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:
  1. Improve the outcome of children with high-risk acute lymphoblastic leukemia treated with 2 different chemotherapy regimens.

  2. Determine the relative safety and efficacy of dexamethasone given for 14 days vs prednisone given for 28 days during induction.

  3. 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.

  4. Correlate Day 29 minimal residual disease (MRD) with event-free survival (EFS) and overall survival (OS).

  5. 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

  1. 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:
  • (-)-Cyclophosphamide
  • 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate
  • Carloxan
  • Ciclofosfamida
  • Ciclofosfamide
  • Cicloxal
  • Clafen
  • Claphene
  • CP monohydrate
  • CTX
  • CYCLO-cell
  • Cycloblastin
  • Cycloblastine
  • Cyclophospham
  • Cyclophosphamid monohydrate
  • Cyclophosphamide Monohydrate
  • Cyclophosphamidum
  • Cyclophosphan
  • Cyclophosphane
  • Cyclophosphanum
  • Cyclostin
  • Cyclostine
  • Cytophosphan
  • Cytophosphane
  • Cytoxan
  • Fosfaseron
  • Genoxal
  • Genuxal
  • Ledoxina
  • Mitoxan
  • Neosar
  • Revimmune
  • Syklofosfamid
  • WR- 138719
  • Drug: Cytarabine
    Given IT, SC, or IV
    Other Names:
  • .beta.-Cytosine arabinoside
  • 1-.beta.-D-Arabinofuranosyl-4-amino-2(1H)pyrimidinone
  • 1-.beta.-D-Arabinofuranosylcytosine
  • 1-Beta-D-arabinofuranosyl-4-amino-2(1H)pyrimidinone
  • 1-Beta-D-arabinofuranosylcytosine
  • 1.beta.-D-Arabinofuranosylcytosine
  • 2(1H)-Pyrimidinone, 4-Amino-1-beta-D-arabinofuranosyl-
  • 2(1H)-Pyrimidinone, 4-amino-1.beta.-D-arabinofuranosyl-
  • Alexan
  • Ara-C
  • ARA-cell
  • Arabine
  • Arabinofuranosylcytosine
  • Arabinosylcytosine
  • Aracytidine
  • Aracytin
  • Aracytine
  • Beta-Cytosine Arabinoside
  • CHX-3311
  • Cytarabinum
  • Cytarbel
  • Cytosar
  • Cytosine Arabinoside
  • Cytosine-.beta.-arabinoside
  • Cytosine-beta-arabinoside
  • Erpalfa
  • Starasid
  • Tarabine PFS
  • U 19920
  • U-19920
  • Udicil
  • WR-28453
  • Drug: Daunorubicin Hydrochloride
    Given IV
    Other Names:
  • Cerubidin
  • Cerubidine
  • Cloridrato de Daunorubicina
  • Daunoblastin
  • Daunoblastina
  • Daunoblastine
  • Daunomycin Hydrochloride
  • Daunomycin, hydrochloride
  • Daunorubicin.HCl
  • Daunorubicini Hydrochloridum
  • FI-6339
  • Ondena
  • RP-13057
  • Rubidomycin Hydrochloride
  • Rubilem
  • Drug: Dexamethasone
    Given PO or IV
    Other Names:
  • Aacidexam
  • Adexone
  • Aknichthol Dexa
  • Alba-Dex
  • Alin
  • Alin Depot
  • Alin Oftalmico
  • Amplidermis
  • Anemul mono
  • Auricularum
  • Auxiloson
  • Baycadron
  • Baycuten
  • Baycuten N
  • Cortidexason
  • Cortisumman
  • Decacort
  • Decadrol
  • Decadron
  • Decadron DP
  • Decalix
  • Decameth
  • Decasone R.p.
  • Dectancyl
  • Dekacort
  • Deltafluorene
  • Deronil
  • Desamethasone
  • Desameton
  • Dexa-Mamallet
  • Dexa-Rhinosan
  • Dexa-Scheroson
  • Dexa-sine
  • Dexacortal
  • Dexacortin
  • Dexafarma
  • Dexafluorene
  • Dexalocal
  • Dexamecortin
  • Dexameth
  • Dexamethasone Intensol
  • Dexamethasonum
  • Dexamonozon
  • Dexapos
  • Dexinoral
  • Dexone
  • Dinormon
  • Dxevo
  • Fluorodelta
  • Fortecortin
  • Gammacorten
  • Hexadecadrol
  • Hexadrol
  • Lokalison-F
  • Loverine
  • Methylfluorprednisolone
  • Millicorten
  • Mymethasone
  • Orgadrone
  • Spersadex
  • TaperDex
  • Visumetazone
  • ZoDex
  • Drug: Doxorubicin Hydrochloride
    Given IV
    Other Names:
  • 5,12-Naphthacenedione, 10-[(3-amino-2,3,6-trideoxy-alpha-L-lyxo-hexopyranosyl)oxy]-7,8, 9,10-tetrahydro-6,8,11-trihydroxy-8-(hydroxyacetyl)-1-methoxy-, hydrochloride, (8S-cis)- (9CI)
  • ADM
  • Adriacin
  • Adriamycin
  • Adriamycin Hydrochloride
  • Adriamycin PFS
  • Adriamycin RDF
  • ADRIAMYCIN, HYDROCHLORIDE
  • Adriamycine
  • Adriblastina
  • Adriblastine
  • Adrimedac
  • Chloridrato de Doxorrubicina
  • DOX
  • DOXO-CELL
  • Doxolem
  • Doxorubicin HCl
  • Doxorubicin.HCl
  • Doxorubin
  • Farmiblastina
  • FI 106
  • FI-106
  • hydroxydaunorubicin
  • Rubex
  • Drug: Mercaptopurine
    Given PO
    Other Names:
  • 3H-Purine-6-thiol
  • 6 MP
  • 6 Thiohypoxanthine
  • 6 Thiopurine
  • 6-Mercaptopurine
  • 6-Mercaptopurine Monohydrate
  • 6-MP
  • 6-Purinethiol
  • 6-Thiopurine
  • 6-Thioxopurine
  • 6H-Purine-6-thione, 1,7-dihydro- (9CI)
  • 7-Mercapto-1,3,4,6-tetrazaindene
  • Alti-Mercaptopurine
  • Azathiopurine
  • Bw 57-323H
  • Flocofil
  • Ismipur
  • Leukerin
  • Leupurin
  • Mercaleukim
  • Mercaleukin
  • Mercaptina
  • Mercaptopurinum
  • Mercapurin
  • Mern
  • NCI-C04886
  • Puri-Nethol
  • Purimethol
  • Purine, 6-mercapto-
  • Purine-6-thiol (8CI)
  • Purine-6-thiol, monohydrate
  • Purinethiol
  • Purinethol
  • U-4748
  • WR-2785
  • Drug: Methotrexate
    Given IT or IV
    Other Names:
  • Abitrexate
  • Alpha-Methopterin
  • Amethopterin
  • Brimexate
  • CL 14377
  • CL-14377
  • Emtexate
  • Emthexat
  • Emthexate
  • Farmitrexat
  • Fauldexato
  • Folex
  • Folex PFS
  • Lantarel
  • Ledertrexate
  • Lumexon
  • Maxtrex
  • Medsatrexate
  • Metex
  • Methoblastin
  • Methotrexate LPF
  • Methotrexate Methylaminopterin
  • Methotrexatum
  • Metotrexato
  • Metrotex
  • Mexate
  • Mexate-AQ
  • MTX
  • Novatrex
  • Rheumatrex
  • Texate
  • Tremetex
  • Trexeron
  • Trixilem
  • WR-19039
  • Drug: Pegaspargase
    Given IM
    Other Names:
  • L-Asparaginase with Polyethylene Glycol
  • Oncaspar
  • Oncaspar-IV
  • PEG-Asparaginase
  • PEG-L-Asparaginase
  • PEG-L-Asparaginase (Enzon - Kyowa Hakko)
  • PEGLA
  • Polyethylene Glycol L-Asparaginase
  • Polyethylene Glycol-L-Asparaginase
  • Radiation: Radiation Therapy
    Undergo radiation therapy
    Other Names:
  • Cancer Radiotherapy
  • ENERGY_TYPE
  • Irradiate
  • Irradiated
  • Irradiation
  • Radiation
  • Radiation Therapy, NOS
  • Radiotherapeutics
  • Radiotherapy
  • RT
  • Therapy, Radiation
  • Drug: Thioguanine
    Given PO
    Other Names:
  • 2-Amino 6MP
  • 2-Amino-1,7-dihydro-6H-purine-6-thione
  • 2-Amino-6-mercaptopurine
  • 2-Amino-6-purinethiol
  • 2-Aminopurin-6-thiol
  • 2-Aminopurine-6(1H)-thione
  • 2-Aminopurine-6-thiol
  • 2-Aminopurine-6-thiol Hemihydrate
  • 2-Mercapto-6-aminopurine
  • 6-Amino-2-mercaptopurine
  • 6-Mercapto-2-aminopurine
  • 6-Mercaptoguanine
  • 6-TG
  • 6H-Purine-6-thione, 2-amino-1,7-dihydro- (9CI)
  • BW 5071
  • Lanvis
  • Tabloid
  • Thioguanine Hemihydrate
  • Thioguanine Hydrate
  • Tioguanin
  • Tioguanine
  • Wellcome U3B
  • WR-1141
  • X 27
  • Drug: Vincristine Sulfate
    Given IV
    Other Names:
  • Kyocristine
  • Leurocristine Sulfate
  • Leurocristine, sulfate
  • Oncovin
  • Vincasar
  • Vincosid
  • Vincrex
  • Vincristine, sulfate
  • 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:
  • (-)-Cyclophosphamide
  • 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate
  • Carloxan
  • Ciclofosfamida
  • Ciclofosfamide
  • Cicloxal
  • Clafen
  • Claphene
  • CP monohydrate
  • CTX
  • CYCLO-cell
  • Cycloblastin
  • Cycloblastine
  • Cyclophospham
  • Cyclophosphamid monohydrate
  • Cyclophosphamide Monohydrate
  • Cyclophosphamidum
  • Cyclophosphan
  • Cyclophosphane
  • Cyclophosphanum
  • Cyclostin
  • Cyclostine
  • Cytophosphan
  • Cytophosphane
  • Cytoxan
  • Fosfaseron
  • Genoxal
  • Genuxal
  • Ledoxina
  • Mitoxan
  • Neosar
  • Revimmune
  • Syklofosfamid
  • WR- 138719
  • Drug: Cytarabine
    Given IT, SC, or IV
    Other Names:
  • .beta.-Cytosine arabinoside
  • 1-.beta.-D-Arabinofuranosyl-4-amino-2(1H)pyrimidinone
  • 1-.beta.-D-Arabinofuranosylcytosine
  • 1-Beta-D-arabinofuranosyl-4-amino-2(1H)pyrimidinone
  • 1-Beta-D-arabinofuranosylcytosine
  • 1.beta.-D-Arabinofuranosylcytosine
  • 2(1H)-Pyrimidinone, 4-Amino-1-beta-D-arabinofuranosyl-
  • 2(1H)-Pyrimidinone, 4-amino-1.beta.-D-arabinofuranosyl-
  • Alexan
  • Ara-C
  • ARA-cell
  • Arabine
  • Arabinofuranosylcytosine
  • Arabinosylcytosine
  • Aracytidine
  • Aracytin
  • Aracytine
  • Beta-Cytosine Arabinoside
  • CHX-3311
  • Cytarabinum
  • Cytarbel
  • Cytosar
  • Cytosine Arabinoside
  • Cytosine-.beta.-arabinoside
  • Cytosine-beta-arabinoside
  • Erpalfa
  • Starasid
  • Tarabine PFS
  • U 19920
  • U-19920
  • Udicil
  • WR-28453
  • Drug: Daunorubicin Hydrochloride
    Given IV
    Other Names:
  • Cerubidin
  • Cerubidine
  • Cloridrato de Daunorubicina
  • Daunoblastin
  • Daunoblastina
  • Daunoblastine
  • Daunomycin Hydrochloride
  • Daunomycin, hydrochloride
  • Daunorubicin.HCl
  • Daunorubicini Hydrochloridum
  • FI-6339
  • Ondena
  • RP-13057
  • Rubidomycin Hydrochloride
  • Rubilem
  • Drug: Dexamethasone
    Given PO or IV
    Other Names:
  • Aacidexam
  • Adexone
  • Aknichthol Dexa
  • Alba-Dex
  • Alin
  • Alin Depot
  • Alin Oftalmico
  • Amplidermis
  • Anemul mono
  • Auricularum
  • Auxiloson
  • Baycadron
  • Baycuten
  • Baycuten N
  • Cortidexason
  • Cortisumman
  • Decacort
  • Decadrol
  • Decadron
  • Decadron DP
  • Decalix
  • Decameth
  • Decasone R.p.
  • Dectancyl
  • Dekacort
  • Deltafluorene
  • Deronil
  • Desamethasone
  • Desameton
  • Dexa-Mamallet
  • Dexa-Rhinosan
  • Dexa-Scheroson
  • Dexa-sine
  • Dexacortal
  • Dexacortin
  • Dexafarma
  • Dexafluorene
  • Dexalocal
  • Dexamecortin
  • Dexameth
  • Dexamethasone Intensol
  • Dexamethasonum
  • Dexamonozon
  • Dexapos
  • Dexinoral
  • Dexone
  • Dinormon
  • Dxevo
  • Fluorodelta
  • Fortecortin
  • Gammacorten
  • Hexadecadrol
  • Hexadrol
  • Lokalison-F
  • Loverine
  • Methylfluorprednisolone
  • Millicorten
  • Mymethasone
  • Orgadrone
  • Spersadex
  • TaperDex
  • Visumetazone
  • ZoDex
  • Drug: Doxorubicin Hydrochloride
    Given IV
    Other Names:
  • 5,12-Naphthacenedione, 10-[(3-amino-2,3,6-trideoxy-alpha-L-lyxo-hexopyranosyl)oxy]-7,8, 9,10-tetrahydro-6,8,11-trihydroxy-8-(hydroxyacetyl)-1-methoxy-, hydrochloride, (8S-cis)- (9CI)
  • ADM
  • Adriacin
  • Adriamycin
  • Adriamycin Hydrochloride
  • Adriamycin PFS
  • Adriamycin RDF
  • ADRIAMYCIN, HYDROCHLORIDE
  • Adriamycine
  • Adriblastina
  • Adriblastine
  • Adrimedac
  • Chloridrato de Doxorrubicina
  • DOX
  • DOXO-CELL
  • Doxolem
  • Doxorubicin HCl
  • Doxorubicin.HCl
  • Doxorubin
  • Farmiblastina
  • FI 106
  • FI-106
  • hydroxydaunorubicin
  • Rubex
  • Drug: Leucovorin Calcium
    Given IV
    Other Names:
  • Adinepar
  • Calcifolin
  • Calcium (6S)-Folinate
  • Calcium Folinate
  • Calcium Leucovorin
  • Calfolex
  • Calinat
  • Cehafolin
  • Citofolin
  • Citrec
  • Citrovorum Factor
  • Cromatonbic Folinico
  • Dalisol
  • Disintox
  • Divical
  • Ecofol
  • Emovis
  • Factor, Citrovorum
  • Flynoken A
  • Folaren
  • Folaxin
  • FOLI-cell
  • Foliben
  • Folidan
  • Folidar
  • Folinac
  • Folinate Calcium
  • folinic acid
  • Folinic Acid Calcium Salt Pentahydrate
  • Folinoral
  • Folinvit
  • Foliplus
  • Folix
  • Imo
  • Lederfolat
  • Lederfolin
  • Leucosar
  • leucovorin
  • Rescufolin
  • Rescuvolin
  • Tonofolin
  • Wellcovorin
  • Drug: Mercaptopurine
    Given PO
    Other Names:
  • 3H-Purine-6-thiol
  • 6 MP
  • 6 Thiohypoxanthine
  • 6 Thiopurine
  • 6-Mercaptopurine
  • 6-Mercaptopurine Monohydrate
  • 6-MP
  • 6-Purinethiol
  • 6-Thiopurine
  • 6-Thioxopurine
  • 6H-Purine-6-thione, 1,7-dihydro- (9CI)
  • 7-Mercapto-1,3,4,6-tetrazaindene
  • Alti-Mercaptopurine
  • Azathiopurine
  • Bw 57-323H
  • Flocofil
  • Ismipur
  • Leukerin
  • Leupurin
  • Mercaleukim
  • Mercaleukin
  • Mercaptina
  • Mercaptopurinum
  • Mercapurin
  • Mern
  • NCI-C04886
  • Puri-Nethol
  • Purimethol
  • Purine, 6-mercapto-
  • Purine-6-thiol (8CI)
  • Purine-6-thiol, monohydrate
  • Purinethiol
  • Purinethol
  • U-4748
  • WR-2785
  • Drug: Methotrexate
    Given IT or IV
    Other Names:
  • Abitrexate
  • Alpha-Methopterin
  • Amethopterin
  • Brimexate
  • CL 14377
  • CL-14377
  • Emtexate
  • Emthexat
  • Emthexate
  • Farmitrexat
  • Fauldexato
  • Folex
  • Folex PFS
  • Lantarel
  • Ledertrexate
  • Lumexon
  • Maxtrex
  • Medsatrexate
  • Metex
  • Methoblastin
  • Methotrexate LPF
  • Methotrexate Methylaminopterin
  • Methotrexatum
  • Metotrexato
  • Metrotex
  • Mexate
  • Mexate-AQ
  • MTX
  • Novatrex
  • Rheumatrex
  • Texate
  • Tremetex
  • Trexeron
  • Trixilem
  • WR-19039
  • Drug: Pegaspargase
    Given IM
    Other Names:
  • L-Asparaginase with Polyethylene Glycol
  • Oncaspar
  • Oncaspar-IV
  • PEG-Asparaginase
  • PEG-L-Asparaginase
  • PEG-L-Asparaginase (Enzon - Kyowa Hakko)
  • PEGLA
  • Polyethylene Glycol L-Asparaginase
  • Polyethylene Glycol-L-Asparaginase
  • Radiation: Radiation Therapy
    Undergo radiation therapy
    Other Names:
  • Cancer Radiotherapy
  • ENERGY_TYPE
  • Irradiate
  • Irradiated
  • Irradiation
  • Radiation
  • Radiation Therapy, NOS
  • Radiotherapeutics
  • Radiotherapy
  • RT
  • Therapy, Radiation
  • Drug: Thioguanine
    Given PO
    Other Names:
  • 2-Amino 6MP
  • 2-Amino-1,7-dihydro-6H-purine-6-thione
  • 2-Amino-6-mercaptopurine
  • 2-Amino-6-purinethiol
  • 2-Aminopurin-6-thiol
  • 2-Aminopurine-6(1H)-thione
  • 2-Aminopurine-6-thiol
  • 2-Aminopurine-6-thiol Hemihydrate
  • 2-Mercapto-6-aminopurine
  • 6-Amino-2-mercaptopurine
  • 6-Mercapto-2-aminopurine
  • 6-Mercaptoguanine
  • 6-TG
  • 6H-Purine-6-thione, 2-amino-1,7-dihydro- (9CI)
  • BW 5071
  • Lanvis
  • Tabloid
  • Thioguanine Hemihydrate
  • Thioguanine Hydrate
  • Tioguanin
  • Tioguanine
  • Wellcome U3B
  • WR-1141
  • X 27
  • Drug: Vincristine Sulfate
    Given IV
    Other Names:
  • Kyocristine
  • Leurocristine Sulfate
  • Leurocristine, sulfate
  • Oncovin
  • Vincasar
  • Vincosid
  • Vincrex
  • Vincristine, sulfate
  • 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:
  • (-)-Cyclophosphamide
  • 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate
  • Carloxan
  • Ciclofosfamida
  • Ciclofosfamide
  • Cicloxal
  • Clafen
  • Claphene
  • CP monohydrate
  • CTX
  • CYCLO-cell
  • Cycloblastin
  • Cycloblastine
  • Cyclophospham
  • Cyclophosphamid monohydrate
  • Cyclophosphamide Monohydrate
  • Cyclophosphamidum
  • Cyclophosphan
  • Cyclophosphane
  • Cyclophosphanum
  • Cyclostin
  • Cyclostine
  • Cytophosphan
  • Cytophosphane
  • Cytoxan
  • Fosfaseron
  • Genoxal
  • Genuxal
  • Ledoxina
  • Mitoxan
  • Neosar
  • Revimmune
  • Syklofosfamid
  • WR- 138719
  • Drug: Cytarabine
    Given IT, SC, or IV
    Other Names:
  • .beta.-Cytosine arabinoside
  • 1-.beta.-D-Arabinofuranosyl-4-amino-2(1H)pyrimidinone
  • 1-.beta.-D-Arabinofuranosylcytosine
  • 1-Beta-D-arabinofuranosyl-4-amino-2(1H)pyrimidinone
  • 1-Beta-D-arabinofuranosylcytosine
  • 1.beta.-D-Arabinofuranosylcytosine
  • 2(1H)-Pyrimidinone, 4-Amino-1-beta-D-arabinofuranosyl-
  • 2(1H)-Pyrimidinone, 4-amino-1.beta.-D-arabinofuranosyl-
  • Alexan
  • Ara-C
  • ARA-cell
  • Arabine
  • Arabinofuranosylcytosine
  • Arabinosylcytosine
  • Aracytidine
  • Aracytin
  • Aracytine
  • Beta-Cytosine Arabinoside
  • CHX-3311
  • Cytarabinum
  • Cytarbel
  • Cytosar
  • Cytosine Arabinoside
  • Cytosine-.beta.-arabinoside
  • Cytosine-beta-arabinoside
  • Erpalfa
  • Starasid
  • Tarabine PFS
  • U 19920
  • U-19920
  • Udicil
  • WR-28453
  • Drug: Daunorubicin Hydrochloride
    Given IV
    Other Names:
  • Cerubidin
  • Cerubidine
  • Cloridrato de Daunorubicina
  • Daunoblastin
  • Daunoblastina
  • Daunoblastine
  • Daunomycin Hydrochloride
  • Daunomycin, hydrochloride
  • Daunorubicin.HCl
  • Daunorubicini Hydrochloridum
  • FI-6339
  • Ondena
  • RP-13057
  • Rubidomycin Hydrochloride
  • Rubilem
  • Drug: Dexamethasone
    Given PO or IV
    Other Names:
  • Aacidexam
  • Adexone
  • Aknichthol Dexa
  • Alba-Dex
  • Alin
  • Alin Depot
  • Alin Oftalmico
  • Amplidermis
  • Anemul mono
  • Auricularum
  • Auxiloson
  • Baycadron
  • Baycuten
  • Baycuten N
  • Cortidexason
  • Cortisumman
  • Decacort
  • Decadrol
  • Decadron
  • Decadron DP
  • Decalix
  • Decameth
  • Decasone R.p.
  • Dectancyl
  • Dekacort
  • Deltafluorene
  • Deronil
  • Desamethasone
  • Desameton
  • Dexa-Mamallet
  • Dexa-Rhinosan
  • Dexa-Scheroson
  • Dexa-sine
  • Dexacortal
  • Dexacortin
  • Dexafarma
  • Dexafluorene
  • Dexalocal
  • Dexamecortin
  • Dexameth
  • Dexamethasone Intensol
  • Dexamethasonum
  • Dexamonozon
  • Dexapos
  • Dexinoral
  • Dexone
  • Dinormon
  • Dxevo
  • Fluorodelta
  • Fortecortin
  • Gammacorten
  • Hexadecadrol
  • Hexadrol
  • Lokalison-F
  • Loverine
  • Methylfluorprednisolone
  • Millicorten
  • Mymethasone
  • Orgadrone
  • Spersadex
  • TaperDex
  • Visumetazone
  • ZoDex
  • Drug: Doxorubicin Hydrochloride
    Given IV
    Other Names:
  • 5,12-Naphthacenedione, 10-[(3-amino-2,3,6-trideoxy-alpha-L-lyxo-hexopyranosyl)oxy]-7,8, 9,10-tetrahydro-6,8,11-trihydroxy-8-(hydroxyacetyl)-1-methoxy-, hydrochloride, (8S-cis)- (9CI)
  • ADM
  • Adriacin
  • Adriamycin
  • Adriamycin Hydrochloride
  • Adriamycin PFS
  • Adriamycin RDF
  • ADRIAMYCIN, HYDROCHLORIDE
  • Adriamycine
  • Adriblastina
  • Adriblastine
  • Adrimedac
  • Chloridrato de Doxorrubicina
  • DOX
  • DOXO-CELL
  • Doxolem
  • Doxorubicin HCl
  • Doxorubicin.HCl
  • Doxorubin
  • Farmiblastina
  • FI 106
  • FI-106
  • hydroxydaunorubicin
  • Rubex
  • Drug: Mercaptopurine
    Given PO
    Other Names:
  • 3H-Purine-6-thiol
  • 6 MP
  • 6 Thiohypoxanthine
  • 6 Thiopurine
  • 6-Mercaptopurine
  • 6-Mercaptopurine Monohydrate
  • 6-MP
  • 6-Purinethiol
  • 6-Thiopurine
  • 6-Thioxopurine
  • 6H-Purine-6-thione, 1,7-dihydro- (9CI)
  • 7-Mercapto-1,3,4,6-tetrazaindene
  • Alti-Mercaptopurine
  • Azathiopurine
  • Bw 57-323H
  • Flocofil
  • Ismipur
  • Leukerin
  • Leupurin
  • Mercaleukim
  • Mercaleukin
  • Mercaptina
  • Mercaptopurinum
  • Mercapurin
  • Mern
  • NCI-C04886
  • Puri-Nethol
  • Purimethol
  • Purine, 6-mercapto-
  • Purine-6-thiol (8CI)
  • Purine-6-thiol, monohydrate
  • Purinethiol
  • Purinethol
  • U-4748
  • WR-2785
  • Drug: Methotrexate
    Given IT or IV
    Other Names:
  • Abitrexate
  • Alpha-Methopterin
  • Amethopterin
  • Brimexate
  • CL 14377
  • CL-14377
  • Emtexate
  • Emthexat
  • Emthexate
  • Farmitrexat
  • Fauldexato
  • Folex
  • Folex PFS
  • Lantarel
  • Ledertrexate
  • Lumexon
  • Maxtrex
  • Medsatrexate
  • Metex
  • Methoblastin
  • Methotrexate LPF
  • Methotrexate Methylaminopterin
  • Methotrexatum
  • Metotrexato
  • Metrotex
  • Mexate
  • Mexate-AQ
  • MTX
  • Novatrex
  • Rheumatrex
  • Texate
  • Tremetex
  • Trexeron
  • Trixilem
  • WR-19039
  • Drug: Pegaspargase
    Given IM
    Other Names:
  • L-Asparaginase with Polyethylene Glycol
  • Oncaspar
  • Oncaspar-IV
  • PEG-Asparaginase
  • PEG-L-Asparaginase
  • PEG-L-Asparaginase (Enzon - Kyowa Hakko)
  • PEGLA
  • Polyethylene Glycol L-Asparaginase
  • Polyethylene Glycol-L-Asparaginase
  • Drug: Prednisone
    Given PO or IV
    Other Names:
  • .delta.1-Cortisone
  • 1, 2-Dehydrocortisone
  • Adasone
  • Cortancyl
  • Dacortin
  • DeCortin
  • Decortisyl
  • Decorton
  • Delta 1-Cortisone
  • Delta-Dome
  • Deltacortene
  • Deltacortisone
  • Deltadehydrocortisone
  • Deltasone
  • Deltison
  • Deltra
  • Econosone
  • Lisacort
  • Meprosona-F
  • Metacortandracin
  • Meticorten
  • Ofisolona
  • Orasone
  • Panafcort
  • Panasol-S
  • Paracort
  • Perrigo Prednisone
  • PRED
  • Predicor
  • Predicorten
  • Prednicen-M
  • Prednicort
  • Prednidib
  • Prednilonga
  • Predniment
  • Prednisone Intensol
  • Prednisonum
  • Prednitone
  • Promifen
  • Rayos
  • Servisone
  • SK-Prednisone
  • Radiation: Radiation Therapy
    Undergo radiation therapy
    Other Names:
  • Cancer Radiotherapy
  • ENERGY_TYPE
  • Irradiate
  • Irradiated
  • Irradiation
  • Radiation
  • Radiation Therapy, NOS
  • Radiotherapeutics
  • Radiotherapy
  • RT
  • Therapy, Radiation
  • Drug: Thioguanine
    Given PO
    Other Names:
  • 2-Amino 6MP
  • 2-Amino-1,7-dihydro-6H-purine-6-thione
  • 2-Amino-6-mercaptopurine
  • 2-Amino-6-purinethiol
  • 2-Aminopurin-6-thiol
  • 2-Aminopurine-6(1H)-thione
  • 2-Aminopurine-6-thiol
  • 2-Aminopurine-6-thiol Hemihydrate
  • 2-Mercapto-6-aminopurine
  • 6-Amino-2-mercaptopurine
  • 6-Mercapto-2-aminopurine
  • 6-Mercaptoguanine
  • 6-TG
  • 6H-Purine-6-thione, 2-amino-1,7-dihydro- (9CI)
  • BW 5071
  • Lanvis
  • Tabloid
  • Thioguanine Hemihydrate
  • Thioguanine Hydrate
  • Tioguanin
  • Tioguanine
  • Wellcome U3B
  • WR-1141
  • X 27
  • Drug: Vincristine Sulfate
    Given IV
    Other Names:
  • Kyocristine
  • Leurocristine Sulfate
  • Leurocristine, sulfate
  • Oncovin
  • Vincasar
  • Vincosid
  • Vincrex
  • Vincristine, sulfate
  • 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:
  • (-)-Cyclophosphamide
  • 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate
  • Carloxan
  • Ciclofosfamida
  • Ciclofosfamide
  • Cicloxal
  • Clafen
  • Claphene
  • CP monohydrate
  • CTX
  • CYCLO-cell
  • Cycloblastin
  • Cycloblastine
  • Cyclophospham
  • Cyclophosphamid monohydrate
  • Cyclophosphamide Monohydrate
  • Cyclophosphamidum
  • Cyclophosphan
  • Cyclophosphane
  • Cyclophosphanum
  • Cyclostin
  • Cyclostine
  • Cytophosphan
  • Cytophosphane
  • Cytoxan
  • Fosfaseron
  • Genoxal
  • Genuxal
  • Ledoxina
  • Mitoxan
  • Neosar
  • Revimmune
  • Syklofosfamid
  • WR- 138719
  • Drug: Cytarabine
    Given IT, SC, or IV
    Other Names:
  • .beta.-Cytosine arabinoside
  • 1-.beta.-D-Arabinofuranosyl-4-amino-2(1H)pyrimidinone
  • 1-.beta.-D-Arabinofuranosylcytosine
  • 1-Beta-D-arabinofuranosyl-4-amino-2(1H)pyrimidinone
  • 1-Beta-D-arabinofuranosylcytosine
  • 1.beta.-D-Arabinofuranosylcytosine
  • 2(1H)-Pyrimidinone, 4-Amino-1-beta-D-arabinofuranosyl-
  • 2(1H)-Pyrimidinone, 4-amino-1.beta.-D-arabinofuranosyl-
  • Alexan
  • Ara-C
  • ARA-cell
  • Arabine
  • Arabinofuranosylcytosine
  • Arabinosylcytosine
  • Aracytidine
  • Aracytin
  • Aracytine
  • Beta-Cytosine Arabinoside
  • CHX-3311
  • Cytarabinum
  • Cytarbel
  • Cytosar
  • Cytosine Arabinoside
  • Cytosine-.beta.-arabinoside
  • Cytosine-beta-arabinoside
  • Erpalfa
  • Starasid
  • Tarabine PFS
  • U 19920
  • U-19920
  • Udicil
  • WR-28453
  • Drug: Daunorubicin Hydrochloride
    Given IV
    Other Names:
  • Cerubidin
  • Cerubidine
  • Cloridrato de Daunorubicina
  • Daunoblastin
  • Daunoblastina
  • Daunoblastine
  • Daunomycin Hydrochloride
  • Daunomycin, hydrochloride
  • Daunorubicin.HCl
  • Daunorubicini Hydrochloridum
  • FI-6339
  • Ondena
  • RP-13057
  • Rubidomycin Hydrochloride
  • Rubilem
  • Drug: Dexamethasone
    Given PO or IV
    Other Names:
  • Aacidexam
  • Adexone
  • Aknichthol Dexa
  • Alba-Dex
  • Alin
  • Alin Depot
  • Alin Oftalmico
  • Amplidermis
  • Anemul mono
  • Auricularum
  • Auxiloson
  • Baycadron
  • Baycuten
  • Baycuten N
  • Cortidexason
  • Cortisumman
  • Decacort
  • Decadrol
  • Decadron
  • Decadron DP
  • Decalix
  • Decameth
  • Decasone R.p.
  • Dectancyl
  • Dekacort
  • Deltafluorene
  • Deronil
  • Desamethasone
  • Desameton
  • Dexa-Mamallet
  • Dexa-Rhinosan
  • Dexa-Scheroson
  • Dexa-sine
  • Dexacortal
  • Dexacortin
  • Dexafarma
  • Dexafluorene
  • Dexalocal
  • Dexamecortin
  • Dexameth
  • Dexamethasone Intensol
  • Dexamethasonum
  • Dexamonozon
  • Dexapos
  • Dexinoral
  • Dexone
  • Dinormon
  • Dxevo
  • Fluorodelta
  • Fortecortin
  • Gammacorten
  • Hexadecadrol
  • Hexadrol
  • Lokalison-F
  • Loverine
  • Methylfluorprednisolone
  • Millicorten
  • Mymethasone
  • Orgadrone
  • Spersadex
  • TaperDex
  • Visumetazone
  • ZoDex
  • Drug: Doxorubicin Hydrochloride
    Given IV
    Other Names:
  • 5,12-Naphthacenedione, 10-[(3-amino-2,3,6-trideoxy-alpha-L-lyxo-hexopyranosyl)oxy]-7,8, 9,10-tetrahydro-6,8,11-trihydroxy-8-(hydroxyacetyl)-1-methoxy-, hydrochloride, (8S-cis)- (9CI)
  • ADM
  • Adriacin
  • Adriamycin
  • Adriamycin Hydrochloride
  • Adriamycin PFS
  • Adriamycin RDF
  • ADRIAMYCIN, HYDROCHLORIDE
  • Adriamycine
  • Adriblastina
  • Adriblastine
  • Adrimedac
  • Chloridrato de Doxorrubicina
  • DOX
  • DOXO-CELL
  • Doxolem
  • Doxorubicin HCl
  • Doxorubicin.HCl
  • Doxorubin
  • Farmiblastina
  • FI 106
  • FI-106
  • hydroxydaunorubicin
  • Rubex
  • Drug: Leucovorin Calcium
    Given IV
    Other Names:
  • Adinepar
  • Calcifolin
  • Calcium (6S)-Folinate
  • Calcium Folinate
  • Calcium Leucovorin
  • Calfolex
  • Calinat
  • Cehafolin
  • Citofolin
  • Citrec
  • Citrovorum Factor
  • Cromatonbic Folinico
  • Dalisol
  • Disintox
  • Divical
  • Ecofol
  • Emovis
  • Factor, Citrovorum
  • Flynoken A
  • Folaren
  • Folaxin
  • FOLI-cell
  • Foliben
  • Folidan
  • Folidar
  • Folinac
  • Folinate Calcium
  • folinic acid
  • Folinic Acid Calcium Salt Pentahydrate
  • Folinoral
  • Folinvit
  • Foliplus
  • Folix
  • Imo
  • Lederfolat
  • Lederfolin
  • Leucosar
  • leucovorin
  • Rescufolin
  • Rescuvolin
  • Tonofolin
  • Wellcovorin
  • Drug: Mercaptopurine
    Given PO
    Other Names:
  • 3H-Purine-6-thiol
  • 6 MP
  • 6 Thiohypoxanthine
  • 6 Thiopurine
  • 6-Mercaptopurine
  • 6-Mercaptopurine Monohydrate
  • 6-MP
  • 6-Purinethiol
  • 6-Thiopurine
  • 6-Thioxopurine
  • 6H-Purine-6-thione, 1,7-dihydro- (9CI)
  • 7-Mercapto-1,3,4,6-tetrazaindene
  • Alti-Mercaptopurine
  • Azathiopurine
  • Bw 57-323H
  • Flocofil
  • Ismipur
  • Leukerin
  • Leupurin
  • Mercaleukim
  • Mercaleukin
  • Mercaptina
  • Mercaptopurinum
  • Mercapurin
  • Mern
  • NCI-C04886
  • Puri-Nethol
  • Purimethol
  • Purine, 6-mercapto-
  • Purine-6-thiol (8CI)
  • Purine-6-thiol, monohydrate
  • Purinethiol
  • Purinethol
  • U-4748
  • WR-2785
  • Drug: Methotrexate
    Given IT or IV
    Other Names:
  • Abitrexate
  • Alpha-Methopterin
  • Amethopterin
  • Brimexate
  • CL 14377
  • CL-14377
  • Emtexate
  • Emthexat
  • Emthexate
  • Farmitrexat
  • Fauldexato
  • Folex
  • Folex PFS
  • Lantarel
  • Ledertrexate
  • Lumexon
  • Maxtrex
  • Medsatrexate
  • Metex
  • Methoblastin
  • Methotrexate LPF
  • Methotrexate Methylaminopterin
  • Methotrexatum
  • Metotrexato
  • Metrotex
  • Mexate
  • Mexate-AQ
  • MTX
  • Novatrex
  • Rheumatrex
  • Texate
  • Tremetex
  • Trexeron
  • Trixilem
  • WR-19039
  • Drug: Pegaspargase
    Given IM
    Other Names:
  • L-Asparaginase with Polyethylene Glycol
  • Oncaspar
  • Oncaspar-IV
  • PEG-Asparaginase
  • PEG-L-Asparaginase
  • PEG-L-Asparaginase (Enzon - Kyowa Hakko)
  • PEGLA
  • Polyethylene Glycol L-Asparaginase
  • Polyethylene Glycol-L-Asparaginase
  • Drug: Prednisone
    Given PO or IV
    Other Names:
  • .delta.1-Cortisone
  • 1, 2-Dehydrocortisone
  • Adasone
  • Cortancyl
  • Dacortin
  • DeCortin
  • Decortisyl
  • Decorton
  • Delta 1-Cortisone
  • Delta-Dome
  • Deltacortene
  • Deltacortisone
  • Deltadehydrocortisone
  • Deltasone
  • Deltison
  • Deltra
  • Econosone
  • Lisacort
  • Meprosona-F
  • Metacortandracin
  • Meticorten
  • Ofisolona
  • Orasone
  • Panafcort
  • Panasol-S
  • Paracort
  • Perrigo Prednisone
  • PRED
  • Predicor
  • Predicorten
  • Prednicen-M
  • Prednicort
  • Prednidib
  • Prednilonga
  • Predniment
  • Prednisone Intensol
  • Prednisonum
  • Prednitone
  • Promifen
  • Rayos
  • Servisone
  • SK-Prednisone
  • Radiation: Radiation Therapy
    Undergo radiation therapy
    Other Names:
  • Cancer Radiotherapy
  • ENERGY_TYPE
  • Irradiate
  • Irradiated
  • Irradiation
  • Radiation
  • Radiation Therapy, NOS
  • Radiotherapeutics
  • Radiotherapy
  • RT
  • Therapy, Radiation
  • Drug: Thioguanine
    Given PO
    Other Names:
  • 2-Amino 6MP
  • 2-Amino-1,7-dihydro-6H-purine-6-thione
  • 2-Amino-6-mercaptopurine
  • 2-Amino-6-purinethiol
  • 2-Aminopurin-6-thiol
  • 2-Aminopurine-6(1H)-thione
  • 2-Aminopurine-6-thiol
  • 2-Aminopurine-6-thiol Hemihydrate
  • 2-Mercapto-6-aminopurine
  • 6-Amino-2-mercaptopurine
  • 6-Mercapto-2-aminopurine
  • 6-Mercaptoguanine
  • 6-TG
  • 6H-Purine-6-thione, 2-amino-1,7-dihydro- (9CI)
  • BW 5071
  • Lanvis
  • Tabloid
  • Thioguanine Hemihydrate
  • Thioguanine Hydrate
  • Tioguanin
  • Tioguanine
  • Wellcome U3B
  • WR-1141
  • X 27
  • Drug: Vincristine Sulfate
    Given IV
    Other Names:
  • Kyocristine
  • Leurocristine Sulfate
  • Leurocristine, sulfate
  • Oncovin
  • Vincasar
  • Vincosid
  • Vincrex
  • Vincristine, sulfate
  • Outcome Measures

    Primary Outcome Measures

    1. 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

    1. 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.

    2. 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.

    3. 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.

    4. 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.

    5. 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.

    6. 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

    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

    1. Primary Outcome
    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%
    2. Secondary Outcome
    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%
    3. Secondary Outcome
    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%
    4. Secondary Outcome
    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%
    5. Secondary Outcome
    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%
    6. Secondary Outcome
    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%
    7. Secondary Outcome
    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
    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
    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
    Email 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