Reduced Intensity Regimen vs Myeloablative Regimen for My... | NCT01339910

ID	Type	Description	Link
U01HL069294	U.S. NIH Grant/Contract		View source
U01HL069294-05	U.S. NIH Grant/Contract		View source
BMT CTN 0901	Other Identifier	Blood and Marrow Transplant Clinical Trial Network
5U24CA076518	U.S. NIH Grant/Contract		View source

Status Module

Name	Class
National Heart, Lung, and Blood Institute (NHLBI)	NIH
National Cancer Institute (NCI)	NIH
Blood and Marrow Transplant Clinical Trials Network	NETWORK

Description Module

Label	Type	Description	Intervention Names
Reduced Intensity Conditioning (RIC)	Experimental	One of two different regimens in RIC will be administered; fludarabine and busulfan, or fludarabine and melphalan.	Drug: Fludarabine and Busulfan Drug: Fludarabine and Melphalan
Myeloablative Conditioning Regimen (MAC)	Active Comparator	One of three different regimens in MAC will be administered; busulfan and fludarabine, busulfan and cyclophosphamide, or cyclophosphamide and total body irradiation.	Drug: Busulfan and Fludarabine Drug: Busulfan and Cyclophosphamide Drug: Cyclophosphamide and Total Body Irradiation

Name	Type	Description	Arm Group Labels	Other Names
Fludarabine and Busulfan	Drug	(Flu/Bu) Fludarabine: 30 mg/m^2/day on Days -6 to -2 (total dose of 150 mg/m^2) Busulfan: 4 mg/kg/day PO or 3.2 mg/kg/day (total dose of 8 mg/kg or 6.4 mg/kg, respectively) on Days -5 to -4

Measure	Description	Time Frame
Percentage of Participants With Overall Survival (OS)	Overall survival is defined as survival of death from any cause.	18 months post-randomization

Measure	Description	Time Frame
Percentage of Participants With Relapse-Free Survival (RFS)	Relapse-free survival is defined as survival without relapse of the primary disease.	18 months post-randomization
Percentage of Participants With Disease Relapse

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Age equal or less than 65 years old and equal to or greater than 18 years old.
Patients with the diagnosis of MDS or AML with fewer than 5% myeloblasts in the bone marrow and no leukemic myeloblasts in the peripheral blood on morphologic analysis performed within 30 days of start of the conditioning regimen enrollment.
For patients receiving treatment of their MDS or AML prior to transplantation: a)Interval between the start of the most recent cycle of conventional cytotoxic chemotherapy and enrollment must be at least 30 days; b)Interval between completing treatment with a hypomethylating agent or other non-cytotoxic chemotherapy and enrollment must be at least 10 days.
Patients must have a related or unrelated bone marrow or peripheral blood donor who is human leukocyte antigen (HLA)-matched at 7 or 8 of 8 HLA-A, -B, -C and -DRB1 at high resolution using DNA-based typing.
HCT-Specific Comorbidity Index Score (HCT-CI) less than or equal to 4.
Organ function: a) Cardiac function: Ejection fraction greater than or equal to 40%; b) Hepatic function: total bilirubin less than or equal to 2 times the upper limit of normal and alanine aminotransferase (ALT) and aspartate aminotransferase (AST) less than or equal to 3 times the upper limit of normal.; c)Pulmonary function: Diffusing capacity of the lung for carbon monoxide (DLCO) greater than or equal to 40% and forced expiratory volume in one second (FEV1) greater than or equal to 50% (corrected for hemoglobin).
Creatinine clearance greater than or equal to 50mL/min based on the Cockcroft-Gault formula.
Signed informed consent.

Exclusion Criteria:

Prior allograft or prior autograft.
Symptomatic coronary artery disease.
Leukemia involvement in the central nervous system (CNS) within 4 weeks of enrollment for patients with a history of prior CNS leukemia involvement (i.e., leukemic blasts previously detected in the cerebral spinal fluid).
Karnofsky Performance Score less than 70.
Patients receiving supplemental oxygen.
Planned use of donor lymphocyte infusion (DLI) therapy.
Patients with uncontrolled bacterial, viral or fungal infections (undergoing appropriate treatment and with progression of clinical symptoms).
Patients seropositive for the human immunodeficiency virus (HIV).
Patients with prior malignancies, except resected basal cell carcinoma or treated cervical carcinoma in situ. Cancer treated with curative intent greater than 5 years previously. Cancer treated with curative intent less than 5 years previously will not be allowed unless approved by the Protocol Officer or one of the Protocol Chairs.
Females who are pregnant or breastfeeding.
Fertile men and women unwilling to use contraceptive techniques during and for 12 months following treatment.

Name	Affiliation	Role
Mary Horowitz, MD	Center for International Blood and Marrow Transplant Research	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Mayo Clinic Phoenix		Phoenix	Arizona	85054	United States
University of California, San Diego Medical Center

PubMed Identifier	Type	Citation	Retractions
19357394	Background	Vardiman JW, Thiele J, Arber DA, Brunning RD, Borowitz MJ, Porwit A, Harris NL, Le Beau MM, Hellstrom-Lindberg E, Tefferi A, Bloomfield CD. The 2008 revision of the World Health Organization (WHO) classification of myeloid neoplasms and acute leukemia: rationale and important changes. Blood. 2009 Jul 30;114(5):937-51. doi: 10.1182/blood-2009-03-209262. Epub 2009 Apr 8.
15994282	Background	Sorror ML, Maris MB, Storb R, Baron F, Sandmaier BM, Maloney DG, Storer B. Hematopoietic cell transplantation (HCT)-specific comorbidity index: a new tool for risk assessment before allogeneic HCT. Blood. 2005 Oct 15;106(8):2912-9. doi: 10.1182/blood-2005-05-2004. Epub 2005 Jun 30.

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Myeloablative Conditioning Regimen (MAC)	One of three different regimens in MAC will be administered; busulfan and fludarabine, busulfan and cyclophosphamide, or cyclophosphamide and total body irradiation. Busulfan and Fludarabine: (Bu/Flu) Busulfan: 4 mg/kg/day PO, 3.2 mg/kg/day IV or mg/m^2/day with Bu Css 900±100 ng/mL (total dose of 16 mg/kg, 12.8 mg/kg or 520 mg/m^2, respectively) on Days -5 to -2 Fludarabine: 30 mg/m^2/day on Days -5 to -2: Flu (total dose of 120 mg/m^2) Busulfan and Cyclophosphamide: (Bu/Cy) Busulfan: 4 mg/kg/day PO, 3.2 mg/kg/day IV or 130 mg/m^2/day with Bu Css 900 ± 100 ng/mL (total dose of 16 mg/kg or 12.8 mg/kg or 520 mg/m^2, respectively) on Days -7 to -4 Cyclophosphamide: 60 mg/kg/day on Days -3 to -2 (total dose of 120 mg/kg) Cyclophosphamide and Total Body Irradiation: (Cy/TBI) TBI: 1200-1420 cGy on Days -7 to -4 Cyclophosphamide: 60 mg/kg/day on Days -3 to -2 (total dose of 120 mg/kg)

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot_ICF	Yes	No	Yes	Study Protocol and Informed Consent Form	Mar 3, 2014

Arm/Group Information

ID	Title	Description
BG000	Myeloablative Conditioning Regimen (MAC)	One of three different regimens in MAC will be administered; busulfan and fludarabine, busulfan and cyclophosphamide, or cyclophosphamide and total body irradiation. Busulfan and Fludarabine: (Bu/Flu) Busulfan: 4 mg/kg/day PO, 3.2 mg/kg/day IV or mg/m^2/day with Bu Css 900±100 ng/mL (total dose of 16 mg/kg, 12.8 mg/kg or 520 mg/m^2, respectively) on Days -5 to -2 Fludarabine: 30 mg/m^2/day on Days -5 to -2: Flu (total dose of 120 mg/m^2) Busulfan and Cyclophosphamide: (Bu/Cy) Busulfan: 4 mg/kg/day PO, 3.2 mg/kg/day IV or 130 mg/m^2/day with Bu Css 900 ± 100 ng/mL (total dose of 16 mg/kg or 12.8 mg/kg or 520 mg/m^2, respectively) on Days -7 to -4 Cyclophosphamide: 60 mg/kg/day on Days -3 to -2 (total dose of 120 mg/kg) Cyclophosphamide and Total Body Irradiation: (Cy/TBI) TBI: 1200-1420 cGy on Days -7 to -4 Cyclophosphamide: 60 mg/kg/day on Days -3 to -2 (total dose of 120 mg/kg)
BG001	Reduced Intensity Conditioning (RIC)	One of two different regimens in RIC will be administered; fludarabine and busulfan, or fludarabine and melphalan. Fludarabine and Busulfan: (Flu/Bu) Fludarabine: 30 mg/m^2/day on Days -6 to -2 (total dose of 150 mg/m^2) Busulfan: 4 mg/kg/day PO or 3.2 mg/kg/day (total dose of 8 mg/kg or 6.4 mg/kg, respectively) on Days -5 to -4 Fludarabine and Melphalan: (Flu/Mel) Fludarabine: 30 mg/m^2/day on Days -5 to -2 (total dose of 120 mg/m^2) Melphalan: 140 mg/m^2 on Day -2
BG002	Total	Total of all reporting groups

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age, Continuous

Median

Full Range

years

Title

Denominators

Categories

Title	Measurements
	OG00077.5(69.4 to 83.7) OG00167.7(59.1 to 74.9)

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001	The null hypothesis is that there is no difference in overall survival at 18 months post-randomization between AML/MDS participants receiving MAC and RIC conditioning regimens. 18 month overall survival was compared between treatment arms using the difference in Kaplan-Meier estimators, which should be close to 0 under the null hypothesis.	Difference in Kaplan-Meier estimators		0.07	This final test was performed at a 0.049 significance level, since 0.001 was spent at interim analyses and the overall significance level was 0.050.	Difference in 18 month OS (MAC-RIC)	9.8			2-Sided	95	-0.8	20.3

Secondary

Percentage of Participants With Relapse-Free Survival (RFS)

Relapse-free survival is defined as survival without relapse of the primary disease.

Posted

Number

95% Confidence Interval

percentage

18 months post-randomization

ID	Title	Description
OG000	Myeloablative Conditioning Regimen (MAC)	One of three different regimens in MAC will be administered; busulfan and fludarabine, busulfan and cyclophosphamide, or cyclophosphamide and total body irradiation. Busulfan and Fludarabine: (Bu/Flu) Busulfan: 4 mg/kg/day PO, 3.2 mg/kg/day IV or mg/m^2/day with Bu Css 900±100 ng/mL (total dose of 16 mg/kg, 12.8 mg/kg or 520 mg/m^2, respectively) on Days -5 to -2 Fludarabine: 30 mg/m^2/day on Days -5 to -2: Flu (total dose of 120 mg/m^2) Busulfan and Cyclophosphamide: (Bu/Cy) Busulfan: 4 mg/kg/day PO, 3.2 mg/kg/day IV or 130 mg/m^2/day with Bu Css 900 ± 100 ng/mL (total dose of 16 mg/kg or 12.8 mg/kg or 520 mg/m^2, respectively) on Days -7 to -4 Cyclophosphamide: 60 mg/kg/day on Days -3 to -2 (total dose of 120 mg/kg) Cyclophosphamide and Total Body Irradiation: (Cy/TBI) TBI: 1200-1420 cGy on Days -7 to -4 Cyclophosphamide: 60 mg/kg/day on Days -3 to -2 (total dose of 120 mg/kg)
OG001	Reduced Intensity Conditioning (RIC)	One of two different regimens in RIC will be administered; fludarabine and busulfan, or fludarabine and melphalan. Fludarabine and Busulfan: (Flu/Bu) Fludarabine: 30 mg/m^2/day on Days -6 to -2 (total dose of 150 mg/m^2) Busulfan: 4 mg/kg/day PO or 3.2 mg/kg/day (total dose of 8 mg/kg or 6.4 mg/kg, respectively) on Days -5 to -4 Fludarabine and Melphalan: (Flu/Mel) Fludarabine: 30 mg/m^2/day on Days -5 to -2 (total dose of 120 mg/m^2) Melphalan: 140 mg/m^2 on Day -2

Secondary

Percentage of Participants With Disease Relapse

Disease Relapse is defined as relapse of the primary disease.

Posted

Number

95% Confidence Interval

percentage

18 months post-randomization

ID	Title	Description
OG000	Myeloablative Conditioning Regimen (MAC)	One of three different regimens in MAC will be administered; busulfan and fludarabine, busulfan and cyclophosphamide, or cyclophosphamide and total body irradiation. Busulfan and Fludarabine: (Bu/Flu) Busulfan: 4 mg/kg/day PO, 3.2 mg/kg/day IV or mg/m^2/day with Bu Css 900±100 ng/mL (total dose of 16 mg/kg, 12.8 mg/kg or 520 mg/m^2, respectively) on Days -5 to -2 Fludarabine: 30 mg/m^2/day on Days -5 to -2: Flu (total dose of 120 mg/m^2) Busulfan and Cyclophosphamide: (Bu/Cy) Busulfan: 4 mg/kg/day PO, 3.2 mg/kg/day IV or 130 mg/m^2/day with Bu Css 900 ± 100 ng/mL (total dose of 16 mg/kg or 12.8 mg/kg or 520 mg/m^2, respectively) on Days -7 to -4 Cyclophosphamide: 60 mg/kg/day on Days -3 to -2 (total dose of 120 mg/kg) Cyclophosphamide and Total Body Irradiation: (Cy/TBI) TBI: 1200-1420 cGy on Days -7 to -4 Cyclophosphamide: 60 mg/kg/day on Days -3 to -2 (total dose of 120 mg/kg)
OG001	Reduced Intensity Conditioning (RIC)	One of two different regimens in RIC will be administered; fludarabine and busulfan, or fludarabine and melphalan. Fludarabine and Busulfan: (Flu/Bu) Fludarabine: 30 mg/m^2/day on Days -6 to -2 (total dose of 150 mg/m^2) Busulfan: 4 mg/kg/day PO or 3.2 mg/kg/day (total dose of 8 mg/kg or 6.4 mg/kg, respectively) on Days -5 to -4 Fludarabine and Melphalan: (Flu/Mel) Fludarabine: 30 mg/m^2/day on Days -5 to -2 (total dose of 120 mg/m^2) Melphalan: 140 mg/m^2 on Day -2

Secondary

Percentage of Participants With Treatment-related Mortality

Treatment-related mortality is defined as death without a previous relapse of the primary disease.

Posted

Number

95% Confidence Interval

percentage

18 months post-randomization

ID	Title	Description
OG000	Myeloablative Conditioning Regimen (MAC)	One of three different regimens in MAC will be administered; busulfan and fludarabine, busulfan and cyclophosphamide, or cyclophosphamide and total body irradiation. Busulfan and Fludarabine: (Bu/Flu) Busulfan: 4 mg/kg/day PO, 3.2 mg/kg/day IV or mg/m^2/day with Bu Css 900±100 ng/mL (total dose of 16 mg/kg, 12.8 mg/kg or 520 mg/m^2, respectively) on Days -5 to -2 Fludarabine: 30 mg/m^2/day on Days -5 to -2: Flu (total dose of 120 mg/m^2) Busulfan and Cyclophosphamide: (Bu/Cy) Busulfan: 4 mg/kg/day PO, 3.2 mg/kg/day IV or 130 mg/m^2/day with Bu Css 900 ± 100 ng/mL (total dose of 16 mg/kg or 12.8 mg/kg or 520 mg/m^2, respectively) on Days -7 to -4 Cyclophosphamide: 60 mg/kg/day on Days -3 to -2 (total dose of 120 mg/kg) Cyclophosphamide and Total Body Irradiation: (Cy/TBI) TBI: 1200-1420 cGy on Days -7 to -4 Cyclophosphamide: 60 mg/kg/day on Days -3 to -2 (total dose of 120 mg/kg)
OG001	Reduced Intensity Conditioning (RIC)	One of two different regimens in RIC will be administered; fludarabine and busulfan, or fludarabine and melphalan. Fludarabine and Busulfan: (Flu/Bu) Fludarabine: 30 mg/m^2/day on Days -6 to -2 (total dose of 150 mg/m^2) Busulfan: 4 mg/kg/day PO or 3.2 mg/kg/day (total dose of 8 mg/kg or 6.4 mg/kg, respectively) on Days -5 to -4 Fludarabine and Melphalan: (Flu/Mel) Fludarabine: 30 mg/m^2/day on Days -5 to -2 (total dose of 120 mg/m^2) Melphalan: 140 mg/m^2 on Day -2

Secondary

Percentage of Participants With Neutrophil and Platelet Engraftment

Neutrophil engraftment is defined as achieving an absolute neutrophil count greater than 500x10^6/liter for 3 consecutive measurements on different days. The first of the 3 days will be designated the day of neutrophil engraftment. Platelet engraftment is defined as achieving platelet counts greater than 20,000/microliter for consecutive measurements over 7 days without requiring platelet transfusions. The first of the 7 days will be designated the day of platelet engraftment. Subjects must not have had platelet transfusions during the preceding 7 days.

Transplanted participants

Posted

Number

percentage

Days 28 and 60 post-transplant

ID	Title	Description
OG000	Myeloablative Conditioning Regimen (MAC)	One of three different regimens in MAC will be administered; busulfan and fludarabine, busulfan and cyclophosphamide, or cyclophosphamide and total body irradiation. Busulfan and Fludarabine: (Bu/Flu) Busulfan: 4 mg/kg/day PO, 3.2 mg/kg/day IV or mg/m^2/day with Bu Css 900±100 ng/mL (total dose of 16 mg/kg, 12.8 mg/kg or 520 mg/m^2, respectively) on Days -5 to -2 Fludarabine: 30 mg/m^2/day on Days -5 to -2: Flu (total dose of 120 mg/m^2) Busulfan and Cyclophosphamide: (Bu/Cy) Busulfan: 4 mg/kg/day PO, 3.2 mg/kg/day IV or 130 mg/m^2/day with Bu Css 900 ± 100 ng/mL (total dose of 16 mg/kg or 12.8 mg/kg or 520 mg/m^2, respectively) on Days -7 to -4 Cyclophosphamide: 60 mg/kg/day on Days -3 to -2 (total dose of 120 mg/kg) Cyclophosphamide and Total Body Irradiation: (Cy/TBI) TBI: 1200-1420 cGy on Days -7 to -4 Cyclophosphamide: 60 mg/kg/day on Days -3 to -2 (total dose of 120 mg/kg)

Secondary

Number of Participants With Donor Cell Engraftment

Donor cell engraftment will be assessed by donor-recipient chimerism assays. Full donor chimerism is defined as the presence of at least 95% donor cells as a proportion of the total population in the peripheral blood or bone marrow. Graft rejection is defined as the presence of no more than 5% donor cells as a proportion of the total population. Mixed chimerism is defined as the presence of between 5% and 95% donor cells. Mixed or full donor chimerism will be considered evidence of donor engraftment.

Transplanted participants

Posted

Count of Participants

Participants

Days 28 and 100 and 18 months post-transplant

ID	Title	Description
OG000	Myeloablative Conditioning Regimen (MAC)	One of three different regimens in MAC will be administered; busulfan and fludarabine, busulfan and cyclophosphamide, or cyclophosphamide and total body irradiation. Busulfan and Fludarabine: (Bu/Flu) Busulfan: 4 mg/kg/day PO, 3.2 mg/kg/day IV or mg/m^2/day with Bu Css 900±100 ng/mL (total dose of 16 mg/kg, 12.8 mg/kg or 520 mg/m^2, respectively) on Days -5 to -2 Fludarabine: 30 mg/m^2/day on Days -5 to -2: Flu (total dose of 120 mg/m^2) Busulfan and Cyclophosphamide: (Bu/Cy) Busulfan: 4 mg/kg/day PO, 3.2 mg/kg/day IV or 130 mg/m^2/day with Bu Css 900 ± 100 ng/mL (total dose of 16 mg/kg or 12.8 mg/kg or 520 mg/m^2, respectively) on Days -7 to -4 Cyclophosphamide: 60 mg/kg/day on Days -3 to -2 (total dose of 120 mg/kg) Cyclophosphamide and Total Body Irradiation: (Cy/TBI) TBI: 1200-1420 cGy on Days -7 to -4 Cyclophosphamide: 60 mg/kg/day on Days -3 to -2 (total dose of 120 mg/kg)

Secondary

Percentage of Participants With Acute Graft Versus Host Disease (GVHD)

Acute GVHD is graded according to the scoring system proposed by Przepiorka et al.1995:

Skin stage:

0: No rash

Rash <25% of body surface area
Rash on 25-50% of body surface area
Rash on > 50% of body surface area
Generalized erythroderma with bullous formation

Liver stage (based on bilirubin level)*:

0: <2 mg/dL

2-3 mg/dL
3.01-6 mg/dL
6.01-15.0 mg/dL
>15 mg/dL

GI stage*:

0: No diarrhea or diarrhea <500 mL/day

Diarrhea 500-999 mL/day or persistent nausea with histologic evidence of GVHD
Diarrhea 1000-1499 mL/day
Diarrhea >1500 mL/day
Severe abdominal pain with or without ileus * If multiple etiologies are listed for liver or GI, the organ system is downstaged by 1.

GVHD grade:

0: All organ stages 0 or GVHD not listed as an etiology I: Skin stage 1-2 and liver and GI stage 0 II: Skin stage 3 or liver or GI stage 1 III: Liver stage 2-3 or GI stage 2-4 IV: Skin or liver stage 4

Transplanted participants

Posted

Number

95% Confidence Interval

percentage

Day 100 post-transplant

ID	Title	Description
OG000	Myeloablative Conditioning Regimen (MAC)	One of three different regimens in MAC will be administered; busulfan and fludarabine, busulfan and cyclophosphamide, or cyclophosphamide and total body irradiation. Busulfan and Fludarabine: (Bu/Flu) Busulfan: 4 mg/kg/day PO, 3.2 mg/kg/day IV or mg/m^2/day with Bu Css 900±100 ng/mL (total dose of 16 mg/kg, 12.8 mg/kg or 520 mg/m^2, respectively) on Days -5 to -2 Fludarabine: 30 mg/m^2/day on Days -5 to -2: Flu (total dose of 120 mg/m^2) Busulfan and Cyclophosphamide: (Bu/Cy) Busulfan: 4 mg/kg/day PO, 3.2 mg/kg/day IV or 130 mg/m^2/day with Bu Css 900 ± 100 ng/mL (total dose of 16 mg/kg or 12.8 mg/kg or 520 mg/m^2, respectively) on Days -7 to -4 Cyclophosphamide: 60 mg/kg/day on Days -3 to -2 (total dose of 120 mg/kg) Cyclophosphamide and Total Body Irradiation: (Cy/TBI) TBI: 1200-1420 cGy on Days -7 to -4 Cyclophosphamide: 60 mg/kg/day on Days -3 to -2 (total dose of 120 mg/kg)

Secondary

Percentage of Participants With Chronic GVHD

Chronic GVHD is classified per 2005 NIH Consensus Criteria (Filipovich et al. 2005) into categories of severity: none, mild, moderate, and severe. Occurrence of chronic GVHD is defined as the occurrence of mild, moderate, or severe chronic GVHD per this classification.

Transplanted participants

Posted

Number

95% Confidence Interval

percentage

18 months post-transplant

ID	Title	Description
OG000	Myeloablative Conditioning Regimen (MAC)	One of three different regimens in MAC will be administered; busulfan and fludarabine, busulfan and cyclophosphamide, or cyclophosphamide and total body irradiation. Busulfan and Fludarabine: (Bu/Flu) Busulfan: 4 mg/kg/day PO, 3.2 mg/kg/day IV or mg/m^2/day with Bu Css 900±100 ng/mL (total dose of 16 mg/kg, 12.8 mg/kg or 520 mg/m^2, respectively) on Days -5 to -2 Fludarabine: 30 mg/m^2/day on Days -5 to -2: Flu (total dose of 120 mg/m^2) Busulfan and Cyclophosphamide: (Bu/Cy) Busulfan: 4 mg/kg/day PO, 3.2 mg/kg/day IV or 130 mg/m^2/day with Bu Css 900 ± 100 ng/mL (total dose of 16 mg/kg or 12.8 mg/kg or 520 mg/m^2, respectively) on Days -7 to -4 Cyclophosphamide: 60 mg/kg/day on Days -3 to -2 (total dose of 120 mg/kg) Cyclophosphamide and Total Body Irradiation: (Cy/TBI) TBI: 1200-1420 cGy on Days -7 to -4 Cyclophosphamide: 60 mg/kg/day on Days -3 to -2 (total dose of 120 mg/kg)
OG001	Reduced Intensity Conditioning (RIC)	One of two different regimens in RIC will be administered; fludarabine and busulfan, or fludarabine and melphalan. Fludarabine and Busulfan: (Flu/Bu) Fludarabine: 30 mg/m^2/day on Days -6 to -2 (total dose of 150 mg/m^2) Busulfan: 4 mg/kg/day PO or 3.2 mg/kg/day (total dose of 8 mg/kg or 6.4 mg/kg, respectively) on Days -5 to -4 Fludarabine and Melphalan: (Flu/Mel) Fludarabine: 30 mg/m^2/day on Days -5 to -2 (total dose of 120 mg/m^2) Melphalan: 140 mg/m^2 on Day -2

Secondary

Number of Participants With Chronic GVHD Severity

Chronic GVHD is classified per 2005 NIH Consensus Criteria (Filipovich et al. 2005) into categories of severity: none, mild, moderate, and severe.

Transplanted participants

Posted

Count of Participants

Participants

18 months post-transplant

ID	Title	Description
OG000	Myeloablative Conditioning Regimen (MAC)	One of three different regimens in MAC will be administered; busulfan and fludarabine, busulfan and cyclophosphamide, or cyclophosphamide and total body irradiation. Busulfan and Fludarabine: (Bu/Flu) Busulfan: 4 mg/kg/day PO, 3.2 mg/kg/day IV or mg/m^2/day with Bu Css 900±100 ng/mL (total dose of 16 mg/kg, 12.8 mg/kg or 520 mg/m^2, respectively) on Days -5 to -2 Fludarabine: 30 mg/m^2/day on Days -5 to -2: Flu (total dose of 120 mg/m^2) Busulfan and Cyclophosphamide: (Bu/Cy) Busulfan: 4 mg/kg/day PO, 3.2 mg/kg/day IV or 130 mg/m^2/day with Bu Css 900 ± 100 ng/mL (total dose of 16 mg/kg or 12.8 mg/kg or 520 mg/m^2, respectively) on Days -7 to -4 Cyclophosphamide: 60 mg/kg/day on Days -3 to -2 (total dose of 120 mg/kg) Cyclophosphamide and Total Body Irradiation: (Cy/TBI) TBI: 1200-1420 cGy on Days -7 to -4 Cyclophosphamide: 60 mg/kg/day on Days -3 to -2 (total dose of 120 mg/kg)
OG001	Reduced Intensity Conditioning (RIC)	One of two different regimens in RIC will be administered; fludarabine and busulfan, or fludarabine and melphalan. Fludarabine and Busulfan: (Flu/Bu) Fludarabine: 30 mg/m^2/day on Days -6 to -2 (total dose of 150 mg/m^2) Busulfan: 4 mg/kg/day PO or 3.2 mg/kg/day (total dose of 8 mg/kg or 6.4 mg/kg, respectively) on Days -5 to -4 Fludarabine and Melphalan: (Flu/Mel) Fludarabine: 30 mg/m^2/day on Days -5 to -2 (total dose of 120 mg/m^2) Melphalan: 140 mg/m^2 on Day -2

Secondary

Number of Participants With Primary Graft Failure

Primary graft failure is defined by lack of neutrophil engraftment.

Transplanted participants

Posted

Count of Participants

Participants

28 days post-transplant

ID	Title	Description
OG000	Myeloablative Conditioning Regimen (MAC)	One of three different regimens in MAC will be administered; busulfan and fludarabine, busulfan and cyclophosphamide, or cyclophosphamide and total body irradiation. Busulfan and Fludarabine: (Bu/Flu) Busulfan: 4 mg/kg/day PO, 3.2 mg/kg/day IV or mg/m^2/day with Bu Css 900±100 ng/mL (total dose of 16 mg/kg, 12.8 mg/kg or 520 mg/m^2, respectively) on Days -5 to -2 Fludarabine: 30 mg/m^2/day on Days -5 to -2: Flu (total dose of 120 mg/m^2) Busulfan and Cyclophosphamide: (Bu/Cy) Busulfan: 4 mg/kg/day PO, 3.2 mg/kg/day IV or 130 mg/m^2/day with Bu Css 900 ± 100 ng/mL (total dose of 16 mg/kg or 12.8 mg/kg or 520 mg/m^2, respectively) on Days -7 to -4 Cyclophosphamide: 60 mg/kg/day on Days -3 to -2 (total dose of 120 mg/kg) Cyclophosphamide and Total Body Irradiation: (Cy/TBI) TBI: 1200-1420 cGy on Days -7 to -4 Cyclophosphamide: 60 mg/kg/day on Days -3 to -2 (total dose of 120 mg/kg)
OG001	Reduced Intensity Conditioning (RIC)	One of two different regimens in RIC will be administered; fludarabine and busulfan, or fludarabine and melphalan. Fludarabine and Busulfan: (Flu/Bu) Fludarabine: 30 mg/m^2/day on Days -6 to -2 (total dose of 150 mg/m^2) Busulfan: 4 mg/kg/day PO or 3.2 mg/kg/day (total dose of 8 mg/kg or 6.4 mg/kg, respectively) on Days -5 to -4 Fludarabine and Melphalan: (Flu/Mel) Fludarabine: 30 mg/m^2/day on Days -5 to -2 (total dose of 120 mg/m^2) Melphalan: 140 mg/m^2 on Day -2

Secondary

Number of Participants With Secondary Graft Failure

Secondary graft failure is defined by initial neutrophil engraftment followed by subsequent decline in neutrophil counts to less than 500x10^6/liter that is unresponsive to growth factor therapy.

Transplanted participants

Posted

Count of Participants

Participants

18 months post-transplant

ID	Title	Description
OG000	Myeloablative Conditioning Regimen (MAC)	One of three different regimens in MAC will be administered; busulfan and fludarabine, busulfan and cyclophosphamide, or cyclophosphamide and total body irradiation. Busulfan and Fludarabine: (Bu/Flu) Busulfan: 4 mg/kg/day PO, 3.2 mg/kg/day IV or mg/m^2/day with Bu Css 900±100 ng/mL (total dose of 16 mg/kg, 12.8 mg/kg or 520 mg/m^2, respectively) on Days -5 to -2 Fludarabine: 30 mg/m^2/day on Days -5 to -2: Flu (total dose of 120 mg/m^2) Busulfan and Cyclophosphamide: (Bu/Cy) Busulfan: 4 mg/kg/day PO, 3.2 mg/kg/day IV or 130 mg/m^2/day with Bu Css 900 ± 100 ng/mL (total dose of 16 mg/kg or 12.8 mg/kg or 520 mg/m^2, respectively) on Days -7 to -4 Cyclophosphamide: 60 mg/kg/day on Days -3 to -2 (total dose of 120 mg/kg) Cyclophosphamide and Total Body Irradiation: (Cy/TBI) TBI: 1200-1420 cGy on Days -7 to -4 Cyclophosphamide: 60 mg/kg/day on Days -3 to -2 (total dose of 120 mg/kg)
OG001	Reduced Intensity Conditioning (RIC)	One of two different regimens in RIC will be administered; fludarabine and busulfan, or fludarabine and melphalan. Fludarabine and Busulfan: (Flu/Bu) Fludarabine: 30 mg/m^2/day on Days -6 to -2 (total dose of 150 mg/m^2) Busulfan: 4 mg/kg/day PO or 3.2 mg/kg/day (total dose of 8 mg/kg or 6.4 mg/kg, respectively) on Days -5 to -4 Fludarabine and Melphalan: (Flu/Mel) Fludarabine: 30 mg/m^2/day on Days -5 to -2 (total dose of 120 mg/m^2) Melphalan: 140 mg/m^2 on Day -2

Secondary

Number of Participants With Maximum Grade 3-5 Toxicities

The maximum grade of toxicities reported by participants over the study duration are tabulated. Per the CTCAE criteria, toxicities are graded on a scale of 0-5, with higher numbers indicating greater severity. The categories correspond as follows:

3 - severe; 4 - life-threatening; 5 - fatal

Transplanted participants

Posted

Count of Participants

Participants

18 months

ID	Title	Description
OG000	Myeloablative Conditioning Regimen (MAC)	One of three different regimens in MAC will be administered; busulfan and fludarabine, busulfan and cyclophosphamide, or cyclophosphamide and total body irradiation. Busulfan and Fludarabine: (Bu/Flu) Busulfan: 4 mg/kg/day PO, 3.2 mg/kg/day IV or mg/m^2/day with Bu Css 900±100 ng/mL (total dose of 16 mg/kg, 12.8 mg/kg or 520 mg/m^2, respectively) on Days -5 to -2 Fludarabine: 30 mg/m^2/day on Days -5 to -2: Flu (total dose of 120 mg/m^2) Busulfan and Cyclophosphamide: (Bu/Cy) Busulfan: 4 mg/kg/day PO, 3.2 mg/kg/day IV or 130 mg/m^2/day with Bu Css 900 ± 100 ng/mL (total dose of 16 mg/kg or 12.8 mg/kg or 520 mg/m^2, respectively) on Days -7 to -4 Cyclophosphamide: 60 mg/kg/day on Days -3 to -2 (total dose of 120 mg/kg) Cyclophosphamide and Total Body Irradiation: (Cy/TBI) TBI: 1200-1420 cGy on Days -7 to -4 Cyclophosphamide: 60 mg/kg/day on Days -3 to -2 (total dose of 120 mg/kg)
OG001	Reduced Intensity Conditioning (RIC)

Secondary

Infection Type

The number and types of infection events reported are tabulated.

Infection events

Posted

Count of Units

Infection events

18 months post-transplant

Infection events

ID	Title	Description
OG000	Myeloablative Conditioning Regimen (MAC)	One of three different regimens in MAC will be administered; busulfan and fludarabine, busulfan and cyclophosphamide, or cyclophosphamide and total body irradiation. Busulfan and Fludarabine: (Bu/Flu) Busulfan: 4 mg/kg/day PO, 3.2 mg/kg/day IV or mg/m^2/day with Bu Css 900±100 ng/mL (total dose of 16 mg/kg, 12.8 mg/kg or 520 mg/m^2, respectively) on Days -5 to -2 Fludarabine: 30 mg/m^2/day on Days -5 to -2: Flu (total dose of 120 mg/m^2) Busulfan and Cyclophosphamide: (Bu/Cy) Busulfan: 4 mg/kg/day PO, 3.2 mg/kg/day IV or 130 mg/m^2/day with Bu Css 900 ± 100 ng/mL (total dose of 16 mg/kg or 12.8 mg/kg or 520 mg/m^2, respectively) on Days -7 to -4 Cyclophosphamide: 60 mg/kg/day on Days -3 to -2 (total dose of 120 mg/kg) Cyclophosphamide and Total Body Irradiation: (Cy/TBI) TBI: 1200-1420 cGy on Days -7 to -4 Cyclophosphamide: 60 mg/kg/day on Days -3 to -2 (total dose of 120 mg/kg)
OG001	Reduced Intensity Conditioning (RIC)	One of two different regimens in RIC will be administered; fludarabine and busulfan, or fludarabine and melphalan. Fludarabine and Busulfan: (Flu/Bu) Fludarabine: 30 mg/m^2/day on Days -6 to -2 (total dose of 150 mg/m^2) Busulfan: 4 mg/kg/day PO or 3.2 mg/kg/day (total dose of 8 mg/kg or 6.4 mg/kg, respectively) on Days -5 to -4 Fludarabine and Melphalan: (Flu/Mel) Fludarabine: 30 mg/m^2/day on Days -5 to -2 (total dose of 120 mg/m^2) Melphalan: 140 mg/m^2 on Day -2

Secondary

Number of Participants With Infections

The maximum severity of infections reported by participants are tabulated.

The number of infections and the number of patients experiencing infections will be tabulated by type of infection, severity, and time period after transplant. The cumulative incidence of severe, life-threatening, or fatal infections will be compared between the two treatment arms at 6, 12, and 18 months from transplant or until death.

Transplanted participants

Posted

Count of Participants

Participants

18 months post-transplant

ID	Title	Description
OG000	Myeloablative Conditioning Regimen (MAC)	One of three different regimens in MAC will be administered; busulfan and fludarabine, busulfan and cyclophosphamide, or cyclophosphamide and total body irradiation. Busulfan and Fludarabine: (Bu/Flu) Busulfan: 4 mg/kg/day PO, 3.2 mg/kg/day IV or mg/m^2/day with Bu Css 900±100 ng/mL (total dose of 16 mg/kg, 12.8 mg/kg or 520 mg/m^2, respectively) on Days -5 to -2 Fludarabine: 30 mg/m^2/day on Days -5 to -2: Flu (total dose of 120 mg/m^2) Busulfan and Cyclophosphamide: (Bu/Cy) Busulfan: 4 mg/kg/day PO, 3.2 mg/kg/day IV or 130 mg/m^2/day with Bu Css 900 ± 100 ng/mL (total dose of 16 mg/kg or 12.8 mg/kg or 520 mg/m^2, respectively) on Days -7 to -4 Cyclophosphamide: 60 mg/kg/day on Days -3 to -2 (total dose of 120 mg/kg) Cyclophosphamide and Total Body Irradiation: (Cy/TBI) TBI: 1200-1420 cGy on Days -7 to -4 Cyclophosphamide: 60 mg/kg/day on Days -3 to -2 (total dose of 120 mg/kg)
OG001	Reduced Intensity Conditioning (RIC)

Secondary

Number of Participants With Cause of Death

Primary cause of death was adjudicated using previously described criteria (Copelan et al. 2007). When relapse occurred, it was considered the primary cause of death regardless of other events.

Posted

Count of Participants

Participants

18 months post-randomization

ID	Title	Description
OG000	Myeloablative Conditioning Regimen (MAC)	One of three different regimens in MAC will be administered; busulfan and fludarabine, busulfan and cyclophosphamide, or cyclophosphamide and total body irradiation. Busulfan and Fludarabine: (Bu/Flu) Busulfan: 4 mg/kg/day PO, 3.2 mg/kg/day IV or mg/m^2/day with Bu Css 900±100 ng/mL (total dose of 16 mg/kg, 12.8 mg/kg or 520 mg/m^2, respectively) on Days -5 to -2 Fludarabine: 30 mg/m^2/day on Days -5 to -2: Flu (total dose of 120 mg/m^2) Busulfan and Cyclophosphamide: (Bu/Cy) Busulfan: 4 mg/kg/day PO, 3.2 mg/kg/day IV or 130 mg/m^2/day with Bu Css 900 ± 100 ng/mL (total dose of 16 mg/kg or 12.8 mg/kg or 520 mg/m^2, respectively) on Days -7 to -4 Cyclophosphamide: 60 mg/kg/day on Days -3 to -2 (total dose of 120 mg/kg) Cyclophosphamide and Total Body Irradiation: (Cy/TBI) TBI: 1200-1420 cGy on Days -7 to -4 Cyclophosphamide: 60 mg/kg/day on Days -3 to -2 (total dose of 120 mg/kg)
OG001	Reduced Intensity Conditioning (RIC)	One of two different regimens in RIC will be administered; fludarabine and busulfan, or fludarabine and melphalan. Fludarabine and Busulfan: (Flu/Bu) Fludarabine: 30 mg/m^2/day on Days -6 to -2 (total dose of 150 mg/m^2) Busulfan: 4 mg/kg/day PO or 3.2 mg/kg/day (total dose of 8 mg/kg or 6.4 mg/kg, respectively) on Days -5 to -4 Fludarabine and Melphalan: (Flu/Mel) Fludarabine: 30 mg/m^2/day on Days -5 to -2 (total dose of 120 mg/m^2) Melphalan: 140 mg/m^2 on Day -2

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Myeloablative Conditioning Regimen (MAC)	One of three different regimens in MAC will be administered; busulfan and fludarabine, busulfan and cyclophosphamide, or cyclophosphamide and total body irradiation. Busulfan and Fludarabine: (Bu/Flu) Busulfan: 4 mg/kg/day PO, 3.2 mg/kg/day IV or mg/m^2/day with Bu Css 900±100 ng/mL (total dose of 16 mg/kg, 12.8 mg/kg or 520 mg/m^2, respectively) on Days -5 to -2 Fludarabine: 30 mg/m^2/day on Days -5 to -2: Flu (total dose of 120 mg/m^2) Busulfan and Cyclophosphamide: (Bu/Cy) Busulfan: 4 mg/kg/day PO, 3.2 mg/kg/day IV or 130 mg/m^2/day with Bu Css 900 ± 100 ng/mL (total dose of 16 mg/kg or 12.8 mg/kg or 520 mg/m^2, respectively) on Days -7 to -4 Cyclophosphamide: 60 mg/kg/day on Days -3 to -2 (total dose of 120 mg/kg) Cyclophosphamide and Total Body Irradiation: (Cy/TBI) TBI: 1200-1420 cGy on Days -7 to -4 Cyclophosphamide: 60 mg/kg/day on Days -3 to -2 (total dose of 120 mg/kg)			21	132	7	132
EG001	Reduced Intensity Conditioning (RIC)	One of two different regimens in RIC will be administered; fludarabine and busulfan, or fludarabine and melphalan. Fludarabine and Busulfan: (Flu/Bu) Fludarabine: 30 mg/m^2/day on Days -6 to -2 (total dose of 150 mg/m^2) Busulfan: 4 mg/kg/day PO or 3.2 mg/kg/day (total dose of 8 mg/kg or 6.4 mg/kg, respectively) on Days -5 to -4 Fludarabine and Melphalan: (Flu/Mel) Fludarabine: 30 mg/m^2/day on Days -5 to -2 (total dose of 120 mg/m^2) Melphalan: 140 mg/m^2 on Day -2			16	133	4	133

Serious Adverse Events

Term	Organ System	Source Vocabulary	Statistical Information
Autoimmune haemolytic anaemia	Blood and lymphatic system disorders	MedDRA 20.0	EG0001 events1 affected132 at risk EG0010 events0 affected133 at risk
Immune thrombocytopenic purpura	Blood and lymphatic system disorders	MedDRA 20.0	EG0001 events1 affected132 at risk EG0010 events0 affected133 at risk
Acute myocardial infarction	Cardiac disorders	MedDRA 20.0	EG0001 events1 affected132 at risk EG0011 events1 affected133 at risk
Atrial fibrillation	Cardiac disorders	MedDRA 20.0	EG0001 events1 affected132 at risk EG0010 events0 affected133 at risk
Cardiac arrest	Cardiac disorders	MedDRA 20.0	EG0000 events0 affected132 at risk EG0011 events1 affected133 at risk
Pericardial effusion	Cardiac disorders	MedDRA 20.0	EG0001 events1 affected132 at risk EG0011 events1 affected133 at risk
Supraventricular tachycardia	Cardiac disorders	MedDRA 20.0	EG0001 events1 affected132 at risk EG0010 events0 affected133 at risk
Vision blurred	Eye disorders	MedDRA 20.0	EG0001 events1 affected132 at risk EG0010 events0 affected133 at risk
Gastrointestinal haemorrhage	Gastrointestinal disorders	MedDRA 20.0	EG0001 events1 affected132 at risk EG0011 events1 affected133 at risk
Oesophagitis	Gastrointestinal disorders	MedDRA 20.0	EG0000 events0 affected132 at risk EG0011 events1 affected133 at risk
Pancreatitis	Gastrointestinal disorders	MedDRA 20.0	EG0000 events0 affected132 at risk EG0011 events1 affected133 at risk
Hepatic haemorrhage	Hepatobiliary disorders	MedDRA 20.0	EG0001 events1 affected132 at risk EG0010 events0 affected133 at risk
Hyperbilirubinaemia	Hepatobiliary disorders	MedDRA 20.0	EG0000 events0 affected132 at risk EG0011 events1 affected133 at risk
Graft versus host disease	Immune system disorders	MedDRA 20.0	EG0001 events1 affected132 at risk EG0010 events0 affected133 at risk
Device related infection	Infections and infestations	MedDRA 20.0	EG0001 events1 affected132 at risk EG0010 events0 affected133 at risk
Enterocolitis infectious	Infections and infestations	MedDRA 20.0	EG0001 events1 affected132 at risk EG0010 events0 affected133 at risk
Respiratory tract infection	Infections and infestations	MedDRA 20.0	EG0001 events1 affected132 at risk EG0010 events0 affected133 at risk
Fall	Injury, poisoning and procedural complications	MedDRA 20.0	EG0000 events0 affected132 at risk EG0011 events1 affected133 at risk
Hip fracture	Injury, poisoning and procedural complications	MedDRA 20.0	EG0001 events1 affected132 at risk EG0010 events0 affected133 at risk
Spinal compression fracture	Injury, poisoning and procedural complications	MedDRA 20.0	EG0000 events0 affected132 at risk EG0011 events1 affected133 at risk
Spinal fracture	Injury, poisoning and procedural complications	MedDRA 20.0	EG0000 events0 affected132 at risk EG0011 events1 affected133 at risk
Blood bilirubin increased	Investigations	MedDRA 20.0	EG0000 events0 affected132 at risk EG0011 events1 affected133 at risk
Liver function test increased	Investigations	MedDRA 20.0	EG0000 events0 affected132 at risk EG0011 events1 affected133 at risk
Gout	Metabolism and nutrition disorders	MedDRA 20.0	EG0000 events0 affected132 at risk EG0011 events1 affected133 at risk
Back pain	Musculoskeletal and connective tissue disorders	MedDRA 20.0	EG0000 events0 affected132 at risk EG0012 events2 affected133 at risk
Flank pain	Musculoskeletal and connective tissue disorders	MedDRA 20.0	EG0001 events1 affected132 at risk EG0010 events0 affected133 at risk
Haemorrhage intracranial	Nervous system disorders	MedDRA 20.0	EG0001 events1 affected132 at risk EG0010 events0 affected133 at risk
Posterior reversible encephalopathy syndrome	Nervous system disorders	MedDRA 20.0	EG0001 events1 affected132 at risk EG0010 events0 affected133 at risk
Syncope	Nervous system disorders	MedDRA 20.0	EG0002 events2 affected132 at risk EG0010 events0 affected133 at risk
Vocal cord paralysis	Nervous system disorders	MedDRA 20.0	EG0000 events0 affected132 at risk EG0011 events1 affected133 at risk
Mental status changes	Psychiatric disorders	MedDRA 20.0	EG0001 events1 affected132 at risk EG0010 events0 affected133 at risk
Hydronephrosis	Renal and urinary disorders	MedDRA 20.0	EG0000 events0 affected132 at risk EG0011 events1 affected133 at risk
Acute respiratory distress syndrome	Respiratory, thoracic and mediastinal disorders	MedDRA 20.0	EG0001 events1 affected132 at risk EG0010 events0 affected133 at risk
Dyspnoea at rest	Respiratory, thoracic and mediastinal disorders	MedDRA 20.0	EG0001 events1 affected132 at risk EG0010 events0 affected133 at risk
Pulmonary embolism	Respiratory, thoracic and mediastinal disorders	MedDRA 20.0	EG0004 events4 affected132 at risk EG0011 events1 affected133 at risk
Respiratory distress	Respiratory, thoracic and mediastinal disorders	MedDRA 20.0	EG0000 events0 affected132 at risk EG0011 events1 affected133 at risk
Respiratory failure	Respiratory, thoracic and mediastinal disorders	MedDRA 20.0	EG0002 events2 affected132 at risk EG0011 events1 affected133 at risk
Stevens-Johnson syndrome	Skin and subcutaneous tissue disorders	MedDRA 20.0	EG0000 events0 affected132 at risk EG0011 events1 affected133 at risk
Cholecystectomy	Surgical and medical procedures	MedDRA 20.0	EG0002 events2 affected132 at risk EG0010 events0 affected133 at risk
Finger amputation	Surgical and medical procedures	MedDRA 20.0	EG0000 events0 affected132 at risk EG0011 events1 affected133 at risk
Prostatectomy	Surgical and medical procedures	MedDRA 20.0	EG0000 events0 affected132 at risk EG0011 events1 affected133 at risk
Embolism	Vascular disorders	MedDRA 20.0	EG0002 events1 affected132 at risk EG0010 events0 affected133 at risk
Hypotension	Vascular disorders	MedDRA 20.0	EG0000 events0 affected132 at risk EG0012 events2 affected133 at risk
Venoocclusive disease	Vascular disorders	MedDRA 20.0	EG0001 events1 affected132 at risk EG0010 events0 affected133 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Statistical Information
Chest pain	General disorders	MedDRA 20.0	EG0001 events1 affected132 at risk EG0010 events0 affected133 at risk
Weight decreased	Investigations	MedDRA 20.0	EG0002 events2 affected132 at risk EG0011 events1 affected133 at risk
Arthritis	Musculoskeletal and connective tissue disorders	MedDRA 20.0	EG0001 events1 affected132 at risk EG0010 events0 affected133 at risk
Musculoskeletal pain	Musculoskeletal and connective tissue disorders	MedDRA 20.0	EG0001 events1 affected132 at risk EG0010 events0 affected133 at risk
Large granular lymphocytosis	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 20.0	EG0001 events1 affected132 at risk EG0011 events1 affected133 at risk
Syncope	Nervous system disorders	MedDRA 20.0	EG0001 events1 affected132 at risk EG0010 events0 affected133 at risk
Mania	Psychiatric disorders	MedDRA 20.0	EG0000 events0 affected132 at risk EG0011 events1 affected133 at risk
Acute respiratory failure	Respiratory, thoracic and mediastinal disorders	MedDRA 20.0	EG0001 events1 affected132 at risk EG0010 events0 affected133 at risk
Hernia repair	Surgical and medical procedures	MedDRA 20.0	EG0000 events0 affected132 at risk EG0011 events1 affected133 at risk

ID	Term
D015470	Leukemia, Myeloid, Acute
D009190	Myelodysplastic Syndromes

ID	Term
D007951	Leukemia, Myeloid
D007938	Leukemia
D009370	Neoplasms by Histologic Type
D009369	Neoplasms
D006402	Hematologic Diseases
D006425	Hemic and Lymphatic Diseases
D001855	Bone Marrow Diseases

ID	Term
C024352	fludarabine
D002066	Busulfan
C042382	fludarabine phosphate
D008558	Melphalan
D003520	Cyclophosphamide
D014916	Whole-Body Irradiation
D011827	Radiation

ID	Term
D002072	Butylene Glycols
D006018	Glycols
D000438	Alcohols
D009930	Organic Chemicals
D008698	Mesylates
D000476	Alkanesulfonates
D017738	Alkanesulfonic Acids
D000473	Alkanes
D006839	Hydrocarbons, Acyclic
D006838	Hydrocarbons
D013451	Sulfonic Acids
D013456	Sulfur Acids
D013457	Sulfur Compounds
D009588	Nitrogen Mustard Compounds
D009150	Mustard Compounds
D006846	Hydrocarbons, Halogenated
D010649	Phenylalanine
D024322	Amino Acids, Aromatic
D000598	Amino Acids, Cyclic
D000596	Amino Acids
D000602	Amino Acids, Peptides, and Proteins
D010752	Phosphoramide Mustards
D063088	Phosphoramides
D009943	Organophosphorus Compounds
D011878	Radiotherapy
D013812	Therapeutics
D008919	Investigative Techniques
D055585	Physical Phenomena