Trial Outcomes & Findings for Treosulfan, Fludarabine Phosphate, and Total-Body Irradiation in Treating Patients With Hematological Cancer Who Are Undergoing Umbilical Cord Blood Transplant (NCT NCT00796068)

Last Updated: 2023-02-17

Results Overview

Patients will be considered primary graft failure provided they meet any criteria listed below, in the absence of documented disease persistence/recurrence or active bone marrow infection (ex. Cytomegalovirus (CMV)): i. Absence of 3 consecutive days with neutrophils \>500/u1 combined with host CD3+ peripheral blood chimerism ≥50% at day 42 ii. Absence of 3 consecutive days with neutrophils \>500/u1 under any circumstances at day 55 iii. Death after day 28 with neutrophil count \<100/u1 without any evidence of engraftment (\< 5% donor CD3+) iv. Primary autologous count recovery with \< 5% donor CD3+ peripheral blood chimerism at count recovery and without relapse

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

130 participants

Primary outcome timeframe

Up to 100 days

Results posted on

2023-02-17

Participant Flow

Between February 2009 and October 2019, 130 cord blood transplant (CBT) recipients were enrolled in this prospective multi-center phase II study.

All participants who signed consent were assigned to one of two arms and all completed enrollment.

Participant milestones

Participant milestones
Measure	Arm I (Low Risk for Graft Failure) Patients receive a conditioning regimen comprising fludarabine phosphate intravenously (IV) over 1 hour every day (QD) on days -6 to -2 and treosulfan IV over 120 minutes on days - 6 to -4. Patients undergo total body irradiation (TBI) on day -1. Patients then undergo donor cord blood transplant (CBT) on day 0. Patients receive graft versus host disease (GVHD) prophylaxis comprising cyclosporine IV over 1 hour or by mouth (PO) 2-3 times daily on days -3 to 100, followed by a taper in the absence of GVHD. Patients also receive mycophenolate mofetil IV 3 times daily on days 0 to 40, followed by a taper in the absence of GVHD. Cyclosporine: Given IV or PO Fludarabine Phosphate: Given IV Laboratory Biomarker Analysis: Correlative studies Mycophenolate Mofetil: Given IV Total-Body Irradiation: TBI administered day -1: 200 centigray (cGy) (or escalated to 300 cGy, 400 cGy, or 450 cGy per protocol statistical section) Treosulfan: Given IV Umbilical Cord Blood Transplantation (UCBT): Undergo single or double unit UCBT	Arm II (High Risk for Graft Failure) Patients receive a conditioning regimen, total body irradiation (TBI), donor cord blood transplant (CBT), graft versus host disease (GVHD) prophylaxis, and mycophenolate mofetil as in Arm I. Cyclosporine: Given intravenously (IV) or by mouth (PO) Fludarabine Phosphate: Given IV Laboratory Biomarker Analysis: Correlative studies Mycophenolate Mofetil: Given IV Total-Body Irradiation: TBI administered day -1: 200 centigray (cGy) (or escalated to 300 cGy, 400 cGy, or 450 cGy per protocol statistical section) Treosulfan: Given IV Umbilical Cord Blood Transplantation (UCBT): Undergo single or double unit UCBT
Overall Study STARTED	66	64
Overall Study COMPLETED	66	64
Overall Study NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Treosulfan, Fludarabine Phosphate, and Total-Body Irradiation in Treating Patients With Hematological Cancer Who Are Undergoing Umbilical Cord Blood Transplant

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Arm I (Low Risk for Graft Failure) n=66 Participants Patients receive a conditioning regimen comprising fludarabine phosphate IV over 1 hour every day (QD) on days -6 to -2 and treosulfan IV over 120 minutes on days - 6 to -4. Patients undergo total body irradiation (TBI) on day -1. Patients then undergo donor umbilical cord blood transplantation (UCBT) on day 0. Patients receive graft-versus-host disease (GVHD) prophylaxis comprising cyclosporine IV over 1 hour or by mouth (PO) 2-3 times daily on days -3 to 100, followed by a taper in the absence of GVHD. Patients also receive mycophenolate mofetil IV 3 times daily on days 0 to 40, followed by a taper in the absence of GVHD. Cyclosporine: Given IV or PO Fludarabine Phosphate: Given IV Laboratory Biomarker Analysis: Correlative studies Mycophenolate Mofetil (MMF): Given IV Total-Body Irradiation: TBI administered day -1: 200 cGy (or escalated to 300 cGy, 400 cGy, or 450 cGy per protocol statistical section) Treosulfan: Given IV Umbilical Cord Blood Transplantation: Undergo single or double unit UCBT	Arm II (High Risk for Graft Failure) n=64 Participants Patients receive a conditioning regimen, TBI, donor UCBT, GVHD prophylaxis, and mycophenolate mofetil as in Arm I. Cyclosporine: Given IV or PO Fludarabine Phosphate: Given IV Laboratory Biomarker Analysis: Correlative studies Mycophenolate Mofetil: Given IV Total-Body Irradiation: TBI administered day -1: 200 cGy (or escalated to 300 cGy, 400 cGy, or 450 cGy per protocol statistical section) Treosulfan: Given IV Umbilical Cord Blood Transplantation: Undergo single or double unit UCBT	Total n=130 Participants Total of all reporting groups
Age, Categorical <=18 years	18 Participants n=5 Participants	13 Participants n=7 Participants	31 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	46 Participants n=5 Participants	51 Participants n=7 Participants	97 Participants n=5 Participants
Age, Categorical >=65 years	2 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants
Age, Continuous	47 years n=5 Participants	43 years n=7 Participants	45 years n=5 Participants
Sex: Female, Male Female	36 Participants n=5 Participants	33 Participants n=7 Participants	69 Participants n=5 Participants
Sex: Female, Male Male	30 Participants n=5 Participants	31 Participants n=7 Participants	61 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	1 Participants n=5 Participants	2 Participants n=7 Participants	3 Participants n=5 Participants
Race (NIH/OMB) Asian	7 Participants n=5 Participants	12 Participants n=7 Participants	19 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	4 Participants n=5 Participants	4 Participants n=7 Participants	8 Participants n=5 Participants
Race (NIH/OMB) Black or African American	1 Participants n=5 Participants	4 Participants n=7 Participants	5 Participants n=5 Participants
Race (NIH/OMB) White	38 Participants n=5 Participants	36 Participants n=7 Participants	74 Participants n=5 Participants
Race (NIH/OMB) More than one race	2 Participants n=5 Participants	1 Participants n=7 Participants	3 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	13 Participants n=5 Participants	5 Participants n=7 Participants	18 Participants n=5 Participants
Region of Enrollment United States	66 Participants n=5 Participants	64 Participants n=7 Participants	130 Participants n=5 Participants
Hematopoietic Cell Transplantation-Comorbidity Index (HCT-CI)	2 units on a scale n=5 Participants	2 units on a scale n=7 Participants	2 units on a scale n=5 Participants
Diagnosis Acute myeloid leukemia (AML)	38 Participants n=5 Participants	25 Participants n=7 Participants	63 Participants n=5 Participants
Diagnosis Acute lymphoblastic leukemia (ALL)	24 Participants n=5 Participants	13 Participants n=7 Participants	37 Participants n=5 Participants
Diagnosis Biphenotypic	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Diagnosis Myelodysplastic Syndrome (MDS)	3 Participants n=5 Participants	22 Participants n=7 Participants	25 Participants n=5 Participants
Diagnosis Myeloproliferative	0 Participants n=5 Participants	3 Participants n=7 Participants	3 Participants n=5 Participants
Human leukocyte antigens (HLA) matching to recipients 6/6	3 Participants n=5 Participants	2 Participants n=7 Participants	5 Participants n=5 Participants
Human leukocyte antigens (HLA) matching to recipients 5/6	25 Participants n=5 Participants	17 Participants n=7 Participants	42 Participants n=5 Participants
Human leukocyte antigens (HLA) matching to recipients 4/6	38 Participants n=5 Participants	45 Participants n=7 Participants	83 Participants n=5 Participants

PRIMARY outcome

Timeframe: Up to 100 days

Outcome measures

Outcome measures
Measure	Arm I (Low Risk for Graft Failure) n=66 Participants Patients receive a conditioning regimen comprising fludarabine phosphate IV over 1 hour QD on days -6 to -2 and treosulfan IV over 120 minutes on days - 6 to -4. Patients undergo TBI on day -1. Patients then undergo donor UCBT on day 0. Patients receive GVHD prophylaxis comprising cyclosporine IV over 1 hour or PO 2-3 times daily on days -3 to 100, followed by a taper in the absence of GVHD. Patients also receive mycophenolate mofetil IV 3 times daily on days 0 to 40, followed by a taper in the absence of GVHD. Cyclosporine: Given IV or PO Fludarabine Phosphate: Given IV Laboratory Biomarker Analysis: Correlative studies Mycophenolate Mofetil: Given IV Total-Body Irradiation: TBI administered day -1: 200 cGy (or escalated to 300 cGy, 400 cGy, or 450 cGy per protocol statistical section) Treosulfan: Given IV Umbilical Cord Blood Transplantation: Undergo single or double unit UCBT	Arm II (High Risk for Graft Failure) n=64 Participants Patients receive a conditioning regimen, TBI, donor UCBT, GVHD prophylaxis, and mycophenolate mofetil as in Arm I. Cyclosporine: Given IV or PO Fludarabine Phosphate: Given IV Laboratory Biomarker Analysis: Correlative studies Mycophenolate Mofetil: Given IV Total-Body Irradiation: TBI administered day -1: 200 cGy (or escalated to 300 cGy, 400 cGy, or 450 cGy per protocol statistical section) Treosulfan: Given IV Umbilical Cord Blood Transplantation: Undergo single or double unit UCBT
Number of Participants With Graft Failure/Rejection	2 Participants	5 Participants

PRIMARY outcome

Timeframe: Up to 2 years

Secondary graft failure is defined as decline of neutrophil count to \<500/ul with loss of donor chimerism after day 55

Outcome measures

Outcome measures
Measure	Arm I (Low Risk for Graft Failure) n=66 Participants Patients receive a conditioning regimen comprising fludarabine phosphate IV over 1 hour QD on days -6 to -2 and treosulfan IV over 120 minutes on days - 6 to -4. Patients undergo TBI on day -1. Patients then undergo donor UCBT on day 0. Patients receive GVHD prophylaxis comprising cyclosporine IV over 1 hour or PO 2-3 times daily on days -3 to 100, followed by a taper in the absence of GVHD. Patients also receive mycophenolate mofetil IV 3 times daily on days 0 to 40, followed by a taper in the absence of GVHD. Cyclosporine: Given IV or PO Fludarabine Phosphate: Given IV Laboratory Biomarker Analysis: Correlative studies Mycophenolate Mofetil: Given IV Total-Body Irradiation: TBI administered day -1: 200 cGy (or escalated to 300 cGy, 400 cGy, or 450 cGy per protocol statistical section) Treosulfan: Given IV Umbilical Cord Blood Transplantation: Undergo single or double unit UCBT	Arm II (High Risk for Graft Failure) n=64 Participants Patients receive a conditioning regimen, TBI, donor UCBT, GVHD prophylaxis, and mycophenolate mofetil as in Arm I. Cyclosporine: Given IV or PO Fludarabine Phosphate: Given IV Laboratory Biomarker Analysis: Correlative studies Mycophenolate Mofetil: Given IV Total-Body Irradiation: TBI administered day -1: 200 cGy (or escalated to 300 cGy, 400 cGy, or 450 cGy per protocol statistical section) Treosulfan: Given IV Umbilical Cord Blood Transplantation: Undergo single or double unit UCBT
Number of Participants With Secondary Graft Failure	0 Participants	0 Participants

PRIMARY outcome

Timeframe: At day -200

Defined as death from any cause without sign of disease progression or relapse. Loss to follow up are censored, whereas disease relapse or progression are considered competing risks.

Outcome measures

Outcome measures
Measure	Arm I (Low Risk for Graft Failure) n=66 Participants Patients receive a conditioning regimen comprising fludarabine phosphate IV over 1 hour QD on days -6 to -2 and treosulfan IV over 120 minutes on days - 6 to -4. Patients undergo TBI on day -1. Patients then undergo donor UCBT on day 0. Patients receive GVHD prophylaxis comprising cyclosporine IV over 1 hour or PO 2-3 times daily on days -3 to 100, followed by a taper in the absence of GVHD. Patients also receive mycophenolate mofetil IV 3 times daily on days 0 to 40, followed by a taper in the absence of GVHD. Cyclosporine: Given IV or PO Fludarabine Phosphate: Given IV Laboratory Biomarker Analysis: Correlative studies Mycophenolate Mofetil: Given IV Total-Body Irradiation: TBI administered day -1: 200 cGy (or escalated to 300 cGy, 400 cGy, or 450 cGy per protocol statistical section) Treosulfan: Given IV Umbilical Cord Blood Transplantation: Undergo single or double unit UCBT	Arm II (High Risk for Graft Failure) n=64 Participants Patients receive a conditioning regimen, TBI, donor UCBT, GVHD prophylaxis, and mycophenolate mofetil as in Arm I. Cyclosporine: Given IV or PO Fludarabine Phosphate: Given IV Laboratory Biomarker Analysis: Correlative studies Mycophenolate Mofetil: Given IV Total-Body Irradiation: TBI administered day -1: 200 cGy (or escalated to 300 cGy, 400 cGy, or 450 cGy per protocol statistical section) Treosulfan: Given IV Umbilical Cord Blood Transplantation: Undergo single or double unit UCBT
Number of Patients With Non-relapse Mortality (NRM)	7 Participants	6 Participants

SECONDARY outcome

Timeframe: At 1 year

Overall survival was measured from the first day of CBT infusion until death from any cause.

Outcome measures

Outcome measures
Measure	Arm I (Low Risk for Graft Failure) n=66 Participants Patients receive a conditioning regimen comprising fludarabine phosphate IV over 1 hour QD on days -6 to -2 and treosulfan IV over 120 minutes on days - 6 to -4. Patients undergo TBI on day -1. Patients then undergo donor UCBT on day 0. Patients receive GVHD prophylaxis comprising cyclosporine IV over 1 hour or PO 2-3 times daily on days -3 to 100, followed by a taper in the absence of GVHD. Patients also receive mycophenolate mofetil IV 3 times daily on days 0 to 40, followed by a taper in the absence of GVHD. Cyclosporine: Given IV or PO Fludarabine Phosphate: Given IV Laboratory Biomarker Analysis: Correlative studies Mycophenolate Mofetil: Given IV Total-Body Irradiation: TBI administered day -1: 200 cGy (or escalated to 300 cGy, 400 cGy, or 450 cGy per protocol statistical section) Treosulfan: Given IV Umbilical Cord Blood Transplantation: Undergo single or double unit UCBT	Arm II (High Risk for Graft Failure) n=64 Participants Patients receive a conditioning regimen, TBI, donor UCBT, GVHD prophylaxis, and mycophenolate mofetil as in Arm I. Cyclosporine: Given IV or PO Fludarabine Phosphate: Given IV Laboratory Biomarker Analysis: Correlative studies Mycophenolate Mofetil: Given IV Total-Body Irradiation: TBI administered day -1: 200 cGy (or escalated to 300 cGy, 400 cGy, or 450 cGy per protocol statistical section) Treosulfan: Given IV Umbilical Cord Blood Transplantation: Undergo single or double unit UCBT
Number of Participants Surviving by 1 Year	51 Participants	47 Participants

SECONDARY outcome

Timeframe: Up to 2 years

Overall survival of participants after two-years of follow up.

Outcome measures

Outcome measures
Measure	Arm I (Low Risk for Graft Failure) n=66 Participants Patients receive a conditioning regimen comprising fludarabine phosphate IV over 1 hour QD on days -6 to -2 and treosulfan IV over 120 minutes on days - 6 to -4. Patients undergo TBI on day -1. Patients then undergo donor UCBT on day 0. Patients receive GVHD prophylaxis comprising cyclosporine IV over 1 hour or PO 2-3 times daily on days -3 to 100, followed by a taper in the absence of GVHD. Patients also receive mycophenolate mofetil IV 3 times daily on days 0 to 40, followed by a taper in the absence of GVHD. Cyclosporine: Given IV or PO Fludarabine Phosphate: Given IV Laboratory Biomarker Analysis: Correlative studies Mycophenolate Mofetil: Given IV Total-Body Irradiation: TBI administered day -1: 200 cGy (or escalated to 300 cGy, 400 cGy, or 450 cGy per protocol statistical section) Treosulfan: Given IV Umbilical Cord Blood Transplantation: Undergo single or double unit UCBT	Arm II (High Risk for Graft Failure) n=64 Participants Patients receive a conditioning regimen, TBI, donor UCBT, GVHD prophylaxis, and mycophenolate mofetil as in Arm I. Cyclosporine: Given IV or PO Fludarabine Phosphate: Given IV Laboratory Biomarker Analysis: Correlative studies Mycophenolate Mofetil: Given IV Total-Body Irradiation: TBI administered day -1: 200 cGy (or escalated to 300 cGy, 400 cGy, or 450 cGy per protocol statistical section) Treosulfan: Given IV Umbilical Cord Blood Transplantation: Undergo single or double unit UCBT
The Number of Participants Alive at Two-years Follow up.	50 Participants	44 Participants

SECONDARY outcome

Timeframe: Up to 2 years

Death of any cause other than relapse or disease progression was considered.

Outcome measures

Outcome measures
Measure	Arm I (Low Risk for Graft Failure) n=66 Participants Patients receive a conditioning regimen comprising fludarabine phosphate IV over 1 hour QD on days -6 to -2 and treosulfan IV over 120 minutes on days - 6 to -4. Patients undergo TBI on day -1. Patients then undergo donor UCBT on day 0. Patients receive GVHD prophylaxis comprising cyclosporine IV over 1 hour or PO 2-3 times daily on days -3 to 100, followed by a taper in the absence of GVHD. Patients also receive mycophenolate mofetil IV 3 times daily on days 0 to 40, followed by a taper in the absence of GVHD. Cyclosporine: Given IV or PO Fludarabine Phosphate: Given IV Laboratory Biomarker Analysis: Correlative studies Mycophenolate Mofetil: Given IV Total-Body Irradiation: TBI administered day -1: 200 cGy (or escalated to 300 cGy, 400 cGy, or 450 cGy per protocol statistical section) Treosulfan: Given IV Umbilical Cord Blood Transplantation: Undergo single or double unit UCBT	Arm II (High Risk for Graft Failure) n=64 Participants Patients receive a conditioning regimen, TBI, donor UCBT, GVHD prophylaxis, and mycophenolate mofetil as in Arm I. Cyclosporine: Given IV or PO Fludarabine Phosphate: Given IV Laboratory Biomarker Analysis: Correlative studies Mycophenolate Mofetil: Given IV Total-Body Irradiation: TBI administered day -1: 200 cGy (or escalated to 300 cGy, 400 cGy, or 450 cGy per protocol statistical section) Treosulfan: Given IV Umbilical Cord Blood Transplantation: Undergo single or double unit UCBT
Non-relapse Mortality	8 Participants	10 Participants

SECONDARY outcome

Timeframe: At 6 months

Summarized using a range and median of measure in days until participants reached platelet engraftment. Platelet engraftment was defined as the first of 7 consecutive days when the platelet count exceeded 20 x 109/L (untransfused).

Outcome measures

Outcome measures
Measure	Arm I (Low Risk for Graft Failure) n=66 Participants Patients receive a conditioning regimen comprising fludarabine phosphate IV over 1 hour QD on days -6 to -2 and treosulfan IV over 120 minutes on days - 6 to -4. Patients undergo TBI on day -1. Patients then undergo donor UCBT on day 0. Patients receive GVHD prophylaxis comprising cyclosporine IV over 1 hour or PO 2-3 times daily on days -3 to 100, followed by a taper in the absence of GVHD. Patients also receive mycophenolate mofetil IV 3 times daily on days 0 to 40, followed by a taper in the absence of GVHD. Cyclosporine: Given IV or PO Fludarabine Phosphate: Given IV Laboratory Biomarker Analysis: Correlative studies Mycophenolate Mofetil: Given IV Total-Body Irradiation: TBI administered day -1: 200 cGy (or escalated to 300 cGy, 400 cGy, or 450 cGy per protocol statistical section) Treosulfan: Given IV Umbilical Cord Blood Transplantation: Undergo single or double unit UCBT	Arm II (High Risk for Graft Failure) n=64 Participants Patients receive a conditioning regimen, TBI, donor UCBT, GVHD prophylaxis, and mycophenolate mofetil as in Arm I. Cyclosporine: Given IV or PO Fludarabine Phosphate: Given IV Laboratory Biomarker Analysis: Correlative studies Mycophenolate Mofetil: Given IV Total-Body Irradiation: TBI administered day -1: 200 cGy (or escalated to 300 cGy, 400 cGy, or 450 cGy per protocol statistical section) Treosulfan: Given IV Umbilical Cord Blood Transplantation: Undergo single or double unit UCBT
Duration (Days) Until Participants Obtained Platelet Engraftment	31 days Interval 16.0 to 83.0	31 days Interval 12.0 to 87.0

SECONDARY outcome

Timeframe: Day 100

Grade I GVHD is characterized as mild disease, grade II GVHD as moderate, grade III as severe, and grade IV life-threatening. Diagnosing and grading acute GVHD is based on clinical findings (the organ stage, response to treatment and whether GVHD was a major cause of death) and frequently varies between transplant centers and independent reviewers.

Outcome measures

Outcome measures
Measure	Arm I (Low Risk for Graft Failure) n=66 Participants Patients receive a conditioning regimen comprising fludarabine phosphate IV over 1 hour QD on days -6 to -2 and treosulfan IV over 120 minutes on days - 6 to -4. Patients undergo TBI on day -1. Patients then undergo donor UCBT on day 0. Patients receive GVHD prophylaxis comprising cyclosporine IV over 1 hour or PO 2-3 times daily on days -3 to 100, followed by a taper in the absence of GVHD. Patients also receive mycophenolate mofetil IV 3 times daily on days 0 to 40, followed by a taper in the absence of GVHD. Cyclosporine: Given IV or PO Fludarabine Phosphate: Given IV Laboratory Biomarker Analysis: Correlative studies Mycophenolate Mofetil: Given IV Total-Body Irradiation: TBI administered day -1: 200 cGy (or escalated to 300 cGy, 400 cGy, or 450 cGy per protocol statistical section) Treosulfan: Given IV Umbilical Cord Blood Transplantation: Undergo single or double unit UCBT	Arm II (High Risk for Graft Failure) n=64 Participants Patients receive a conditioning regimen, TBI, donor UCBT, GVHD prophylaxis, and mycophenolate mofetil as in Arm I. Cyclosporine: Given IV or PO Fludarabine Phosphate: Given IV Laboratory Biomarker Analysis: Correlative studies Mycophenolate Mofetil: Given IV Total-Body Irradiation: TBI administered day -1: 200 cGy (or escalated to 300 cGy, 400 cGy, or 450 cGy per protocol statistical section) Treosulfan: Given IV Umbilical Cord Blood Transplantation: Undergo single or double unit UCBT
Number of Participants With Acute Graft-versus-host Disease (GVHD) Grade II-IV by Day 100	36 Participants	37 Participants

SECONDARY outcome

Timeframe: At 1 year

Overall GVHD is determined based on the organ stage, response to treatment and whether GVHD was a major cause of death. Chronic GVHD will be defined according to the National Institutes of Health Consensus Development Project on Criteria for Clinical Trials in Chronic Graft-versus-Host Disease. Described as mild, moderate, or severe as graded according to the attached Organ Scoring Sheet. Symptoms consistent with both chronic and acute GVHD occurring after day 100 will be considered overlap chronic GVHD syndrome.

Outcome measures

Outcome measures
Measure	Arm I (Low Risk for Graft Failure) n=66 Participants Patients receive a conditioning regimen comprising fludarabine phosphate IV over 1 hour QD on days -6 to -2 and treosulfan IV over 120 minutes on days - 6 to -4. Patients undergo TBI on day -1. Patients then undergo donor UCBT on day 0. Patients receive GVHD prophylaxis comprising cyclosporine IV over 1 hour or PO 2-3 times daily on days -3 to 100, followed by a taper in the absence of GVHD. Patients also receive mycophenolate mofetil IV 3 times daily on days 0 to 40, followed by a taper in the absence of GVHD. Cyclosporine: Given IV or PO Fludarabine Phosphate: Given IV Laboratory Biomarker Analysis: Correlative studies Mycophenolate Mofetil: Given IV Total-Body Irradiation: TBI administered day -1: 200 cGy (or escalated to 300 cGy, 400 cGy, or 450 cGy per protocol statistical section) Treosulfan: Given IV Umbilical Cord Blood Transplantation: Undergo single or double unit UCBT	Arm II (High Risk for Graft Failure) n=64 Participants Patients receive a conditioning regimen, TBI, donor UCBT, GVHD prophylaxis, and mycophenolate mofetil as in Arm I. Cyclosporine: Given IV or PO Fludarabine Phosphate: Given IV Laboratory Biomarker Analysis: Correlative studies Mycophenolate Mofetil: Given IV Total-Body Irradiation: TBI administered day -1: 200 cGy (or escalated to 300 cGy, 400 cGy, or 450 cGy per protocol statistical section) Treosulfan: Given IV Umbilical Cord Blood Transplantation: Undergo single or double unit UCBT
Incidence of Acute or Chronic Graft-versus-host Disease (GVHD)	7 Participants	6 Participants

SECONDARY outcome

Timeframe: Up to 2 years

Cumulative incidence estimates using non-relapse mortality as competitive event.

Outcome measures

Outcome measures
Measure	Arm I (Low Risk for Graft Failure) n=66 Participants Patients receive a conditioning regimen comprising fludarabine phosphate IV over 1 hour QD on days -6 to -2 and treosulfan IV over 120 minutes on days - 6 to -4. Patients undergo TBI on day -1. Patients then undergo donor UCBT on day 0. Patients receive GVHD prophylaxis comprising cyclosporine IV over 1 hour or PO 2-3 times daily on days -3 to 100, followed by a taper in the absence of GVHD. Patients also receive mycophenolate mofetil IV 3 times daily on days 0 to 40, followed by a taper in the absence of GVHD. Cyclosporine: Given IV or PO Fludarabine Phosphate: Given IV Laboratory Biomarker Analysis: Correlative studies Mycophenolate Mofetil: Given IV Total-Body Irradiation: TBI administered day -1: 200 cGy (or escalated to 300 cGy, 400 cGy, or 450 cGy per protocol statistical section) Treosulfan: Given IV Umbilical Cord Blood Transplantation: Undergo single or double unit UCBT	Arm II (High Risk for Graft Failure) n=64 Participants Patients receive a conditioning regimen, TBI, donor UCBT, GVHD prophylaxis, and mycophenolate mofetil as in Arm I. Cyclosporine: Given IV or PO Fludarabine Phosphate: Given IV Laboratory Biomarker Analysis: Correlative studies Mycophenolate Mofetil: Given IV Total-Body Irradiation: TBI administered day -1: 200 cGy (or escalated to 300 cGy, 400 cGy, or 450 cGy per protocol statistical section) Treosulfan: Given IV Umbilical Cord Blood Transplantation: Undergo single or double unit UCBT
Incidence of Relapse or Disease Progression	17 Participants	11 Participants

SECONDARY outcome

Timeframe: Up to 2 years

Progression-free survival is the time interval from start of treatment to documented evidence of disease progression. Disease progression was defined by European LeukemiaNet 2017 criteria and International Working Group (IWG) within 3 years of transplant.

Outcome measures

Outcome measures
Measure	Arm I (Low Risk for Graft Failure) n=66 Participants Patients receive a conditioning regimen comprising fludarabine phosphate IV over 1 hour QD on days -6 to -2 and treosulfan IV over 120 minutes on days - 6 to -4. Patients undergo TBI on day -1. Patients then undergo donor UCBT on day 0. Patients receive GVHD prophylaxis comprising cyclosporine IV over 1 hour or PO 2-3 times daily on days -3 to 100, followed by a taper in the absence of GVHD. Patients also receive mycophenolate mofetil IV 3 times daily on days 0 to 40, followed by a taper in the absence of GVHD. Cyclosporine: Given IV or PO Fludarabine Phosphate: Given IV Laboratory Biomarker Analysis: Correlative studies Mycophenolate Mofetil: Given IV Total-Body Irradiation: TBI administered day -1: 200 cGy (or escalated to 300 cGy, 400 cGy, or 450 cGy per protocol statistical section) Treosulfan: Given IV Umbilical Cord Blood Transplantation: Undergo single or double unit UCBT	Arm II (High Risk for Graft Failure) n=64 Participants Patients receive a conditioning regimen, TBI, donor UCBT, GVHD prophylaxis, and mycophenolate mofetil as in Arm I. Cyclosporine: Given IV or PO Fludarabine Phosphate: Given IV Laboratory Biomarker Analysis: Correlative studies Mycophenolate Mofetil: Given IV Total-Body Irradiation: TBI administered day -1: 200 cGy (or escalated to 300 cGy, 400 cGy, or 450 cGy per protocol statistical section) Treosulfan: Given IV Umbilical Cord Blood Transplantation: Undergo single or double unit UCBT
Number of Participants Surviving up to 2 Years Without Disease Progression	37 Participants	41 Participants

SECONDARY outcome

Timeframe: At 6 months

Collected and graded according to the modified National Cancer Institute Common Toxicity Criteria.

Outcome measures

Outcome measures
Measure	Arm I (Low Risk for Graft Failure) n=66 Participants Patients receive a conditioning regimen comprising fludarabine phosphate IV over 1 hour QD on days -6 to -2 and treosulfan IV over 120 minutes on days - 6 to -4. Patients undergo TBI on day -1. Patients then undergo donor UCBT on day 0. Patients receive GVHD prophylaxis comprising cyclosporine IV over 1 hour or PO 2-3 times daily on days -3 to 100, followed by a taper in the absence of GVHD. Patients also receive mycophenolate mofetil IV 3 times daily on days 0 to 40, followed by a taper in the absence of GVHD. Cyclosporine: Given IV or PO Fludarabine Phosphate: Given IV Laboratory Biomarker Analysis: Correlative studies Mycophenolate Mofetil: Given IV Total-Body Irradiation: TBI administered day -1: 200 cGy (or escalated to 300 cGy, 400 cGy, or 450 cGy per protocol statistical section) Treosulfan: Given IV Umbilical Cord Blood Transplantation: Undergo single or double unit UCBT	Arm II (High Risk for Graft Failure) n=64 Participants Patients receive a conditioning regimen, TBI, donor UCBT, GVHD prophylaxis, and mycophenolate mofetil as in Arm I. Cyclosporine: Given IV or PO Fludarabine Phosphate: Given IV Laboratory Biomarker Analysis: Correlative studies Mycophenolate Mofetil: Given IV Total-Body Irradiation: TBI administered day -1: 200 cGy (or escalated to 300 cGy, 400 cGy, or 450 cGy per protocol statistical section) Treosulfan: Given IV Umbilical Cord Blood Transplantation: Undergo single or double unit UCBT
Incidence of Clinically Significant Infections	53 Participants	61 Participants

Adverse Events

Arm I (Low Risk for Graft Failure)

Serious events: 27 serious events

Other events: 63 other events

Deaths: 16 deaths

Arm II (High Risk for Graft Failure)

Serious events: 23 serious events

Other events: 59 other events

Deaths: 20 deaths

Serious adverse events

Other adverse events

Additional Information

Dr. Filippo Milano

Fred Hutchinson Cancer Center

Phone: 206-667-5925

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Serious adverse events
Measure	Arm I (Low Risk for Graft Failure) n=66 participants at risk Patients receive a conditioning regimen comprising fludarabine phosphate IV over 1 hour every day (QD) on days -6 to -2 and treosulfan IV over 120 minutes on days - 6 to -4. Patients undergo (total body irradiation (TBI) on day -1. Patients then undergo donor cord blood transplantation (CBT) on day 0. Patients receive graft-versus-host disease (GVHD) prophylaxis comprising cyclosporine IV over 1 hour or by mouth (PO) 2-3 times daily on days -3 to 100, followed by a taper in the absence of GVHD. Patients also receive mycophenolate mofetil IV 3 times daily on days 0 to 40, followed by a taper in the absence of GVHD. Cyclosporine: Given IV or PO Fludarabine Phosphate: Given IV Laboratory Biomarker Analysis: Correlative studies Mycophenolate Mofetil: Given IV Total-Body Irradiation: TBI administered day -1: 200 centigray (cGy) (or escalated to 300 cGy, 400 cGy, or 450 cGy per protocol statistical section) Treosulfan: Given IV Umbilical Cord Blood Transplantation (UCBT): Undergo single or double unit UCBT	Arm II (High Risk for Graft Failure) n=64 participants at risk Patients receive a conditioning regimen, TBI, donor UCBT, GVHD prophylaxis, and mycophenolate mofetil as in Arm I. Cyclosporine: Given IV or PO Fludarabine Phosphate: Given IV Laboratory Biomarker Analysis: Correlative studies Mycophenolate Mofetil: Given IV Total-Body Irradiation: TBI administered day -1: 200 cGy (or escalated to 300 cGy, 400 cGy, or 450 cGy per protocol statistical section) Treosulfan: Given IV Umbilical Cord Blood Transplantation: Undergo single or double unit UCBT
Immune system disorders Allergic Reaction	0.00% 0/66 • Adverse events (AE) will be monitored and recorded in study-specific case report forms (CRFs) from the time of first exposure to an investigational product in this study through day +100 post-transplant. The start of the adverse event reporting for a study subject will coincide with signing of the informed consent. All-cause mortality data was censored at two-year follow-up.	1.6% 1/64 • Number of events 1 • Adverse events (AE) will be monitored and recorded in study-specific case report forms (CRFs) from the time of first exposure to an investigational product in this study through day +100 post-transplant. The start of the adverse event reporting for a study subject will coincide with signing of the informed consent. All-cause mortality data was censored at two-year follow-up.
Cardiac disorders Acute cardiomyopathy	0.00% 0/66 • Adverse events (AE) will be monitored and recorded in study-specific case report forms (CRFs) from the time of first exposure to an investigational product in this study through day +100 post-transplant. The start of the adverse event reporting for a study subject will coincide with signing of the informed consent. All-cause mortality data was censored at two-year follow-up.	1.6% 1/64 • Number of events 1 • Adverse events (AE) will be monitored and recorded in study-specific case report forms (CRFs) from the time of first exposure to an investigational product in this study through day +100 post-transplant. The start of the adverse event reporting for a study subject will coincide with signing of the informed consent. All-cause mortality data was censored at two-year follow-up.
Cardiac disorders Left Ventricular Systolic dysfunction	4.5% 3/66 • Number of events 3 • Adverse events (AE) will be monitored and recorded in study-specific case report forms (CRFs) from the time of first exposure to an investigational product in this study through day +100 post-transplant. The start of the adverse event reporting for a study subject will coincide with signing of the informed consent. All-cause mortality data was censored at two-year follow-up.	1.6% 1/64 • Number of events 1 • Adverse events (AE) will be monitored and recorded in study-specific case report forms (CRFs) from the time of first exposure to an investigational product in this study through day +100 post-transplant. The start of the adverse event reporting for a study subject will coincide with signing of the informed consent. All-cause mortality data was censored at two-year follow-up.
Investigations Cardiac troponin I increased	0.00% 0/66 • Adverse events (AE) will be monitored and recorded in study-specific case report forms (CRFs) from the time of first exposure to an investigational product in this study through day +100 post-transplant. The start of the adverse event reporting for a study subject will coincide with signing of the informed consent. All-cause mortality data was censored at two-year follow-up.	1.6% 1/64 • Number of events 1 • Adverse events (AE) will be monitored and recorded in study-specific case report forms (CRFs) from the time of first exposure to an investigational product in this study through day +100 post-transplant. The start of the adverse event reporting for a study subject will coincide with signing of the informed consent. All-cause mortality data was censored at two-year follow-up.
Vascular disorders Hypertension	1.5% 1/66 • Number of events 1 • Adverse events (AE) will be monitored and recorded in study-specific case report forms (CRFs) from the time of first exposure to an investigational product in this study through day +100 post-transplant. The start of the adverse event reporting for a study subject will coincide with signing of the informed consent. All-cause mortality data was censored at two-year follow-up.	0.00% 0/64 • Adverse events (AE) will be monitored and recorded in study-specific case report forms (CRFs) from the time of first exposure to an investigational product in this study through day +100 post-transplant. The start of the adverse event reporting for a study subject will coincide with signing of the informed consent. All-cause mortality data was censored at two-year follow-up.
Vascular disorders Hypotension	1.5% 1/66 • Number of events 1 • Adverse events (AE) will be monitored and recorded in study-specific case report forms (CRFs) from the time of first exposure to an investigational product in this study through day +100 post-transplant. The start of the adverse event reporting for a study subject will coincide with signing of the informed consent. All-cause mortality data was censored at two-year follow-up.	3.1% 2/64 • Number of events 2 • Adverse events (AE) will be monitored and recorded in study-specific case report forms (CRFs) from the time of first exposure to an investigational product in this study through day +100 post-transplant. The start of the adverse event reporting for a study subject will coincide with signing of the informed consent. All-cause mortality data was censored at two-year follow-up.
Cardiac disorders Pericarditis	1.5% 1/66 • Number of events 1 • Adverse events (AE) will be monitored and recorded in study-specific case report forms (CRFs) from the time of first exposure to an investigational product in this study through day +100 post-transplant. The start of the adverse event reporting for a study subject will coincide with signing of the informed consent. All-cause mortality data was censored at two-year follow-up.	0.00% 0/64 • Adverse events (AE) will be monitored and recorded in study-specific case report forms (CRFs) from the time of first exposure to an investigational product in this study through day +100 post-transplant. The start of the adverse event reporting for a study subject will coincide with signing of the informed consent. All-cause mortality data was censored at two-year follow-up.
General disorders Multi-organ failure	3.0% 2/66 • Number of events 2 • Adverse events (AE) will be monitored and recorded in study-specific case report forms (CRFs) from the time of first exposure to an investigational product in this study through day +100 post-transplant. The start of the adverse event reporting for a study subject will coincide with signing of the informed consent. All-cause mortality data was censored at two-year follow-up.	0.00% 0/64 • Adverse events (AE) will be monitored and recorded in study-specific case report forms (CRFs) from the time of first exposure to an investigational product in this study through day +100 post-transplant. The start of the adverse event reporting for a study subject will coincide with signing of the informed consent. All-cause mortality data was censored at two-year follow-up.
Cardiac disorders Infusional Toxicity/Stunned Heart	0.00% 0/66 • Adverse events (AE) will be monitored and recorded in study-specific case report forms (CRFs) from the time of first exposure to an investigational product in this study through day +100 post-transplant. The start of the adverse event reporting for a study subject will coincide with signing of the informed consent. All-cause mortality data was censored at two-year follow-up.	1.6% 1/64 • Number of events 1 • Adverse events (AE) will be monitored and recorded in study-specific case report forms (CRFs) from the time of first exposure to an investigational product in this study through day +100 post-transplant. The start of the adverse event reporting for a study subject will coincide with signing of the informed consent. All-cause mortality data was censored at two-year follow-up.
Cardiac disorders Heart Failure	0.00% 0/66 • Adverse events (AE) will be monitored and recorded in study-specific case report forms (CRFs) from the time of first exposure to an investigational product in this study through day +100 post-transplant. The start of the adverse event reporting for a study subject will coincide with signing of the informed consent. All-cause mortality data was censored at two-year follow-up.	1.6% 1/64 • Number of events 1 • Adverse events (AE) will be monitored and recorded in study-specific case report forms (CRFs) from the time of first exposure to an investigational product in this study through day +100 post-transplant. The start of the adverse event reporting for a study subject will coincide with signing of the informed consent. All-cause mortality data was censored at two-year follow-up.
Hepatobiliary disorders Sinusoidal obstruction syndrome	0.00% 0/66 • Adverse events (AE) will be monitored and recorded in study-specific case report forms (CRFs) from the time of first exposure to an investigational product in this study through day +100 post-transplant. The start of the adverse event reporting for a study subject will coincide with signing of the informed consent. All-cause mortality data was censored at two-year follow-up.	3.1% 2/64 • Number of events 2 • Adverse events (AE) will be monitored and recorded in study-specific case report forms (CRFs) from the time of first exposure to an investigational product in this study through day +100 post-transplant. The start of the adverse event reporting for a study subject will coincide with signing of the informed consent. All-cause mortality data was censored at two-year follow-up.
Gastrointestinal disorders Gastrointestinal hemorrhage	3.0% 2/66 • Number of events 2 • Adverse events (AE) will be monitored and recorded in study-specific case report forms (CRFs) from the time of first exposure to an investigational product in this study through day +100 post-transplant. The start of the adverse event reporting for a study subject will coincide with signing of the informed consent. All-cause mortality data was censored at two-year follow-up.	0.00% 0/64 • Adverse events (AE) will be monitored and recorded in study-specific case report forms (CRFs) from the time of first exposure to an investigational product in this study through day +100 post-transplant. The start of the adverse event reporting for a study subject will coincide with signing of the informed consent. All-cause mortality data was censored at two-year follow-up.
Gastrointestinal disorders Anal hemorrhage	1.5% 1/66 • Number of events 1 • Adverse events (AE) will be monitored and recorded in study-specific case report forms (CRFs) from the time of first exposure to an investigational product in this study through day +100 post-transplant. The start of the adverse event reporting for a study subject will coincide with signing of the informed consent. All-cause mortality data was censored at two-year follow-up.	0.00% 0/64 • Adverse events (AE) will be monitored and recorded in study-specific case report forms (CRFs) from the time of first exposure to an investigational product in this study through day +100 post-transplant. The start of the adverse event reporting for a study subject will coincide with signing of the informed consent. All-cause mortality data was censored at two-year follow-up.
Respiratory, thoracic and mediastinal disorders Bronchopulmonary hemorrhage	3.0% 2/66 • Number of events 2 • Adverse events (AE) will be monitored and recorded in study-specific case report forms (CRFs) from the time of first exposure to an investigational product in this study through day +100 post-transplant. The start of the adverse event reporting for a study subject will coincide with signing of the informed consent. All-cause mortality data was censored at two-year follow-up.	0.00% 0/64 • Adverse events (AE) will be monitored and recorded in study-specific case report forms (CRFs) from the time of first exposure to an investigational product in this study through day +100 post-transplant. The start of the adverse event reporting for a study subject will coincide with signing of the informed consent. All-cause mortality data was censored at two-year follow-up.
Respiratory, thoracic and mediastinal disorders Respiratory failure	4.5% 3/66 • Number of events 5 • Adverse events (AE) will be monitored and recorded in study-specific case report forms (CRFs) from the time of first exposure to an investigational product in this study through day +100 post-transplant. The start of the adverse event reporting for a study subject will coincide with signing of the informed consent. All-cause mortality data was censored at two-year follow-up.	1.6% 1/64 • Number of events 1 • Adverse events (AE) will be monitored and recorded in study-specific case report forms (CRFs) from the time of first exposure to an investigational product in this study through day +100 post-transplant. The start of the adverse event reporting for a study subject will coincide with signing of the informed consent. All-cause mortality data was censored at two-year follow-up.
Respiratory, thoracic and mediastinal disorders Hypoxia	4.5% 3/66 • Number of events 3 • Adverse events (AE) will be monitored and recorded in study-specific case report forms (CRFs) from the time of first exposure to an investigational product in this study through day +100 post-transplant. The start of the adverse event reporting for a study subject will coincide with signing of the informed consent. All-cause mortality data was censored at two-year follow-up.	1.6% 1/64 • Number of events 1 • Adverse events (AE) will be monitored and recorded in study-specific case report forms (CRFs) from the time of first exposure to an investigational product in this study through day +100 post-transplant. The start of the adverse event reporting for a study subject will coincide with signing of the informed consent. All-cause mortality data was censored at two-year follow-up.
Renal and urinary disorders Renal failure	1.5% 1/66 • Number of events 1 • Adverse events (AE) will be monitored and recorded in study-specific case report forms (CRFs) from the time of first exposure to an investigational product in this study through day +100 post-transplant. The start of the adverse event reporting for a study subject will coincide with signing of the informed consent. All-cause mortality data was censored at two-year follow-up.	0.00% 0/64 • Adverse events (AE) will be monitored and recorded in study-specific case report forms (CRFs) from the time of first exposure to an investigational product in this study through day +100 post-transplant. The start of the adverse event reporting for a study subject will coincide with signing of the informed consent. All-cause mortality data was censored at two-year follow-up.
Nervous system disorders Seizure	0.00% 0/66 • Adverse events (AE) will be monitored and recorded in study-specific case report forms (CRFs) from the time of first exposure to an investigational product in this study through day +100 post-transplant. The start of the adverse event reporting for a study subject will coincide with signing of the informed consent. All-cause mortality data was censored at two-year follow-up.	3.1% 2/64 • Number of events 2 • Adverse events (AE) will be monitored and recorded in study-specific case report forms (CRFs) from the time of first exposure to an investigational product in this study through day +100 post-transplant. The start of the adverse event reporting for a study subject will coincide with signing of the informed consent. All-cause mortality data was censored at two-year follow-up.
Psychiatric disorders Psychosis	0.00% 0/66 • Adverse events (AE) will be monitored and recorded in study-specific case report forms (CRFs) from the time of first exposure to an investigational product in this study through day +100 post-transplant. The start of the adverse event reporting for a study subject will coincide with signing of the informed consent. All-cause mortality data was censored at two-year follow-up.	1.6% 1/64 • Number of events 1 • Adverse events (AE) will be monitored and recorded in study-specific case report forms (CRFs) from the time of first exposure to an investigational product in this study through day +100 post-transplant. The start of the adverse event reporting for a study subject will coincide with signing of the informed consent. All-cause mortality data was censored at two-year follow-up.
Infections and infestations Myelitis	0.00% 0/66 • Adverse events (AE) will be monitored and recorded in study-specific case report forms (CRFs) from the time of first exposure to an investigational product in this study through day +100 post-transplant. The start of the adverse event reporting for a study subject will coincide with signing of the informed consent. All-cause mortality data was censored at two-year follow-up.	1.6% 1/64 • Number of events 1 • Adverse events (AE) will be monitored and recorded in study-specific case report forms (CRFs) from the time of first exposure to an investigational product in this study through day +100 post-transplant. The start of the adverse event reporting for a study subject will coincide with signing of the informed consent. All-cause mortality data was censored at two-year follow-up.
Nervous system disorders Encephalopathy	3.0% 2/66 • Number of events 3 • Adverse events (AE) will be monitored and recorded in study-specific case report forms (CRFs) from the time of first exposure to an investigational product in this study through day +100 post-transplant. The start of the adverse event reporting for a study subject will coincide with signing of the informed consent. All-cause mortality data was censored at two-year follow-up.	0.00% 0/64 • Adverse events (AE) will be monitored and recorded in study-specific case report forms (CRFs) from the time of first exposure to an investigational product in this study through day +100 post-transplant. The start of the adverse event reporting for a study subject will coincide with signing of the informed consent. All-cause mortality data was censored at two-year follow-up.
Nervous system disorders Cognitive disturbance	0.00% 0/66 • Adverse events (AE) will be monitored and recorded in study-specific case report forms (CRFs) from the time of first exposure to an investigational product in this study through day +100 post-transplant. The start of the adverse event reporting for a study subject will coincide with signing of the informed consent. All-cause mortality data was censored at two-year follow-up.	1.6% 1/64 • Number of events 1 • Adverse events (AE) will be monitored and recorded in study-specific case report forms (CRFs) from the time of first exposure to an investigational product in this study through day +100 post-transplant. The start of the adverse event reporting for a study subject will coincide with signing of the informed consent. All-cause mortality data was censored at two-year follow-up.
Nervous system disorders Other - autonomic dysreflexia exacerbation	0.00% 0/66 • Adverse events (AE) will be monitored and recorded in study-specific case report forms (CRFs) from the time of first exposure to an investigational product in this study through day +100 post-transplant. The start of the adverse event reporting for a study subject will coincide with signing of the informed consent. All-cause mortality data was censored at two-year follow-up.	1.6% 1/64 • Number of events 1 • Adverse events (AE) will be monitored and recorded in study-specific case report forms (CRFs) from the time of first exposure to an investigational product in this study through day +100 post-transplant. The start of the adverse event reporting for a study subject will coincide with signing of the informed consent. All-cause mortality data was censored at two-year follow-up.
Renal and urinary disorders Proteinuria	0.00% 0/66 • Adverse events (AE) will be monitored and recorded in study-specific case report forms (CRFs) from the time of first exposure to an investigational product in this study through day +100 post-transplant. The start of the adverse event reporting for a study subject will coincide with signing of the informed consent. All-cause mortality data was censored at two-year follow-up.	1.6% 1/64 • Number of events 1 • Adverse events (AE) will be monitored and recorded in study-specific case report forms (CRFs) from the time of first exposure to an investigational product in this study through day +100 post-transplant. The start of the adverse event reporting for a study subject will coincide with signing of the informed consent. All-cause mortality data was censored at two-year follow-up.
Infections and infestations Sepsis	4.5% 3/66 • Number of events 3 • Adverse events (AE) will be monitored and recorded in study-specific case report forms (CRFs) from the time of first exposure to an investigational product in this study through day +100 post-transplant. The start of the adverse event reporting for a study subject will coincide with signing of the informed consent. All-cause mortality data was censored at two-year follow-up.	4.7% 3/64 • Number of events 3 • Adverse events (AE) will be monitored and recorded in study-specific case report forms (CRFs) from the time of first exposure to an investigational product in this study through day +100 post-transplant. The start of the adverse event reporting for a study subject will coincide with signing of the informed consent. All-cause mortality data was censored at two-year follow-up.
Infections and infestations Upper respiratory infection	1.5% 1/66 • Number of events 1 • Adverse events (AE) will be monitored and recorded in study-specific case report forms (CRFs) from the time of first exposure to an investigational product in this study through day +100 post-transplant. The start of the adverse event reporting for a study subject will coincide with signing of the informed consent. All-cause mortality data was censored at two-year follow-up.	0.00% 0/64 • Adverse events (AE) will be monitored and recorded in study-specific case report forms (CRFs) from the time of first exposure to an investigational product in this study through day +100 post-transplant. The start of the adverse event reporting for a study subject will coincide with signing of the informed consent. All-cause mortality data was censored at two-year follow-up.
Infections and infestations Anorectal infection	1.5% 1/66 • Number of events 1 • Adverse events (AE) will be monitored and recorded in study-specific case report forms (CRFs) from the time of first exposure to an investigational product in this study through day +100 post-transplant. The start of the adverse event reporting for a study subject will coincide with signing of the informed consent. All-cause mortality data was censored at two-year follow-up.	0.00% 0/64 • Adverse events (AE) will be monitored and recorded in study-specific case report forms (CRFs) from the time of first exposure to an investigational product in this study through day +100 post-transplant. The start of the adverse event reporting for a study subject will coincide with signing of the informed consent. All-cause mortality data was censored at two-year follow-up.
Infections and infestations Encephalitis infection	0.00% 0/66 • Adverse events (AE) will be monitored and recorded in study-specific case report forms (CRFs) from the time of first exposure to an investigational product in this study through day +100 post-transplant. The start of the adverse event reporting for a study subject will coincide with signing of the informed consent. All-cause mortality data was censored at two-year follow-up.	1.6% 1/64 • Number of events 1 • Adverse events (AE) will be monitored and recorded in study-specific case report forms (CRFs) from the time of first exposure to an investigational product in this study through day +100 post-transplant. The start of the adverse event reporting for a study subject will coincide with signing of the informed consent. All-cause mortality data was censored at two-year follow-up.

Other adverse events
Measure	Arm I (Low Risk for Graft Failure) n=66 participants at risk Patients receive a conditioning regimen comprising fludarabine phosphate IV over 1 hour every day (QD) on days -6 to -2 and treosulfan IV over 120 minutes on days - 6 to -4. Patients undergo (total body irradiation (TBI) on day -1. Patients then undergo donor cord blood transplantation (CBT) on day 0. Patients receive graft-versus-host disease (GVHD) prophylaxis comprising cyclosporine IV over 1 hour or by mouth (PO) 2-3 times daily on days -3 to 100, followed by a taper in the absence of GVHD. Patients also receive mycophenolate mofetil IV 3 times daily on days 0 to 40, followed by a taper in the absence of GVHD. Cyclosporine: Given IV or PO Fludarabine Phosphate: Given IV Laboratory Biomarker Analysis: Correlative studies Mycophenolate Mofetil: Given IV Total-Body Irradiation: TBI administered day -1: 200 centigray (cGy) (or escalated to 300 cGy, 400 cGy, or 450 cGy per protocol statistical section) Treosulfan: Given IV Umbilical Cord Blood Transplantation (UCBT): Undergo single or double unit UCBT	Arm II (High Risk for Graft Failure) n=64 participants at risk Patients receive a conditioning regimen, TBI, donor UCBT, GVHD prophylaxis, and mycophenolate mofetil as in Arm I. Cyclosporine: Given IV or PO Fludarabine Phosphate: Given IV Laboratory Biomarker Analysis: Correlative studies Mycophenolate Mofetil: Given IV Total-Body Irradiation: TBI administered day -1: 200 cGy (or escalated to 300 cGy, 400 cGy, or 450 cGy per protocol statistical section) Treosulfan: Given IV Umbilical Cord Blood Transplantation: Undergo single or double unit UCBT
Immune system disorders Allergic Reaction	3.0% 2/66 • Number of events 2 • Adverse events (AE) will be monitored and recorded in study-specific case report forms (CRFs) from the time of first exposure to an investigational product in this study through day +100 post-transplant. The start of the adverse event reporting for a study subject will coincide with signing of the informed consent. All-cause mortality data was censored at two-year follow-up.	1.6% 1/64 • Number of events 1 • Adverse events (AE) will be monitored and recorded in study-specific case report forms (CRFs) from the time of first exposure to an investigational product in this study through day +100 post-transplant. The start of the adverse event reporting for a study subject will coincide with signing of the informed consent. All-cause mortality data was censored at two-year follow-up.
Blood and lymphatic system disorders Hemolysis	1.5% 1/66 • Number of events 1 • Adverse events (AE) will be monitored and recorded in study-specific case report forms (CRFs) from the time of first exposure to an investigational product in this study through day +100 post-transplant. The start of the adverse event reporting for a study subject will coincide with signing of the informed consent. All-cause mortality data was censored at two-year follow-up.	0.00% 0/64 • Adverse events (AE) will be monitored and recorded in study-specific case report forms (CRFs) from the time of first exposure to an investigational product in this study through day +100 post-transplant. The start of the adverse event reporting for a study subject will coincide with signing of the informed consent. All-cause mortality data was censored at two-year follow-up.
Cardiac disorders Atrial Fibrillation	0.00% 0/66 • Adverse events (AE) will be monitored and recorded in study-specific case report forms (CRFs) from the time of first exposure to an investigational product in this study through day +100 post-transplant. The start of the adverse event reporting for a study subject will coincide with signing of the informed consent. All-cause mortality data was censored at two-year follow-up.	1.6% 1/64 • Number of events 1 • Adverse events (AE) will be monitored and recorded in study-specific case report forms (CRFs) from the time of first exposure to an investigational product in this study through day +100 post-transplant. The start of the adverse event reporting for a study subject will coincide with signing of the informed consent. All-cause mortality data was censored at two-year follow-up.
Cardiac disorders Atrial Flutter	3.0% 2/66 • Number of events 2 • Adverse events (AE) will be monitored and recorded in study-specific case report forms (CRFs) from the time of first exposure to an investigational product in this study through day +100 post-transplant. The start of the adverse event reporting for a study subject will coincide with signing of the informed consent. All-cause mortality data was censored at two-year follow-up.	0.00% 0/64 • Adverse events (AE) will be monitored and recorded in study-specific case report forms (CRFs) from the time of first exposure to an investigational product in this study through day +100 post-transplant. The start of the adverse event reporting for a study subject will coincide with signing of the informed consent. All-cause mortality data was censored at two-year follow-up.
Cardiac disorders Sinus tachycardia	1.5% 1/66 • Number of events 1 • Adverse events (AE) will be monitored and recorded in study-specific case report forms (CRFs) from the time of first exposure to an investigational product in this study through day +100 post-transplant. The start of the adverse event reporting for a study subject will coincide with signing of the informed consent. All-cause mortality data was censored at two-year follow-up.	0.00% 0/64 • Adverse events (AE) will be monitored and recorded in study-specific case report forms (CRFs) from the time of first exposure to an investigational product in this study through day +100 post-transplant. The start of the adverse event reporting for a study subject will coincide with signing of the informed consent. All-cause mortality data was censored at two-year follow-up.
Cardiac disorders Heart Failure	1.5% 1/66 • Number of events 1 • Adverse events (AE) will be monitored and recorded in study-specific case report forms (CRFs) from the time of first exposure to an investigational product in this study through day +100 post-transplant. The start of the adverse event reporting for a study subject will coincide with signing of the informed consent. All-cause mortality data was censored at two-year follow-up.	0.00% 0/64 • Adverse events (AE) will be monitored and recorded in study-specific case report forms (CRFs) from the time of first exposure to an investigational product in this study through day +100 post-transplant. The start of the adverse event reporting for a study subject will coincide with signing of the informed consent. All-cause mortality data was censored at two-year follow-up.
Vascular disorders Hypotension	16.7% 11/66 • Number of events 11 • Adverse events (AE) will be monitored and recorded in study-specific case report forms (CRFs) from the time of first exposure to an investigational product in this study through day +100 post-transplant. The start of the adverse event reporting for a study subject will coincide with signing of the informed consent. All-cause mortality data was censored at two-year follow-up.	15.6% 10/64 • Number of events 10 • Adverse events (AE) will be monitored and recorded in study-specific case report forms (CRFs) from the time of first exposure to an investigational product in this study through day +100 post-transplant. The start of the adverse event reporting for a study subject will coincide with signing of the informed consent. All-cause mortality data was censored at two-year follow-up.
Hepatobiliary disorders Portal vein thrombosis	1.5% 1/66 • Number of events 1 • Adverse events (AE) will be monitored and recorded in study-specific case report forms (CRFs) from the time of first exposure to an investigational product in this study through day +100 post-transplant. The start of the adverse event reporting for a study subject will coincide with signing of the informed consent. All-cause mortality data was censored at two-year follow-up.	0.00% 0/64 • Adverse events (AE) will be monitored and recorded in study-specific case report forms (CRFs) from the time of first exposure to an investigational product in this study through day +100 post-transplant. The start of the adverse event reporting for a study subject will coincide with signing of the informed consent. All-cause mortality data was censored at two-year follow-up.
Blood and lymphatic system disorders Disemminated vascular coagulation	1.5% 1/66 • Number of events 1 • Adverse events (AE) will be monitored and recorded in study-specific case report forms (CRFs) from the time of first exposure to an investigational product in this study through day +100 post-transplant. The start of the adverse event reporting for a study subject will coincide with signing of the informed consent. All-cause mortality data was censored at two-year follow-up.	1.6% 1/64 • Number of events 1 • Adverse events (AE) will be monitored and recorded in study-specific case report forms (CRFs) from the time of first exposure to an investigational product in this study through day +100 post-transplant. The start of the adverse event reporting for a study subject will coincide with signing of the informed consent. All-cause mortality data was censored at two-year follow-up.
Hepatobiliary disorders Sinusoidal obstruction syndrome	1.5% 1/66 • Number of events 1 • Adverse events (AE) will be monitored and recorded in study-specific case report forms (CRFs) from the time of first exposure to an investigational product in this study through day +100 post-transplant. The start of the adverse event reporting for a study subject will coincide with signing of the informed consent. All-cause mortality data was censored at two-year follow-up.	0.00% 0/64 • Adverse events (AE) will be monitored and recorded in study-specific case report forms (CRFs) from the time of first exposure to an investigational product in this study through day +100 post-transplant. The start of the adverse event reporting for a study subject will coincide with signing of the informed consent. All-cause mortality data was censored at two-year follow-up.
Skin and subcutaneous tissue disorders Rash maculopapular	19.7% 13/66 • Number of events 13 • Adverse events (AE) will be monitored and recorded in study-specific case report forms (CRFs) from the time of first exposure to an investigational product in this study through day +100 post-transplant. The start of the adverse event reporting for a study subject will coincide with signing of the informed consent. All-cause mortality data was censored at two-year follow-up.	9.4% 6/64 • Number of events 6 • Adverse events (AE) will be monitored and recorded in study-specific case report forms (CRFs) from the time of first exposure to an investigational product in this study through day +100 post-transplant. The start of the adverse event reporting for a study subject will coincide with signing of the informed consent. All-cause mortality data was censored at two-year follow-up.
Gastrointestinal disorders Colitis	4.5% 3/66 • Number of events 3 • Adverse events (AE) will be monitored and recorded in study-specific case report forms (CRFs) from the time of first exposure to an investigational product in this study through day +100 post-transplant. The start of the adverse event reporting for a study subject will coincide with signing of the informed consent. All-cause mortality data was censored at two-year follow-up.	3.1% 2/64 • Number of events 2 • Adverse events (AE) will be monitored and recorded in study-specific case report forms (CRFs) from the time of first exposure to an investigational product in this study through day +100 post-transplant. The start of the adverse event reporting for a study subject will coincide with signing of the informed consent. All-cause mortality data was censored at two-year follow-up.
Gastrointestinal disorders Diarrhea	10.6% 7/66 • Number of events 7 • Adverse events (AE) will be monitored and recorded in study-specific case report forms (CRFs) from the time of first exposure to an investigational product in this study through day +100 post-transplant. The start of the adverse event reporting for a study subject will coincide with signing of the informed consent. All-cause mortality data was censored at two-year follow-up.	0.00% 0/64 • Adverse events (AE) will be monitored and recorded in study-specific case report forms (CRFs) from the time of first exposure to an investigational product in this study through day +100 post-transplant. The start of the adverse event reporting for a study subject will coincide with signing of the informed consent. All-cause mortality data was censored at two-year follow-up.
Gastrointestinal disorders Gastric Ulcer	1.5% 1/66 • Number of events 1 • Adverse events (AE) will be monitored and recorded in study-specific case report forms (CRFs) from the time of first exposure to an investigational product in this study through day +100 post-transplant. The start of the adverse event reporting for a study subject will coincide with signing of the informed consent. All-cause mortality data was censored at two-year follow-up.	0.00% 0/64 • Adverse events (AE) will be monitored and recorded in study-specific case report forms (CRFs) from the time of first exposure to an investigational product in this study through day +100 post-transplant. The start of the adverse event reporting for a study subject will coincide with signing of the informed consent. All-cause mortality data was censored at two-year follow-up.
Gastrointestinal disorders Mucositis	15.2% 10/66 • Number of events 10 • Adverse events (AE) will be monitored and recorded in study-specific case report forms (CRFs) from the time of first exposure to an investigational product in this study through day +100 post-transplant. The start of the adverse event reporting for a study subject will coincide with signing of the informed consent. All-cause mortality data was censored at two-year follow-up.	17.2% 11/64 • Number of events 11 • Adverse events (AE) will be monitored and recorded in study-specific case report forms (CRFs) from the time of first exposure to an investigational product in this study through day +100 post-transplant. The start of the adverse event reporting for a study subject will coincide with signing of the informed consent. All-cause mortality data was censored at two-year follow-up.
Gastrointestinal disorders Pancreatitis	3.0% 2/66 • Number of events 2 • Adverse events (AE) will be monitored and recorded in study-specific case report forms (CRFs) from the time of first exposure to an investigational product in this study through day +100 post-transplant. The start of the adverse event reporting for a study subject will coincide with signing of the informed consent. All-cause mortality data was censored at two-year follow-up.	0.00% 0/64 • Adverse events (AE) will be monitored and recorded in study-specific case report forms (CRFs) from the time of first exposure to an investigational product in this study through day +100 post-transplant. The start of the adverse event reporting for a study subject will coincide with signing of the informed consent. All-cause mortality data was censored at two-year follow-up.
Respiratory, thoracic and mediastinal disorders Bronchopulmonary hemorrhage	1.5% 1/66 • Number of events 1 • Adverse events (AE) will be monitored and recorded in study-specific case report forms (CRFs) from the time of first exposure to an investigational product in this study through day +100 post-transplant. The start of the adverse event reporting for a study subject will coincide with signing of the informed consent. All-cause mortality data was censored at two-year follow-up.	1.6% 1/64 • Number of events 1 • Adverse events (AE) will be monitored and recorded in study-specific case report forms (CRFs) from the time of first exposure to an investigational product in this study through day +100 post-transplant. The start of the adverse event reporting for a study subject will coincide with signing of the informed consent. All-cause mortality data was censored at two-year follow-up.
Gastrointestinal disorders Gastric hemorrhage	1.5% 1/66 • Number of events 1 • Adverse events (AE) will be monitored and recorded in study-specific case report forms (CRFs) from the time of first exposure to an investigational product in this study through day +100 post-transplant. The start of the adverse event reporting for a study subject will coincide with signing of the informed consent. All-cause mortality data was censored at two-year follow-up.	1.6% 1/64 • Number of events 1 • Adverse events (AE) will be monitored and recorded in study-specific case report forms (CRFs) from the time of first exposure to an investigational product in this study through day +100 post-transplant. The start of the adverse event reporting for a study subject will coincide with signing of the informed consent. All-cause mortality data was censored at two-year follow-up.
Investigations Blood bilirubin increased	16.7% 11/66 • Number of events 11 • Adverse events (AE) will be monitored and recorded in study-specific case report forms (CRFs) from the time of first exposure to an investigational product in this study through day +100 post-transplant. The start of the adverse event reporting for a study subject will coincide with signing of the informed consent. All-cause mortality data was censored at two-year follow-up.	18.8% 12/64 • Number of events 12 • Adverse events (AE) will be monitored and recorded in study-specific case report forms (CRFs) from the time of first exposure to an investigational product in this study through day +100 post-transplant. The start of the adverse event reporting for a study subject will coincide with signing of the informed consent. All-cause mortality data was censored at two-year follow-up.
Blood and lymphatic system disorders Febrile Neutropenia	40.9% 27/66 • Number of events 27 • Adverse events (AE) will be monitored and recorded in study-specific case report forms (CRFs) from the time of first exposure to an investigational product in this study through day +100 post-transplant. The start of the adverse event reporting for a study subject will coincide with signing of the informed consent. All-cause mortality data was censored at two-year follow-up.	43.8% 28/64 • Number of events 28 • Adverse events (AE) will be monitored and recorded in study-specific case report forms (CRFs) from the time of first exposure to an investigational product in this study through day +100 post-transplant. The start of the adverse event reporting for a study subject will coincide with signing of the informed consent. All-cause mortality data was censored at two-year follow-up.
Infections and infestations Sepsis	37.9% 25/66 • Number of events 33 • Adverse events (AE) will be monitored and recorded in study-specific case report forms (CRFs) from the time of first exposure to an investigational product in this study through day +100 post-transplant. The start of the adverse event reporting for a study subject will coincide with signing of the informed consent. All-cause mortality data was censored at two-year follow-up.	48.4% 31/64 • Number of events 45 • Adverse events (AE) will be monitored and recorded in study-specific case report forms (CRFs) from the time of first exposure to an investigational product in this study through day +100 post-transplant. The start of the adverse event reporting for a study subject will coincide with signing of the informed consent. All-cause mortality data was censored at two-year follow-up.
Infections and infestations Lung infection	6.1% 4/66 • Number of events 4 • Adverse events (AE) will be monitored and recorded in study-specific case report forms (CRFs) from the time of first exposure to an investigational product in this study through day +100 post-transplant. The start of the adverse event reporting for a study subject will coincide with signing of the informed consent. All-cause mortality data was censored at two-year follow-up.	6.2% 4/64 • Number of events 6 • Adverse events (AE) will be monitored and recorded in study-specific case report forms (CRFs) from the time of first exposure to an investigational product in this study through day +100 post-transplant. The start of the adverse event reporting for a study subject will coincide with signing of the informed consent. All-cause mortality data was censored at two-year follow-up.
Infections and infestations Urinary tract infection	7.6% 5/66 • Number of events 6 • Adverse events (AE) will be monitored and recorded in study-specific case report forms (CRFs) from the time of first exposure to an investigational product in this study through day +100 post-transplant. The start of the adverse event reporting for a study subject will coincide with signing of the informed consent. All-cause mortality data was censored at two-year follow-up.	10.9% 7/64 • Number of events 7 • Adverse events (AE) will be monitored and recorded in study-specific case report forms (CRFs) from the time of first exposure to an investigational product in this study through day +100 post-transplant. The start of the adverse event reporting for a study subject will coincide with signing of the informed consent. All-cause mortality data was censored at two-year follow-up.
Infections and infestations Skin infection	3.0% 2/66 • Number of events 2 • Adverse events (AE) will be monitored and recorded in study-specific case report forms (CRFs) from the time of first exposure to an investigational product in this study through day +100 post-transplant. The start of the adverse event reporting for a study subject will coincide with signing of the informed consent. All-cause mortality data was censored at two-year follow-up.	7.8% 5/64 • Number of events 6 • Adverse events (AE) will be monitored and recorded in study-specific case report forms (CRFs) from the time of first exposure to an investigational product in this study through day +100 post-transplant. The start of the adverse event reporting for a study subject will coincide with signing of the informed consent. All-cause mortality data was censored at two-year follow-up.
Infections and infestations Encephalitis infection	3.0% 2/66 • Number of events 2 • Adverse events (AE) will be monitored and recorded in study-specific case report forms (CRFs) from the time of first exposure to an investigational product in this study through day +100 post-transplant. The start of the adverse event reporting for a study subject will coincide with signing of the informed consent. All-cause mortality data was censored at two-year follow-up.	0.00% 0/64 • Adverse events (AE) will be monitored and recorded in study-specific case report forms (CRFs) from the time of first exposure to an investigational product in this study through day +100 post-transplant. The start of the adverse event reporting for a study subject will coincide with signing of the informed consent. All-cause mortality data was censored at two-year follow-up.
Infections and infestations Enterocolitis infectious	6.1% 4/66 • Number of events 4 • Adverse events (AE) will be monitored and recorded in study-specific case report forms (CRFs) from the time of first exposure to an investigational product in this study through day +100 post-transplant. The start of the adverse event reporting for a study subject will coincide with signing of the informed consent. All-cause mortality data was censored at two-year follow-up.	4.7% 3/64 • Number of events 3 • Adverse events (AE) will be monitored and recorded in study-specific case report forms (CRFs) from the time of first exposure to an investigational product in this study through day +100 post-transplant. The start of the adverse event reporting for a study subject will coincide with signing of the informed consent. All-cause mortality data was censored at two-year follow-up.
Infections and infestations Eye infection	1.5% 1/66 • Number of events 1 • Adverse events (AE) will be monitored and recorded in study-specific case report forms (CRFs) from the time of first exposure to an investigational product in this study through day +100 post-transplant. The start of the adverse event reporting for a study subject will coincide with signing of the informed consent. All-cause mortality data was censored at two-year follow-up.	0.00% 0/64 • Adverse events (AE) will be monitored and recorded in study-specific case report forms (CRFs) from the time of first exposure to an investigational product in this study through day +100 post-transplant. The start of the adverse event reporting for a study subject will coincide with signing of the informed consent. All-cause mortality data was censored at two-year follow-up.
Infections and infestations Upper respiratory infection	4.5% 3/66 • Number of events 3 • Adverse events (AE) will be monitored and recorded in study-specific case report forms (CRFs) from the time of first exposure to an investigational product in this study through day +100 post-transplant. The start of the adverse event reporting for a study subject will coincide with signing of the informed consent. All-cause mortality data was censored at two-year follow-up.	7.8% 5/64 • Number of events 5 • Adverse events (AE) will be monitored and recorded in study-specific case report forms (CRFs) from the time of first exposure to an investigational product in this study through day +100 post-transplant. The start of the adverse event reporting for a study subject will coincide with signing of the informed consent. All-cause mortality data was censored at two-year follow-up.
Nervous system disorders Syncope	1.5% 1/66 • Number of events 1 • Adverse events (AE) will be monitored and recorded in study-specific case report forms (CRFs) from the time of first exposure to an investigational product in this study through day +100 post-transplant. The start of the adverse event reporting for a study subject will coincide with signing of the informed consent. All-cause mortality data was censored at two-year follow-up.	0.00% 0/64 • Adverse events (AE) will be monitored and recorded in study-specific case report forms (CRFs) from the time of first exposure to an investigational product in this study through day +100 post-transplant. The start of the adverse event reporting for a study subject will coincide with signing of the informed consent. All-cause mortality data was censored at two-year follow-up.
Respiratory, thoracic and mediastinal disorders Apnea	1.5% 1/66 • Number of events 1 • Adverse events (AE) will be monitored and recorded in study-specific case report forms (CRFs) from the time of first exposure to an investigational product in this study through day +100 post-transplant. The start of the adverse event reporting for a study subject will coincide with signing of the informed consent. All-cause mortality data was censored at two-year follow-up.	0.00% 0/64 • Adverse events (AE) will be monitored and recorded in study-specific case report forms (CRFs) from the time of first exposure to an investigational product in this study through day +100 post-transplant. The start of the adverse event reporting for a study subject will coincide with signing of the informed consent. All-cause mortality data was censored at two-year follow-up.
Respiratory, thoracic and mediastinal disorders Hypoxia	24.2% 16/66 • Number of events 16 • Adverse events (AE) will be monitored and recorded in study-specific case report forms (CRFs) from the time of first exposure to an investigational product in this study through day +100 post-transplant. The start of the adverse event reporting for a study subject will coincide with signing of the informed consent. All-cause mortality data was censored at two-year follow-up.	28.1% 18/64 • Number of events 19 • Adverse events (AE) will be monitored and recorded in study-specific case report forms (CRFs) from the time of first exposure to an investigational product in this study through day +100 post-transplant. The start of the adverse event reporting for a study subject will coincide with signing of the informed consent. All-cause mortality data was censored at two-year follow-up.
Investigations Creatinine increased	3.0% 2/66 • Number of events 2 • Adverse events (AE) will be monitored and recorded in study-specific case report forms (CRFs) from the time of first exposure to an investigational product in this study through day +100 post-transplant. The start of the adverse event reporting for a study subject will coincide with signing of the informed consent. All-cause mortality data was censored at two-year follow-up.	7.8% 5/64 • Number of events 5 • Adverse events (AE) will be monitored and recorded in study-specific case report forms (CRFs) from the time of first exposure to an investigational product in this study through day +100 post-transplant. The start of the adverse event reporting for a study subject will coincide with signing of the informed consent. All-cause mortality data was censored at two-year follow-up.
Renal and urinary disorders Renal failure	1.5% 1/66 • Number of events 1 • Adverse events (AE) will be monitored and recorded in study-specific case report forms (CRFs) from the time of first exposure to an investigational product in this study through day +100 post-transplant. The start of the adverse event reporting for a study subject will coincide with signing of the informed consent. All-cause mortality data was censored at two-year follow-up.	6.2% 4/64 • Number of events 4 • Adverse events (AE) will be monitored and recorded in study-specific case report forms (CRFs) from the time of first exposure to an investigational product in this study through day +100 post-transplant. The start of the adverse event reporting for a study subject will coincide with signing of the informed consent. All-cause mortality data was censored at two-year follow-up.
Cardiac disorders Left Ventricular Systolic dysfunction	0.00% 0/66 • Adverse events (AE) will be monitored and recorded in study-specific case report forms (CRFs) from the time of first exposure to an investigational product in this study through day +100 post-transplant. The start of the adverse event reporting for a study subject will coincide with signing of the informed consent. All-cause mortality data was censored at two-year follow-up.	14.1% 9/64 • Number of events 9 • Adverse events (AE) will be monitored and recorded in study-specific case report forms (CRFs) from the time of first exposure to an investigational product in this study through day +100 post-transplant. The start of the adverse event reporting for a study subject will coincide with signing of the informed consent. All-cause mortality data was censored at two-year follow-up.
Cardiac disorders Pericarditis	0.00% 0/66 • Adverse events (AE) will be monitored and recorded in study-specific case report forms (CRFs) from the time of first exposure to an investigational product in this study through day +100 post-transplant. The start of the adverse event reporting for a study subject will coincide with signing of the informed consent. All-cause mortality data was censored at two-year follow-up.	1.6% 1/64 • Number of events 1 • Adverse events (AE) will be monitored and recorded in study-specific case report forms (CRFs) from the time of first exposure to an investigational product in this study through day +100 post-transplant. The start of the adverse event reporting for a study subject will coincide with signing of the informed consent. All-cause mortality data was censored at two-year follow-up.
Cardiac disorders Hypertension	0.00% 0/66 • Adverse events (AE) will be monitored and recorded in study-specific case report forms (CRFs) from the time of first exposure to an investigational product in this study through day +100 post-transplant. The start of the adverse event reporting for a study subject will coincide with signing of the informed consent. All-cause mortality data was censored at two-year follow-up.	3.1% 2/64 • Number of events 2 • Adverse events (AE) will be monitored and recorded in study-specific case report forms (CRFs) from the time of first exposure to an investigational product in this study through day +100 post-transplant. The start of the adverse event reporting for a study subject will coincide with signing of the informed consent. All-cause mortality data was censored at two-year follow-up.
Cardiac disorders Pericardial effusion	0.00% 0/66 • Adverse events (AE) will be monitored and recorded in study-specific case report forms (CRFs) from the time of first exposure to an investigational product in this study through day +100 post-transplant. The start of the adverse event reporting for a study subject will coincide with signing of the informed consent. All-cause mortality data was censored at two-year follow-up.	1.6% 1/64 • Number of events 1 • Adverse events (AE) will be monitored and recorded in study-specific case report forms (CRFs) from the time of first exposure to an investigational product in this study through day +100 post-transplant. The start of the adverse event reporting for a study subject will coincide with signing of the informed consent. All-cause mortality data was censored at two-year follow-up.
Gastrointestinal disorders Gatritis	0.00% 0/66 • Adverse events (AE) will be monitored and recorded in study-specific case report forms (CRFs) from the time of first exposure to an investigational product in this study through day +100 post-transplant. The start of the adverse event reporting for a study subject will coincide with signing of the informed consent. All-cause mortality data was censored at two-year follow-up.	3.1% 2/64 • Number of events 2 • Adverse events (AE) will be monitored and recorded in study-specific case report forms (CRFs) from the time of first exposure to an investigational product in this study through day +100 post-transplant. The start of the adverse event reporting for a study subject will coincide with signing of the informed consent. All-cause mortality data was censored at two-year follow-up.
Nervous system disorders Seizure	0.00% 0/66 • Adverse events (AE) will be monitored and recorded in study-specific case report forms (CRFs) from the time of first exposure to an investigational product in this study through day +100 post-transplant. The start of the adverse event reporting for a study subject will coincide with signing of the informed consent. All-cause mortality data was censored at two-year follow-up.	1.6% 1/64 • Number of events 1 • Adverse events (AE) will be monitored and recorded in study-specific case report forms (CRFs) from the time of first exposure to an investigational product in this study through day +100 post-transplant. The start of the adverse event reporting for a study subject will coincide with signing of the informed consent. All-cause mortality data was censored at two-year follow-up.
Infections and infestations Otitis Externa	0.00% 0/66 • Adverse events (AE) will be monitored and recorded in study-specific case report forms (CRFs) from the time of first exposure to an investigational product in this study through day +100 post-transplant. The start of the adverse event reporting for a study subject will coincide with signing of the informed consent. All-cause mortality data was censored at two-year follow-up.	1.6% 1/64 • Number of events 1 • Adverse events (AE) will be monitored and recorded in study-specific case report forms (CRFs) from the time of first exposure to an investigational product in this study through day +100 post-transplant. The start of the adverse event reporting for a study subject will coincide with signing of the informed consent. All-cause mortality data was censored at two-year follow-up.