Total Body Irradiation/Fludarabine Based Ablative Haploidentical Transplant for Hematologic Diseases

• Sponsor: Northside Hospital, Inc. (Other)
• Overall Status: Completed
• CT.gov ID: NCT01336712
• Collaborator: Blood and Marrow Transplant Group of Georgia (Other)
• Enrollment: 30
• Location: 1
• Arm: 1
• Duration (Months): 51
• Patients Per Site Per Month: 0.6

Study Details

Study Description

Brief Summary

In this study, patients will receive a myeloablative preparative regimen consisting of fludarabine and total body irradiation (TBI), followed by a T cell replete, mobilized peripheral blood stem cell (PBSC) allograft from a partially matched related donor. All patients will receive post-transplant Cy in addition to standard post transplant immunosuppression with tacrolimus and MMF. The treatment protocol will be essentially identical to the prior study, with the exception of the substitution of TBI for Busulfan. The investigators hypothesize that this change will significantly reduce the risk of HC, while maintaining the efficacy of the transplant.

Condition or Disease	Intervention/Treatment	Phase
Chronic Leukemia; Acute Leukemia; Hodgkin's Disease; Non-Hodgkin's Lymphoma; Myelodysplastic Syndrome	Procedure: Peripheral Blood Stem Cell Transplant	Phase 2

Detailed Description

Historically, haploidentical HSCT has been associated with significant risks of graft rejection and severe graft versus host disease (GVHD), leading to high treatment related mortality and poor outcomes. The risk of engraftment failure and GVHD may be reduced in intensively conditioned recipients of grafts that have been rigorously depleted of T cells, but the risks of serious infection and death from prolonged immune compromise in these patients remains high. Recently, investigators from Johns Hopkins University demonstrated a new approach to haploidentical transplantation, utilizing a nonmyeloablative preparative regimen, followed by a T cell-replete bone marrow infusion and post-transplantation immunosuppression with high dose Cyclophosphamide (Cy), tacrolimus, and MMF. Clinical studies have shown this approach to be safe and effective with a low incidence of graft rejection, GVHD, and treatment-related mortality. Relapse represents the major cause of treatment failure in these patients, particularly with high-risk myeloid malignancies.

In order to decrease this relapse risk in high-risk patients, the investigators initiated a myeloablative haploidentical HSCT study in January 2009 utilizing Busulfan-based conditioning, post-transplant Cy, and PBSC, instead of BM, as the stem cell source. Outcomes of the 15 patients transplanted to date have been promising with 100% engraftment, low rates of treatment-related mortality, relapse and GVHD, and excellent survival rates. An unexpected outcome of the study was a higher-than-expected rate of BK virus-induced hemorrhagic cystitis (HC) occurring in 7 of 14 evaluable patients. Although there were no deaths attributable to HC, it was associated with significant morbidity in some patients.

HC is a recognized complication of allogeneic transplant therapy. Late onset HC, occurring after engraftment, is due almost exclusively to reactivation of the polyoma BK virus (BKV). Other important risk factors associated with HC include Busulfan-based conditioning, acute GVHD, HLA mismatched transplants, and use of bone marrow as the stem cell source. TBI-based conditioning, prior to myeloablative allogeneic transplant, has been associated with significantly less HC than Busulfan-based conditioning in both retrospective and prospective randomized trials.

Eighteen patients will be accrued to this study. The primary end point of this study is the incidence of HC. The investigators will also examine the incidence of acute and chronic GVHD, engraftment, degree of donor-host chimerism, transplant related morbidity and mortality, as well as disease-free and overall survival. Stopping rules will minimize the risk of untoward or unexpected side effects.

Study Design

• Study Type: Interventional
• Actual Enrollment: 30 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase II Trial of Total Body Irradiation-Based Myeloablative Conditioning and Transplantation of Partially HLA-Mismatched Peripheral Blood Stem Cells for Patients With Hematologic Malignancies
• Study Start Date: Apr 1, 2011
• Actual Primary Completion Date: Dec 1, 2014
• Actual Study Completion Date: Jul 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Myeloablative Haploidentical Transplant Haplo transplant	Procedure: Peripheral Blood Stem Cell Transplant; Total Body Irradiation 1200cGy (150cGy given in 8 fractions twice a day six hours apart on days -4, -3, -2 and -1. Fludarabine 30 mg/m^2 given once a day for 3 days on days -7, -6 and -5 Cyclophosphamide 50mg/kg given one a day on days +3 and +4; Other Names: TBI Fludara Cytoxan

Outcome Measures

Primary Outcome Measures

1. Percentage of Patients Experiencing Hemorrhagic Cystitis Post Transplant [6 months]

   1.1 To estimate the incidence of BK virus-associated hemorrhagic cystitis following a TBI-based myeloablative haploidentical HSCT in patients with high risk hematologic malignancies.

Secondary Outcome Measures

1. Survival [2 year]

   To obtain estimate of overall survival (OS)

2. Percentage of Participatns With Donor Chimerism Post-transplant [Day 30]

   Characterize donor hematopoietic chimerism in peripheral blood at day 30 after HSCT.

3. Disease Free Survival (DFS) Percentage [2 year]

4. Non-relapsed Mortality (NRM) Percentage [2 year]

5. Relapse Rate [2 year]

6. Cumulative Incidence of Chronic Graft-versus-host Disease [2 year]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 60 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• No available matched related or unrelated donor OR a matched related or unrelated donor that is unavailable in the time frame necessary

• Availability of a 3/6 or 5/6 matched (HLA-A, B, DR) related donor

• Donor must have a negative HLA cross-match in the host vs. graft direction

• Donor must be willing to donate mobilized peripheral blood stem cells

• Age 18 to </=60 years

• Karnofsky Status >/= 70%

• Must have one of the following high-risk malignancies

• Chronic Myelogenous Leukemia (CML) in chronic phase, resistant and/or intolerant to TKI

• CML in accelerated phase

• CML blast crisis that has entered into 2nd Chronic phase following induction

• Acute Myelogenous Leukemia (AML) in 2nd or subsequent complete remission (CR)

• AML primary induction failure but subsequently in CR

• AML in 1st CR with poor risk cytogenetics or arising from preceding hematologic disease

• AML with marrow blasts <5% but persistence of minimal residual disease by flow cytometry, cytogenetics or FISH

• Myelodysplastic Syndrome (MDS) that is treatment related

• MDS that has monosomy 7 or complex cytogenetics

• MDS with IPSS score of 1.5 or greater

• Chronic myelomonocytic leukemia (CMML)

• Acute Lymphocytic Leukemia/lymphoblastic lymphoma (ALL) in 2nd or subsequent complete remission (CR)

• ALL with poor-risk karyotype [t(9;22) or bcr-abl fusion, t(4;11) or other MLL translocation] and in 1st CR

• ALL with marrow blasts < 5% but persistence of minimal residual disease by flow cytometry, cytogenetics or FISH

• Chronic Lymphocytic Leukemia (CLL)/Prolymphocytic Leukemia (PLL) with previously treated disease that has either relapsed or failed to respond adequately to conventional-dose therapy including purine analogs AND in the opinion of the transplant physician is unlikely to benefit from reduced intensity transplantation due to the presence of one or more high risk features (i.e. bulky tumor masses, B symptoms, and/or inadequate response to salvage chemotherapy)

• Hodgkin's or Non-Hodgkin's Lymphoma (including low-grade, mantle cell, and intermediate-grade/diffuse) with previously treated disease that has either relapsed or failed to respond adequately to conventional-dose therapy or autologous transplantation AND in the opinion of the transplant physician is unlikely to benefit from reduced intensity transplantation due to the presence of one or more high risk features (i.e. bulky tumor masses, B symptoms, and/or inadequate response to salvage chemotherapy)

• Advance Myelofibrosis, Primary or Post-Polycythemia Vera/Essential Thrombocythemia. Patients must have one of more of the following accelerate phase features, which have been associated with a median overall survival of </= 15 months

• Blood or bone marrow blasts >/= 10%

• Platelets < 50 x 10*9/L

• Chromosome 17 aberrations

Exclusion Criteria:

• Patients will not be excluded on the basis of sex, racial or ethnic background

• Poor cardiac function: Left ventricular ejection fraction < 45%

• Poor pulmonary function: FEV1 and FVD < 60% predicted

• Poor liver function: bilirubin >/= 2.5 mg/dl (not due to hemolysis, Gilbert's or primary malignancy), AST/ALT > 3x ULN

• Poor renal function: Creatinine >/= 2.0 mg/dl or creatinine clearance (calculated creatinine clearance is permitted) < 40 mL/min based on Traditional Cockcroft-Gault formula: 140-age (yrs) x smaller of actual weight vs ideal body weight (kg)/72 x serum creatinine (mg/dl)

• HIV positive

• Women of childbearing potential who currently are pregnant or who are not practicing adequate contraception

• Patients who have any debilitating medical or psychiatric illness which would preclude their giving informed consent or their receiving optimal treatment and follow-up.

• Prior irradiation therapy rendering patient ineligible for TBI

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Northside Hospital	Atlanta	Georgia	United States	30342

Sponsors and Collaborators

• Northside Hospital, Inc.
• Blood and Marrow Transplant Group of Georgia

Investigators

• Principal Investigator: Scott R Solomon, MD, Blood and Marrow Transplant Group of Georgia

Study Documents (Full-Text)

None provided.

More Information

Publications

• Anasetti C, Amos D, Beatty PG, Appelbaum FR, Bensinger W, Buckner CD, Clift R, Doney K, Martin PJ, Mickelson E, et al. Effect of HLA compatibility on engraftment of bone marrow transplants in patients with leukemia or lymphoma. N Engl J Med. 1989 Jan 26;320(4):197-204.
• Anasetti C, Beatty PG, Storb R, Martin PJ, Mori M, Sanders JE, Thomas ED, Hansen JA. Effect of HLA incompatibility on graft-versus-host disease, relapse, and survival after marrow transplantation for patients with leukemia or lymphoma. Hum Immunol. 1990 Oct;29(2):79-91.
• Aversa F, Tabilio A, Velardi A, Cunningham I, Terenzi A, Falzetti F, Ruggeri L, Barbabietola G, Aristei C, Latini P, Reisner Y, Martelli MF. Treatment of high-risk acute leukemia with T-cell-depleted stem cells from related donors with one fully mismatched HLA haplotype. N Engl J Med. 1998 Oct 22;339(17):1186-93.
• Aversa F, Terenzi A, Tabilio A, Falzetti F, Carotti A, Ballanti S, Felicini R, Falcinelli F, Velardi A, Ruggeri L, Aloisi T, Saab JP, Santucci A, Perruccio K, Martelli MP, Mecucci C, Reisner Y, Martelli MF. Full haplotype-mismatched hematopoietic stem-cell transplantation: a phase II study in patients with acute leukemia at high risk of relapse. J Clin Oncol. 2005 May 20;23(15):3447-54. Epub 2005 Mar 7.
• Guinan EC, Boussiotis VA, Neuberg D, Brennan LL, Hirano N, Nadler LM, Gribben JG. Transplantation of anergic histoincompatible bone marrow allografts. N Engl J Med. 1999 Jun 3;340(22):1704-14.
• Kanda Y, Chiba S, Hirai H, Sakamaki H, Iseki T, Kodera Y, Karasuno T, Okamoto S, Hirabayashi N, Iwato K, Maruta A, Fujimori Y, Furukawa T, Mineishi S, Matsuo K, Hamajima N, Imamura M. Allogeneic hematopoietic stem cell transplantation from family members other than HLA-identical siblings over the last decade (1991-2000). Blood. 2003 Aug 15;102(4):1541-7. Epub 2003 Apr 24.
• Kernan NA, Collins NH, Juliano L, Cartagena T, Dupont B, O'Reilly RJ. Clonable T lymphocytes in T cell-depleted bone marrow transplants correlate with development of graft-v-host disease. Blood. 1986 Sep;68(3):770-3.
• Kernan NA, Flomenberg N, Dupont B, O'Reilly RJ. Graft rejection in recipients of T-cell-depleted HLA-nonidentical marrow transplants for leukemia. Identification of host-derived antidonor allocytotoxic T lymphocytes. Transplantation. 1987 Jun;43(6):842-7.
• Lang P, Greil J, Bader P, Handgretinger R, Klingebiel T, Schumm M, Schlegel PG, Feuchtinger T, Pfeiffer M, Scheel-Walter H, Führer M, Martin D, Niethammer D. Long-term outcome after haploidentical stem cell transplantation in children. Blood Cells Mol Dis. 2004 Nov-Dec;33(3):281-7.
• Mehta J, Singhal S, Gee AP, Chiang KY, Godder K, Rhee Fv Fv, DeRienzo S, O'Neal W, Lamb L, Henslee-Downey PJ. Bone marrow transplantation from partially HLA-mismatched family donors for acute leukemia: single-center experience of 201 patients. Bone Marrow Transplant. 2004 Feb;33(4):389-96.
• Rizzieri DA, Koh LP, Long GD, Gasparetto C, Sullivan KM, Horwitz M, Chute J, Smith C, Gong JZ, Lagoo A, Niedzwiecki D, Dowell JM, Waters-Pick B, Liu C, Marshall D, Vredenburgh JJ, Gockerman J, Decastro C, Moore J, Chao NJ. Partially matched, nonmyeloablative allogeneic transplantation: clinical outcomes and immune reconstitution. J Clin Oncol. 2007 Feb 20;25(6):690-7. Epub 2007 Jan 16.
• Szydlo R, Goldman JM, Klein JP, Gale RP, Ash RC, Bach FH, Bradley BA, Casper JT, Flomenberg N, Gajewski JL, Gluckman E, Henslee-Downey PJ, Hows JM, Jacobsen N, Kolb HJ, Lowenberg B, Masaoka T, Rowlings PA, Sondel PM, van Bekkum DW, van Rood JJ, Vowels MR, Zhang MJ, Horowitz MM. Results of allogeneic bone marrow transplants for leukemia using donors other than HLA-identical siblings. J Clin Oncol. 1997 May;15(5):1767-77.
• Waller EK, Giver CR, Rosenthal H, Somani J, Langston AA, Lonial S, Roback JD, Li JM, Hossain MS, Redei I. Facilitating T-cell immune reconstitution after haploidentical transplantation in adults. Blood Cells Mol Dis. 2004 Nov-Dec;33(3):233-7.
• Zuckerman T, Rowe JM. Alternative donor transplantation in acute myeloid leukemia: which source and when? Curr Opin Hematol. 2007 Mar;14(2):152-61. Review.

• Responsible Party: Northside Hospital, Inc.
• ClinicalTrials.gov Identifier: NCT01336712
• Other Study ID Numbers: NSH 922
• First Posted: Apr 18, 2011
• Last Update Posted: Jan 14, 2016
• Last Verified: Dec 1, 2015

• Keywords provided by Northside Hospital, Inc.: CML; CLL; AML; ALL; MDS; HD; NHL; MFB; P.vera; Essential Thrombocytosis
• Additional relevant MeSH terms: Leukemia; Hodgkin Disease; Myelodysplastic Syndromes

Study Results

Participant Flow

Arm/Group Title	Myeloablative Haploidentical Transplant
Arm/Group Description	Haplo transplant Peripheral Blood Stem Cell Transplant: Total Body Irradiation 1200cGy (150cGy given in 8 fractions twice a day six hours apart on days -4, -3, -2 and -1. Fludarabine 30 mg/m^2 given once a day for 3 days on days -7, -6 and -5 Cyclophosphamide 50mg/kg given one a day on days +3 and +4 Patient follow up x6 months
Period Title: Overall Study
STARTED	30
COMPLETED	27
NOT COMPLETED	3

Baseline Characteristics

Arm/Group Title	Myeloablative Haploidentical Transplant
Arm/Group Description	Haplo transplant Peripheral Blood Stem Cell Transplant: Total Body Irradiation 1200cGy (150cGy given in 8 fractions twice a day six hours apart on days -4, -3, -2 and -1. Fludarabine 30 mg/m2 given once a day for 3 days on days -7, -6 and -5 Cyclophosphamide 50mg/kg given one a day on days +3 and +4
Overall Participants	30
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	30 100%
>=65 years	0 0%
Sex: Female, Male (Count of Participants)
Female	17 56.7%
Male	13 43.3%
Race/Ethnicity, Customized (participants) [Number]
White	10 33.3%
Black/African America	20 66.7%

Outcome Measures

1. Primary Outcome

Title	Percentage of Patients Experiencing Hemorrhagic Cystitis Post Transplant
Description	1.1 To estimate the incidence of BK virus-associated hemorrhagic cystitis following a TBI-based myeloablative haploidentical HSCT in patients with high risk hematologic malignancies.
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Myeloablative Haploidentical Transplant
Arm/Group Description	Haplo transplant Peripheral Blood Stem Cell Transplant: Total Body Irradiation 1200cGy (150cGy given in 8 fractions twice a day six hours apart on days -4, -3, -2 and -1. Fludarabine 30 mg/m2 given once a day for 3 days on days -7, -6 and -5 Cyclophosphamide 50mg/kg given one a day on days +3 and +4
Measure Participants	30
Number [percentage of patients]	30

2. Secondary Outcome

Title	Survival
Description	To obtain estimate of overall survival (OS)
Time Frame	2 year

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Myeloablative Haploidentical Transplant
Arm/Group Description	Haplo transplant Peripheral Blood Stem Cell Transplant: Total Body Irradiation 1200cGy (150cGy given in 8 fractions twice a day six hours apart on days -4, -3, -2 and -1. Fludarabine 30 mg/m2 given once a day for 3 days on days -7, -6 and -5 Cyclophosphamide 50mg/kg given one a day on days +3 and +4
Measure Participants	30
Number [percentage of patients analyzed]	78

3. Secondary Outcome

Title	Percentage of Participatns With Donor Chimerism Post-transplant
Description	Characterize donor hematopoietic chimerism in peripheral blood at day 30 after HSCT.
Time Frame	Day 30

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Myeloablative Haploidentical Transplant
Arm/Group Description	Haplo transplant Peripheral Blood Stem Cell Transplant: Total Body Irradiation 1200cGy (150cGy given in 8 fractions twice a day six hours apart on days -4, -3, -2 and -1. Fludarabine 30 mg/m2 given once a day for 3 days on days -7, -6 and -5 Cyclophosphamide 50mg/kg given one a day on days +3 and +4
Measure Participants	30
Number [percentage of patients]	100

4. Secondary Outcome

Title	Disease Free Survival (DFS) Percentage
Time Frame	2 year

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Myeloablative Haploidentical Transplant
Arm/Group Description	Haplo transplant Peripheral Blood Stem Cell Transplant: Total Body Irradiation 1200cGy (150cGy given in 8 fractions twice a day six hours apart on days -4, -3, -2 and -1. Fludarabine 30 mg/m2 given once a day for 3 days on days -7, -6 and -5 Cyclophosphamide 50mg/kg given one a day on days +3 and +4
Measure Participants	30
Number [percentage of patients analyzed]	73

5. Secondary Outcome

Title	Non-relapsed Mortality (NRM) Percentage
Time Frame	2 year

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Myeloablative Haploidentical Transplant
Arm/Group Description	Haplo transplant Peripheral Blood Stem Cell Transplant: Total Body Irradiation 1200cGy (150cGy given in 8 fractions twice a day six hours apart on days -4, -3, -2 and -1. Fludarabine 30 mg/m2 given once a day for 3 days on days -7, -6 and -5 Cyclophosphamide 50mg/kg given one a day on days +3 and +4
Measure Participants	30
Number [percentage of patients]	3

6. Secondary Outcome

Title	Relapse Rate
Time Frame	2 year

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Myeloablative Haploidentical Transplant
Arm/Group Description	Haplo transplant Peripheral Blood Stem Cell Transplant: Total Body Irradiation 1200cGy (150cGy given in 8 fractions twice a day six hours apart on days -4, -3, -2 and -1. Fludarabine 30 mg/m2 given once a day for 3 days on days -7, -6 and -5 Cyclophosphamide 50mg/kg given one a day on days +3 and +4
Measure Participants	30
Number [percentage of patients analyzed]	24

7. Secondary Outcome

Title	Cumulative Incidence of Chronic Graft-versus-host Disease
Time Frame	2 year

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Myeloablative Haploidentical Transplant
Arm/Group Description	Haplo transplant Peripheral Blood Stem Cell Transplant: Total Body Irradiation 1200cGy (150cGy given in 8 fractions twice a day six hours apart on days -4, -3, -2 and -1. Fludarabine 30 mg/m2 given once a day for 3 days on days -7, -6 and -5 Cyclophosphamide 50mg/kg given one a day on days +3 and +4
Measure Participants	30
Number [percentage of patients analyzed]	56

Adverse Events

Arm/Group Title	Myeloablative Haploidentical Transplant
Arm/Group Description	Haplo transplant Peripheral Blood Stem Cell Transplant: Total Body Irradiation 1200cGy (150cGy given in 8 fractions twice a day six hours apart on days -4, -3, -2 and -1. Fludarabine 30 mg/m2 given once a day for 3 days on days -7, -6 and -5 Cyclophosphamide 50mg/kg given one a day on days +3 and +4
All Cause Mortality
	Myeloablative Haploidentical Transplant
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Myeloablative Haploidentical Transplant
	Affected / at Risk (%)	# Events
Total	13/30 (43.3%)
Blood and lymphatic system disorders
Hemolytic Uremic Syndrom	1/30 (3.3%)	1
Cardiac disorders
Syncope	1/30 (3.3%)	1
Gastrointestinal disorders
anorexia	1/30 (3.3%)	1
Nausea & vomiting	1/30 (3.3%)	1
Hepatobiliary disorders
Veno-Occlusive Disease	1/30 (3.3%)	1
Infections and infestations
BK Virus	1/30 (3.3%)	1
Sepsis syndrome	1/30 (3.3%)	1
Renal and urinary disorders
Renal Insufficiency	2/30 (6.7%)	2
Respiratory, thoracic and mediastinal disorders
Pneumonia	3/30 (10%)	3
Alveolar Hemorrhage	1/30 (3.3%)	1
Other (Not Including Serious) Adverse Events
	Myeloablative Haploidentical Transplant
	Affected / at Risk (%)	# Events
Total	30/30 (100%)
Blood and lymphatic system disorders
neutropenia	26/30 (86.7%)	26
bleeding gums	5/30 (16.7%)	5
blood in sputum	2/30 (6.7%)	2
bruising	6/30 (20%)	6
CMV reactivation	15/30 (50%)	15
epistaxis	11/30 (36.7%)	11
hemoptysis	2/30 (6.7%)	2
anemia	28/30 (93.3%)	28
lymphocytopenia	12/30 (40%)	12
febrile neutropenia	26/30 (86.7%)	26
petechiae	5/30 (16.7%)	5
thrombocytopenia	29/30 (96.7%)	29
leukopenia	28/30 (93.3%)	28
Cardiac disorders
bradycardia	6/30 (20%)	6
chest tightness	2/30 (6.7%)	2
edema of hands and feet	2/30 (6.7%)	2
lower extremity edema	18/30 (60%)	18
fluid overload	11/30 (36.7%)	11
hypertension	27/30 (90%)	27
hypotension	19/30 (63.3%)	19
irregular heartbeat	4/30 (13.3%)	4
orthostatic hypotension	3/30 (10%)	3
palpitations	4/30 (13.3%)	4
pericardial effusion	3/30 (10%)	3
tachycardia	25/30 (83.3%)	25
tachypnea	3/30 (10%)	3
Ear and labyrinth disorders
ear fullness	2/30 (6.7%)	2
serous otitis	2/30 (6.7%)	2
Endocrine disorders
splenomegaly	2/30 (6.7%)	2
Gastrointestinal disorders
abcessed tooth	2/30 (6.7%)	2
abdominal bloating	6/30 (20%)	6
abdominal cramping/discomfort	20/30 (66.7%)	20
abdominal fullness	2/30 (6.7%)	2
abdominal muscle soreness (secondary to cough)	2/30 (6.7%)	2
abdominal tenderness	8/30 (26.7%)	8
acidosis	4/30 (13.3%)	4
anorexia	15/30 (50%)	15
coated tongue	5/30 (16.7%)	5
constipation	19/30 (63.3%)	19
decreased appetite	22/30 (73.3%)	22
decreased fluid intake	7/30 (23.3%)	7
decreased oral intake	5/30 (16.7%)	5
diarrhea	30/30 (100%)	30
difficulty swallowing	10/30 (33.3%)	10
abdominal distention	8/30 (26.7%)	8
dry heaves	5/30 (16.7%)	5
dry lips	3/30 (10%)	3
dry mouth	18/30 (60%)	18
dry throat	3/30 (10%)	3
dysgeusia	5/30 (16.7%)	5
dyspepsia	2/30 (6.7%)	2
dysphagia	6/30 (20%)	6
esophagitis	9/30 (30%)	9
esophageal pain	3/30 (10%)	3
flatulence	3/30 (10%)	3
gastritis	3/30 (10%)	3
GERD	24/30 (80%)	24
gastrointenstinal bleed	2/30 (6.7%)	2
hemorrhoids	5/30 (16.7%)	5
hiccups	4/30 (13.3%)	4
hyperactive bowel sounds	3/30 (10%)	3
hypoactive bowel sounds	5/30 (16.7%)	5
stool incontinence	7/30 (23.3%)	7
malnutrition	2/30 (6.7%)	2
melena	2/30 (6.7%)	2
mouth sores	10/30 (33.3%)	10
mucositis	25/30 (83.3%)	25
nausea	29/30 (96.7%)	29
oral lesions	2/30 (6.7%)	2
abdominal pain	13/30 (43.3%)	13
hemorrhoidal pain	2/30 (6.7%)	2
mouth pain	13/30 (43.3%)	13
throat pain (2nd mucositis)	5/30 (16.7%)	5
tooth pain	2/30 (6.7%)	2
pain with swallowing	4/30 (13.3%)	4
perirectal irritation	5/30 (16.7%)	5
perirectal pain	3/30 (10%)	3
saliva thickening	3/30 (10%)	3
scalloped tongue border	7/30 (23.3%)	7
small bowel obstruction	2/30 (6.7%)	2
sore throat	18/30 (60%)	18
stomatitis	9/30 (30%)	9
thick oral secretions	2/30 (6.7%)	2
tongue ridging	3/30 (10%)	3
vomiting	24/30 (80%)	24
weight gain	3/30 (10%)	3
weight loss	22/30 (73.3%)	22
General disorders
rigors	6/30 (20%)	6
seasonal allergies	6/30 (20%)	6
sinus pressure	2/30 (6.7%)	2
sinus tenderness	3/30 (10%)	3
sinusitis	5/30 (16.7%)	5
sneezing	4/30 (13.3%)	4
facial swelling	2/30 (6.7%)	2
throat swelling	2/30 (6.7%)	2
tongue swelling	2/30 (6.7%)	2
volume depletion	6/30 (20%)	6
volume overload	3/30 (10%)	3
weakness	24/30 (80%)	24
Hepatobiliary disorders
increased alkaline phosphatase	20/30 (66.7%)	20
increased ALT	22/30 (73.3%)	22
increased AST	29/30 (96.7%)	29
hyperbilirubinemia	8/30 (26.7%)	8
Immune system disorders
acute GVHD - gut	10/30 (33.3%)	10
acute GVHD - skin	8/30 (26.7%)	8
Infections and infestations
c.difficile colitis	5/30 (16.7%)	5
folliculitis	4/30 (13.3%)	4
bacteremia infection (NOS)	6/30 (20%)	6
influenza	2/30 (6.7%)	2
oral candida	2/30 (6.7%)	2
parainfluenza	2/30 (6.7%)	2
parotitis	2/30 (6.7%)	2
pneumonia	4/30 (13.3%)	4
rhinovirus	2/30 (6.7%)	2
staphylococcus hemolyticus bacteremia	2/30 (6.7%)	2
vancomycin-resistant enterococci	5/30 (16.7%)	5
Investigations
chills	22/30 (73.3%)	22
CVC site bleeding	2/30 (6.7%)	2
CVC site edema	2/30 (6.7%)	2
CVC site soreness	3/30 (10%)	3
CVC site tenderness	7/30 (23.3%)	7
deconditioned	20/30 (66.7%)	20
dehydration	5/30 (16.7%)	5
fatigue	29/30 (96.7%)	29
fever	24/30 (80%)	24
lethargy	11/30 (36.7%)	11
malaise	7/30 (23.3%)	7
night sweats	3/30 (10%)	3
oral thrush	10/30 (33.3%)	10
CVC site pain	3/30 (10%)	3
parotid gland edema	2/30 (6.7%)	2
parotid gland tenderness	2/30 (6.7%)	2
platelet infusion reaction	2/30 (6.7%)	2
Metabolism and nutrition disorders
electrolyte wasting syndrome	6/30 (20%)	6
hypercalcemia	10/30 (33.3%)	10
hyperglycemia	30/30 (100%)	30
hyperkalemia	15/30 (50%)	15
hypermagnesemia	3/30 (10%)	3
hypernatremia	19/30 (63.3%)	19
hypoalbuminemia	24/30 (80%)	24
hypocalcemia	25/30 (83.3%)	25
hypoglycemia	2/30 (6.7%)	2
hypokalemia	23/30 (76.7%)	23
hypomagnesemia	27/30 (90%)	27
hyponatremia	10/30 (33.3%)	10
steroid-induced diabetes	3/30 (10%)	3
Musculoskeletal and connective tissue disorders
left lower flank pain	2/30 (6.7%)	2
generalized body aches	11/30 (36.7%)	11
leg cramping	5/30 (16.7%)	5
leg discomfort (2nd lower extremity edema)	2/30 (6.7%)	2
limited mobility	9/30 (30%)	9
lower extremity pain	3/30 (10%)	3
myalgias	2/30 (6.7%)	2
ankle pain	3/30 (10%)	3
arm pain	3/30 (10%)	3
back pain	10/30 (33.3%)	10
bone pain	4/30 (13.3%)	4
chest pain	6/30 (20%)	6
chest pain (2nd cough)	3/30 (10%)	3
fingertip pain	2/30 (6.7%)	2
foot pain	5/30 (16.7%)	5
hand pain	6/30 (20%)	6
jaw pain	4/30 (13.3%)	4
joint pain	8/30 (26.7%)	8
knee pain	4/30 (13.3%)	4
leg pain	10/30 (33.3%)	10
muscle pain	3/30 (10%)	3
shoulder pain	4/30 (13.3%)	4
suprapubic tenderness	2/30 (6.7%)	2
Nervous system disorders
abnormal gait	2/30 (6.7%)	2
blurred vision	7/30 (23.3%)	7
confusion	2/30 (6.7%)	2
dizziness	16/30 (53.3%)	16
drowsiness	18/30 (60%)	18
headache	24/30 (80%)	24
lightheadedness	3/30 (10%)	3
limited sensory perception	6/30 (20%)	6
loss of balance	8/30 (26.7%)	8
migraine headaches	3/30 (10%)	3
panic attack	2/30 (6.7%)	2
peripheral neuropathy	16/30 (53.3%)	16
photosensitivity	2/30 (6.7%)	2
restless legs	2/30 (6.7%)	2
sedation	3/30 (10%)	3
sinus headache	2/30 (6.7%)	2
somnolence	3/30 (10%)	3
taste alteration	10/30 (33.3%)	10
tremors	9/30 (30%)	9
tremors (hands)	2/30 (6.7%)	2
unsteady gait	2/30 (6.7%)	2
Psychiatric disorders
agitation	2/30 (6.7%)	2
anxiety	26/30 (86.7%)	26
depression	19/30 (63.3%)	19
flat affect	11/30 (36.7%)	11
hallucinations	2/30 (6.7%)	2
insomnia	23/30 (76.7%)	23
Renal and urinary disorders
BK Virus	10/30 (33.3%)	10
bladder mass	2/30 (6.7%)	2
bladder pressure	2/30 (6.7%)	2
bladder spasms	3/30 (10%)	3
blood clots in urine	2/30 (6.7%)	2
benign prostatic hyperplasia	3/30 (10%)	3
increased creatinine	16/30 (53.3%)	16
dysuria	18/30 (60%)	18
hematuria	11/30 (36.7%)	11
nocturia	3/30 (10%)	3
bladder pain	2/30 (6.7%)	2
prolonged urine stream	2/30 (6.7%)	2
renal failure	2/30 (6.7%)	2
acute renal insufficiency	13/30 (43.3%)	13
urinary frequency	23/30 (76.7%)	23
urinary hesitancy	5/30 (16.7%)	5
urinary incontinence	6/30 (20%)	6
urinary retention	4/30 (13.3%)	4
urinary urgency	16/30 (53.3%)	16
Reproductive system and breast disorders
menstrual cramps	3/30 (10%)	3
scrotal edema	2/30 (6.7%)	2
vaginal bleeding/spotting	7/30 (23.3%)	7
Respiratory, thoracic and mediastinal disorders
atelectasis	2/30 (6.7%)	2
chest discomfort with inspiration	2/30 (6.7%)	2
coarse breath sounds	6/30 (20%)	6
dry cough	5/30 (16.7%)	5
productive cough	4/30 (13.3%)	4
cough NOS	21/30 (70%)	21
decreased breath sounds	15/30 (50%)	15
labored breathing	2/30 (6.7%)	2
exertional shortness of breath	5/30 (16.7%)	5
hypoxia	2/30 (6.7%)	2
lung crackles	7/30 (23.3%)	7
lung infiltrates	4/30 (13.3%)	4
metapneumovirus	2/30 (6.7%)	2
nasal congestion	9/30 (30%)	9
postnasal drainage	8/30 (26.7%)	8
rales	4/30 (13.3%)	4
respiratory insufficiency	4/30 (13.3%)	4
rhinitis	2/30 (6.7%)	2
rhinorrhea	12/30 (40%)	12
rhonchi	5/30 (16.7%)	5
sinus congestion	9/30 (30%)	9
sinus drainage	3/30 (10%)	3
shortness of breath	14/30 (46.7%)	14
wheezing	6/30 (20%)	6
Skin and subcutaneous tissue disorders
bumps on skin	2/30 (6.7%)	2
diaphoresis	2/30 (6.7%)	2
dry skin	19/30 (63.3%)	19
generalized erythema	7/30 (23.3%)	7
throat erythema	3/30 (10%)	3
erythematous palms	2/30 (6.7%)	2
facial flushing	4/30 (13.3%)	4
hyperpigmented skin	13/30 (43.3%)	13
pale skin	2/30 (6.7%)	2
pruritus	26/30 (86.7%)	26
rash	17/30 (56.7%)	17
rash (arms, thighs)	2/30 (6.7%)	2
skin dyspigmentation	2/30 (6.7%)	2
skin irriation	2/30 (6.7%)	2
skin lesions	3/30 (10%)	3
skin tenderness	3/30 (10%)	3

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.