0.8%) | 2 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Immune system disorders | ||||||||||||||||||||||||
| Allergic reaction | 1/218 (0.5%) | 1 | 2/90 (2.2%) | 2 | 2/261 (0.8%) | 2 | 1/206 (0.5%) | 2 | 2/214 (0.9%) | 2 | 9/598 (1.5%) | 9 | 1/213 (0.5%) | 2 | 8/601 (1.3%) | 8 | 0/262 (0%) | 0 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Anaphylaxis | 30/218 (13.8%) | 33 | 9/90 (10%) | 9 | 36/261 (13.8%) | 40 | 29/206 (14.1%) | 29 | 24/214 (11.2%) | 24 | 97/598 (16.2%) | 106 | 24/213 (11.3%) | 25 | 83/601 (13.8%) | 86 | 38/262 (14.5%) | 40 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 4/23 (17.4%) | 4 |
| Immune system disorders - Other, specify | 2/218 (0.9%) | 2 | 0/90 (0%) | 0 | 2/261 (0.8%) | 2 | 2/206 (1%) | 3 | 1/214 (0.5%) | 1 | 2/598 (0.3%) | 2 | 1/213 (0.5%) | 1 | 1/601 (0.2%) | 1 | 0/262 (0%) | 0 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Infections and infestations | ||||||||||||||||||||||||
| Abdominal infection | 2/218 (0.9%) | 2 | 0/90 (0%) | 0 | 2/261 (0.8%) | 2 | 1/206 (0.5%) | 1 | 4/214 (1.9%) | 4 | 6/598 (1%) | 6 | 2/213 (0.9%) | 2 | 1/601 (0.2%) | 2 | 1/262 (0.4%) | 1 | 1/30 (3.3%) | 1 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Anorectal infection | 2/218 (0.9%) | 2 | 2/90 (2.2%) | 3 | 1/261 (0.4%) | 1 | 1/206 (0.5%) | 1 | 0/214 (0%) | 0 | 1/598 (0.2%) | 1 | 2/213 (0.9%) | 2 | 5/601 (0.8%) | 5 | 2/262 (0.8%) | 4 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Appendicitis | 0/218 (0%) | 0 | 0/90 (0%) | 0 | 0/261 (0%) | 0 | 0/206 (0%) | 0 | 0/214 (0%) | 0 | 4/598 (0.7%) | 4 | 0/213 (0%) | 0 | 4/601 (0.7%) | 4 | 0/262 (0%) | 0 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Appendicitis perforated | 0/218 (0%) | 0 | 0/90 (0%) | 0 | 0/261 (0%) | 0 | 0/206 (0%) | 0 | 0/214 (0%) | 0 | 0/598 (0%) | 0 | 0/213 (0%) | 0 | 1/601 (0.2%) | 1 | 0/262 (0%) | 0 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Biliary tract infection | 0/218 (0%) | 0 | 0/90 (0%) | 0 | 1/261 (0.4%) | 1 | 0/206 (0%) | 0 | 0/214 (0%) | 0 | 1/598 (0.2%) | 1 | 0/213 (0%) | 0 | 0/601 (0%) | 0 | 0/262 (0%) | 0 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Bladder infection | 2/218 (0.9%) | 2 | 1/90 (1.1%) | 1 | 1/261 (0.4%) | 1 | 0/206 (0%) | 0 | 3/214 (1.4%) | 3 | 7/598 (1.2%) | 7 | 0/213 (0%) | 0 | 4/601 (0.7%) | 4 | 3/262 (1.1%) | 3 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Bone infection | 1/218 (0.5%) | 1 | 2/90 (2.2%) | 2 | 0/261 (0%) | 0 | 0/206 (0%) | 0 | 0/214 (0%) | 0 | 1/598 (0.2%) | 1 | 2/213 (0.9%) | 2 | 3/601 (0.5%) | 5 | 0/262 (0%) | 0 | 1/30 (3.3%) | 1 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Bronchial infection | 2/218 (0.9%) | 3 | 1/90 (1.1%) | 1 | 1/261 (0.4%) | 1 | 3/206 (1.5%) | 3 | 1/214 (0.5%) | 1 | 11/598 (1.8%) | 11 | 5/213 (2.3%) | 5 | 4/601 (0.7%) | 4 | 1/262 (0.4%) | 1 | 1/30 (3.3%) | 1 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Catheter related infection | 16/218 (7.3%) | 25 | 10/90 (11.1%) | 19 | 9/261 (3.4%) | 9 | 10/206 (4.9%) | 12 | 10/214 (4.7%) | 14 | 29/598 (4.8%) | 37 | 24/213 (11.3%) | 30 | 23/601 (3.8%) | 25 | 8/262 (3.1%) | 9 | 3/30 (10%) | 5 | 1/9 (11.1%) | 1 | 0/23 (0%) | 0 |
| Conjunctivitis infective | 0/218 (0%) | 0 | 0/90 (0%) | 0 | 0/261 (0%) | 0 | 2/206 (1%) | 2 | 0/214 (0%) | 0 | 0/598 (0%) | 0 | 0/213 (0%) | 0 | 2/601 (0.3%) | 2 | 1/262 (0.4%) | 1 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Device related infection | 0/218 (0%) | 0 | 0/90 (0%) | 0 | 0/261 (0%) | 0 | 2/206 (1%) | 2 | 0/214 (0%) | 0 | 0/598 (0%) | 0 | 0/213 (0%) | 0 | 1/601 (0.2%) | 1 | 0/262 (0%) | 0 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Duodenal infection | 0/218 (0%) | 0 | 0/90 (0%) | 0 | 0/261 (0%) | 0 | 0/206 (0%) | 0 | 0/214 (0%) | 0 | 0/598 (0%) | 0 | 0/213 (0%) | 0 | 1/601 (0.2%) | 1 | 0/262 (0%) | 0 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Encephalitis infection | 0/218 (0%) | 0 | 0/90 (0%) | 0 | 1/261 (0.4%) | 1 | 0/206 (0%) | 0 | 0/214 (0%) | 0 | 0/598 (0%) | 0 | 0/213 (0%) | 0 | 0/601 (0%) | 0 | 0/262 (0%) | 0 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Encephalomyelitis infection | 0/218 (0%) | 0 | 0/90 (0%) | 0 | 0/261 (0%) | 0 | 0/206 (0%) | 0 | 0/214 (0%) | 0 | 0/598 (0%) | 0 | 0/213 (0%) | 0 | 2/601 (0.3%) | 2 | 0/262 (0%) | 0 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Endocarditis infective | 0/218 (0%) | 0 | 0/90 (0%) | 0 | 0/261 (0%) | 0 | 1/206 (0.5%) | 1 | 0/214 (0%) | 0 | 0/598 (0%) | 0 | 0/213 (0%) | 0 | 0/601 (0%) | 0 | 0/262 (0%) | 0 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Enterocolitis infectious | 9/218 (4.1%) | 12 | 5/90 (5.6%) | 8 | 17/261 (6.5%) | 19 | 14/206 (6.8%) | 16 | 8/214 (3.7%) | 10 | 24/598 (4%) | 29 | 13/213 (6.1%) | 14 | 16/601 (2.7%) | 17 | 10/262 (3.8%) | 10 | 3/30 (10%) | 3 | 2/9 (22.2%) | 5 | 3/23 (13%) | 3 |
| Esophageal infection | 0/218 (0%) | 0 | 0/90 (0%) | 0 | 0/261 (0%) | 0 | 0/206 (0%) | 0 | 0/214 (0%) | 0 | 0/598 (0%) | 0 | 0/213 (0%) | 0 | 0/601 (0%) | 0 | 0/262 (0%) | 0 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 1/23 (4.3%) | 1 |
| Eye infection | 0/218 (0%) | 0 | 0/90 (0%) | 0 | 0/261 (0%) | 0 | 0/206 (0%) | 0 | 2/214 (0.9%) | 2 | 1/598 (0.2%) | 1 | 0/213 (0%) | 0 | 0/601 (0%) | 0 | 1/262 (0.4%) | 1 | 1/30 (3.3%) | 1 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Gum infection | 1/218 (0.5%) | 1 | 0/90 (0%) | 0 | 1/261 (0.4%) | 1 | 0/206 (0%) | 0 | 2/214 (0.9%) | 2 | 3/598 (0.5%) | 3 | 2/213 (0.9%) | 2 | 3/601 (0.5%) | 3 | 4/262 (1.5%) | 4 | 1/30 (3.3%) | 1 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Hepatic infection | 2/218 (0.9%) | 2 | 1/90 (1.1%) | 1 | 2/261 (0.8%) | 2 | 0/206 (0%) | 0 | 2/214 (0.9%) | 2 | 4/598 (0.7%) | 4 | 0/213 (0%) | 0 | 2/601 (0.3%) | 2 | 1/262 (0.4%) | 1 | 1/30 (3.3%) | 2 | 1/9 (11.1%) | 1 | 0/23 (0%) | 0 |
| Hepatitis viral | 0/218 (0%) | 0 | 0/90 (0%) | 0 | 0/261 (0%) | 0 | 1/206 (0.5%) | 1 | 1/214 (0.5%) | 1 | 0/598 (0%) | 0 | 0/213 (0%) | 0 | 4/601 (0.7%) | 4 | 0/262 (0%) | 0 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Infections and infestations - Other, specify | 147/218 (67.4%) | 347 | 63/90 (70%) | 179 | 149/261 (57.1%) | 322 | 141/206 (68.4%) | 347 | 146/214 (68.2%) | 324 | 297/598 (49.7%) | 595 | 136/213 (63.8%) | 322 | 288/601 (47.9%) | 545 | 145/262 (55.3%) | 290 | 23/30 (76.7%) | 76 | 7/9 (77.8%) | 25 | 14/23 (60.9%) | 27 |
| Infective myositis | 0/218 (0%) | 0 | 0/90 (0%) | 0 | 1/261 (0.4%) | 1 | 0/206 (0%) | 0 | 1/214 (0.5%) | 1 | 1/598 (0.2%) | 1 | 1/213 (0.5%) | 1 | 2/601 (0.3%) | 2 | 0/262 (0%) | 0 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Joint infection | 1/218 (0.5%) | 1 | 0/90 (0%) | 0 | 0/261 (0%) | 0 | 0/206 (0%) | 0 | 0/214 (0%) | 0 | 0/598 (0%) | 0 | 1/213 (0.5%) | 1 | 1/601 (0.2%) | 1 | 2/262 (0.8%) | 2 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Kidney infection | 1/218 (0.5%) | 1 | 0/90 (0%) | 0 | 1/261 (0.4%) | 1 | 0/206 (0%) | 0 | 1/214 (0.5%) | 1 | 1/598 (0.2%) | 1 | 0/213 (0%) | 0 | 0/601 (0%) | 0 | 0/262 (0%) | 0 | 0/30 (0%) | 0 | 1/9 (11.1%) | 1 | 0/23 (0%) | 0 |
| Lip infection | 1/218 (0.5%) | 1 | 1/90 (1.1%) | 2 | 0/261 (0%) | 0 | 0/206 (0%) | 0 | 0/214 (0%) | 0 | 4/598 (0.7%) | 4 | 1/213 (0.5%) | 1 | 3/601 (0.5%) | 3 | 1/262 (0.4%) | 1 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Lung infection | 29/218 (13.3%) | 37 | 5/90 (5.6%) | 5 | 21/261 (8%) | 23 | 14/206 (6.8%) | 16 | 17/214 (7.9%) | 21 | 40/598 (6.7%) | 47 | 19/213 (8.9%) | 23 | 47/601 (7.8%) | 52 | 10/262 (3.8%) | 11 | 3/30 (10%) | 6 | 1/9 (11.1%) | 1 | 0/23 (0%) | 0 |
| Lymph gland infection | 0/218 (0%) | 0 | 0/90 (0%) | 0 | 1/261 (0.4%) | 1 | 0/206 (0%) | 0 | 0/214 (0%) | 0 | 1/598 (0.2%) | 1 | 0/213 (0%) | 0 | 0/601 (0%) | 0 | 0/262 (0%) | 0 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Meningitis | 1/218 (0.5%) | 1 | 1/90 (1.1%) | 2 | 0/261 (0%) | 0 | 0/206 (0%) | 0 | 1/214 (0.5%) | 1 | 3/598 (0.5%) | 3 | 0/213 (0%) | 0 | 4/601 (0.7%) | 4 | 0/262 (0%) | 0 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Mucosal infection | 2/218 (0.9%) | 2 | 0/90 (0%) | 0 | 0/261 (0%) | 0 | 1/206 (0.5%) | 1 | 1/214 (0.5%) | 1 | 4/598 (0.7%) | 4 | 2/213 (0.9%) | 2 | 4/601 (0.7%) | 4 | 1/262 (0.4%) | 1 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Nail infection | 0/218 (0%) | 0 | 0/90 (0%) | 0 | 1/261 (0.4%) | 2 | 1/206 (0.5%) | 1 | 0/214 (0%) | 0 | 4/598 (0.7%) | 4 | 0/213 (0%) | 0 | 2/601 (0.3%) | 3 | 0/262 (0%) | 0 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Otitis externa | 3/218 (1.4%) | 3 | 0/90 (0%) | 0 | 0/261 (0%) | 0 | 0/206 (0%) | 0 | 3/214 (1.4%) | 3 | 0/598 (0%) | 0 | 2/213 (0.9%) | 2 | 0/601 (0%) | 0 | 0/262 (0%) | 0 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Otitis media | 16/218 (7.3%) | 18 | 3/90 (3.3%) | 3 | 1/261 (0.4%) | 1 | 9/206 (4.4%) | 9 | 13/214 (6.1%) | 15 | 5/598 (0.8%) | 5 | 12/213 (5.6%) | 12 | 8/601 (1.3%) | 8 | 2/262 (0.8%) | 2 | 2/30 (6.7%) | 3 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Pancreas infection | 0/218 (0%) | 0 | 0/90 (0%) | 0 | 2/261 (0.8%) | 2 | 0/206 (0%) | 0 | 0/214 (0%) | 0 | 2/598 (0.3%) | 2 | 0/213 (0%) | 0 | 2/601 (0.3%) | 3 | 1/262 (0.4%) | 1 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Paronychia | 0/218 (0%) | 0 | 0/90 (0%) | 0 | 0/261 (0%) | 0 | 0/206 (0%) | 0 | 0/214 (0%) | 0 | 1/598 (0.2%) | 1 | 0/213 (0%) | 0 | 3/601 (0.5%) | 3 | 0/262 (0%) | 0 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Pelvic infection | 0/218 (0%) | 0 | 0/90 (0%) | 0 | 0/261 (0%) | 0 | 0/206 (0%) | 0 | 0/214 (0%) | 0 | 0/598 (0%) | 0 | 0/213 (0%) | 0 | 0/601 (0%) | 0 | 1/262 (0.4%) | 1 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Penile infection | 0/218 (0%) | 0 | 0/90 (0%) | 0 | 0/261 (0%) | 0 | 1/206 (0.5%) | 1 | 0/214 (0%) | 0 | 0/598 (0%) | 0 | 0/213 (0%) | 0 | 0/601 (0%) | 0 | 0/262 (0%) | 0 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Peripheral nerve infection | 0/218 (0%) | 0 | 1/90 (1.1%) | 1 | 0/261 (0%) | 0 | 0/206 (0%) | 0 | 1/214 (0.5%) | 1 | 1/598 (0.2%) | 1 | 0/213 (0%) | 0 | 1/601 (0.2%) | 1 | 1/262 (0.4%) | 1 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Peritoneal infection | 0/218 (0%) | 0 | 1/90 (1.1%) | 1 | 0/261 (0%) | 0 | 0/206 (0%) | 0 | 0/214 (0%) | 0 | 0/598 (0%) | 0 | 0/213 (0%) | 0 | 1/601 (0.2%) | 1 | 0/262 (0%) | 0 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Pharyngitis | 3/218 (1.4%) | 4 | 0/90 (0%) | 0 | 2/261 (0.8%) | 2 | 1/206 (0.5%) | 1 | 2/214 (0.9%) | 2 | 3/598 (0.5%) | 3 | 1/213 (0.5%) | 1 | 4/601 (0.7%) | 4 | 1/262 (0.4%) | 1 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Phlebitis infective | 0/218 (0%) | 0 | 0/90 (0%) | 0 | 0/261 (0%) | 0 | 0/206 (0%) | 0 | 1/214 (0.5%) | 1 | 0/598 (0%) | 0 | 0/213 (0%) | 0 | 1/601 (0.2%) | 1 | 0/262 (0%) | 0 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Rash pustular | 0/218 (0%) | 0 | 0/90 (0%) | 0 | 0/261 (0%) | 0 | 0/206 (0%) | 0 | 1/214 (0.5%) | 1 | 1/598 (0.2%) | 1 | 0/213 (0%) | 0 | 0/601 (0%) | 0 | 0/262 (0%) | 0 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Rhinitis infective | 1/218 (0.5%) | 1 | 0/90 (0%) | 0 | 0/261 (0%) | 0 | 0/206 (0%) | 0 | 0/214 (0%) | 0 | 0/598 (0%) | 0 | 0/213 (0%) | 0 | 0/601 (0%) | 0 | 0/262 (0%) | 0 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Salivary gland infection | 0/218 (0%) | 0 | 0/90 (0%) | 0 | 0/261 (0%) | 0 | 0/206 (0%) | 0 | 1/214 (0.5%) | 1 | 2/598 (0.3%) | 2 | 0/213 (0%) | 0 | 0/601 (0%) | 0 | 0/262 (0%) | 0 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Sepsis | 2/218 (0.9%) | 2 | 3/90 (3.3%) | 5 | 1/261 (0.4%) | 1 | 3/206 (1.5%) | 3 | 4/214 (1.9%) | 4 | 17/598 (2.8%) | 21 | 3/213 (1.4%) | 3 | 12/601 (2%) | 13 | 2/262 (0.8%) | 3 | 2/30 (6.7%) | 3 | 0/9 (0%) | 0 | 1/23 (4.3%) | 1 |
| Sinusitis | 6/218 (2.8%) | 6 | 6/90 (6.7%) | 10 | 9/261 (3.4%) | 10 | 7/206 (3.4%) | 9 | 5/214 (2.3%) | 5 | 15/598 (2.5%) | 17 | 6/213 (2.8%) | 10 | 11/601 (1.8%) | 13 | 2/262 (0.8%) | 2 | 1/30 (3.3%) | 1 | 0/9 (0%) | 0 | 2/23 (8.7%) | 2 |
| Skin infection | 9/218 (4.1%) | 11 | 8/90 (8.9%) | 9 | 13/261 (5%) | 14 | 6/206 (2.9%) | 6 | 15/214 (7%) | 15 | 40/598 (6.7%) | 44 | 8/213 (3.8%) | 9 | 32/601 (5.3%) | 34 | 9/262 (3.4%) | 10 | 1/30 (3.3%) | 1 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Small intestine infection | 1/218 (0.5%) | 3 | 0/90 (0%) | 0 | 0/261 (0%) | 0 | 0/206 (0%) | 0 | 6/214 (2.8%) | 8 | 1/598 (0.2%) | 1 | 0/213 (0%) | 0 | 2/601 (0.3%) | 2 | 1/262 (0.4%) | 1 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Soft tissue infection | 1/218 (0.5%) | 1 | 2/90 (2.2%) | 3 | 1/261 (0.4%) | 1 | 0/206 (0%) | 0 | 2/214 (0.9%) | 2 | 5/598 (0.8%) | 6 | 0/213 (0%) | 0 | 4/601 (0.7%) | 4 | 2/262 (0.8%) | 2 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Splenic infection | 1/218 (0.5%) | 1 | 1/90 (1.1%) | 1 | 1/261 (0.4%) | 1 | 0/206 (0%) | 0 | 1/214 (0.5%) | 1 | 1/598 (0.2%) | 1 | 0/213 (0%) | 0 | 0/601 (0%) | 0 | 0/262 (0%) | 0 | 1/30 (3.3%) | 1 | 1/9 (11.1%) | 1 | 0/23 (0%) | 0 |
| Stoma site infection | 0/218 (0%) | 0 | 0/90 (0%) | 0 | 0/261 (0%) | 0 | 1/206 (0.5%) | 1 | 0/214 (0%) | 0 | 0/598 (0%) | 0 | 0/213 (0%) | 0 | 0/601 (0%) | 0 | 0/262 (0%) | 0 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Tooth infection | 0/218 (0%) | 0 | 0/90 (0%) | 0 | 0/261 (0%) | 0 | 0/206 (0%) | 0 | 0/214 (0%) | 0 | 4/598 (0.7%) | 4 | 1/213 (0.5%) | 1 | 2/601 (0.3%) | 2 | 0/262 (0%) | 0 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Tracheitis | 0/218 (0%) | 0 | 1/90 (1.1%) | 1 | 0/261 (0%) | 0 | 0/206 (0%) | 0 | 0/214 (0%) | 0 | 1/598 (0.2%) | 1 | 0/213 (0%) | 0 | 0/601 (0%) | 0 | 0/262 (0%) | 0 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Upper respiratory infection | 28/218 (12.8%) | 38 | 5/90 (5.6%) | 8 | 14/261 (5.4%) | 15 | 18/206 (8.7%) | 24 | 21/214 (9.8%) | 26 | 19/598 (3.2%) | 20 | 17/213 (8%) | 21 | 23/601 (3.8%) | 26 | 9/262 (3.4%) | 9 | 1/30 (3.3%) | 1 | 0/9 (0%) | 0 | 3/23 (13%) | 3 |
| Urethral infection | 0/218 (0%) | 0 | 0/90 (0%) | 0 | 0/261 (0%) | 0 | 0/206 (0%) | 0 | 0/214 (0%) | 0 | 0/598 (0%) | 0 | 1/213 (0.5%) | 1 | 0/601 (0%) | 0 | 0/262 (0%) | 0 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Urinary tract infection | 7/218 (3.2%) | 8 | 5/90 (5.6%) | 7 | 8/261 (3.1%) | 9 | 9/206 (4.4%) | 11 | 11/214 (5.1%) | 11 | 19/598 (3.2%) | 22 | 7/213 (3.3%) | 10 | 18/601 (3%) | 18 | 9/262 (3.4%) | 12 | 2/30 (6.7%) | 2 | 1/9 (11.1%) | 1 | 1/23 (4.3%) | 1 |
| Vaginal infection | 0/218 (0%) | 0 | 0/90 (0%) | 0 | 0/261 (0%) | 0 | 0/206 (0%) | 0 | 0/214 (0%) | 0 | 2/598 (0.3%) | 2 | 1/213 (0.5%) | 1 | 2/601 (0.3%) | 2 | 0/262 (0%) | 0 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Wound infection | 1/218 (0.5%) | 1 | 3/90 (3.3%) | 3 | 1/261 (0.4%) | 1 | 3/206 (1.5%) | 3 | 2/214 (0.9%) | 3 | 16/598 (2.7%) | 17 | 3/213 (1.4%) | 3 | 8/601 (1.3%) | 10 | 4/262 (1.5%) | 4 | 1/30 (3.3%) | 1 | 0/9 (0%) | 0 | 1/23 (4.3%) | 1 |
| Injury, poisoning and procedural complications | ||||||||||||||||||||||||
| Bladder anastomotic leak | 0/218 (0%) | 0 | 0/90 (0%) | 0 | 0/261 (0%) | 0 | 0/206 (0%) | 0 | 0/214 (0%) | 0 | 0/598 (0%) | 0 | 0/213 (0%) | 0 | 1/601 (0.2%) | 1 | 0/262 (0%) | 0 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Burn | 0/218 (0%) | 0 | 0/90 (0%) | 0 | 1/261 (0.4%) | 1 | 0/206 (0%) | 0 | 0/214 (0%) | 0 | 0/598 (0%) | 0 | 0/213 (0%) | 0 | 0/601 (0%) | 0 | 0/262 (0%) | 0 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Dermatitis radiation | 0/218 (0%) | 0 | 0/90 (0%) | 0 | 0/261 (0%) | 0 | 0/206 (0%) | 0 | 0/214 (0%) | 0 | 0/598 (0%) | 0 | 0/213 (0%) | 0 | 0/601 (0%) | 0 | 1/262 (0.4%) | 1 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Fall | 0/218 (0%) | 0 | 0/90 (0%) | 0 | 0/261 (0%) | 0 | 0/206 (0%) | 0 | 0/214 (0%) | 0 | 1/598 (0.2%) | 1 | 0/213 (0%) | 0 | 0/601 (0%) | 0 | 0/262 (0%) | 0 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Fracture | 1/218 (0.5%) | 1 | 2/90 (2.2%) | 2 | 1/261 (0.4%) | 1 | 0/206 (0%) | 0 | 0/214 (0%) | 0 | 4/598 (0.7%) | 4 | 0/213 (0%) | 0 | 2/601 (0.3%) | 2 | 1/262 (0.4%) | 1 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Injury, poisoning and procedural complications - Other, specify | 0/218 (0%) | 0 | 1/90 (1.1%) | 1 | 0/261 (0%) | 0 | 0/206 (0%) | 0 | 1/214 (0.5%) | 1 | 2/598 (0.3%) | 2 | 0/213 (0%) | 0 | 1/601 (0.2%) | 1 | 0/262 (0%) | 0 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Intraoperative respiratory injury | 0/218 (0%) | 0 | 0/90 (0%) | 0 | 1/261 (0.4%) | 1 | 0/206 (0%) | 0 | 0/214 (0%) | 0 | 0/598 (0%) | 0 | 0/213 (0%) | 0 | 0/601 (0%) | 0 | 0/262 (0%) | 0 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Intraoperative skin injury | 0/218 (0%) | 0 | 0/90 (0%) | 0 | 0/261 (0%) | 0 | 0/206 (0%) | 0 | 0/214 (0%) | 0 | 0/598 (0%) | 0 | 0/213 (0%) | 0 | 1/601 (0.2%) | 3 | 0/262 (0%) | 0 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Pancreatic anastomotic leak | 0/218 (0%) | 0 | 0/90 (0%) | 0 | 0/261 (0%) | 0 | 0/206 (0%) | 0 | 0/214 (0%) | 0 | 1/598 (0.2%) | 1 | 0/213 (0%) | 0 | 0/601 (0%) | 0 | 0/262 (0%) | 0 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Postoperative hemorrhage | 0/218 (0%) | 0 | 1/90 (1.1%) | 1 | 0/261 (0%) | 0 | 1/206 (0.5%) | 1 | 1/214 (0.5%) | 1 | 1/598 (0.2%) | 1 | 0/213 (0%) | 0 | 1/601 (0.2%) | 1 | 0/262 (0%) | 0 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Postoperative thoracic procedure complication | 0/218 (0%) | 0 | 0/90 (0%) | 0 | 0/261 (0%) | 0 | 0/206 (0%) | 0 | 0/214 (0%) | 0 | 1/598 (0.2%) | 1 | 0/213 (0%) | 0 | 1/601 (0.2%) | 1 | 0/262 (0%) | 0 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Radiation recall reaction (dermatologic) | 0/218 (0%) | 0 | 0/90 (0%) | 0 | 0/261 (0%) | 0 | 0/206 (0%) | 0 | 0/214 (0%) | 0 | 0/598 (0%) | 0 | 1/213 (0.5%) | 1 | 0/601 (0%) | 0 | 0/262 (0%) | 0 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Vascular access complication | 0/218 (0%) | 0 | 4/90 (4.4%) | 5 | 6/261 (2.3%) | 6 | 0/206 (0%) | 0 | 0/214 (0%) | 0 | 12/598 (2%) | 12 | 1/213 (0.5%) | 1 | 11/601 (1.8%) | 12 | 5/262 (1.9%) | 6 | 1/30 (3.3%) | 1 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Wound dehiscence | 0/218 (0%) | 0 | 1/90 (1.1%) | 1 | 0/261 (0%) | 0 | 1/206 (0.5%) | 1 | 1/214 (0.5%) | 1 | 0/598 (0%) | 0 | 0/213 (0%) | 0 | 1/601 (0.2%) | 1 | 0/262 (0%) | 0 | 1/30 (3.3%) | 1 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Investigations | ||||||||||||||||||||||||
| Activated partial thromboplastin time prolonged | 4/218 (1.8%) | 5 | 5/90 (5.6%) | 6 | 11/261 (4.2%) | 18 | 6/206 (2.9%) | 8 | 4/214 (1.9%) | 5 | 18/598 (3%) | 19 | 6/213 (2.8%) | 6 | 18/601 (3%) | 22 | 10/262 (3.8%) | 13 | 2/30 (6.7%) | 2 | 1/9 (11.1%) | 1 | 0/23 (0%) | 0 |
| Alanine aminotransferase increased | 96/218 (44%) | 272 | 33/90 (36.7%) | 88 | 122/261 (46.7%) | 305 | 94/206 (45.6%) | 294 | 92/214 (43%) | 263 | 274/598 (45.8%) | 780 | 101/213 (47.4%) | 352 | 275/601 (45.8%) | 749 | 125/262 (47.7%) | 303 | 12/30 (40%) | 27 | 2/9 (22.2%) | 3 | 10/23 (43.5%) | 18 |
| Alkaline phosphatase increased | 3/218 (1.4%) | 3 | 3/90 (3.3%) | 3 | 1/261 (0.4%) | 1 | 1/206 (0.5%) | 1 | 3/214 (1.4%) | 4 | 4/598 (0.7%) | 5 | 3/213 (1.4%) | 4 | 1/601 (0.2%) | 1 | 2/262 (0.8%) | 2 | 0/30 (0%) | 0 | 1/9 (11.1%) | 2 | 2/23 (8.7%) | 2 |
| Aspartate aminotransferase increased | 44/218 (20.2%) | 66 | 22/90 (24.4%) | 35 | 63/261 (24.1%) | 91 | 54/206 (26.2%) | 78 | 42/214 (19.6%) | 60 | 146/598 (24.4%) | 257 | 54/213 (25.4%) | 97 | 143/601 (23.8%) | 202 | 71/262 (27.1%) | 121 | 5/30 (16.7%) | 7 | 1/9 (11.1%) | 1 | 4/23 (17.4%) | 6 |
| Blood antidiuretic hormone abnormal | 0/218 (0%) | 0 | 0/90 (0%) | 0 | 0/261 (0%) | 0 | 0/206 (0%) | 0 | 0/214 (0%) | 0 | 1/598 (0.2%) | 1 | 0/213 (0%) | 0 | 0/601 (0%) | 0 | 0/262 (0%) | 0 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Blood bilirubin increased | 15/218 (6.9%) | 17 | 13/90 (14.4%) | 17 | 47/261 (18%) | 83 | 15/206 (7.3%) | 18 | 4/214 (1.9%) | 4 | 104/598 (17.4%) | 178 | 7/213 (3.3%) | 9 | 95/601 (15.8%) | 133 | 50/262 (19.1%) | 74 | 2/30 (6.7%) | 2 | 2/9 (22.2%) | 3 | 2/23 (8.7%) | 2 |
| Blood corticotrophin decreased | 0/218 (0%) | 0 | 1/90 (1.1%) | 1 | 1/261 (0.4%) | 1 | 0/206 (0%) | 0 | 0/214 (0%) | 0 | 0/598 (0%) | 0 | 0/213 (0%) | 0 | 0/601 (0%) | 0 | 1/262 (0.4%) | 1 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| CD4 lymphocytes decreased | 0/218 (0%) | 0 | 0/90 (0%) | 0 | 0/261 (0%) | 0 | 0/206 (0%) | 0 | 0/214 (0%) | 0 | 1/598 (0.2%) | 1 | 0/213 (0%) | 0 | 0/601 (0%) | 0 | 0/262 (0%) | 0 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Cholesterol high | 2/218 (0.9%) | 3 | 2/90 (2.2%) | 2 | 1/261 (0.4%) | 1 | 0/206 (0%) | 0 | 0/214 (0%) | 0 | 3/598 (0.5%) | 3 | 0/213 (0%) | 0 | 4/601 (0.7%) | 8 | 4/262 (1.5%) | 5 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| CPK increased | 1/218 (0.5%) | 1 | 0/90 (0%) | 0 | 0/261 (0%) | 0 | 0/206 (0%) | 0 | 0/214 (0%) | 0 | 0/598 (0%) | 0 | 1/213 (0.5%) | 1 | 2/601 (0.3%) | 2 | 0/262 (0%) | 0 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Creatinine increased | 1/218 (0.5%) | 1 | 0/90 (0%) | 0 | 9/261 (3.4%) | 11 | 2/206 (1%) | 2 | 1/214 (0.5%) | 1 | 7/598 (1.2%) | 7 | 0/213 (0%) | 0 | 9/601 (1.5%) | 9 | 7/262 (2.7%) | 8 | 1/30 (3.3%) | 1 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Electrocardiogram QT corrected interval prolonged | 0/218 (0%) | 0 | 0/90 (0%) | 0 | 0/261 (0%) | 0 | 0/206 (0%) | 0 | 1/214 (0.5%) | 1 | 1/598 (0.2%) | 1 | 0/213 (0%) | 0 | 0/601 (0%) | 0 | 1/262 (0.4%) | 1 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Fibrinogen decreased | 7/218 (3.2%) | 12 | 7/90 (7.8%) | 8 | 20/261 (7.7%) | 22 | 8/206 (3.9%) | 11 | 9/214 (4.2%) | 12 | 41/598 (6.9%) | 53 | 10/213 (4.7%) | 15 | 32/601 (5.3%) | 37 | 15/262 (5.7%) | 16 | 3/30 (10%) | 4 | 1/9 (11.1%) | 1 | 2/23 (8.7%) | 2 |
| GGT increased | 5/218 (2.3%) | 10 | 6/90 (6.7%) | 7 | 10/261 (3.8%) | 16 | 5/206 (2.4%) | 10 | 7/214 (3.3%) | 12 | 36/598 (6%) | 75 | 8/213 (3.8%) | 14 | 35/601 (5.8%) | 58 | 10/262 (3.8%) | 12 | 1/30 (3.3%) | 1 | 1/9 (11.1%) | 1 | 1/23 (4.3%) | 2 |
| Hemoglobin increased | 2/218 (0.9%) | 2 | 0/90 (0%) | 0 | 0/261 (0%) | 0 | 0/206 (0%) | 0 | 1/214 (0.5%) | 1 | 1/598 (0.2%) | 1 | 1/213 (0.5%) | 1 | 0/601 (0%) | 0 | 0/262 (0%) | 0 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 1/23 (4.3%) | 2 |
| INR increased | 0/218 (0%) | 0 | 1/90 (1.1%) | 1 | 6/261 (2.3%) | 10 | 0/206 (0%) | 0 | 0/214 (0%) | 0 | 5/598 (0.8%) | 5 | 2/213 (0.9%) | 2 | 5/601 (0.8%) | 5 | 3/262 (1.1%) | 5 | 1/30 (3.3%) | 1 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Investigations - Other, specify | 3/218 (1.4%) | 3 | 2/90 (2.2%) | 2 | 2/261 (0.8%) | 2 | 2/206 (1%) | 2 | 2/214 (0.9%) | 2 | 19/598 (3.2%) | 26 | 3/213 (1.4%) | 6 | 12/601 (2%) | 16 | 5/262 (1.9%) | 5 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Lipase increased | 8/218 (3.7%) | 8 | 7/90 (7.8%) | 8 | 39/261 (14.9%) | 69 | 10/206 (4.9%) | 12 | 10/214 (4.7%) | 14 | 44/598 (7.4%) | 58 | 6/213 (2.8%) | 8 | 35/601 (5.8%) | 52 | 12/262 (4.6%) | 17 | 1/30 (3.3%) | 1 | 1/9 (11.1%) | 1 | 3/23 (13%) | 3 |
| Lymphocyte count decreased | 15/218 (6.9%) | 38 | 9/90 (10%) | 29 | 14/261 (5.4%) | 32 | 21/206 (10.2%) | 48 | 16/214 (7.5%) | 32 | 35/598 (5.9%) | 73 | 17/213 (8%) | 33 | 38/601 (6.3%) | 93 | 10/262 (3.8%) | 23 | 2/30 (6.7%) | 3 | 1/9 (11.1%) | 1 | 0/23 (0%) | 0 |
| Neutrophil count decreased | 184/218 (84.4%) | 682 | 61/90 (67.8%) | 248 | 187/261 (71.6%) | 585 | 168/206 (81.6%) | 636 | 172/214 (80.4%) | 595 | 437/598 (73.1%) | 1393 | 168/213 (78.9%) | 652 | 442/601 (73.5%) | 1279 | 188/262 (71.8%) | 661 | 23/30 (76.7%) | 85 | 7/9 (77.8%) | 13 | 15/23 (65.2%) | 42 |
| Platelet count decreased | 96/218 (44%) | 199 | 39/90 (43.3%) | 85 | 101/261 (38.7%) | 217 | 78/206 (37.9%) | 151 | 77/214 (36%) | 130 | 249/598 (41.6%) | 481 | 74/213 (34.7%) | 125 | 226/601 (37.6%) | 444 | 102/262 (38.9%) | 223 | 16/30 (53.3%) | 31 | 5/9 (55.6%) | 8 | 8/23 (34.8%) | 12 |
| Serum amylase increased | 4/218 (1.8%) | 4 | 4/90 (4.4%) | 5 | 17/261 (6.5%) | 32 | 10/206 (4.9%) | 11 | 6/214 (2.8%) | 6 | 25/598 (4.2%) | 31 | 5/213 (2.3%) | 7 | 22/601 (3.7%) | 26 | 8/262 (3.1%) | 10 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 2/23 (8.7%) | 2 |
| Urine output decreased | 0/218 (0%) | 0 | 0/90 (0%) | 0 | 0/261 (0%) | 0 | 0/206 (0%) | 0 | 0/214 (0%) | 0 | 0/598 (0%) | 0 | 0/213 (0%) | 0 | 1/601 (0.2%) | 1 | 0/262 (0%) | 0 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Weight gain | 0/218 (0%) | 0 | 0/90 (0%) | 0 | 3/261 (1.1%) | 3 | 3/206 (1.5%) | 3 | 2/214 (0.9%) | 2 | 0/598 (0%) | 0 | 1/213 (0.5%) | 1 | 4/601 (0.7%) | 7 | 5/262 (1.9%) | 19 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Weight loss | 11/218 (5%) | 13 | 3/90 (3.3%) | 3 | 17/261 (6.5%) | 19 | 5/206 (2.4%) | 15 | 4/214 (1.9%) | 5 | 34/598 (5.7%) | 44 | 8/213 (3.8%) | 13 | 21/601 (3.5%) | 24 | 12/262 (4.6%) | 17 | 2/30 (6.7%) | 2 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| White blood cell decreased | 91/218 (41.7%) | 292 | 41/90 (45.6%) | 125 | 103/261 (39.5%) | 307 | 92/206 (44.7%) | 289 | 83/214 (38.8%) | 260 | 213/598 (35.6%) | 603 | 81/213 (38%) | 225 | 218/601 (36.3%) | 549 | 124/262 (47.3%) | 350 | 16/30 (53.3%) | 46 | 5/9 (55.6%) | 8 | 6/23 (26.1%) | 15 |
| Metabolism and nutrition disorders | ||||||||||||||||||||||||
| Acidosis | 5/218 (2.3%) | 7 | 3/90 (3.3%) | 4 | 4/261 (1.5%) | 4 | 1/206 (0.5%) | 1 | 3/214 (1.4%) | 3 | 10/598 (1.7%) | 10 | 0/213 (0%) | 0 | 14/601 (2.3%) | 14 | 6/262 (2.3%) | 7 | 2/30 (6.7%) | 2 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Alcohol intolerance | 0/218 (0%) | 0 | 0/90 (0%) | 0 | 0/261 (0%) | 0 | 0/206 (0%) | 0 | 0/214 (0%) | 0 | 0/598 (0%) | 0 | 0/213 (0%) | 0 | 1/601 (0.2%) | 1 | 0/262 (0%) | 0 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Alkalosis | 0/218 (0%) | 0 | 0/90 (0%) | 0 | 0/261 (0%) | 0 | 0/206 (0%) | 0 | 3/214 (1.4%) | 3 | 3/598 (0.5%) | 3 | 1/213 (0.5%) | 1 | 1/601 (0.2%) | 1 | 0/262 (0%) | 0 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Anorexia | 16/218 (7.3%) | 21 | 17/90 (18.9%) | 19 | 43/261 (16.5%) | 68 | 21/206 (10.2%) | 30 | 18/214 (8.4%) | 32 | 51/598 (8.5%) | 68 | 15/213 (7%) | 21 | 38/601 (6.3%) | 53 | 20/262 (7.6%) | 24 | 4/30 (13.3%) | 4 | 4/9 (44.4%) | 4 | 4/23 (17.4%) | 4 |
| Dehydration | 9/218 (4.1%) | 12 | 13/90 (14.4%) | 21 | 34/261 (13%) | 41 | 21/206 (10.2%) | 27 | 17/214 (7.9%) | 19 | 73/598 (12.2%) | 85 | 20/213 (9.4%) | 22 | 59/601 (9.8%) | 71 | 30/262 (11.5%) | 37 | 5/30 (16.7%) | 6 | 3/9 (33.3%) | 3 | 3/23 (13%) | 3 |
| Glucose intolerance | 1/218 (0.5%) | 1 | 6/90 (6.7%) | 9 | 8/261 (3.1%) | 9 | 0/206 (0%) | 0 | 1/214 (0.5%) | 1 | 17/598 (2.8%) | 20 | 0/213 (0%) | 0 | 22/601 (3.7%) | 24 | 11/262 (4.2%) | 11 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 1/23 (4.3%) | 1 |
| Hypercalcemia | 0/218 (0%) | 0 | 2/90 (2.2%) | 2 | 6/261 (2.3%) | 6 | 2/206 (1%) | 2 | 0/214 (0%) | 0 | 6/598 (1%) | 7 | 0/213 (0%) | 0 | 4/601 (0.7%) | 4 | 6/262 (2.3%) | 8 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Hyperglycemia | 28/218 (12.8%) | 28 | 20/90 (22.2%) | 33 | 84/261 (32.2%) | 126 | 24/206 (11.7%) | 26 | 21/214 (9.8%) | 23 | 155/598 (25.9%) | 214 | 20/213 (9.4%) | 25 | 159/601 (26.5%) | 222 | 86/262 (32.8%) | 131 | 14/30 (46.7%) | 29 | 6/9 (66.7%) | 9 | 3/23 (13%) | 4 |
| Hyperkalemia | 5/218 (2.3%) | 5 | 8/90 (8.9%) | 8 | 13/261 (5%) | 13 | 4/206 (1.9%) | 5 | 5/214 (2.3%) | 5 | 23/598 (3.8%) | 28 | 6/213 (2.8%) | 6 | 19/601 (3.2%) | 19 | 10/262 (3.8%) | 11 | 6/30 (20%) | 7 | 1/9 (11.1%) | 2 | 0/23 (0%) | 0 |
| Hypermagnesemia | 2/218 (0.9%) | 2 | 1/90 (1.1%) | 1 | 8/261 (3.1%) | 8 | 0/206 (0%) | 0 | 2/214 (0.9%) | 2 | 4/598 (0.7%) | 4 | 2/213 (0.9%) | 2 | 7/601 (1.2%) | 7 | 4/262 (1.5%) | 4 | 0/30 (0%) | 0 | 1/9 (11.1%) | 1 | 0/23 (0%) | 0 |
| Hypernatremia | 0/218 (0%) | 0 | 4/90 (4.4%) | 5 | 4/261 (1.5%) | 4 | 1/206 (0.5%) | 1 | 2/214 (0.9%) | 2 | 6/598 (1%) | 6 | 0/213 (0%) | 0 | 4/601 (0.7%) | 4 | 2/262 (0.8%) | 2 | 2/30 (6.7%) | 2 | 2/9 (22.2%) | 2 | 1/23 (4.3%) | 1 |
| Hypertriglyceridemia | 1/218 (0.5%) | 1 | 4/90 (4.4%) | 6 | 10/261 (3.8%) | 14 | 0/206 (0%) | 0 | 5/214 (2.3%) | 6 | 13/598 (2.2%) | 16 | 0/213 (0%) | 0 | 13/601 (2.2%) | 18 | 10/262 (3.8%) | 12 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Hyperuricemia | 2/218 (0.9%) | 2 | 2/90 (2.2%) | 2 | 3/261 (1.1%) | 4 | 2/206 (1%) | 2 | 2/214 (0.9%) | 2 | 11/598 (1.8%) | 12 | 1/213 (0.5%) | 1 | 7/601 (1.2%) | 7 | 3/262 (1.1%) | 3 | 0/30 (0%) | 0 | 1/9 (11.1%) | 1 | 1/23 (4.3%) | 1 |
| Hypoalbuminemia | 19/218 (8.7%) | 25 | 10/90 (11.1%) | 12 | 24/261 (9.2%) | 33 | 11/206 (5.3%) | 14 | 8/214 (3.7%) | 9 | 37/598 (6.2%) | 45 | 6/213 (2.8%) | 6 | 28/601 (4.7%) | 32 | 16/262 (6.1%) | 19 | 5/30 (16.7%) | 11 | 3/9 (33.3%) | 4 | 0/23 (0%) | 0 |
| Hypocalcemia | 21/218 (9.6%) | 23 | 14/90 (15.6%) | 15 | 26/261 (10%) | 31 | 15/206 (7.3%) | 20 | 11/214 (5.1%) | 12 | 56/598 (9.4%) | 58 | 5/213 (2.3%) | 5 | 51/601 (8.5%) | 54 | 32/262 (12.2%) | 38 | 6/30 (20%) | 7 | 4/9 (44.4%) | 6 | 2/23 (8.7%) | 2 |
| Hypoglycemia | 8/218 (3.7%) | 10 | 3/90 (3.3%) | 3 | 4/261 (1.5%) | 4 | 7/206 (3.4%) | 7 | 13/214 (6.1%) | 14 | 6/598 (1%) | 9 | 8/213 (3.8%) | 9 | 7/601 (1.2%) | 9 | 3/262 (1.1%) | 3 | 1/30 (3.3%) | 1 | 1/9 (11.1%) | 1 | 1/23 (4.3%) | 1 |
| Hypokalemia | 30/218 (13.8%) | 43 | 33/90 (36.7%) | 60 | 49/261 (18.8%) | 68 | 42/206 (20.4%) | 60 | 30/214 (14%) | 39 | 98/598 (16.4%) | 127 | 48/213 (22.5%) | 69 | 126/601 (21%) | 170 | 59/262 (22.5%) | 78 | 6/30 (20%) | 8 | 4/9 (44.4%) | 5 | 6/23 (26.1%) | 7 |
| Hypomagnesemia | 1/218 (0.5%) | 1 | 2/90 (2.2%) | 2 | 3/261 (1.1%) | 3 | 1/206 (0.5%) | 1 | 0/214 (0%) | 0 | 3/598 (0.5%) | 3 | 0/213 (0%) | 0 | 4/601 (0.7%) | 5 | 5/262 (1.9%) | 5 | 1/30 (3.3%) | 1 | 0/9 (0%) | 0 | 1/23 (4.3%) | 1 |
| Hyponatremia | 34/218 (15.6%) | 36 | 22/90 (24.4%) | 27 | 46/261 (17.6%) | 54 | 26/206 (12.6%) | 31 | 20/214 (9.3%) | 23 | 84/598 (14%) | 100 | 19/213 (8.9%) | 21 | 78/601 (13%) | 89 | 51/262 (19.5%) | 63 | 5/30 (16.7%) | 6 | 4/9 (44.4%) | 5 | 3/23 (13%) | 3 |
| Hypophosphatemia | 6/218 (2.8%) | 6 | 8/90 (8.9%) | 9 | 15/261 (5.7%) | 20 | 6/206 (2.9%) | 6 | 2/214 (0.9%) | 2 | 34/598 (5.7%) | 36 | 6/213 (2.8%) | 6 | 15/601 (2.5%) | 18 | 13/262 (5%) | 13 | 1/30 (3.3%) | 1 | 1/9 (11.1%) | 1 | 2/23 (8.7%) | 2 |
| Iron overload | 0/218 (0%) | 0 | 0/90 (0%) | 0 | 2/261 (0.8%) | 3 | 0/206 (0%) | 0 | 0/214 (0%) | 0 | 4/598 (0.7%) | 11 | 1/213 (0.5%) | 1 | 3/601 (0.5%) | 4 | 2/262 (0.8%) | 5 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Obesity | 0/218 (0%) | 0 | 0/90 (0%) | 0 | 1/261 (0.4%) | 1 | 0/206 (0%) | 0 | 0/214 (0%) | 0 | 2/598 (0.3%) | 3 | 0/213 (0%) | 0 | 4/601 (0.7%) | 17 | 4/262 (1.5%) | 11 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Tumor lysis syndrome | 1/218 (0.5%) | 1 | 2/90 (2.2%) | 2 | 8/261 (3.1%) | 8 | 4/206 (1.9%) | 4 | 3/214 (1.4%) | 3 | 14/598 (2.3%) | 14 | 1/213 (0.5%) | 1 | 12/601 (2%) | 12 | 11/262 (4.2%) | 11 | 2/30 (6.7%) | 2 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Musculoskeletal and connective tissue disorders | ||||||||||||||||||||||||
| Arthralgia | 1/218 (0.5%) | 1 | 3/90 (3.3%) | 13 | 12/261 (4.6%) | 14 | 2/206 (1%) | 2 | 1/214 (0.5%) | 1 | 22/598 (3.7%) | 22 | 1/213 (0.5%) | 1 | 17/601 (2.8%) | 19 | 11/262 (4.2%) | 13 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Avascular necrosis | 1/218 (0.5%) | 1 | 6/90 (6.7%) | 20 | 19/261 (7.3%) | 22 | 1/206 (0.5%) | 1 | 3/214 (1.4%) | 7 | 26/598 (4.3%) | 35 | 1/213 (0.5%) | 1 | 35/601 (5.8%) | 53 | 22/262 (8.4%) | 33 | 1/30 (3.3%) | 2 | 0/9 (0%) | 0 | 1/23 (4.3%) | 1 |
| Back pain | 2/218 (0.9%) | 2 | 6/90 (6.7%) | 6 | 18/261 (6.9%) | 19 | 1/206 (0.5%) | 1 | 3/214 (1.4%) | 3 | 44/598 (7.4%) | 51 | 3/213 (1.4%) | 3 | 34/601 (5.7%) | 39 | 20/262 (7.6%) | 23 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 1/23 (4.3%) | 1 |
| Bone pain | 1/218 (0.5%) | 1 | 0/90 (0%) | 0 | 10/261 (3.8%) | 11 | 0/206 (0%) | 0 | 1/214 (0.5%) | 1 | 11/598 (1.8%) | 14 | 1/213 (0.5%) | 1 | 14/601 (2.3%) | 15 | 2/262 (0.8%) | 2 | 1/30 (3.3%) | 1 | 1/9 (11.1%) | 1 | 1/23 (4.3%) | 1 |
| Buttock pain | 0/218 (0%) | 0 | 0/90 (0%) | 0 | 0/261 (0%) | 0 | 2/206 (1%) | 2 | 0/214 (0%) | 0 | 0/598 (0%) | 0 | 0/213 (0%) | 0 | 1/601 (0.2%) | 1 | 0/262 (0%) | 0 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Chest wall pain | 0/218 (0%) | 0 | 0/90 (0%) | 0 | 0/261 (0%) | 0 | 0/206 (0%) | 0 | 0/214 (0%) | 0 | 2/598 (0.3%) | 2 | 0/213 (0%) | 0 | 2/601 (0.3%) | 2 | 1/262 (0.4%) | 1 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Generalized muscle weakness | 1/218 (0.5%) | 1 | 0/90 (0%) | 0 | 0/261 (0%) | 0 | 1/206 (0.5%) | 1 | 1/214 (0.5%) | 2 | 3/598 (0.5%) | 3 | 0/213 (0%) | 0 | 5/601 (0.8%) | 6 | 0/262 (0%) | 0 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Joint effusion | 0/218 (0%) | 0 | 0/90 (0%) | 0 | 1/261 (0.4%) | 1 | 0/206 (0%) | 0 | 0/214 (0%) | 0 | 3/598 (0.5%) | 3 | 1/213 (0.5%) | 1 | 2/601 (0.3%) | 2 | 4/262 (1.5%) | 6 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Joint range of motion decreased | 0/218 (0%) | 0 | 0/90 (0%) | 0 | 1/261 (0.4%) | 1 | 0/206 (0%) | 0 | 0/214 (0%) | 0 | 0/598 (0%) | 0 | 0/213 (0%) | 0 | 1/601 (0.2%) | 1 | 0/262 (0%) | 0 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Joint range of motion decreased lumbar spine | 0/218 (0%) | 0 | 0/90 (0%) | 0 | 0/261 (0%) | 0 | 0/206 (0%) | 0 | 0/214 (0%) | 0 | 1/598 (0.2%) | 1 | 0/213 (0%) | 0 | 0/601 (0%) | 0 | 0/262 (0%) | 0 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Muscle weakness left-sided | 0/218 (0%) | 0 | 0/90 (0%) | 0 | 0/261 (0%) | 0 | 0/206 (0%) | 0 | 0/214 (0%) | 0 | 3/598 (0.5%) | 3 | 1/213 (0.5%) | 5 | 1/601 (0.2%) | 1 | 1/262 (0.4%) | 1 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Muscle weakness lower limb | 0/218 (0%) | 0 | 0/90 (0%) | 0 | 3/261 (1.1%) | 3 | 1/206 (0.5%) | 1 | 1/214 (0.5%) | 1 | 7/598 (1.2%) | 8 | 2/213 (0.9%) | 2 | 6/601 (1%) | 9 | 5/262 (1.9%) | 11 | 1/30 (3.3%) | 1 | 1/9 (11.1%) | 1 | 1/23 (4.3%) | 1 |
| Muscle weakness right-sided | 0/218 (0%) | 0 | 0/90 (0%) | 0 | 0/261 (0%) | 0 | 0/206 (0%) | 0 | 0/214 (0%) | 0 | 3/598 (0.5%) | 3 | 0/213 (0%) | 0 | 3/601 (0.5%) | 4 | 1/262 (0.4%) | 1 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Muscle weakness upper limb | 0/218 (0%) | 0 | 1/90 (1.1%) | 1 | 1/261 (0.4%) | 1 | 1/206 (0.5%) | 1 | 0/214 (0%) | 0 | 2/598 (0.3%) | 2 | 0/213 (0%) | 0 | 3/601 (0.5%) | 3 | 0/262 (0%) | 0 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Musculoskeletal and connective tissue disorder - Other, specify | 1/218 (0.5%) | 1 | 0/90 (0%) | 0 | 2/261 (0.8%) | 2 | 0/206 (0%) | 0 | 0/214 (0%) | 0 | 0/598 (0%) | 0 | 0/213 (0%) | 0 | 1/601 (0.2%) | 1 | 0/262 (0%) | 0 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Myalgia | 0/218 (0%) | 0 | 1/90 (1.1%) | 1 | 1/261 (0.4%) | 1 | 1/206 (0.5%) | 1 | 0/214 (0%) | 0 | 2/598 (0.3%) | 2 | 2/213 (0.9%) | 2 | 4/601 (0.7%) | 4 | 5/262 (1.9%) | 6 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Myositis | 0/218 (0%) | 0 | 1/90 (1.1%) | 1 | 3/261 (1.1%) | 3 | 0/206 (0%) | 0 | 1/214 (0.5%) | 1 | 2/598 (0.3%) | 2 | 1/213 (0.5%) | 1 | 2/601 (0.3%) | 2 | 2/262 (0.8%) | 2 | 0/30 (0%) | 0 | 1/9 (11.1%) | 1 | 0/23 (0%) | 0 |
| Neck pain | 1/218 (0.5%) | 1 | 1/90 (1.1%) | 1 | 1/261 (0.4%) | 1 | 0/206 (0%) | 0 | 0/214 (0%) | 0 | 3/598 (0.5%) | 4 | 0/213 (0%) | 0 | 3/601 (0.5%) | 4 | 1/262 (0.4%) | 1 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Neck soft tissue necrosis | 0/218 (0%) | 0 | 0/90 (0%) | 0 | 0/261 (0%) | 0 | 0/206 (0%) | 0 | 0/214 (0%) | 0 | 0/598 (0%) | 0 | 0/213 (0%) | 0 | 1/601 (0.2%) | 1 | 0/262 (0%) | 0 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Osteoporosis | 0/218 (0%) | 0 | 1/90 (1.1%) | 1 | 1/261 (0.4%) | 1 | 0/206 (0%) | 0 | 0/214 (0%) | 0 | 0/598 (0%) | 0 | 1/213 (0.5%) | 3 | 1/601 (0.2%) | 1 | 2/262 (0.8%) | 2 | 2/30 (6.7%) | 2 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Pain in extremity | 4/218 (1.8%) | 4 | 5/90 (5.6%) | 7 | 13/261 (5%) | 15 | 2/206 (1%) | 2 | 8/214 (3.7%) | 8 | 22/598 (3.7%) | 24 | 4/213 (1.9%) | 4 | 27/601 (4.5%) | 33 | 17/262 (6.5%) | 19 | 1/30 (3.3%) | 1 | 1/9 (11.1%) | 1 | 0/23 (0%) | 0 |
| Soft tissue necrosis upper limb | 0/218 (0%) | 0 | 0/90 (0%) | 0 | 0/261 (0%) | 0 | 0/206 (0%) | 0 | 0/214 (0%) | 0 | 0/598 (0%) | 0 | 0/213 (0%) | 0 | 0/601 (0%) | 0 | 0/262 (0%) | 0 | 0/30 (0%) | 0 | 1/9 (11.1%) | 1 | 0/23 (0%) | 0 |
| Trismus | 0/218 (0%) | 0 | 1/90 (1.1%) | 1 | 0/261 (0%) | 0 | 0/206 (0%) | 0 | 0/214 (0%) | 0 | 0/598 (0%) | 0 | 0/213 (0%) | 0 | 0/601 (0%) | 0 | 0/262 (0%) | 0 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||||||||||||||||||||
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) - Other, specify | 0/218 (0%) | 0 | 0/90 (0%) | 0 | 0/261 (0%) | 0 | 0/206 (0%) | 0 | 0/214 (0%) | 0 | 0/598 (0%) | 0 | 0/213 (0%) | 0 | 0/601 (0%) | 0 | 1/262 (0.4%) | 1 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Treatment related secondary malignancy | 0/218 (0%) | 0 | 0/90 (0%) | 0 | 0/261 (0%) | 0 | 0/206 (0%) | 0 | 0/214 (0%) | 0 | 2/598 (0.3%) | 2 | 0/213 (0%) | 0 | 0/601 (0%) | 0 | 0/262 (0%) | 0 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Nervous system disorders | ||||||||||||||||||||||||
| Accessory nerve disorder | 0/218 (0%) | 0 | 0/90 (0%) | 0 | 0/261 (0%) | 0 | 0/206 (0%) | 0 | 0/214 (0%) | 0 | 0/598 (0%) | 0 | 0/213 (0%) | 0 | 1/601 (0.2%) | 1 | 1/262 (0.4%) | 1 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Arachnoiditis | 0/218 (0%) | 0 | 0/90 (0%) | 0 | 0/261 (0%) | 0 | 0/206 (0%) | 0 | 0/214 (0%) | 0 | 4/598 (0.7%) | 4 | 0/213 (0%) | 0 | 3/601 (0.5%) | 3 | 0/262 (0%) | 0 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Ataxia | 0/218 (0%) | 0 | 1/90 (1.1%) | 1 | 0/261 (0%) | 0 | 1/206 (0.5%) | 1 | 1/214 (0.5%) | 1 | 5/598 (0.8%) | 5 | 1/213 (0.5%) | 1 | 5/601 (0.8%) | 5 | 1/262 (0.4%) | 1 | 1/30 (3.3%) | 1 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Central nervous system necrosis | 0/218 (0%) | 0 | 0/90 (0%) | 0 | 1/261 (0.4%) | 1 | 0/206 (0%) | 0 | 0/214 (0%) | 0 | 0/598 (0%) | 0 | 0/213 (0%) | 0 | 0/601 (0%) | 0 | 0/262 (0%) | 0 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Cerebrospinal fluid leakage | 0/218 (0%) | 0 | 0/90 (0%) | 0 | 1/261 (0.4%) | 1 | 0/206 (0%) | 0 | 0/214 (0%) | 0 | 2/598 (0.3%) | 2 | 0/213 (0%) | 0 | 2/601 (0.3%) | 2 | 3/262 (1.1%) | 3 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Cognitive disturbance | 0/218 (0%) | 0 | 1/90 (1.1%) | 1 | 0/261 (0%) | 0 | 0/206 (0%) | 0 | 0/214 (0%) | 0 | 1/598 (0.2%) | 1 | 0/213 (0%) | 0 | 2/601 (0.3%) | 2 | 4/262 (1.5%) | 4 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Depressed level of consciousness | 3/218 (1.4%) | 3 | 2/90 (2.2%) | 2 | 1/261 (0.4%) | 1 | 2/206 (1%) | 2 | 1/214 (0.5%) | 1 | 8/598 (1.3%) | 8 | 0/213 (0%) | 0 | 6/601 (1%) | 6 | 1/262 (0.4%) | 1 | 1/30 (3.3%) | 1 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Dizziness | 0/218 (0%) | 0 | 1/90 (1.1%) | 2 | 2/261 (0.8%) | 2 | 0/206 (0%) | 0 | 0/214 (0%) | 0 | 4/598 (0.7%) | 4 | 0/213 (0%) | 0 | 6/601 (1%) | 7 | 5/262 (1.9%) | 5 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Dysarthria | 0/218 (0%) | 0 | 0/90 (0%) | 0 | 0/261 (0%) | 0 | 0/206 (0%) | 0 | 0/214 (0%) | 0 | 1/598 (0.2%) | 1 | 0/213 (0%) | 0 | 1/601 (0.2%) | 1 | 0/262 (0%) | 0 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Dysphasia | 1/218 (0.5%) | 1 | 2/90 (2.2%) | 2 | 4/261 (1.5%) | 4 | 1/206 (0.5%) | 2 | 1/214 (0.5%) | 1 | 15/598 (2.5%) | 15 | 2/213 (0.9%) | 7 | 18/601 (3%) | 19 | 3/262 (1.1%) | 3 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Encephalopathy | 2/218 (0.9%) | 2 | 4/90 (4.4%) | 5 | 7/261 (2.7%) | 7 | 1/206 (0.5%) | 1 | 3/214 (1.4%) | 3 | 16/598 (2.7%) | 16 | 1/213 (0.5%) | 1 | 14/601 (2.3%) | 15 | 7/262 (2.7%) | 7 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 3/23 (13%) | 3 |
| Extrapyramidal disorder | 0/218 (0%) | 0 | 0/90 (0%) | 0 | 0/261 (0%) | 0 | 0/206 (0%) | 0 | 0/214 (0%) | 0 | 1/598 (0.2%) | 1 | 0/213 (0%) | 0 | 2/601 (0.3%) | 3 | 0/262 (0%) | 0 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Facial muscle weakness | 0/218 (0%) | 0 | 0/90 (0%) | 0 | 0/261 (0%) | 0 | 0/206 (0%) | 0 | 0/214 (0%) | 0 | 2/598 (0.3%) | 2 | 0/213 (0%) | 0 | 1/601 (0.2%) | 1 | 1/262 (0.4%) | 1 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Facial nerve disorder | 0/218 (0%) | 0 | 2/90 (2.2%) | 2 | 3/261 (1.1%) | 3 | 0/206 (0%) | 0 | 0/214 (0%) | 0 | 2/598 (0.3%) | 2 | 0/213 (0%) | 0 | 4/601 (0.7%) | 4 | 1/262 (0.4%) | 1 | 1/30 (3.3%) | 1 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Glossopharyngeal nerve disorder | 0/218 (0%) | 0 | 1/90 (1.1%) | 1 | 0/261 (0%) | 0 | 0/206 (0%) | 0 | 0/214 (0%) | 0 | 1/598 (0.2%) | 1 | 0/213 (0%) | 0 | 1/601 (0.2%) | 1 | 1/262 (0.4%) | 1 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Headache | 3/218 (1.4%) | 4 | 11/90 (12.2%) | 17 | 34/261 (13%) | 45 | 2/206 (1%) | 2 | 2/214 (0.9%) | 3 | 81/598 (13.5%) | 115 | 4/213 (1.9%) | 4 | 74/601 (12.3%) | 104 | 31/262 (11.8%) | 40 | 2/30 (6.7%) | 3 | 0/9 (0%) | 0 | 2/23 (8.7%) | 2 |
| Hydrocephalus | 0/218 (0%) | 0 | 2/90 (2.2%) | 2 | 0/261 (0%) | 0 | 0/206 (0%) | 0 | 0/214 (0%) | 0 | 1/598 (0.2%) | 1 | 0/213 (0%) | 0 | 2/601 (0.3%) | 2 | 0/262 (0%) | 0 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Hypersomnia | 0/218 (0%) | 0 | 0/90 (0%) | 0 | 0/261 (0%) | 0 | 0/206 (0%) | 0 | 0/214 (0%) | 0 | 0/598 (0%) | 0 | 0/213 (0%) | 0 | 1/601 (0.2%) | 1 | 0/262 (0%) | 0 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Hypoglossal nerve disorder | 0/218 (0%) | 0 | 0/90 (0%) | 0 | 0/261 (0%) | 0 | 0/206 (0%) | 0 | 0/214 (0%) | 0 | 2/598 (0.3%) | 2 | 0/213 (0%) | 0 | 0/601 (0%) | 0 | 2/262 (0.8%) | 2 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 1/23 (4.3%) | 1 |
| Intracranial hemorrhage | 0/218 (0%) | 0 | 0/90 (0%) | 0 | 2/261 (0.8%) | 2 | 1/206 (0.5%) | 1 | 2/214 (0.9%) | 2 | 0/598 (0%) | 0 | 1/213 (0.5%) | 2 | 4/601 (0.7%) | 4 | 3/262 (1.1%) | 3 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Leukoencephalopathy | 1/218 (0.5%) | 1 | 1/90 (1.1%) | 1 | 0/261 (0%) | 0 | 1/206 (0.5%) | 1 | 1/214 (0.5%) | 1 | 1/598 (0.2%) | 1 | 1/213 (0.5%) | 1 | 2/601 (0.3%) | 3 | 2/262 (0.8%) | 2 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Memory impairment | 0/218 (0%) | 0 | 0/90 (0%) | 0 | 0/261 (0%) | 0 | 0/206 (0%) | 0 | 0/214 (0%) | 0 | 0/598 (0%) | 0 | 0/213 (0%) | 0 | 1/601 (0.2%) | 1 | 2/262 (0.8%) | 3 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Myelitis | 0/218 (0%) | 0 | 1/90 (1.1%) | 1 | 0/261 (0%) | 0 | 0/206 (0%) | 0 | 0/214 (0%) | 0 | 0/598 (0%) | 0 | 0/213 (0%) | 0 | 0/601 (0%) | 0 | 0/262 (0%) | 0 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Nervous system disorders - Other, specify | 3/218 (1.4%) | 3 | 1/90 (1.1%) | 1 | 7/261 (2.7%) | 7 | 2/206 (1%) | 2 | 0/214 (0%) | 0 | 12/598 (2%) | 12 | 2/213 (0.9%) | 3 | 13/601 (2.2%) | 15 | 6/262 (2.3%) | 6 | 1/30 (3.3%) | 2 | 0/9 (0%) | 0 | 1/23 (4.3%) | 1 |
| Neuralgia | 4/218 (1.8%) | 4 | 1/90 (1.1%) | 1 | 0/261 (0%) | 0 | 3/206 (1.5%) | 4 | 2/214 (0.9%) | 2 | 2/598 (0.3%) | 2 | 0/213 (0%) | 0 | 4/601 (0.7%) | 5 | 4/262 (1.5%) | 4 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Nystagmus | 0/218 (0%) | 0 | 0/90 (0%) | 0 | 1/261 (0.4%) | 1 | 0/206 (0%) | 0 | 1/214 (0.5%) | 1 | 0/598 (0%) | 0 | 0/213 (0%) | 0 | 1/601 (0.2%) | 1 | 0/262 (0%) | 0 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Oculomotor nerve disorder | 0/218 (0%) | 0 | 1/90 (1.1%) | 1 | 0/261 (0%) | 0 | 0/206 (0%) | 0 | 1/214 (0.5%) | 1 | 1/598 (0.2%) | 1 | 0/213 (0%) | 0 | 0/601 (0%) | 0 | 0/262 (0%) | 0 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Paresthesia | 0/218 (0%) | 0 | 0/90 (0%) | 0 | 0/261 (0%) | 0 | 0/206 (0%) | 0 | 0/214 (0%) | 0 | 1/598 (0.2%) | 1 | 0/213 (0%) | 0 | 1/601 (0.2%) | 1 | 0/262 (0%) | 0 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Peripheral motor neuropathy | 12/218 (5.5%) | 21 | 12/90 (13.3%) | 14 | 34/261 (13%) | 67 | 10/206 (4.9%) | 20 | 13/214 (6.1%) | 18 | 68/598 (11.4%) | 100 | 6/213 (2.8%) | 16 | 54/601 (9%) | 97 | 31/262 (11.8%) | 60 | 5/30 (16.7%) | 9 | 1/9 (11.1%) | 1 | 5/23 (21.7%) | 8 |
| Peripheral sensory neuropathy | 11/218 (5%) | 20 | 7/90 (7.8%) | 10 | 22/261 (8.4%) | 27 | 8/206 (3.9%) | 10 | 4/214 (1.9%) | 4 | 42/598 (7%) | 64 | 9/213 (4.2%) | 18 | 37/601 (6.2%) | 62 | 15/262 (5.7%) | 19 | 1/30 (3.3%) | 2 | 0/9 (0%) | 0 | 3/23 (13%) | 4 |
| Pyramidal tract syndrome | 0/218 (0%) | 0 | 0/90 (0%) | 0 | 0/261 (0%) | 0 | 0/206 (0%) | 0 | 0/214 (0%) | 0 | 0/598 (0%) | 0 | 0/213 (0%) | 0 | 1/601 (0.2%) | 1 | 0/262 (0%) | 0 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Seizure | 3/218 (1.4%) | 3 | 3/90 (3.3%) | 3 | 9/261 (3.4%) | 10 | 4/206 (1.9%) | 4 | 3/214 (1.4%) | 4 | 19/598 (3.2%) | 21 | 5/213 (2.3%) | 5 | 15/601 (2.5%) | 18 | 5/262 (1.9%) | 5 | 2/30 (6.7%) | 2 | 2/9 (22.2%) | 2 | 1/23 (4.3%) | 1 |
| Stroke | 0/218 (0%) | 0 | 0/90 (0%) | 0 | 0/261 (0%) | 0 | 0/206 (0%) | 0 | 0/214 (0%) | 0 | 1/598 (0.2%) | 1 | 0/213 (0%) | 0 | 1/601 (0.2%) | 1 | 0/262 (0%) | 0 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Syncope | 1/218 (0.5%) | 1 | 2/90 (2.2%) | 3 | 7/261 (2.7%) | 8 | 0/206 (0%) | 0 | 1/214 (0.5%) | 1 | 17/598 (2.8%) | 19 | 3/213 (1.4%) | 3 | 14/601 (2.3%) | 15 | 4/262 (1.5%) | 4 | 1/30 (3.3%) | 1 | 1/9 (11.1%) | 1 | 1/23 (4.3%) | 1 |
| Tremor | 0/218 (0%) | 0 | 0/90 (0%) | 0 | 0/261 (0%) | 0 | 0/206 (0%) | 0 | 1/214 (0.5%) | 1 | 1/598 (0.2%) | 1 | 0/213 (0%) | 0 | 1/601 (0.2%) | 1 | 1/262 (0.4%) | 1 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Trigeminal nerve disorder | 0/218 (0%) | 0 | 0/90 (0%) | 0 | 1/261 (0.4%) | 1 | 1/206 (0.5%) | 1 | 0/214 (0%) | 0 | 2/598 (0.3%) | 2 | 0/213 (0%) | 0 | 2/601 (0.3%) | 2 | 0/262 (0%) | 0 | 1/30 (3.3%) | 1 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Vagus nerve disorder | 0/218 (0%) | 0 | 0/90 (0%) | 0 | 0/261 (0%) | 0 | 0/206 (0%) | 0 | 1/214 (0.5%) | 1 | 1/598 (0.2%) | 1 | 0/213 (0%) | 0 | 2/601 (0.3%) | 2 | 2/262 (0.8%) | 2 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Vasovagal reaction | 0/218 (0%) | 0 | 0/90 (0%) | 0 | 1/261 (0.4%) | 1 | 0/206 (0%) | 0 | 1/214 (0.5%) | 1 | 1/598 (0.2%) | 1 | 0/213 (0%) | 0 | 4/601 (0.7%) | 4 | 0/262 (0%) | 0 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Psychiatric disorders | ||||||||||||||||||||||||
| Agitation | 2/218 (0.9%) | 2 | 2/90 (2.2%) | 2 | 0/261 (0%) | 0 | 3/206 (1.5%) | 3 | 2/214 (0.9%) | 2 | 6/598 (1%) | 8 | 3/213 (1.4%) | 3 | 4/601 (0.7%) | 5 | 0/262 (0%) | 0 | 1/30 (3.3%) | 1 | 0/9 (0%) | 0 | 1/23 (4.3%) | 1 |
| Anxiety | 0/218 (0%) | 0 | 3/90 (3.3%) | 4 | 7/261 (2.7%) | 8 | 2/206 (1%) | 3 | 0/214 (0%) | 0 | 4/598 (0.7%) | 4 | 0/213 (0%) | 0 | 12/601 (2%) | 16 | 2/262 (0.8%) | 2 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Confusion | 0/218 (0%) | 0 | 3/90 (3.3%) | 3 | 4/261 (1.5%) | 4 | 1/206 (0.5%) | 1 | 0/214 (0%) | 0 | 4/598 (0.7%) | 4 | 0/213 (0%) | 0 | 5/601 (0.8%) | 5 | 1/262 (0.4%) | 1 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 1/23 (4.3%) | 1 |
| Delirium | 0/218 (0%) | 0 | 0/90 (0%) | 0 | 0/261 (0%) | 0 | 0/206 (0%) | 0 | 0/214 (0%) | 0 | 1/598 (0.2%) | 1 | 0/213 (0%) | 0 | 0/601 (0%) | 0 | 0/262 (0%) | 0 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Depression | 2/218 (0.9%) | 2 | 2/90 (2.2%) | 2 | 15/261 (5.7%) | 23 | 2/206 (1%) | 2 | 1/214 (0.5%) | 3 | 15/598 (2.5%) | 16 | 0/213 (0%) | 0 | 10/601 (1.7%) | 14 | 7/262 (2.7%) | 8 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Euphoria | 1/218 (0.5%) | 1 | 0/90 (0%) | 0 | 0/261 (0%) | 0 | 0/206 (0%) | 0 | 0/214 (0%) | 0 | 0/598 (0%) | 0 | 0/213 (0%) | 0 | 0/601 (0%) | 0 | 0/262 (0%) | 0 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Hallucinations | 0/218 (0%) | 0 | 0/90 (0%) | 0 | 0/261 (0%) | 0 | 0/206 (0%) | 0 | 0/214 (0%) | 0 | 1/598 (0.2%) | 1 | 0/213 (0%) | 0 | 0/601 (0%) | 0 | 0/262 (0%) | 0 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Insomnia | 1/218 (0.5%) | 1 | 2/90 (2.2%) | 3 | 3/261 (1.1%) | 4 | 2/206 (1%) | 2 | 1/214 (0.5%) | 1 | 3/598 (0.5%) | 3 | 2/213 (0.9%) | 2 | 2/601 (0.3%) | 2 | 3/262 (1.1%) | 4 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Personality change | 1/218 (0.5%) | 1 | 1/90 (1.1%) | 1 | 5/261 (1.9%) | 5 | 1/206 (0.5%) | 1 | 0/214 (0%) | 0 | 7/598 (1.2%) | 7 | 2/213 (0.9%) | 2 | 6/601 (1%) | 6 | 0/262 (0%) | 0 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Psychiatric disorders - Other, specify | 0/218 (0%) | 0 | 0/90 (0%) | 0 | 0/261 (0%) | 0 | 0/206 (0%) | 0 | 0/214 (0%) | 0 | 4/598 (0.7%) | 4 | 0/213 (0%) | 0 | 2/601 (0.3%) | 2 | 0/262 (0%) | 0 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Psychosis | 0/218 (0%) | 0 | 0/90 (0%) | 0 | 3/261 (1.1%) | 4 | 0/206 (0%) | 0 | 1/214 (0.5%) | 1 | 7/598 (1.2%) | 9 | 0/213 (0%) | 0 | 4/601 (0.7%) | 4 | 0/262 (0%) | 0 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Suicidal ideation | 0/218 (0%) | 0 | 0/90 (0%) | 0 | 0/261 (0%) | 0 | 0/206 (0%) | 0 | 0/214 (0%) | 0 | 0/598 (0%) | 0 | 0/213 (0%) | 0 | 1/601 (0.2%) | 1 | 0/262 (0%) | 0 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Suicide attempt | 0/218 (0%) | 0 | 0/90 (0%) | 0 | 0/261 (0%) | 0 | 0/206 (0%) | 0 | 0/214 (0%) | 0 | 1/598 (0.2%) | 1 | 0/213 (0%) | 0 | 1/601 (0.2%) | 1 | 0/262 (0%) | 0 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Renal and urinary disorders | ||||||||||||||||||||||||
| Acute kidney injury | 2/218 (0.9%) | 2 | 2/90 (2.2%) | 2 | 12/261 (4.6%) | 13 | 1/206 (0.5%) | 1 | 2/214 (0.9%) | 2 | 16/598 (2.7%) | 17 | 1/213 (0.5%) | 1 | 13/601 (2.2%) | 13 | 12/262 (4.6%) | 15 | 1/30 (3.3%) | 1 | 2/9 (22.2%) | 2 | 0/23 (0%) | 0 |
| Bladder spasm | 0/218 (0%) | 0 | 0/90 (0%) | 0 | 0/261 (0%) | 0 | 0/206 (0%) | 0 | 0/214 (0%) | 0 | 0/598 (0%) | 0 | 0/213 (0%) | 0 | 0/601 (0%) | 0 | 2/262 (0.8%) | 2 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Chronic kidney disease | 0/218 (0%) | 0 | 0/90 (0%) | 0 | 0/261 (0%) | 0 | 0/206 (0%) | 0 | 0/214 (0%) | 0 | 1/598 (0.2%) | 1 | 0/213 (0%) | 0 | 0/601 (0%) | 0 | 0/262 (0%) | 0 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Cystitis noninfective | 1/218 (0.5%) | 1 | 0/90 (0%) | 0 | 1/261 (0.4%) | 1 | 0/206 (0%) | 0 | 0/214 (0%) | 0 | 0/598 (0%) | 0 | 0/213 (0%) | 0 | 0/601 (0%) | 0 | 1/262 (0.4%) | 1 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Hematuria | 1/218 (0.5%) | 1 | 0/90 (0%) | 0 | 1/261 (0.4%) | 1 | 1/206 (0.5%) | 1 | 0/214 (0%) | 0 | 3/598 (0.5%) | 3 | 0/213 (0%) | 0 | 1/601 (0.2%) | 1 | 1/262 (0.4%) | 1 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Proteinuria | 0/218 (0%) | 0 | 0/90 (0%) | 0 | 2/261 (0.8%) | 2 | 1/206 (0.5%) | 1 | 0/214 (0%) | 0 | 1/598 (0.2%) | 1 | 0/213 (0%) | 0 | 1/601 (0.2%) | 2 | 0/262 (0%) | 0 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 1/23 (4.3%) | 1 |
| Renal and urinary disorders - Other, specify | 0/218 (0%) | 0 | 0/90 (0%) | 0 | 1/261 (0.4%) | 1 | 1/206 (0.5%) | 1 | 1/214 (0.5%) | 1 | 3/598 (0.5%) | 3 | 0/213 (0%) | 0 | 3/601 (0.5%) | 3 | 2/262 (0.8%) | 2 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Renal calculi | 0/218 (0%) | 0 | 0/90 (0%) | 0 | 0/261 (0%) | 0 | 0/206 (0%) | 0 | 0/214 (0%) | 0 | 2/598 (0.3%) | 3 | 0/213 (0%) | 0 | 1/601 (0.2%) | 1 | 0/262 (0%) | 0 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Renal colic | 0/218 (0%) | 0 | 0/90 (0%) | 0 | 0/261 (0%) | 0 | 0/206 (0%) | 0 | 0/214 (0%) | 0 | 1/598 (0.2%) | 1 | 0/213 (0%) | 0 | 0/601 (0%) | 0 | 0/262 (0%) | 0 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Urinary incontinence | 0/218 (0%) | 0 | 0/90 (0%) | 0 | 0/261 (0%) | 0 | 0/206 (0%) | 0 | 0/214 (0%) | 0 | 1/598 (0.2%) | 1 | 0/213 (0%) | 0 | 1/601 (0.2%) | 1 | 0/262 (0%) | 0 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Urinary retention | 0/218 (0%) | 0 | 0/90 (0%) | 0 | 0/261 (0%) | 0 | 0/206 (0%) | 0 | 0/214 (0%) | 0 | 1/598 (0.2%) | 1 | 0/213 (0%) | 0 | 0/601 (0%) | 0 | 1/262 (0.4%) | 1 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Urinary tract obstruction | 1/218 (0.5%) | 1 | 0/90 (0%) | 0 | 0/261 (0%) | 0 | 0/206 (0%) | 0 | 0/214 (0%) | 0 | 2/598 (0.3%) | 2 | 0/213 (0%) | 0 | 2/601 (0.3%) | 2 | 0/262 (0%) | 0 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Urinary tract pain | 0/218 (0%) | 0 | 0/90 (0%) | 0 | 1/261 (0.4%) | 1 | 0/206 (0%) | 0 | 2/214 (0.9%) | 2 | 1/598 (0.2%) | 1 | 0/213 (0%) | 0 | 1/601 (0.2%) | 1 | 1/262 (0.4%) | 2 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Reproductive system and breast disorders | ||||||||||||||||||||||||
| Breast pain | 0/218 (0%) | 0 | 0/90 (0%) | 0 | 0/261 (0%) | 0 | 0/206 (0%) | 0 | 0/214 (0%) | 0 | 0/598 (0%) | 0 | 0/213 (0%) | 0 | 1/601 (0.2%) | 1 | 0/262 (0%) | 0 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Female genital tract fistula | 0/218 (0%) | 0 | 0/90 (0%) | 0 | 0/261 (0%) | 0 | 0/206 (0%) | 0 | 0/214 (0%) | 0 | 0/598 (0%) | 0 | 0/213 (0%) | 0 | 1/601 (0.2%) | 1 | 0/262 (0%) | 0 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Gynecomastia | 0/218 (0%) | 0 | 0/90 (0%) | 0 | 0/261 (0%) | 0 | 0/206 (0%) | 0 | 0/214 (0%) | 0 | 0/598 (0%) | 0 | 0/213 (0%) | 0 | 1/601 (0.2%) | 2 | 0/262 (0%) | 0 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Pelvic floor muscle weakness | 0/218 (0%) | 0 | 0/90 (0%) | 0 | 0/261 (0%) | 0 | 0/206 (0%) | 0 | 0/214 (0%) | 0 | 0/598 (0%) | 0 | 0/213 (0%) | 0 | 0/601 (0%) | 0 | 1/262 (0.4%) | 1 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Pelvic pain | 0/218 (0%) | 0 | 0/90 (0%) | 0 | 0/261 (0%) | 0 | 0/206 (0%) | 0 | 0/214 (0%) | 0 | 2/598 (0.3%) | 2 | 0/213 (0%) | 0 | 1/601 (0.2%) | 1 | 0/262 (0%) | 0 | 2/30 (6.7%) | 2 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Penile pain | 0/218 (0%) | 0 | 0/90 (0%) | 0 | 0/261 (0%) | 0 | 0/206 (0%) | 0 | 1/214 (0.5%) | 1 | 0/598 (0%) | 0 | 1/213 (0.5%) | 1 | 0/601 (0%) | 0 | 0/262 (0%) | 0 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Perineal pain | 1/218 (0.5%) | 1 | 0/90 (0%) | 0 | 0/261 (0%) | 0 | 0/206 (0%) | 0 | 1/214 (0.5%) | 1 | 1/598 (0.2%) | 1 | 0/213 (0%) | 0 | 0/601 (0%) | 0 | 1/262 (0.4%) | 2 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Reproductive system and breast disorders - Other, specify | 0/218 (0%) | 0 | 0/90 (0%) | 0 | 0/261 (0%) | 0 | 0/206 (0%) | 0 | 0/214 (0%) | 0 | 1/598 (0.2%) | 1 | 0/213 (0%) | 0 | 0/601 (0%) | 0 | 0/262 (0%) | 0 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Testicular pain | 0/218 (0%) | 0 | 0/90 (0%) | 0 | 0/261 (0%) | 0 | 0/206 (0%) | 0 | 0/214 (0%) | 0 | 1/598 (0.2%) | 1 | 0/213 (0%) | 0 | 1/601 (0.2%) | 1 | 0/262 (0%) | 0 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Uterine hemorrhage | 0/218 (0%) | 0 | 0/90 (0%) | 0 | 0/261 (0%) | 0 | 0/206 (0%) | 0 | 0/214 (0%) | 0 | 0/598 (0%) | 0 | 0/213 (0%) | 0 | 0/601 (0%) | 0 | 1/262 (0.4%) | 1 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Vaginal hemorrhage | 0/218 (0%) | 0 | 0/90 (0%) | 0 | 1/261 (0.4%) | 1 | 0/206 (0%) | 0 | 0/214 (0%) | 0 | 0/598 (0%) | 0 | 0/213 (0%) | 0 | 0/601 (0%) | 0 | 0/262 (0%) | 0 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Vaginal pain | 0/218 (0%) | 0 | 0/90 (0%) | 0 | 0/261 (0%) | 0 | 0/206 (0%) | 0 | 1/214 (0.5%) | 1 | 0/598 (0%) | 0 | 0/213 (0%) | 0 | 0/601 (0%) | 0 | 0/262 (0%) | 0 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Respiratory, thoracic and mediastinal disorders | ||||||||||||||||||||||||
| Adult respiratory distress syndrome | 0/218 (0%) | 0 | 0/90 (0%) | 0 | 3/261 (1.1%) | 3 | 0/206 (0%) | 0 | 0/214 (0%) | 0 | 6/598 (1%) | 6 | 0/213 (0%) | 0 | 4/601 (0.7%) | 5 | 7/262 (2.7%) | 8 | 0/30 (0%) | 0 | 1/9 (11.1%) | 1 | 0/23 (0%) | 0 |
| Allergic rhinitis | 0/218 (0%) | 0 | 0/90 (0%) | 0 | 0/261 (0%) | 0 | 0/206 (0%) | 0 | 0/214 (0%) | 0 | 0/598 (0%) | 0 | 0/213 (0%) | 0 | 1/601 (0.2%) | 1 | 0/262 (0%) | 0 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Apnea | 0/218 (0%) | 0 | 1/90 (1.1%) | 1 | 0/261 (0%) | 0 | 1/206 (0.5%) | 1 | 0/214 (0%) | 0 | 2/598 (0.3%) | 2 | 1/213 (0.5%) | 1 | 2/601 (0.3%) | 2 | 0/262 (0%) | 0 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Aspiration | 0/218 (0%) | 0 | 0/90 (0%) | 0 | 0/261 (0%) | 0 | 1/206 (0.5%) | 1 | 0/214 (0%) | 0 | 0/598 (0%) | 0 | 1/213 (0.5%) | 1 | 2/601 (0.3%) | 2 | 0/262 (0%) | 0 | 1/30 (3.3%) | 1 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Atelectasis | 0/218 (0%) | 0 | 1/90 (1.1%) | 1 | 0/261 (0%) | 0 | 0/206 (0%) | 0 | 0/214 (0%) | 0 | 1/598 (0.2%) | 1 | 1/213 (0.5%) | 1 | 1/601 (0.2%) | 1 | 0/262 (0%) | 0 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Bronchial obstruction | 0/218 (0%) | 0 | 0/90 (0%) | 0 | 0/261 (0%) | 0 | 0/206 (0%) | 0 | 0/214 (0%) | 0 | 0/598 (0%) | 0 | 1/213 (0.5%) | 1 | 0/601 (0%) | 0 | 0/262 (0%) | 0 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Bronchopulmonary hemorrhage | 1/218 (0.5%) | 1 | 2/90 (2.2%) | 2 | 0/261 (0%) | 0 | 0/206 (0%) | 0 | 0/214 (0%) | 0 | 1/598 (0.2%) | 1 | 0/213 (0%) | 0 | 1/601 (0.2%) | 1 | 2/262 (0.8%) | 2 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Bronchospasm | 1/218 (0.5%) | 1 | 1/90 (1.1%) | 1 | 1/261 (0.4%) | 2 | 0/206 (0%) | 0 | 1/214 (0.5%) | 1 | 1/598 (0.2%) | 1 | 2/213 (0.9%) | 2 | 3/601 (0.5%) | 3 | 3/262 (1.1%) | 3 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Cough | 3/218 (1.4%) | 3 | 2/90 (2.2%) | 2 | 4/261 (1.5%) | 4 | 3/206 (1.5%) | 3 | 3/214 (1.4%) | 4 | 7/598 (1.2%) | 7 | 2/213 (0.9%) | 2 | 5/601 (0.8%) | 5 | 1/262 (0.4%) | 1 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Dyspnea | 1/218 (0.5%) | 1 | 2/90 (2.2%) | 3 | 11/261 (4.2%) | 12 | 1/206 (0.5%) | 1 | 0/214 (0%) | 0 | 7/598 (1.2%) | 8 | 1/213 (0.5%) | 1 | 8/601 (1.3%) | 8 | 5/262 (1.9%) | 6 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Epistaxis | 1/218 (0.5%) | 1 | 2/90 (2.2%) | 2 | 12/261 (4.6%) | 12 | 2/206 (1%) | 4 | 2/214 (0.9%) | 2 | 10/598 (1.7%) | 10 | 3/213 (1.4%) | 3 | 11/601 (1.8%) | 11 | 4/262 (1.5%) | 4 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 1/23 (4.3%) | 1 |
| Hiccups | 0/218 (0%) | 0 | 1/90 (1.1%) | 1 | 1/261 (0.4%) | 1 | 0/206 (0%) | 0 | 0/214 (0%) | 0 | 0/598 (0%) | 0 | 0/213 (0%) | 0 | 0/601 (0%) | 0 | 0/262 (0%) | 0 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Hypoxia | 12/218 (5.5%) | 12 | 14/90 (15.6%) | 14 | 20/261 (7.7%) | 26 | 10/206 (4.9%) | 12 | 9/214 (4.2%) | 10 | 34/598 (5.7%) | 40 | 8/213 (3.8%) | 8 | 32/601 (5.3%) | 33 | 12/262 (4.6%) | 14 | 5/30 (16.7%) | 6 | 4/9 (44.4%) | 5 | 0/23 (0%) | 0 |
| Laryngeal edema | 3/218 (1.4%) | 3 | 0/90 (0%) | 0 | 0/261 (0%) | 0 | 1/206 (0.5%) | 1 | 1/214 (0.5%) | 1 | 0/598 (0%) | 0 | 1/213 (0.5%) | 1 | 1/601 (0.2%) | 1 | 1/262 (0.4%) | 1 | 1/30 (3.3%) | 1 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Laryngeal mucositis | 0/218 (0%) | 0 | 0/90 (0%) | 0 | 0/261 (0%) | 0 | 0/206 (0%) | 0 | 0/214 (0%) | 0 | 1/598 (0.2%) | 1 | 0/213 (0%) | 0 | 0/601 (0%) | 0 | 0/262 (0%) | 0 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Pharyngeal mucositis | 1/218 (0.5%) | 1 | 0/90 (0%) | 0 | 2/261 (0.8%) | 2 | 0/206 (0%) | 0 | 0/214 (0%) | 0 | 5/598 (0.8%) | 5 | 1/213 (0.5%) | 1 | 2/601 (0.3%) | 2 | 3/262 (1.1%) | 3 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Pharyngeal stenosis | 0/218 (0%) | 0 | 0/90 (0%) | 0 | 0/261 (0%) | 0 | 0/206 (0%) | 0 | 0/214 (0%) | 0 | 1/598 (0.2%) | 1 | 0/213 (0%) | 0 | 1/601 (0.2%) | 1 | 0/262 (0%) | 0 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Pharyngolaryngeal pain | 0/218 (0%) | 0 | 0/90 (0%) | 0 | 2/261 (0.8%) | 2 | 0/206 (0%) | 0 | 0/214 (0%) | 0 | 7/598 (1.2%) | 7 | 0/213 (0%) | 0 | 7/601 (1.2%) | 7 | 4/262 (1.5%) | 4 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Pleural effusion | 2/218 (0.9%) | 2 | 4/90 (4.4%) | 4 | 5/261 (1.9%) | 5 | 5/206 (2.4%) | 5 | 1/214 (0.5%) | 1 | 13/598 (2.2%) | 15 | 3/213 (1.4%) | 3 | 8/601 (1.3%) | 8 | 4/262 (1.5%) | 4 | 1/30 (3.3%) | 1 | 1/9 (11.1%) | 1 | 1/23 (4.3%) | 1 |
| Pleural hemorrhage | 0/218 (0%) | 0 | 0/90 (0%) | 0 | 0/261 (0%) | 0 | 0/206 (0%) | 0 | 0/214 (0%) | 0 | 0/598 (0%) | 0 | 1/213 (0.5%) | 1 | 0/601 (0%) | 0 | 0/262 (0%) | 0 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Pleuritic pain | 0/218 (0%) | 0 | 0/90 (0%) | 0 | 0/261 (0%) | 0 | 0/206 (0%) | 0 | 1/214 (0.5%) | 1 | 1/598 (0.2%) | 1 | 0/213 (0%) | 0 | 1/601 (0.2%) | 1 | 0/262 (0%) | 0 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Pneumonitis | 7/218 (3.2%) | 7 | 5/90 (5.6%) | 5 | 9/261 (3.4%) | 9 | 6/206 (2.9%) | 7 | 6/214 (2.8%) | 7 | 13/598 (2.2%) | 13 | 5/213 (2.3%) | 7 | 11/601 (1.8%) | 11 | 10/262 (3.8%) | 11 | 1/30 (3.3%) | 1 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Pneumothorax | 0/218 (0%) | 0 | 0/90 (0%) | 0 | 2/261 (0.8%) | 2 | 0/206 (0%) | 0 | 0/214 (0%) | 0 | 1/598 (0.2%) | 1 | 0/213 (0%) | 0 | 2/601 (0.3%) | 2 | 1/262 (0.4%) | 1 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Respiratory failure | 0/218 (0%) | 0 | 0/90 (0%) | 0 | 0/261 (0%) | 0 | 0/206 (0%) | 0 | 0/214 (0%) | 0 | 2/598 (0.3%) | 2 | 0/213 (0%) | 0 | 0/601 (0%) | 0 | 0/262 (0%) | 0 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 1/23 (4.3%) | 1 |
| Respiratory, thoracic and mediastinal disorders - Other, specify | 2/218 (0.9%) | 2 | 2/90 (2.2%) | 2 | 3/261 (1.1%) | 3 | 5/206 (2.4%) | 11 | 3/214 (1.4%) | 4 | 8/598 (1.3%) | 8 | 3/213 (1.4%) | 3 | 6/601 (1%) | 7 | 2/262 (0.8%) | 2 | 2/30 (6.7%) | 2 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Sinus disorder | 0/218 (0%) | 0 | 0/90 (0%) | 0 | 0/261 (0%) | 0 | 0/206 (0%) | 0 | 1/214 (0.5%) | 1 | 0/598 (0%) | 0 | 0/213 (0%) | 0 | 0/601 (0%) | 0 | 0/262 (0%) | 0 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Sore throat | 0/218 (0%) | 0 | 0/90 (0%) | 0 | 0/261 (0%) | 0 | 0/206 (0%) | 0 | 0/214 (0%) | 0 | 1/598 (0.2%) | 1 | 0/213 (0%) | 0 | 0/601 (0%) | 0 | 0/262 (0%) | 0 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Tracheal mucositis | 0/218 (0%) | 0 | 0/90 (0%) | 0 | 0/261 (0%) | 0 | 0/206 (0%) | 0 | 0/214 (0%) | 0 | 0/598 (0%) | 0 | 0/213 (0%) | 0 | 1/601 (0.2%) | 1 | 0/262 (0%) | 0 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Voice alteration | 0/218 (0%) | 0 | 1/90 (1.1%) | 1 | 0/261 (0%) | 0 | 1/206 (0.5%) | 1 | 0/214 (0%) | 0 | 0/598 (0%) | 0 | 0/213 (0%) | 0 | 0/601 (0%) | 0 | 0/262 (0%) | 0 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Wheezing | 0/218 (0%) | 0 | 0/90 (0%) | 0 | 0/261 (0%) | 0 | 0/206 (0%) | 0 | 1/214 (0.5%) | 1 | 1/598 (0.2%) | 1 | 0/213 (0%) | 0 | 0/601 (0%) | 0 | 0/262 (0%) | 0 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Skin and subcutaneous tissue disorders | ||||||||||||||||||||||||
| Erythema multiforme | 0/218 (0%) | 0 | 0/90 (0%) | 0 | 0/261 (0%) | 0 | 0/206 (0%) | 0 | 0/214 (0%) | 0 | 3/598 (0.5%) | 3 | 0/213 (0%) | 0 | 0/601 (0%) | 0 | 0/262 (0%) | 0 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Pain of skin | 1/218 (0.5%) | 1 | 1/90 (1.1%) | 1 | 0/261 (0%) | 0 | 0/206 (0%) | 0 | 0/214 (0%) | 0 | 3/598 (0.5%) | 3 | 0/213 (0%) | 0 | 0/601 (0%) | 0 | 1/262 (0.4%) | 1 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Palmar-plantar erythrodysesthesia syndrome | 0/218 (0%) | 0 | 0/90 (0%) | 0 | 0/261 (0%) | 0 | 0/206 (0%) | 0 | 0/214 (0%) | 0 | 3/598 (0.5%) | 3 | 1/213 (0.5%) | 1 | 0/601 (0%) | 0 | 1/262 (0.4%) | 1 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Periorbital edema | 0/218 (0%) | 0 | 0/90 (0%) | 0 | 1/261 (0.4%) | 1 | 0/206 (0%) | 0 | 0/214 (0%) | 0 | 0/598 (0%) | 0 | 0/213 (0%) | 0 | 0/601 (0%) | 0 | 0/262 (0%) | 0 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Photosensitivity | 0/218 (0%) | 0 | 0/90 (0%) | 0 | 1/261 (0.4%) | 1 | 0/206 (0%) | 0 | 0/214 (0%) | 0 | 1/598 (0.2%) | 1 | 0/213 (0%) | 0 | 0/601 (0%) | 0 | 0/262 (0%) | 0 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Pruritus | 0/218 (0%) | 0 | 2/90 (2.2%) | 2 | 0/261 (0%) | 0 | 1/206 (0.5%) | 1 | 2/214 (0.9%) | 2 | 0/598 (0%) | 0 | 0/213 (0%) | 0 | 1/601 (0.2%) | 1 | 0/262 (0%) | 0 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Purpura | 1/218 (0.5%) | 2 | 0/90 (0%) | 0 | 0/261 (0%) | 0 | 0/206 (0%) | 0 | 0/214 (0%) | 0 | 0/598 (0%) | 0 | 1/213 (0.5%) | 1 | 1/601 (0.2%) | 1 | 2/262 (0.8%) | 2 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Rash maculo-papular | 1/218 (0.5%) | 1 | 4/90 (4.4%) | 4 | 7/261 (2.7%) | 7 | 7/206 (3.4%) | 8 | 4/214 (1.9%) | 4 | 6/598 (1%) | 6 | 1/213 (0.5%) | 1 | 4/601 (0.7%) | 5 | 3/262 (1.1%) | 3 | 0/30 (0%) | 0 | 1/9 (11.1%) | 1 | 0/23 (0%) | 0 |
| Skin and subcutaneous tissue disorders - Other, specify | 1/218 (0.5%) | 1 | 1/90 (1.1%) | 1 | 0/261 (0%) | 0 | 1/206 (0.5%) | 1 | 3/214 (1.4%) | 3 | 5/598 (0.8%) | 6 | 1/213 (0.5%) | 1 | 3/601 (0.5%) | 3 | 1/262 (0.4%) | 1 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Skin ulceration | 0/218 (0%) | 0 | 0/90 (0%) | 0 | 2/261 (0.8%) | 2 | 1/206 (0.5%) | 1 | 0/214 (0%) | 0 | 2/598 (0.3%) | 2 | 1/213 (0.5%) | 1 | 1/601 (0.2%) | 1 | 1/262 (0.4%) | 1 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Stevens-Johnson syndrome | 0/218 (0%) | 0 | 1/90 (1.1%) | 1 | 0/261 (0%) | 0 | 0/206 (0%) | 0 | 0/214 (0%) | 0 | 0/598 (0%) | 0 | 0/213 (0%) | 0 | 0/601 (0%) | 0 | 0/262 (0%) | 0 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Urticaria | 0/218 (0%) | 0 | 1/90 (1.1%) | 1 | 5/261 (1.9%) | 5 | 1/206 (0.5%) | 1 | 2/214 (0.9%) | 2 | 10/598 (1.7%) | 10 | 1/213 (0.5%) | 1 | 8/601 (1.3%) | 8 | 2/262 (0.8%) | 2 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Surgical and medical procedures | ||||||||||||||||||||||||
| Surgical and medical procedures - Other, specify | 0/218 (0%) | 0 | 0/90 (0%) | 0 | 0/261 (0%) | 0 | 0/206 (0%) | 0 | 0/214 (0%) | 0 | 2/598 (0.3%) | 2 | 0/213 (0%) | 0 | 1/601 (0.2%) | 1 | 0/262 (0%) | 0 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Vascular disorders | ||||||||||||||||||||||||
| Capillary leak syndrome | 0/218 (0%) | 0 | 0/90 (0%) | 0 | 2/261 (0.8%) | 2 | 0/206 (0%) | 0 | 0/214 (0%) | 0 | 0/598 (0%) | 0 | 0/213 (0%) | 0 | 0/601 (0%) | 0 | 0/262 (0%) | 0 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Hematoma | 0/218 (0%) | 0 | 0/90 (0%) | 0 | 2/261 (0.8%) | 2 | 1/206 (0.5%) | 1 | 0/214 (0%) | 0 | 2/598 (0.3%) | 2 | 0/213 (0%) | 0 | 3/601 (0.5%) | 3 | 1/262 (0.4%) | 1 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Hypertension | 7/218 (3.2%) | 7 | 3/90 (3.3%) | 3 | 10/261 (3.8%) | 17 | 4/206 (1.9%) | 4 | 6/214 (2.8%) | 7 | 16/598 (2.7%) | 17 | 10/213 (4.7%) | 10 | 15/601 (2.5%) | 16 | 8/262 (3.1%) | 11 | 0/30 (0%) | 0 | 1/9 (11.1%) | 1 | 1/23 (4.3%) | 1 |
| Hypotension | 5/218 (2.3%) | 6 | 6/90 (6.7%) | 6 | 16/261 (6.1%) | 16 | 6/206 (2.9%) | 6 | 4/214 (1.9%) | 5 | 30/598 (5%) | 33 | 3/213 (1.4%) | 3 | 22/601 (3.7%) | 23 | 16/262 (6.1%) | 16 | 2/30 (6.7%) | 2 | 2/9 (22.2%) | 2 | 2/23 (8.7%) | 2 |
| Lymphedema | 0/218 (0%) | 0 | 0/90 (0%) | 0 | 0/261 (0%) | 0 | 0/206 (0%) | 0 | 0/214 (0%) | 0 | 1/598 (0.2%) | 1 | 0/213 (0%) | 0 | 0/601 (0%) | 0 | 0/262 (0%) | 0 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Thromboembolic event | 1/218 (0.5%) | 1 | 1/90 (1.1%) | 1 | 8/261 (3.1%) | 9 | 3/206 (1.5%) | 4 | 3/214 (1.4%) | 5 | 17/598 (2.8%) | 21 | 2/213 (0.9%) | 2 | 23/601 (3.8%) | 26 | 13/262 (5%) | 14 | 3/30 (10%) | 4 | 0/9 (0%) | 0 | 1/23 (4.3%) | 1 |
| Vascular disorders - Other, specify | 0/218 (0%) | 0 | 0/90 (0%) | 0 | 5/261 (1.9%) | 5 | 2/206 (1%) | 2 | 1/214 (0.5%) | 2 | 3/598 (0.5%) | 3 | 3/213 (1.4%) | 3 | 3/601 (0.5%) | 3 | 3/262 (1.1%) | 3 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
| Vasculitis | 0/218 (0%) | 0 | 0/90 (0%) | 0 | 1/261 (0.4%) | 2 | 0/206 (0%) | 0 | 0/214 (0%) | 0 | 1/598 (0.2%) | 1 | 0/213 (0%) | 0 | 0/601 (0%) | 0 | 0/262 (0%) | 0 | 0/30 (0%) | 0 | 0/9 (0%) | 0 | 0/23 (0%) | 0 |
Limitations/Caveats
The COG SDC reviewed the NLM notification related to ct.gov AE/SAE reporting. The information in 'Additional Description' is accurate with respect to data supplied to ct.gov.COG plans to submit data AE/SAE data consistent with the text in this field.
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
Must obtain prior Sponsor approval
Results Point of Contact
| Name/Title | Results Reporting Coordinator |
|---|---|
| Organization | Children's Oncology Group |
| Phone | 626-447-0064 |
| resultsreportingcoordinator@childrensoncologygroup.org |
Responsible Party:
Children's Oncology Group
ClinicalTrials.gov Identifier:
NCT00075725
Other Study ID Numbers:
- AALL0232
- NCI-2009-00301
- COG-AALL0232
- CDR0000349182
- 11723
- AALL0232
- AALL0232
- U10CA098543
First Posted:
Jan 13, 2004
Last Update Posted:
Apr 27, 2021
Last Verified:
Apr 1, 2021