Trial Outcomes & Findings for Bone Marrow Transplantation vs Standard of Care in Patients With Severe Sickle Cell Disease (BMT CTN 1503) (NCT NCT02766465)

Results Overview

Due to incomplete accrual, there was not adequate statistical power to analyze the primary endpoint as specified. Instead, point estimates for the observed proportion of patients surviving at two years post-biologic assignment in each arm were generated descriptively, with 95% CI, using the Kaplan Meier methodology. The event of interest was death from any cause.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

138 participants

Primary outcome timeframe

2 Years

Results posted on

2025-04-18

Participant Flow

BMT CTN 1503's enrollment was between March 2017 and August 2021. The study opened to accrual on March 16, 2017 with activated 37 centers. The study closed to accrual on August 31, 2021 and study completed on May 2, 2023. A total of 138 eligible participants were enrolled to Segment 0 from 31 centers.

Among 138 enrolled patients, 123 were biologically assigned and enrolled in Segment A. Of the 15 who were not biologically assigned, 2 died prior to assignment due to SCD complications, 10 withdrew consent, 2 lost to follow-up, and 1 was removed per physician decision. Of the 123 biologically assigned patients, 28 patients across 13 institutions were assigned to the Donor Arm and 95 patients across 26 institutions were assigned to the No Donor Arm. In the donor arm 24 patients were transplanted.

Participant milestones

Participant milestones
Measure	Donor Arm Donor Arm patients will undergo hematopoietic cell transplant. Patients with a matched unrelated donor will receive a bone marrow transplant (unless PBSC graft is pre-approved per section 2.5.1 using a preparative regimen with Busulfan, Fludarabine and rabbit ATG. Patients with an HLA-identical sibling donor can receive a transplant using one of three regimens: A. Busulfan, Fludarabine, and rabbit ATG using a bone marrow graft (preferred regimen) B. Alemtuzumab/TBI 300 cGy using a peripheral blood graft C. Alemtuzumab, fludarabine, melphalan using a bone marrow graft	No-Donor Arm No-donor arm patients will continue with standard of care per their SCD physician. Standard of Care: Continue to receive standard of care treatment per patient's SCD physician.
Overall Study STARTED	28	95
Overall Study COMPLETED	28	85
Overall Study NOT COMPLETED	0	10

Reasons for withdrawal

Reasons for withdrawal
Measure	Donor Arm Donor Arm patients will undergo hematopoietic cell transplant. Patients with a matched unrelated donor will receive a bone marrow transplant (unless PBSC graft is pre-approved per section 2.5.1 using a preparative regimen with Busulfan, Fludarabine and rabbit ATG. Patients with an HLA-identical sibling donor can receive a transplant using one of three regimens: A. Busulfan, Fludarabine, and rabbit ATG using a bone marrow graft (preferred regimen) B. Alemtuzumab/TBI 300 cGy using a peripheral blood graft C. Alemtuzumab, fludarabine, melphalan using a bone marrow graft	No-Donor Arm No-donor arm patients will continue with standard of care per their SCD physician. Standard of Care: Continue to receive standard of care treatment per patient's SCD physician.
Overall Study Withdrawal by Subject	0	10

Baseline Characteristics

Bone Marrow Transplantation vs Standard of Care in Patients With Severe Sickle Cell Disease (BMT CTN 1503)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Donor Arm n=28 Participants Donor Arm patients will undergo hematopoietic cell transplant. Patients with a matched unrelated donor will receive a bone marrow transplant (unless PBSC graft is pre-approved per section 2.5.1 using a preparative regimen with Busulfan, Fludarabine and rabbit ATG. Patients with an HLA-identical sibling donor can receive a transplant using one of three regimens: A. Busulfan, Fludarabine, and rabbit ATG using a bone marrow graft (preferred regimen) B. Alemtuzumab/TBI 300 cGy using a peripheral blood graft C. Alemtuzumab, fludarabine, melphalan using a bone marrow graft	No-Donor Arm n=85 Participants No-donor arm patients will continue with standard of care per their SCD physician. Standard of Care: Continue to receive standard of care treatment per patient's SCD physician.	Total n=113 Participants Total of all reporting groups
Age, Continuous	29.1 years n=5 Participants	25.9 years n=7 Participants	26.2 years n=5 Participants
Sex: Female, Male Female	15 Participants n=5 Participants	39 Participants n=7 Participants	54 Participants n=5 Participants
Sex: Female, Male Male	13 Participants n=5 Participants	46 Participants n=7 Participants	59 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	4 Participants n=5 Participants	8 Participants n=7 Participants	12 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	24 Participants n=5 Participants	75 Participants n=7 Participants	99 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	2 Participants n=7 Participants	2 Participants n=5 Participants
Race/Ethnicity, Customized White	1 Participants n=5 Participants	5 Participants n=7 Participants	6 Participants n=5 Participants
Race/Ethnicity, Customized Black or African American	26 Participants n=5 Participants	73 Participants n=7 Participants	99 Participants n=5 Participants
Race/Ethnicity, Customized Other	1 Participants n=5 Participants	2 Participants n=7 Participants	3 Participants n=5 Participants
Race/Ethnicity, Customized Unknown	0 Participants n=5 Participants	3 Participants n=7 Participants	3 Participants n=5 Participants
Race/Ethnicity, Customized Not answered	0 Participants n=5 Participants	2 Participants n=7 Participants	2 Participants n=5 Participants
Race/Ethnicity, Customized African American	12 Participants n=5 Participants	41 Participants n=7 Participants	53 Participants n=5 Participants
Race/Ethnicity, Customized African Black (both parents African)	0 Participants n=5 Participants	7 Participants n=7 Participants	7 Participants n=5 Participants
Race/Ethnicity, Customized Black (NOS)	13 Participants n=5 Participants	22 Participants n=7 Participants	35 Participants n=5 Participants
Race/Ethnicity, Customized Caribbean Black	1 Participants n=5 Participants	2 Participants n=7 Participants	3 Participants n=5 Participants
Race/Ethnicity, Customized Middle Eastern	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race/Ethnicity, Customized Puerto Rican	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Race/Ethnicity, Customized Saudi Arabian	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race/Ethnicity, Customized South or Central American	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race/Ethnicity, Customized South or Central American Black	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race/Ethnicity, Customized White (NOS)	1 Participants n=5 Participants	3 Participants n=7 Participants	4 Participants n=5 Participants
Sickle Cell Disease Type HbSS	21 Participants n=5 Participants	67 Participants n=7 Participants	88 Participants n=5 Participants
Sickle Cell Disease Type HbSC	1 Participants n=5 Participants	4 Participants n=7 Participants	5 Participants n=5 Participants
Sickle Cell Disease Type HbS beta thalassemia	2 Participants n=5 Participants	9 Participants n=7 Participants	11 Participants n=5 Participants
Sickle Cell Disease Type HbS-OArab	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Sickle Cell Disease Type Unknown	4 Participants n=5 Participants	4 Participants n=7 Participants	8 Participants n=5 Participants
Severity of SCD Criteria Neurologic	7 Participants n=5 Participants	7 Participants n=7 Participants	14 Participants n=5 Participants
Severity of SCD Criteria Acute Chest Syndrome (ACS)	1 Participants n=5 Participants	14 Participants n=7 Participants	15 Participants n=5 Participants
Severity of SCD Criteria Pain Crises	17 Participants n=5 Participants	62 Participants n=7 Participants	79 Participants n=5 Participants
Severity of SCD Criteria Red Blood Cell (RBC) Transfusion	7 Participants n=5 Participants	13 Participants n=7 Participants	20 Participants n=5 Participants
Severity of SCD Criteria Tricuspid valve Regurgitant Jet Velocity (TRJV)	1 Participants n=5 Participants	9 Participants n=7 Participants	10 Participants n=5 Participants
Severity of SCD Criteria High Impact Chronic Pain	10 Participants n=5 Participants	19 Participants n=7 Participants	29 Participants n=5 Participants

PRIMARY outcome

Timeframe: 2 Years

Population: Using the intent-to-treat principle, participants remained in their assigned treatment arm regardless of treatment received.

Due to incomplete accrual, there was not adequate statistical power to analyze the primary endpoint as specified. Instead, point estimates for the observed proportion of patients surviving at two years post-biologic assignment in each arm were generated descriptively, with 95% CI, using the Kaplan Meier methodology. The event of interest was death from any cause.

Outcome measures

Outcome measures
Measure	Donor Arm n=28 Participants Donor Arm patients will undergo hematopoietic cell transplant. Patients with a matched unrelated donor will receive a bone marrow transplant (unless PBSC graft is pre-approved per section 2.5.1 using a preparative regimen with Busulfan, Fludarabine and rabbit ATG. Patients with an HLA-identical sibling donor can receive a transplant using one of three regimens: A. Busulfan, Fludarabine, and rabbit ATG using a bone marrow graft (preferred regimen) B. Alemtuzumab/TBI 300 cGy using a peripheral blood graft C. Alemtuzumab, fludarabine, melphalan using a bone marrow graft	No-Donor Arm n=85 Participants No-donor arm patients will continue with standard of care per their SCD physician. Standard of Care: Continue to receive standard of care treatment per patient's SCD physician.
Percentage of Participants With Overall Survival (OS) at 2 Years After Biologic Assignment	89 percentage of participants Interval 78.0 to 100.0	94 percentage of participants Interval 87.0 to 99.0

SECONDARY outcome

Timeframe: 2 Years

Population: Using the intent-to-treat principle, participants remained in their assigned treatment arm regardless of treatment received.

Examination of the occurrence of the SCD-related events was performed. Participants can have multiple events. The following sickle cell disease related events of special interest (SCD-EOSI) are expected events for all participants, regardless of biologic assignment: * pulmonary hypertension * significant cerebrovascular events, including: stroke; transient ischemic attack; seizure * renal function compromise, including: proteinuria; increased creatinine grades ≥2 per CTCAE version 4.0 * avascular necrosis of the hip or shoulder * leg ulcers * acute chest syndrome (ACS) requiring hospitalization * vaso-occlusive pain crisis (VOC) requiring hospitalization or administration of parenteral opioid drugs in an outpatient setting. Self-reported events without clinical documentation should not be included.

Outcome measures

Outcome measures
Measure	Donor Arm n=28 Participants Donor Arm patients will undergo hematopoietic cell transplant. Patients with a matched unrelated donor will receive a bone marrow transplant (unless PBSC graft is pre-approved per section 2.5.1 using a preparative regimen with Busulfan, Fludarabine and rabbit ATG. Patients with an HLA-identical sibling donor can receive a transplant using one of three regimens: A. Busulfan, Fludarabine, and rabbit ATG using a bone marrow graft (preferred regimen) B. Alemtuzumab/TBI 300 cGy using a peripheral blood graft C. Alemtuzumab, fludarabine, melphalan using a bone marrow graft	No-Donor Arm n=85 Participants No-donor arm patients will continue with standard of care per their SCD physician. Standard of Care: Continue to receive standard of care treatment per patient's SCD physician.
Frequencies of Sickle Cell Disease (SCD) Events of Special Interest Pulmonary hypertension at 1 yr	1 event	6 event
Frequencies of Sickle Cell Disease (SCD) Events of Special Interest Significant cerebrovascular event including stroke, transient ischemic attack, and seizure at 1 yr	8 event	4 event
Frequencies of Sickle Cell Disease (SCD) Events of Special Interest Renal function compromise at 1 yr	7 event	14 event
Frequencies of Sickle Cell Disease (SCD) Events of Special Interest Avascular necrosis at 1 yr	4 event	11 event
Frequencies of Sickle Cell Disease (SCD) Events of Special Interest Leg ulceration at 1 yr	1 event	4 event
Frequencies of Sickle Cell Disease (SCD) Events of Special Interest Acute chest syndrome with hospitalization at 1 yr	3 event	18 event
Frequencies of Sickle Cell Disease (SCD) Events of Special Interest Vaso-occlusive pain w/ hospitalization or parenteral opioid drugs in outpatient setting at 1 yr	11 event	161 event
Frequencies of Sickle Cell Disease (SCD) Events of Special Interest Any event leading to an advanced care setting or intensive care unit admission/transfer at 1 yr	5 event	5 event
Frequencies of Sickle Cell Disease (SCD) Events of Special Interest Pulmonary hypertension at 2 yrs	1 event	7 event
Frequencies of Sickle Cell Disease (SCD) Events of Special Interest Significant cerebrovascular event including stroke, transient ischemic attack, and seizure at 2 yrs	1 event	6 event
Frequencies of Sickle Cell Disease (SCD) Events of Special Interest Renal function compromise at 2 yrs	4 event	8 event
Frequencies of Sickle Cell Disease (SCD) Events of Special Interest Avascular necrosis at 2 yrs	1 event	8 event
Frequencies of Sickle Cell Disease (SCD) Events of Special Interest Leg ulceration at 2 yrs	0 event	1 event
Frequencies of Sickle Cell Disease (SCD) Events of Special Interest Acute chest syndrome with hospitalization at 2 yrs	0 event	10 event
Frequencies of Sickle Cell Disease (SCD) Events of Special Interest Vaso-occlusive pain w/ hospitalization or parenteral opioid drugs in outpatient setting at 2 yrs	3 event	144 event
Frequencies of Sickle Cell Disease (SCD) Events of Special Interest Any event leading to an advanced care setting or intensive care unit admission/transfer at 2 yrs	1 event	6 event

SECONDARY outcome

Timeframe: Baseline, 2 years

Population: Participants that are biologically assigned to different arms and that completed both the baseline and 2-year assessment; this follows the intent-to-treat principle.

The 6-minute walk distance (6MWD) test is a test to measure how far you can walk in 6 minutes. It is used in this study to assess exercise capacity. The number of meters that a participant could walk in 6 minutes was selected as a direct measurement of physical function.

Outcome measures

Outcome measures
Measure	Donor Arm n=7 Participants Donor Arm patients will undergo hematopoietic cell transplant. Patients with a matched unrelated donor will receive a bone marrow transplant (unless PBSC graft is pre-approved per section 2.5.1 using a preparative regimen with Busulfan, Fludarabine and rabbit ATG. Patients with an HLA-identical sibling donor can receive a transplant using one of three regimens: A. Busulfan, Fludarabine, and rabbit ATG using a bone marrow graft (preferred regimen) B. Alemtuzumab/TBI 300 cGy using a peripheral blood graft C. Alemtuzumab, fludarabine, melphalan using a bone marrow graft	No-Donor Arm n=32 Participants No-donor arm patients will continue with standard of care per their SCD physician. Standard of Care: Continue to receive standard of care treatment per patient's SCD physician.
Change in 6-minute Walk Distance (6MWD) Assessment From Baseline	-71 meter Interval -175.0 to 161.0	-26 meter Interval -374.0 to 343.0

SECONDARY outcome

Timeframe: Baseline, 2 years

Population: Participants that are biologically assigned to different arms and that completed both the baseline and 2-year assessment; this follows the intent-to-treat principle.

Transcuspid regurgitant jet velocity (TRJV) is a measure of how fast blood is pumped through one of the heart valves on the right side of the heart, measured using an ultrasound of the heart (echocardiogram). Higher values can indicate pulmonary hypertension and more severe sickle cell disease. Increasing TRJV over time indicates worsening disease.

Outcome measures

Outcome measures
Measure	Donor Arm n=4 Participants Donor Arm patients will undergo hematopoietic cell transplant. Patients with a matched unrelated donor will receive a bone marrow transplant (unless PBSC graft is pre-approved per section 2.5.1 using a preparative regimen with Busulfan, Fludarabine and rabbit ATG. Patients with an HLA-identical sibling donor can receive a transplant using one of three regimens: A. Busulfan, Fludarabine, and rabbit ATG using a bone marrow graft (preferred regimen) B. Alemtuzumab/TBI 300 cGy using a peripheral blood graft C. Alemtuzumab, fludarabine, melphalan using a bone marrow graft	No-Donor Arm n=16 Participants No-donor arm patients will continue with standard of care per their SCD physician. Standard of Care: Continue to receive standard of care treatment per patient's SCD physician.
Change in Transcuspid Regurgitant Jet Velocity (TRJV) Assessment From Baseline	0.1 meters per second (m/s) Interval -0.7 to 0.9	0.05 meters per second (m/s) Interval -3.1 to 2.5

SECONDARY outcome

Timeframe: Baseline, 2 years

Population: Participants that are biologically assigned to different arms and that completed both the baseline and 2-year assessment; this follows the intent-to-treat principle.

Albuminuria is the ratio of albumin (a protein) in the urine to creatinine in the urine. This may be assessed based on a 24-hour urine sample or a spot urine sample. Albumin in the urine may indicate kidney disease. Increases in albuminuria over time indicate increasing renal (kidney) disease.

Outcome measures

Outcome measures
Measure	Donor Arm Donor Arm patients will undergo hematopoietic cell transplant. Patients with a matched unrelated donor will receive a bone marrow transplant (unless PBSC graft is pre-approved per section 2.5.1 using a preparative regimen with Busulfan, Fludarabine and rabbit ATG. Patients with an HLA-identical sibling donor can receive a transplant using one of three regimens: A. Busulfan, Fludarabine, and rabbit ATG using a bone marrow graft (preferred regimen) B. Alemtuzumab/TBI 300 cGy using a peripheral blood graft C. Alemtuzumab, fludarabine, melphalan using a bone marrow graft	No-Donor Arm n=6 Participants No-donor arm patients will continue with standard of care per their SCD physician. Standard of Care: Continue to receive standard of care treatment per patient's SCD physician.
Change in Albuminuria Assessment From Baseline	—	0 mg of albumin per gram of creatine Interval -9.0 to 98.0

SECONDARY outcome

Timeframe: Baseline, 2 years

Population: Participants that are biologically assigned to different arms and that completed both the baseline and 2-year assessment; this follows the intent-to-treat principle.

Health-Related Quality of Life (HRQoL) assessed using the NIH's PROMIS 57 instrument. Physical Function asks about degree of difficulty in performing activities of daily living such as housework, errands, and going up and down stairs. It is scored from 0 to 10 and converted to a standardized T-score with mean 50 and standard deviation 10. A higher T-score represents better physical function.

Outcome measures

Outcome measures
Measure	Donor Arm n=10 Participants Donor Arm patients will undergo hematopoietic cell transplant. Patients with a matched unrelated donor will receive a bone marrow transplant (unless PBSC graft is pre-approved per section 2.5.1 using a preparative regimen with Busulfan, Fludarabine and rabbit ATG. Patients with an HLA-identical sibling donor can receive a transplant using one of three regimens: A. Busulfan, Fludarabine, and rabbit ATG using a bone marrow graft (preferred regimen) B. Alemtuzumab/TBI 300 cGy using a peripheral blood graft C. Alemtuzumab, fludarabine, melphalan using a bone marrow graft	No-Donor Arm n=37 Participants No-donor arm patients will continue with standard of care per their SCD physician. Standard of Care: Continue to receive standard of care treatment per patient's SCD physician.
Health-Related Quality of Life (HRQoL) Component Physical Function Changes From Baseline	5 T-score Interval -10.0 to 16.0	1 T-score Interval -20.0 to 26.0

SECONDARY outcome

Timeframe: Baseline, 2 years

Population: Participants that are biologically assigned to different arms and that completed both the baseline and 2-year assessment; this follows the intent-to-treat principle

Health-Related Quality of Life (HRQoL) assessed using the NIH's PROMIS 57 instrument. Anxiety asks about the frequency of feelings of fear, worry, and anxiety. It is scored from 0 to 10 and converted to a standardized T-score with mean 50 and standard deviation 10. A higher T-score represents more anxiety.

Outcome measures

Outcome measures
Measure	Donor Arm n=9 Participants Donor Arm patients will undergo hematopoietic cell transplant. Patients with a matched unrelated donor will receive a bone marrow transplant (unless PBSC graft is pre-approved per section 2.5.1 using a preparative regimen with Busulfan, Fludarabine and rabbit ATG. Patients with an HLA-identical sibling donor can receive a transplant using one of three regimens: A. Busulfan, Fludarabine, and rabbit ATG using a bone marrow graft (preferred regimen) B. Alemtuzumab/TBI 300 cGy using a peripheral blood graft C. Alemtuzumab, fludarabine, melphalan using a bone marrow graft	No-Donor Arm n=37 Participants No-donor arm patients will continue with standard of care per their SCD physician. Standard of Care: Continue to receive standard of care treatment per patient's SCD physician.
Health-Related Quality of Life (HRQoL) Component Anxiety Changes From Baseline	0 T-score Interval -21.0 to 4.0	0 T-score Interval -13.0 to 20.0

SECONDARY outcome

Timeframe: Baseline, 2 years

Population: Participants that are biologically assigned to different arms and that completed both the baseline and 2-year assessment; this follows the intent-to-treat principle.

Health-Related Quality of Life (HRQoL) assessed using the NIH's PROMIS 57 instrument. Depression asks about the frequency of feelings of worthlessness, failure, unhappiness and depression. It is scored from 0 to 10 and converted to a standardized T-score with mean 50 and standard deviation 10. A higher T-score represents more depression.

Outcome measures

Outcome measures
Measure	Donor Arm n=9 Participants Donor Arm patients will undergo hematopoietic cell transplant. Patients with a matched unrelated donor will receive a bone marrow transplant (unless PBSC graft is pre-approved per section 2.5.1 using a preparative regimen with Busulfan, Fludarabine and rabbit ATG. Patients with an HLA-identical sibling donor can receive a transplant using one of three regimens: A. Busulfan, Fludarabine, and rabbit ATG using a bone marrow graft (preferred regimen) B. Alemtuzumab/TBI 300 cGy using a peripheral blood graft C. Alemtuzumab, fludarabine, melphalan using a bone marrow graft	No-Donor Arm n=37 Participants No-donor arm patients will continue with standard of care per their SCD physician. Standard of Care: Continue to receive standard of care treatment per patient's SCD physician.
Health-Related Quality of Life (HRQoL) Component Depression Changes From Baseline	0 T-score Interval -10.0 to 8.0	0 T-score Interval -20.0 to 26.0

SECONDARY outcome

Timeframe: Baseline, 2 years

Population: Participants that are biologically assigned to different arms and that completed both the baseline and 2-year assessment; this follows the intent-to-treat principle.

Health-Related Quality of Life (HRQoL) assessed using the NIH's PROMIS 57 instrument. Fatigue asks about the extent to which fatigue interferes with physical functioning and completing tasks. It is scored from 0 to 10 and converted to a standardized T-score with mean 50 and standard deviation 10. A higher T-score represents more fatigue.

Outcome measures

Outcome measures
Measure	Donor Arm n=10 Participants Donor Arm patients will undergo hematopoietic cell transplant. Patients with a matched unrelated donor will receive a bone marrow transplant (unless PBSC graft is pre-approved per section 2.5.1 using a preparative regimen with Busulfan, Fludarabine and rabbit ATG. Patients with an HLA-identical sibling donor can receive a transplant using one of three regimens: A. Busulfan, Fludarabine, and rabbit ATG using a bone marrow graft (preferred regimen) B. Alemtuzumab/TBI 300 cGy using a peripheral blood graft C. Alemtuzumab, fludarabine, melphalan using a bone marrow graft	No-Donor Arm n=37 Participants No-donor arm patients will continue with standard of care per their SCD physician. Standard of Care: Continue to receive standard of care treatment per patient's SCD physician.
Health-Related Quality of Life (HRQoL) Component Fatigue Score Changes in From Baseline	-13 T-score Interval -28.0 to 1.0	0 T-score Interval -22.0 to 20.0

SECONDARY outcome

Timeframe: Baseline, 2 years

Population: Participants that are biologically assigned to different arms and that completed both the baseline and 2-year assessment; this follows the intent-to-treat principle.

Health-Related Quality of Life (HRQoL) assessed using the NIH's PROMIS 57 instrument. Sleep Disturbance asks about the quality of sleep and the frequency with which sleep was restless or difficult to achieve. It is scored from 0 to 10 and converted to a standardized T-score with mean 50 and standard deviation 10. A higher T-score represents more sleep disturbance.

Outcome measures

Outcome measures
Measure	Donor Arm n=10 Participants Donor Arm patients will undergo hematopoietic cell transplant. Patients with a matched unrelated donor will receive a bone marrow transplant (unless PBSC graft is pre-approved per section 2.5.1 using a preparative regimen with Busulfan, Fludarabine and rabbit ATG. Patients with an HLA-identical sibling donor can receive a transplant using one of three regimens: A. Busulfan, Fludarabine, and rabbit ATG using a bone marrow graft (preferred regimen) B. Alemtuzumab/TBI 300 cGy using a peripheral blood graft C. Alemtuzumab, fludarabine, melphalan using a bone marrow graft	No-Donor Arm n=37 Participants No-donor arm patients will continue with standard of care per their SCD physician. Standard of Care: Continue to receive standard of care treatment per patient's SCD physician.
Health-Related Quality of Life (HRQoL) Component Sleep Disturbance Changes From Baseline	1 T-score Interval -17.0 to 15.0	0 T-score Interval -24.0 to 14.0

SECONDARY outcome

Timeframe: Baseline, 2 years

Population: Participants that are biologically assigned to different arms and that completed both the baseline and 2-year assessment; this follows the intent-to-treat principle.

Health-Related Quality of Life (HRQoL) assessed using the NIH's PROMIS 57 instrument. Participation in Social Roles asks about the frequency of limitations of social activities with friends and family. It is scored from 0 to 10 and converted to a standardized T-score with mean 50 and standard deviation 10. A higher T-score represents more satisfaction with participation in social roles.

Outcome measures

Outcome measures
Measure	Donor Arm n=10 Participants Donor Arm patients will undergo hematopoietic cell transplant. Patients with a matched unrelated donor will receive a bone marrow transplant (unless PBSC graft is pre-approved per section 2.5.1 using a preparative regimen with Busulfan, Fludarabine and rabbit ATG. Patients with an HLA-identical sibling donor can receive a transplant using one of three regimens: A. Busulfan, Fludarabine, and rabbit ATG using a bone marrow graft (preferred regimen) B. Alemtuzumab/TBI 300 cGy using a peripheral blood graft C. Alemtuzumab, fludarabine, melphalan using a bone marrow graft	No-Donor Arm n=36 Participants No-donor arm patients will continue with standard of care per their SCD physician. Standard of Care: Continue to receive standard of care treatment per patient's SCD physician.
Health-Related Quality of Life (HRQoL) Component Participation in Social Roles Score Changes From Baseline	15 T-score Interval -4.0 to 22.0	2 T-score Interval -25.0 to 21.0

SECONDARY outcome

Timeframe: Baseline, 2 years

Population: Participants that are biologically assigned to different arms and that completed both the baseline and 2-year assessment; this follows the intent-to-treat principle.

Health-Related Quality of Life (HRQoL) assessed using the NIH's PROMIS 57 instrument. Pain Interference asks about the frequency with which pain interferes with household chores, social activities and enjoyment of life. It is scored from 0 to 10 and converted to a standardized T-score with mean 50 and standard deviation 10. A higher T-score represents more pain interference in daily life.

Outcome measures

Outcome measures
Measure	Donor Arm n=10 Participants Donor Arm patients will undergo hematopoietic cell transplant. Patients with a matched unrelated donor will receive a bone marrow transplant (unless PBSC graft is pre-approved per section 2.5.1 using a preparative regimen with Busulfan, Fludarabine and rabbit ATG. Patients with an HLA-identical sibling donor can receive a transplant using one of three regimens: A. Busulfan, Fludarabine, and rabbit ATG using a bone marrow graft (preferred regimen) B. Alemtuzumab/TBI 300 cGy using a peripheral blood graft C. Alemtuzumab, fludarabine, melphalan using a bone marrow graft	No-Donor Arm n=37 Participants No-donor arm patients will continue with standard of care per their SCD physician. Standard of Care: Continue to receive standard of care treatment per patient's SCD physician.
Health-Related Quality of Life (HRQoL) Component Pain Interference Score Changes From Baseline	-12 T-score Interval -21.0 to 16.0	-1 T-score Interval -26.0 to 22.0

SECONDARY outcome

Timeframe: Baseline, 2 years

Population: Participants that are biologically assigned to different arms and that completed both the baseline and 2-year assessment; this follows the intent-to-treat principle.

Health-Related Quality of Life (HRQoL) assessed using the NIH's PROMIS 57 instrument. Pain Intensity is scored from 0 to 10 reflecting the level of pain over the previous 7 days. A score of 0 reflects no pain; a score of 10 reflects the maximum intensity of pain.

Outcome measures

Outcome measures
Measure	Donor Arm n=10 Participants Donor Arm patients will undergo hematopoietic cell transplant. Patients with a matched unrelated donor will receive a bone marrow transplant (unless PBSC graft is pre-approved per section 2.5.1 using a preparative regimen with Busulfan, Fludarabine and rabbit ATG. Patients with an HLA-identical sibling donor can receive a transplant using one of three regimens: A. Busulfan, Fludarabine, and rabbit ATG using a bone marrow graft (preferred regimen) B. Alemtuzumab/TBI 300 cGy using a peripheral blood graft C. Alemtuzumab, fludarabine, melphalan using a bone marrow graft	No-Donor Arm n=37 Participants No-donor arm patients will continue with standard of care per their SCD physician. Standard of Care: Continue to receive standard of care treatment per patient's SCD physician.
Health-Related Quality of Life (HRQoL) Component Pain Intensity Changes From Baseline	-0.5 T-score Interval -5.0 to 2.0	0 T-score Interval -6.0 to 9.0

SECONDARY outcome

Timeframe: Baseline, 2 years

Population: Participants that are biologically assigned to different arms and that completed both the baseline and 2-year assessment; this follows the intent-to-treat principle.

Health-Related Quality of Life (HRQoL) assessed using the NIH's PROMIS 57 instrument. The 28-Day Pain Diary Average Pain Intensity assesses pain on a score of 0 to 10 twice each day for 28 days. A score of 0 reflects no pain, and a score of 10 reflects maximum intensity of pain. The scores on a given day are averaged (if only one score is obtained on a given day, that score is taken as the measure), and then daily scores are averaged over the number of days on which a score is available.

Outcome measures

Outcome measures
Measure	Donor Arm n=5 Participants Donor Arm patients will undergo hematopoietic cell transplant. Patients with a matched unrelated donor will receive a bone marrow transplant (unless PBSC graft is pre-approved per section 2.5.1 using a preparative regimen with Busulfan, Fludarabine and rabbit ATG. Patients with an HLA-identical sibling donor can receive a transplant using one of three regimens: A. Busulfan, Fludarabine, and rabbit ATG using a bone marrow graft (preferred regimen) B. Alemtuzumab/TBI 300 cGy using a peripheral blood graft C. Alemtuzumab, fludarabine, melphalan using a bone marrow graft	No-Donor Arm n=17 Participants No-donor arm patients will continue with standard of care per their SCD physician. Standard of Care: Continue to receive standard of care treatment per patient's SCD physician.
Health-Related Quality of Life (HRQoL) Component 28-Day Pain Diary Average Pain Intensity Changes From Baseline	-0.08 units on a scale Interval -4.28 to 1.24	-0.25 units on a scale Interval -2.89 to 1.75

SECONDARY outcome

Timeframe: Baseline, 2 years

Population: Participants that are biologically assigned to different arms and that completed both the baseline and 2-year assessment; this follows the intent-to-treat principle.

Health-Related Quality of Life (HRQoL) assessed using the NIH's PROMIS 57 instrument. The ASCQ-Me Stiffness Scale asks about the frequency and severity of joint stiffness. It is scored from 0 to 10 and converted to a standardized T-score with mean 50 and standard deviation 10. A higher T-score represents more stiffness.

Outcome measures

Outcome measures
Measure	Donor Arm n=10 Participants Donor Arm patients will undergo hematopoietic cell transplant. Patients with a matched unrelated donor will receive a bone marrow transplant (unless PBSC graft is pre-approved per section 2.5.1 using a preparative regimen with Busulfan, Fludarabine and rabbit ATG. Patients with an HLA-identical sibling donor can receive a transplant using one of three regimens: A. Busulfan, Fludarabine, and rabbit ATG using a bone marrow graft (preferred regimen) B. Alemtuzumab/TBI 300 cGy using a peripheral blood graft C. Alemtuzumab, fludarabine, melphalan using a bone marrow graft	No-Donor Arm n=37 Participants No-donor arm patients will continue with standard of care per their SCD physician. Standard of Care: Continue to receive standard of care treatment per patient's SCD physician.
Health-Related Quality of Life (HRQoL) Component ASCQ-Me Stiffness Changes From Baseline	-1 T-score Interval -23.0 to 13.0	1 T-score Interval -13.0 to 19.0

SECONDARY outcome

Timeframe: Baseline, 2 years

Population: Analysis population includes participants that are biologically assigned to different arms and completed both baseline and 2-year assessment.

Pulmonary function is assessed by the change from baseline in Forced Expiratory Volume 1 second (FEV1). The complete pulmonary function test will include forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), ratio of FEV1 to FVC (FEV1/FVC), vital capacity (VC), total lung capacity (TLC), residual volume (RV), expiratory reserve volume (ERV), inspiratory capacity (IC), functional residual capacity (FRC), diffusing capacity for carbon monoxide (DLCO), and oxygen saturation.

Outcome measures

Outcome measures
Measure	Donor Arm n=12 Participants Donor Arm patients will undergo hematopoietic cell transplant. Patients with a matched unrelated donor will receive a bone marrow transplant (unless PBSC graft is pre-approved per section 2.5.1 using a preparative regimen with Busulfan, Fludarabine and rabbit ATG. Patients with an HLA-identical sibling donor can receive a transplant using one of three regimens: A. Busulfan, Fludarabine, and rabbit ATG using a bone marrow graft (preferred regimen) B. Alemtuzumab/TBI 300 cGy using a peripheral blood graft C. Alemtuzumab, fludarabine, melphalan using a bone marrow graft	No-Donor Arm n=31 Participants No-donor arm patients will continue with standard of care per their SCD physician. Standard of Care: Continue to receive standard of care treatment per patient's SCD physician.
Change in Pulmonary Function of Forced Expiratory Volume 1 Second (FEV1) From Baseline	2.5 percentage of FEV1 Interval -20.0 to 14.0	0.0 percentage of FEV1 Interval -87.0 to 21.0

SECONDARY outcome

Timeframe: Baseline, 2 years

Population: Analysis population includes participants that are biologically assigned to different arms and completed both baseline and 2-year assessment.

Pulmonary function is assessed by the change from baseline in forced vital capacity (FVC). The complete pulmonary function test will include forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), ratio of FEV1 to FVC (FEV1/FVC), vital capacity (VC), total lung capacity (TLC), residual volume (RV), expiratory reserve volume (ERV), inspiratory capacity (IC), functional residual capacity (FRC), diffusing capacity for carbon monoxide (DLCO), and oxygen saturation.

Outcome measures

Outcome measures
Measure	Donor Arm n=12 Participants Donor Arm patients will undergo hematopoietic cell transplant. Patients with a matched unrelated donor will receive a bone marrow transplant (unless PBSC graft is pre-approved per section 2.5.1 using a preparative regimen with Busulfan, Fludarabine and rabbit ATG. Patients with an HLA-identical sibling donor can receive a transplant using one of three regimens: A. Busulfan, Fludarabine, and rabbit ATG using a bone marrow graft (preferred regimen) B. Alemtuzumab/TBI 300 cGy using a peripheral blood graft C. Alemtuzumab, fludarabine, melphalan using a bone marrow graft	No-Donor Arm n=31 Participants No-donor arm patients will continue with standard of care per their SCD physician. Standard of Care: Continue to receive standard of care treatment per patient's SCD physician.
Change in Pulmonary Function of Forced Vital Capacity (FVC) From Baseline	1.5 percentage of FVC Interval -23.0 to 10.0	0.0 percentage of FVC Interval -15.0 to 25.0

SECONDARY outcome

Timeframe: Baseline, 2 years

Population: Analysis population includes participants that are biologically assigned to different arms and completed both baseline and 2-year assessment.

Pulmonary function is assessed by the change from baseline in ratio of FEV1 to FVC (FEV1/FVC). The complete pulmonary function test will include forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), ratio of FEV1 to FVC (FEV1/FVC), vital capacity (VC), total lung capacity (TLC), residual volume (RV), expiratory reserve volume (ERV), inspiratory capacity (IC), functional residual capacity (FRC), diffusing capacity for carbon monoxide (DLCO), and oxygen saturation.

Outcome measures

Outcome measures
Measure	Donor Arm n=10 Participants Donor Arm patients will undergo hematopoietic cell transplant. Patients with a matched unrelated donor will receive a bone marrow transplant (unless PBSC graft is pre-approved per section 2.5.1 using a preparative regimen with Busulfan, Fludarabine and rabbit ATG. Patients with an HLA-identical sibling donor can receive a transplant using one of three regimens: A. Busulfan, Fludarabine, and rabbit ATG using a bone marrow graft (preferred regimen) B. Alemtuzumab/TBI 300 cGy using a peripheral blood graft C. Alemtuzumab, fludarabine, melphalan using a bone marrow graft	No-Donor Arm n=30 Participants No-donor arm patients will continue with standard of care per their SCD physician. Standard of Care: Continue to receive standard of care treatment per patient's SCD physician.
Change in Pulmonary Function of Ratio of FEV1 to FVC (FEV1/FVC) From Baseline	0.5 percentage of FEV1/FVC Interval -8.0 to 28.0	0.5 percentage of FEV1/FVC Interval -97.0 to 21.0

SECONDARY outcome

Timeframe: Baseline, 2 years

Population: Analysis population includes participants that are biologically assigned to different arms and completed both baseline and 2-year assessment.

Pulmonary function is assessed by the change from baseline in vital capacity (VC). The complete pulmonary function test will include forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), ratio of FEV1 to FVC (FEV1/FVC), vital capacity (VC), total lung capacity (TLC), residual volume (RV), expiratory reserve volume (ERV), inspiratory capacity (IC), functional residual capacity (FRC), diffusing capacity for carbon monoxide (DLCO), and oxygen saturation.

Outcome measures

Outcome measures
Measure	Donor Arm n=6 Participants Donor Arm patients will undergo hematopoietic cell transplant. Patients with a matched unrelated donor will receive a bone marrow transplant (unless PBSC graft is pre-approved per section 2.5.1 using a preparative regimen with Busulfan, Fludarabine and rabbit ATG. Patients with an HLA-identical sibling donor can receive a transplant using one of three regimens: A. Busulfan, Fludarabine, and rabbit ATG using a bone marrow graft (preferred regimen) B. Alemtuzumab/TBI 300 cGy using a peripheral blood graft C. Alemtuzumab, fludarabine, melphalan using a bone marrow graft	No-Donor Arm n=13 Participants No-donor arm patients will continue with standard of care per their SCD physician. Standard of Care: Continue to receive standard of care treatment per patient's SCD physician.
Change in Pulmonary Function of Vital Capacity (VC) From Baseline	0.5 percentage of VC Interval -26.0 to 13.0	2 percentage of VC Interval -14.0 to 23.0

SECONDARY outcome

Timeframe: Baseline, 2 years

Population: Analysis population includes participants that are biologically assigned to different arms and completed both baseline and 2-year assessment.

Pulmonary function is assessed by the change from baseline in total lung capacity (TLC). The complete pulmonary function test will include forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), ratio of FEV1 to FVC (FEV1/FVC), vital capacity (VC), total lung capacity (TLC), residual volume (RV), expiratory reserve volume (ERV), inspiratory capacity (IC), functional residual capacity (FRC), diffusing capacity for carbon monoxide (DLCO), and oxygen saturation.

Outcome measures

Outcome measures
Measure	Donor Arm n=6 Participants Donor Arm patients will undergo hematopoietic cell transplant. Patients with a matched unrelated donor will receive a bone marrow transplant (unless PBSC graft is pre-approved per section 2.5.1 using a preparative regimen with Busulfan, Fludarabine and rabbit ATG. Patients with an HLA-identical sibling donor can receive a transplant using one of three regimens: A. Busulfan, Fludarabine, and rabbit ATG using a bone marrow graft (preferred regimen) B. Alemtuzumab/TBI 300 cGy using a peripheral blood graft C. Alemtuzumab, fludarabine, melphalan using a bone marrow graft	No-Donor Arm n=23 Participants No-donor arm patients will continue with standard of care per their SCD physician. Standard of Care: Continue to receive standard of care treatment per patient's SCD physician.
Change in Pulmonary Function of Total Lung Capacity (TLC) From Baseline	-1.0 percentage of TLC Interval -23.0 to 7.0	0 percentage of TLC Interval -10.0 to 86.0

SECONDARY outcome

Timeframe: Baseline, 2 years

Population: Analysis population includes participants that are biologically assigned to different arms and completed both baseline and 2-year assessment.

Pulmonary function is assessed by the change from baseline in residual volume (RV). The complete pulmonary function test will include forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), ratio of FEV1 to FVC (FEV1/FVC), vital capacity (VC), total lung capacity (TLC), residual volume (RV), expiratory reserve volume (ERV), inspiratory capacity (IC), functional residual capacity (FRC), diffusing capacity for carbon monoxide (DLCO), and oxygen saturation.

Outcome measures

Outcome measures
Measure	Donor Arm n=5 Participants Donor Arm patients will undergo hematopoietic cell transplant. Patients with a matched unrelated donor will receive a bone marrow transplant (unless PBSC graft is pre-approved per section 2.5.1 using a preparative regimen with Busulfan, Fludarabine and rabbit ATG. Patients with an HLA-identical sibling donor can receive a transplant using one of three regimens: A. Busulfan, Fludarabine, and rabbit ATG using a bone marrow graft (preferred regimen) B. Alemtuzumab/TBI 300 cGy using a peripheral blood graft C. Alemtuzumab, fludarabine, melphalan using a bone marrow graft	No-Donor Arm n=21 Participants No-donor arm patients will continue with standard of care per their SCD physician. Standard of Care: Continue to receive standard of care treatment per patient's SCD physician.
Change in Pulmonary Function of Residual Volume (RV) From Baseline	6 percentage of RV Interval -27.0 to 36.0	-11 percentage of RV Interval -95.0 to 49.0

SECONDARY outcome

Timeframe: Baseline, 2 years

Population: Analysis population includes participants that are biologically assigned to different arms and completed both baseline and 2-year assessment.

Pulmonary function is assessed by the change from baseline in expiratory reserve volume (ERV). The complete pulmonary function test will include forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), ratio of FEV1 to FVC (FEV1/FVC), vital capacity (VC), total lung capacity (TLC), residual volume (RV), expiratory reserve volume (ERV), inspiratory capacity (IC), functional residual capacity (FRC), diffusing capacity for carbon monoxide (DLCO), and oxygen saturation.

Outcome measures

Outcome measures
Measure	Donor Arm n=6 Participants Donor Arm patients will undergo hematopoietic cell transplant. Patients with a matched unrelated donor will receive a bone marrow transplant (unless PBSC graft is pre-approved per section 2.5.1 using a preparative regimen with Busulfan, Fludarabine and rabbit ATG. Patients with an HLA-identical sibling donor can receive a transplant using one of three regimens: A. Busulfan, Fludarabine, and rabbit ATG using a bone marrow graft (preferred regimen) B. Alemtuzumab/TBI 300 cGy using a peripheral blood graft C. Alemtuzumab, fludarabine, melphalan using a bone marrow graft	No-Donor Arm n=21 Participants No-donor arm patients will continue with standard of care per their SCD physician. Standard of Care: Continue to receive standard of care treatment per patient's SCD physician.
Change in Pulmonary Function of Expiratory Reserve Volume (ERV) From Baseline	9.5 percentage of ERV Interval -5.0 to 36.0	-2 percentage of ERV Interval -47.0 to 61.0

SECONDARY outcome

Timeframe: Baseline, 2 years

Population: Analysis population includes participants that are biologically assigned to different arms and completed both baseline and 2-year assessment.

Pulmonary function is assessed by the change from baseline in inspiratory capacity (IC). The complete pulmonary function test will include forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), ratio of FEV1 to FVC (FEV1/FVC), vital capacity (VC), total lung capacity (TLC), residual volume (RV), expiratory reserve volume (ERV), inspiratory capacity (IC), functional residual capacity (FRC), diffusing capacity for carbon monoxide (DLCO), and oxygen saturation.

Outcome measures

Outcome measures
Measure	Donor Arm n=3 Participants Donor Arm patients will undergo hematopoietic cell transplant. Patients with a matched unrelated donor will receive a bone marrow transplant (unless PBSC graft is pre-approved per section 2.5.1 using a preparative regimen with Busulfan, Fludarabine and rabbit ATG. Patients with an HLA-identical sibling donor can receive a transplant using one of three regimens: A. Busulfan, Fludarabine, and rabbit ATG using a bone marrow graft (preferred regimen) B. Alemtuzumab/TBI 300 cGy using a peripheral blood graft C. Alemtuzumab, fludarabine, melphalan using a bone marrow graft	No-Donor Arm n=18 Participants No-donor arm patients will continue with standard of care per their SCD physician. Standard of Care: Continue to receive standard of care treatment per patient's SCD physician.
Change in Pulmonary Function of Inspiratory Capacity (IC) From Baseline	-1 percentage of IC Interval -15.0 to 13.0	-4.5 percentage of IC Interval -20.0 to 22.0

SECONDARY outcome

Timeframe: Baseline, 2 years

Population: Analysis population includes participants that are biologically assigned to different arms and completed both baseline and 2-year assessment.

Pulmonary function is assessed by the change from baseline in functional residual capacity (FRC). The complete pulmonary function test will include forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), ratio of FEV1 to FVC (FEV1/FVC), vital capacity (VC), total lung capacity (TLC), residual volume (RV), expiratory reserve volume (ERV), inspiratory capacity (IC), functional residual capacity (FRC), diffusing capacity for carbon monoxide (DLCO), and oxygen saturation.

Outcome measures

Outcome measures
Measure	Donor Arm n=4 Participants Donor Arm patients will undergo hematopoietic cell transplant. Patients with a matched unrelated donor will receive a bone marrow transplant (unless PBSC graft is pre-approved per section 2.5.1 using a preparative regimen with Busulfan, Fludarabine and rabbit ATG. Patients with an HLA-identical sibling donor can receive a transplant using one of three regimens: A. Busulfan, Fludarabine, and rabbit ATG using a bone marrow graft (preferred regimen) B. Alemtuzumab/TBI 300 cGy using a peripheral blood graft C. Alemtuzumab, fludarabine, melphalan using a bone marrow graft	No-Donor Arm n=10 Participants No-donor arm patients will continue with standard of care per their SCD physician. Standard of Care: Continue to receive standard of care treatment per patient's SCD physician.
Change in Pulmonary Function of Functional Residual Capacity (FRC) From Baseline	3 percentage of FRC Interval -8.0 to 12.0	-3.5 percentage of FRC Interval -28.0 to 40.0

SECONDARY outcome

Timeframe: Baseline, 2 years

Population: Analysis population includes participants that are biologically assigned to different arms and completed both baseline and 2-year assessment.

Pulmonary function is assessed by the change from baseline in diffusing capacity for carbon monoxide (DLCO). The complete pulmonary function test will include forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), ratio of FEV1 to FVC (FEV1/FVC), vital capacity (VC), total lung capacity (TLC), residual volume (RV), expiratory reserve volume (ERV), inspiratory capacity (IC), functional residual capacity (FRC), diffusing capacity for carbon monoxide (DLCO), and oxygen saturation.

Outcome measures

Outcome measures
Measure	Donor Arm n=10 Participants Donor Arm patients will undergo hematopoietic cell transplant. Patients with a matched unrelated donor will receive a bone marrow transplant (unless PBSC graft is pre-approved per section 2.5.1 using a preparative regimen with Busulfan, Fludarabine and rabbit ATG. Patients with an HLA-identical sibling donor can receive a transplant using one of three regimens: A. Busulfan, Fludarabine, and rabbit ATG using a bone marrow graft (preferred regimen) B. Alemtuzumab/TBI 300 cGy using a peripheral blood graft C. Alemtuzumab, fludarabine, melphalan using a bone marrow graft	No-Donor Arm n=28 Participants No-donor arm patients will continue with standard of care per their SCD physician. Standard of Care: Continue to receive standard of care treatment per patient's SCD physician.
Change in Pulmonary Function of Diffusing Capacity for Carbon Monoxide (DLCO) From Baseline	-4 percentage of DLCO Interval -22.0 to 43.0	0 percentage of DLCO Interval -40.0 to 62.0

SECONDARY outcome

Timeframe: Baseline, 2 years

Population: Analysis population includes participants that are biologically assigned to different arms and completed both baseline and 2-year assessment.

Pulmonary function is assessed by the change from baseline in oxygen saturation. The complete pulmonary function test will include forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), ratio of FEV1 to FVC (FEV1/FVC), vital capacity (VC), total lung capacity (TLC), residual volume (RV), expiratory reserve volume (ERV), inspiratory capacity (IC), functional residual capacity (FRC), diffusing capacity for carbon monoxide (DLCO), and oxygen saturation.

Outcome measures

Outcome measures
Measure	Donor Arm n=11 Participants Donor Arm patients will undergo hematopoietic cell transplant. Patients with a matched unrelated donor will receive a bone marrow transplant (unless PBSC graft is pre-approved per section 2.5.1 using a preparative regimen with Busulfan, Fludarabine and rabbit ATG. Patients with an HLA-identical sibling donor can receive a transplant using one of three regimens: A. Busulfan, Fludarabine, and rabbit ATG using a bone marrow graft (preferred regimen) B. Alemtuzumab/TBI 300 cGy using a peripheral blood graft C. Alemtuzumab, fludarabine, melphalan using a bone marrow graft	No-Donor Arm n=33 Participants No-donor arm patients will continue with standard of care per their SCD physician. Standard of Care: Continue to receive standard of care treatment per patient's SCD physician.
Change in Pulmonary Function of Oxygen Saturation From Baseline	1 percentage of oxygen saturation Interval -2.0 to 6.0	0 percentage of oxygen saturation Interval -3.0 to 6.0

SECONDARY outcome

Timeframe: 2 years

Population: Using the intent-to-treat principle, participants remained in their assigned treatment arm regardless of treatment received.

All Grade 2 and 3 infections were reported according to the BMT CTN Technical Manual of Procedures (MOP) after biological assignment. The frequency of Grade 2-3 infections are tabulated by biological assignment at the event level.

Outcome measures

Outcome measures
Measure	Donor Arm n=28 Participants Donor Arm patients will undergo hematopoietic cell transplant. Patients with a matched unrelated donor will receive a bone marrow transplant (unless PBSC graft is pre-approved per section 2.5.1 using a preparative regimen with Busulfan, Fludarabine and rabbit ATG. Patients with an HLA-identical sibling donor can receive a transplant using one of three regimens: A. Busulfan, Fludarabine, and rabbit ATG using a bone marrow graft (preferred regimen) B. Alemtuzumab/TBI 300 cGy using a peripheral blood graft C. Alemtuzumab, fludarabine, melphalan using a bone marrow graft	No-Donor Arm n=85 Participants No-donor arm patients will continue with standard of care per their SCD physician. Standard of Care: Continue to receive standard of care treatment per patient's SCD physician.
Frequencies of Infections Bacillus	0 infection	1 infection
Frequencies of Infections Herpes Zoster	2 infection	0 infection
Frequencies of Infections Clostridium difficile	4 infection	2 infection
Frequencies of Infections Human Herpes Virus - 6	2 infection	0 infection
Frequencies of Infections Staphylococcus (coag +)	1 infection	0 infection
Frequencies of Infections Respiratory Syncytial virus	1 infection	0 infection
Frequencies of Infections Other Bacteria	2 infection	0 infection
Frequencies of Infections Rhinovirus	2 infection	0 infection
Frequencies of Infections Streptococcus	1 infection	0 infection
Frequencies of Infections Other Viral	5 infection	2 infection
Frequencies of Infections Epstein-Barr Virus	3 infection	0 infection
Frequencies of Infections Staphylococcus (NOS)	2 infection	0 infection
Frequencies of Infections Staphylococcus (coag -)	2 infection	1 infection
Frequencies of Infections Escherichia coli	3 infection	1 infection
Frequencies of Infections Cytomegalovirus	2 infection	0 infection
Frequencies of Infections Influenza	1 infection	0 infection
Frequencies of Infections Klebsiella	0 infection	1 infection
Frequencies of Infections Pseudomonas	0 infection	1 infection
Frequencies of Infections Enterococcus	0 infection	1 infection
Frequencies of Infections Gram Negative Rod (NOS)	0 infection	1 infection
Frequencies of Infections Staphylococcus	0 infection	1 infection

SECONDARY outcome

Timeframe: 180 days after biological assignment

Population: Patients who enrolled on the donor arm and received transplant

The time interval from day 0 of transplant until grade II-IV aGVHD will be described for each treatment arm using the the cumulative incidence estimator developed by Gray, with death prior to aGVHD treated as a competing risk. Estimates and 95% CIs of the cumulative incidence of grade II-IV aGVHD will be provided at Day 180 after day 0 of transplant and compared between matched related and matched unrelated donors using the Gray test. Acute GVHD was graded according to the BMT CTN Technical Manual of Operating Procedures (MOP). Higher aGVHD grade indicate worse outcomes. Grade I is defined as Skin stage 1-2 and stage 0 for both GI and liver. Grade II is stage 3 skin, stage 1 GI, or stage 1 liver. Grade III is stage 2-3 GI or stage 2-3 liver. Grade IV is stage 4 skin or stage 4 liver.

Outcome measures

Outcome measures
Measure	Donor Arm n=10 Participants Donor Arm patients will undergo hematopoietic cell transplant. Patients with a matched unrelated donor will receive a bone marrow transplant (unless PBSC graft is pre-approved per section 2.5.1 using a preparative regimen with Busulfan, Fludarabine and rabbit ATG. Patients with an HLA-identical sibling donor can receive a transplant using one of three regimens: A. Busulfan, Fludarabine, and rabbit ATG using a bone marrow graft (preferred regimen) B. Alemtuzumab/TBI 300 cGy using a peripheral blood graft C. Alemtuzumab, fludarabine, melphalan using a bone marrow graft	No-Donor Arm n=14 Participants No-donor arm patients will continue with standard of care per their SCD physician. Standard of Care: Continue to receive standard of care treatment per patient's SCD physician.
Percentage of Participants With Grades II-IV Acute GVHD at Day 180 After Biological Assignment	30 percentage of participants Interval 6.2 to 59.0	46 percentage of participants Interval 18.0 to 71.0

SECONDARY outcome

Timeframe: Day 600 after biological assignment

Population: Patients who enrolled on the donor arm and received transplant.

Chronic GVHD was collected according to the recommendations of the NIH Consensus Conference. Eight organs will be scored on a 0-3 scale to reflect degree of chronic GVHD involvement. Liver and pulmonary function test results and use of systemic therapy for treatment of chronic GVHD was also recorded. Percentage of Participants with chronic GVHD (cGVHD) at Day 600 was estimated with 95% confidence intervals for each donor type group using the cumulative incidence estimate, treating death prior to cGVHD as a competing event.

Outcome measures

Outcome measures
Measure	Donor Arm n=10 Participants Donor Arm patients will undergo hematopoietic cell transplant. Patients with a matched unrelated donor will receive a bone marrow transplant (unless PBSC graft is pre-approved per section 2.5.1 using a preparative regimen with Busulfan, Fludarabine and rabbit ATG. Patients with an HLA-identical sibling donor can receive a transplant using one of three regimens: A. Busulfan, Fludarabine, and rabbit ATG using a bone marrow graft (preferred regimen) B. Alemtuzumab/TBI 300 cGy using a peripheral blood graft C. Alemtuzumab, fludarabine, melphalan using a bone marrow graft	No-Donor Arm n=14 Participants No-donor arm patients will continue with standard of care per their SCD physician. Standard of Care: Continue to receive standard of care treatment per patient's SCD physician.
Percentage of Participants With Chronic GVHD at Day 600 After Biological Assignment	30 percentage of participants Interval 6.2 to 59.0	57 percentage of participants Interval 26.0 to 79.0

SECONDARY outcome

Timeframe: 2 years

Population: Analysis population includes transplanted participants who were biologically assigned to donor arm.

Primary graft failure defined as never achieving ANC ≥ 500/µL or never achieving ≥ 5% donor whole blood or myeloid chimerism (myeloid is preferable) assessed by bone marrow or peripheral blood chimerism assays by day +42 post-transplant. Second infusion of hematopoietic cells is also considered indicative of primary graft failure by day +42 post-transplant. Secondary graft failure is defined as \< 5% donor whole blood or myeloid chimerism (myeloid is preferable) in peripheral blood or bone marrow beyond day +42 post-transplant in patients with prior documentation of hematopoietic recovery with ≥ 5% donor cells by day +42 post-transplant. Second infusion of hematopoietic cells is also considered indicative of secondary graft failure.

Outcome measures

Outcome measures
Measure	Donor Arm n=24 Participants Donor Arm patients will undergo hematopoietic cell transplant. Patients with a matched unrelated donor will receive a bone marrow transplant (unless PBSC graft is pre-approved per section 2.5.1 using a preparative regimen with Busulfan, Fludarabine and rabbit ATG. Patients with an HLA-identical sibling donor can receive a transplant using one of three regimens: A. Busulfan, Fludarabine, and rabbit ATG using a bone marrow graft (preferred regimen) B. Alemtuzumab/TBI 300 cGy using a peripheral blood graft C. Alemtuzumab, fludarabine, melphalan using a bone marrow graft	No-Donor Arm No-donor arm patients will continue with standard of care per their SCD physician. Standard of Care: Continue to receive standard of care treatment per patient's SCD physician.
Number of Participants With Primary and Secondary Graft Failure Primary graft failure	0 participants	—
Number of Participants With Primary and Secondary Graft Failure Secondary graft failure	3 participants	—

Adverse Events

Donor Arm

Serious events: 0 serious events

Other events: 14 other events

Deaths: 3 deaths

No-Donor Arm

Serious events: 0 serious events

Other events: 65 other events

Deaths: 5 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Additional Information

Adam Mendizabal, PhD

The Emmes Company, LLC

Phone: (301) 251-1161

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Other adverse events
Measure	Donor Arm n=28 participants at risk Donor Arm patients will undergo hematopoietic cell transplant. Patients with a matched unrelated donor will receive a bone marrow transplant (unless PBSC graft is pre-approved per section 2.5.1 using a preparative regimen with Busulfan, Fludarabine and rabbit ATG. Patients with an HLA-identical sibling donor can receive a transplant using one of three regimens: A. Busulfan, Fludarabine, and rabbit ATG using a bone marrow graft (preferred regimen) B. Alemtuzumab/TBI 300 cGy using a peripheral blood graft C. Alemtuzumab, fludarabine, melphalan using a bone marrow graft	No-Donor Arm n=85 participants at risk No-donor arm patients will continue with standard of care per their SCD physician. Standard of Care: Continue to receive standard of care treatment per patient's SCD physician.
Nervous system disorders PRES	3.6% 1/28 • Number of events 1 • Adverse event reporting requirements become effective at the time of the participant's biologic assignment, and up to 2 years AE reporting was conducted according to the BMT CTN's Manual of Operating Procedures. Unexpected, serious AEs (SAEs) were reported through an expedited AE reporting system. Expected AEs were reported using National Cancer Institute (NCI)'s Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0 at regular intervals.	0.00% 0/85 • Adverse event reporting requirements become effective at the time of the participant's biologic assignment, and up to 2 years AE reporting was conducted according to the BMT CTN's Manual of Operating Procedures. Unexpected, serious AEs (SAEs) were reported through an expedited AE reporting system. Expected AEs were reported using National Cancer Institute (NCI)'s Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0 at regular intervals.
Injury, poisoning and procedural complications ACCIDENTAL DRUG OVERDOSE	0.00% 0/28 • Adverse event reporting requirements become effective at the time of the participant's biologic assignment, and up to 2 years AE reporting was conducted according to the BMT CTN's Manual of Operating Procedures. Unexpected, serious AEs (SAEs) were reported through an expedited AE reporting system. Expected AEs were reported using National Cancer Institute (NCI)'s Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0 at regular intervals.	1.2% 1/85 • Number of events 1 • Adverse event reporting requirements become effective at the time of the participant's biologic assignment, and up to 2 years AE reporting was conducted according to the BMT CTN's Manual of Operating Procedures. Unexpected, serious AEs (SAEs) were reported through an expedited AE reporting system. Expected AEs were reported using National Cancer Institute (NCI)'s Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0 at regular intervals.
Nervous system disorders TONIC CLONIC SEIZURE	3.6% 1/28 • Number of events 1 • Adverse event reporting requirements become effective at the time of the participant's biologic assignment, and up to 2 years AE reporting was conducted according to the BMT CTN's Manual of Operating Procedures. Unexpected, serious AEs (SAEs) were reported through an expedited AE reporting system. Expected AEs were reported using National Cancer Institute (NCI)'s Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0 at regular intervals.	0.00% 0/85 • Adverse event reporting requirements become effective at the time of the participant's biologic assignment, and up to 2 years AE reporting was conducted according to the BMT CTN's Manual of Operating Procedures. Unexpected, serious AEs (SAEs) were reported through an expedited AE reporting system. Expected AEs were reported using National Cancer Institute (NCI)'s Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0 at regular intervals.
Nervous system disorders EPILEPTIC SEIZURES	3.6% 1/28 • Number of events 1 • Adverse event reporting requirements become effective at the time of the participant's biologic assignment, and up to 2 years AE reporting was conducted according to the BMT CTN's Manual of Operating Procedures. Unexpected, serious AEs (SAEs) were reported through an expedited AE reporting system. Expected AEs were reported using National Cancer Institute (NCI)'s Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0 at regular intervals.	0.00% 0/85 • Adverse event reporting requirements become effective at the time of the participant's biologic assignment, and up to 2 years AE reporting was conducted according to the BMT CTN's Manual of Operating Procedures. Unexpected, serious AEs (SAEs) were reported through an expedited AE reporting system. Expected AEs were reported using National Cancer Institute (NCI)'s Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0 at regular intervals.
Respiratory, thoracic and mediastinal disorders PULMONARY EMBOLISM	0.00% 0/28 • Adverse event reporting requirements become effective at the time of the participant's biologic assignment, and up to 2 years AE reporting was conducted according to the BMT CTN's Manual of Operating Procedures. Unexpected, serious AEs (SAEs) were reported through an expedited AE reporting system. Expected AEs were reported using National Cancer Institute (NCI)'s Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0 at regular intervals.	1.2% 1/85 • Number of events 1 • Adverse event reporting requirements become effective at the time of the participant's biologic assignment, and up to 2 years AE reporting was conducted according to the BMT CTN's Manual of Operating Procedures. Unexpected, serious AEs (SAEs) were reported through an expedited AE reporting system. Expected AEs were reported using National Cancer Institute (NCI)'s Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0 at regular intervals.
Blood and lymphatic system disorders SICKLE CELL CRISIS AND BIPAP	0.00% 0/28 • Adverse event reporting requirements become effective at the time of the participant's biologic assignment, and up to 2 years AE reporting was conducted according to the BMT CTN's Manual of Operating Procedures. Unexpected, serious AEs (SAEs) were reported through an expedited AE reporting system. Expected AEs were reported using National Cancer Institute (NCI)'s Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0 at regular intervals.	1.2% 1/85 • Number of events 1 • Adverse event reporting requirements become effective at the time of the participant's biologic assignment, and up to 2 years AE reporting was conducted according to the BMT CTN's Manual of Operating Procedures. Unexpected, serious AEs (SAEs) were reported through an expedited AE reporting system. Expected AEs were reported using National Cancer Institute (NCI)'s Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0 at regular intervals.
General disorders DEATH	0.00% 0/28 • Adverse event reporting requirements become effective at the time of the participant's biologic assignment, and up to 2 years AE reporting was conducted according to the BMT CTN's Manual of Operating Procedures. Unexpected, serious AEs (SAEs) were reported through an expedited AE reporting system. Expected AEs were reported using National Cancer Institute (NCI)'s Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0 at regular intervals.	2.4% 2/85 • Number of events 2 • Adverse event reporting requirements become effective at the time of the participant's biologic assignment, and up to 2 years AE reporting was conducted according to the BMT CTN's Manual of Operating Procedures. Unexpected, serious AEs (SAEs) were reported through an expedited AE reporting system. Expected AEs were reported using National Cancer Institute (NCI)'s Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0 at regular intervals.
Injury, poisoning and procedural complications ACUTE SUBARACHNOID HEMORRHAGE	3.6% 1/28 • Number of events 1 • Adverse event reporting requirements become effective at the time of the participant's biologic assignment, and up to 2 years AE reporting was conducted according to the BMT CTN's Manual of Operating Procedures. Unexpected, serious AEs (SAEs) were reported through an expedited AE reporting system. Expected AEs were reported using National Cancer Institute (NCI)'s Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0 at regular intervals.	0.00% 0/85 • Adverse event reporting requirements become effective at the time of the participant's biologic assignment, and up to 2 years AE reporting was conducted according to the BMT CTN's Manual of Operating Procedures. Unexpected, serious AEs (SAEs) were reported through an expedited AE reporting system. Expected AEs were reported using National Cancer Institute (NCI)'s Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0 at regular intervals.
Respiratory, thoracic and mediastinal disorders ACUTE RESPIRATORY FAILURE	0.00% 0/28 • Adverse event reporting requirements become effective at the time of the participant's biologic assignment, and up to 2 years AE reporting was conducted according to the BMT CTN's Manual of Operating Procedures. Unexpected, serious AEs (SAEs) were reported through an expedited AE reporting system. Expected AEs were reported using National Cancer Institute (NCI)'s Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0 at regular intervals.	1.2% 1/85 • Number of events 1 • Adverse event reporting requirements become effective at the time of the participant's biologic assignment, and up to 2 years AE reporting was conducted according to the BMT CTN's Manual of Operating Procedures. Unexpected, serious AEs (SAEs) were reported through an expedited AE reporting system. Expected AEs were reported using National Cancer Institute (NCI)'s Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0 at regular intervals.
Gastrointestinal disorders GRADE 4 MUCOSITIS ORAL	3.6% 1/28 • Number of events 1 • Adverse event reporting requirements become effective at the time of the participant's biologic assignment, and up to 2 years AE reporting was conducted according to the BMT CTN's Manual of Operating Procedures. Unexpected, serious AEs (SAEs) were reported through an expedited AE reporting system. Expected AEs were reported using National Cancer Institute (NCI)'s Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0 at regular intervals.	0.00% 0/85 • Adverse event reporting requirements become effective at the time of the participant's biologic assignment, and up to 2 years AE reporting was conducted according to the BMT CTN's Manual of Operating Procedures. Unexpected, serious AEs (SAEs) were reported through an expedited AE reporting system. Expected AEs were reported using National Cancer Institute (NCI)'s Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0 at regular intervals.
General disorders MULTIPLE ORGAN FAILURE	3.6% 1/28 • Number of events 1 • Adverse event reporting requirements become effective at the time of the participant's biologic assignment, and up to 2 years AE reporting was conducted according to the BMT CTN's Manual of Operating Procedures. Unexpected, serious AEs (SAEs) were reported through an expedited AE reporting system. Expected AEs were reported using National Cancer Institute (NCI)'s Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0 at regular intervals.	0.00% 0/85 • Adverse event reporting requirements become effective at the time of the participant's biologic assignment, and up to 2 years AE reporting was conducted according to the BMT CTN's Manual of Operating Procedures. Unexpected, serious AEs (SAEs) were reported through an expedited AE reporting system. Expected AEs were reported using National Cancer Institute (NCI)'s Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0 at regular intervals.
Vascular disorders HYPERTENSION MANAGEMENT	3.6% 1/28 • Number of events 1 • Adverse event reporting requirements become effective at the time of the participant's biologic assignment, and up to 2 years AE reporting was conducted according to the BMT CTN's Manual of Operating Procedures. Unexpected, serious AEs (SAEs) were reported through an expedited AE reporting system. Expected AEs were reported using National Cancer Institute (NCI)'s Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0 at regular intervals.	0.00% 0/85 • Adverse event reporting requirements become effective at the time of the participant's biologic assignment, and up to 2 years AE reporting was conducted according to the BMT CTN's Manual of Operating Procedures. Unexpected, serious AEs (SAEs) were reported through an expedited AE reporting system. Expected AEs were reported using National Cancer Institute (NCI)'s Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0 at regular intervals.
Nervous system disorders POSTERIOR REVERSIBLE ENCEPHALOPATHY	7.1% 2/28 • Number of events 3 • Adverse event reporting requirements become effective at the time of the participant's biologic assignment, and up to 2 years AE reporting was conducted according to the BMT CTN's Manual of Operating Procedures. Unexpected, serious AEs (SAEs) were reported through an expedited AE reporting system. Expected AEs were reported using National Cancer Institute (NCI)'s Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0 at regular intervals.	0.00% 0/85 • Adverse event reporting requirements become effective at the time of the participant's biologic assignment, and up to 2 years AE reporting was conducted according to the BMT CTN's Manual of Operating Procedures. Unexpected, serious AEs (SAEs) were reported through an expedited AE reporting system. Expected AEs were reported using National Cancer Institute (NCI)'s Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0 at regular intervals.
Respiratory, thoracic and mediastinal disorders ACUTE CHEST SYNDROME	0.00% 0/28 • Adverse event reporting requirements become effective at the time of the participant's biologic assignment, and up to 2 years AE reporting was conducted according to the BMT CTN's Manual of Operating Procedures. Unexpected, serious AEs (SAEs) were reported through an expedited AE reporting system. Expected AEs were reported using National Cancer Institute (NCI)'s Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0 at regular intervals.	2.4% 2/85 • Number of events 2 • Adverse event reporting requirements become effective at the time of the participant's biologic assignment, and up to 2 years AE reporting was conducted according to the BMT CTN's Manual of Operating Procedures. Unexpected, serious AEs (SAEs) were reported through an expedited AE reporting system. Expected AEs were reported using National Cancer Institute (NCI)'s Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0 at regular intervals.
Infections and infestations SEPSIS	3.6% 1/28 • Number of events 1 • Adverse event reporting requirements become effective at the time of the participant's biologic assignment, and up to 2 years AE reporting was conducted according to the BMT CTN's Manual of Operating Procedures. Unexpected, serious AEs (SAEs) were reported through an expedited AE reporting system. Expected AEs were reported using National Cancer Institute (NCI)'s Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0 at regular intervals.	1.2% 1/85 • Number of events 1 • Adverse event reporting requirements become effective at the time of the participant's biologic assignment, and up to 2 years AE reporting was conducted according to the BMT CTN's Manual of Operating Procedures. Unexpected, serious AEs (SAEs) were reported through an expedited AE reporting system. Expected AEs were reported using National Cancer Institute (NCI)'s Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0 at regular intervals.
General disorders MUCOSITIS	3.6% 1/28 • Number of events 1 • Adverse event reporting requirements become effective at the time of the participant's biologic assignment, and up to 2 years AE reporting was conducted according to the BMT CTN's Manual of Operating Procedures. Unexpected, serious AEs (SAEs) were reported through an expedited AE reporting system. Expected AEs were reported using National Cancer Institute (NCI)'s Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0 at regular intervals.	0.00% 0/85 • Adverse event reporting requirements become effective at the time of the participant's biologic assignment, and up to 2 years AE reporting was conducted according to the BMT CTN's Manual of Operating Procedures. Unexpected, serious AEs (SAEs) were reported through an expedited AE reporting system. Expected AEs were reported using National Cancer Institute (NCI)'s Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0 at regular intervals.
Metabolism and nutrition disorders HYPERGLYCEMIA	3.6% 1/28 • Number of events 1 • Adverse event reporting requirements become effective at the time of the participant's biologic assignment, and up to 2 years AE reporting was conducted according to the BMT CTN's Manual of Operating Procedures. Unexpected, serious AEs (SAEs) were reported through an expedited AE reporting system. Expected AEs were reported using National Cancer Institute (NCI)'s Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0 at regular intervals.	0.00% 0/85 • Adverse event reporting requirements become effective at the time of the participant's biologic assignment, and up to 2 years AE reporting was conducted according to the BMT CTN's Manual of Operating Procedures. Unexpected, serious AEs (SAEs) were reported through an expedited AE reporting system. Expected AEs were reported using National Cancer Institute (NCI)'s Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0 at regular intervals.
Cardiac disorders CARDIAC ARRES	0.00% 0/28 • Adverse event reporting requirements become effective at the time of the participant's biologic assignment, and up to 2 years AE reporting was conducted according to the BMT CTN's Manual of Operating Procedures. Unexpected, serious AEs (SAEs) were reported through an expedited AE reporting system. Expected AEs were reported using National Cancer Institute (NCI)'s Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0 at regular intervals.	1.2% 1/85 • Number of events 1 • Adverse event reporting requirements become effective at the time of the participant's biologic assignment, and up to 2 years AE reporting was conducted according to the BMT CTN's Manual of Operating Procedures. Unexpected, serious AEs (SAEs) were reported through an expedited AE reporting system. Expected AEs were reported using National Cancer Institute (NCI)'s Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0 at regular intervals.
Infections and infestations ACUTE PYELONEPHRITIS	3.6% 1/28 • Number of events 2 • Adverse event reporting requirements become effective at the time of the participant's biologic assignment, and up to 2 years AE reporting was conducted according to the BMT CTN's Manual of Operating Procedures. Unexpected, serious AEs (SAEs) were reported through an expedited AE reporting system. Expected AEs were reported using National Cancer Institute (NCI)'s Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0 at regular intervals.	0.00% 0/85 • Adverse event reporting requirements become effective at the time of the participant's biologic assignment, and up to 2 years AE reporting was conducted according to the BMT CTN's Manual of Operating Procedures. Unexpected, serious AEs (SAEs) were reported through an expedited AE reporting system. Expected AEs were reported using National Cancer Institute (NCI)'s Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0 at regular intervals.
Cardiac disorders CONGESTIVE HEART FAILURE	0.00% 0/28 • Adverse event reporting requirements become effective at the time of the participant's biologic assignment, and up to 2 years AE reporting was conducted according to the BMT CTN's Manual of Operating Procedures. Unexpected, serious AEs (SAEs) were reported through an expedited AE reporting system. Expected AEs were reported using National Cancer Institute (NCI)'s Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0 at regular intervals.	1.2% 1/85 • Number of events 1 • Adverse event reporting requirements become effective at the time of the participant's biologic assignment, and up to 2 years AE reporting was conducted according to the BMT CTN's Manual of Operating Procedures. Unexpected, serious AEs (SAEs) were reported through an expedited AE reporting system. Expected AEs were reported using National Cancer Institute (NCI)'s Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0 at regular intervals.
Renal and urinary disorders END STAGE RENAL DISEASE	0.00% 0/28 • Adverse event reporting requirements become effective at the time of the participant's biologic assignment, and up to 2 years AE reporting was conducted according to the BMT CTN's Manual of Operating Procedures. Unexpected, serious AEs (SAEs) were reported through an expedited AE reporting system. Expected AEs were reported using National Cancer Institute (NCI)'s Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0 at regular intervals.	1.2% 1/85 • Number of events 1 • Adverse event reporting requirements become effective at the time of the participant's biologic assignment, and up to 2 years AE reporting was conducted according to the BMT CTN's Manual of Operating Procedures. Unexpected, serious AEs (SAEs) were reported through an expedited AE reporting system. Expected AEs were reported using National Cancer Institute (NCI)'s Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0 at regular intervals.
Infections and infestations SEPTIC SHOCK	3.6% 1/28 • Number of events 1 • Adverse event reporting requirements become effective at the time of the participant's biologic assignment, and up to 2 years AE reporting was conducted according to the BMT CTN's Manual of Operating Procedures. Unexpected, serious AEs (SAEs) were reported through an expedited AE reporting system. Expected AEs were reported using National Cancer Institute (NCI)'s Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0 at regular intervals.	0.00% 0/85 • Adverse event reporting requirements become effective at the time of the participant's biologic assignment, and up to 2 years AE reporting was conducted according to the BMT CTN's Manual of Operating Procedures. Unexpected, serious AEs (SAEs) were reported through an expedited AE reporting system. Expected AEs were reported using National Cancer Institute (NCI)'s Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0 at regular intervals.
Immune system disorders GRAFT VERSUS HOST DISEASE	3.6% 1/28 • Number of events 1 • Adverse event reporting requirements become effective at the time of the participant's biologic assignment, and up to 2 years AE reporting was conducted according to the BMT CTN's Manual of Operating Procedures. Unexpected, serious AEs (SAEs) were reported through an expedited AE reporting system. Expected AEs were reported using National Cancer Institute (NCI)'s Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0 at regular intervals.	0.00% 0/85 • Adverse event reporting requirements become effective at the time of the participant's biologic assignment, and up to 2 years AE reporting was conducted according to the BMT CTN's Manual of Operating Procedures. Unexpected, serious AEs (SAEs) were reported through an expedited AE reporting system. Expected AEs were reported using National Cancer Institute (NCI)'s Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0 at regular intervals.
Nervous system disorders ACUTE CEREBROVASCULAR ACCIDENT	0.00% 0/28 • Adverse event reporting requirements become effective at the time of the participant's biologic assignment, and up to 2 years AE reporting was conducted according to the BMT CTN's Manual of Operating Procedures. Unexpected, serious AEs (SAEs) were reported through an expedited AE reporting system. Expected AEs were reported using National Cancer Institute (NCI)'s Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0 at regular intervals.	1.2% 1/85 • Number of events 1 • Adverse event reporting requirements become effective at the time of the participant's biologic assignment, and up to 2 years AE reporting was conducted according to the BMT CTN's Manual of Operating Procedures. Unexpected, serious AEs (SAEs) were reported through an expedited AE reporting system. Expected AEs were reported using National Cancer Institute (NCI)'s Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0 at regular intervals.
Respiratory, thoracic and mediastinal disorders RESPIRATORY DISTRES	0.00% 0/28 • Adverse event reporting requirements become effective at the time of the participant's biologic assignment, and up to 2 years AE reporting was conducted according to the BMT CTN's Manual of Operating Procedures. Unexpected, serious AEs (SAEs) were reported through an expedited AE reporting system. Expected AEs were reported using National Cancer Institute (NCI)'s Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0 at regular intervals.	1.2% 1/85 • Number of events 1 • Adverse event reporting requirements become effective at the time of the participant's biologic assignment, and up to 2 years AE reporting was conducted according to the BMT CTN's Manual of Operating Procedures. Unexpected, serious AEs (SAEs) were reported through an expedited AE reporting system. Expected AEs were reported using National Cancer Institute (NCI)'s Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0 at regular intervals.
Respiratory, thoracic and mediastinal disorders Pulmonary hypertension	3.6% 1/28 • Number of events 1 • Adverse event reporting requirements become effective at the time of the participant's biologic assignment, and up to 2 years AE reporting was conducted according to the BMT CTN's Manual of Operating Procedures. Unexpected, serious AEs (SAEs) were reported through an expedited AE reporting system. Expected AEs were reported using National Cancer Institute (NCI)'s Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0 at regular intervals.	4.7% 4/85 • Number of events 6 • Adverse event reporting requirements become effective at the time of the participant's biologic assignment, and up to 2 years AE reporting was conducted according to the BMT CTN's Manual of Operating Procedures. Unexpected, serious AEs (SAEs) were reported through an expedited AE reporting system. Expected AEs were reported using National Cancer Institute (NCI)'s Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0 at regular intervals.
Nervous system disorders Significant cerebrovascular event	17.9% 5/28 • Number of events 8 • Adverse event reporting requirements become effective at the time of the participant's biologic assignment, and up to 2 years AE reporting was conducted according to the BMT CTN's Manual of Operating Procedures. Unexpected, serious AEs (SAEs) were reported through an expedited AE reporting system. Expected AEs were reported using National Cancer Institute (NCI)'s Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0 at regular intervals.	3.5% 3/85 • Number of events 4 • Adverse event reporting requirements become effective at the time of the participant's biologic assignment, and up to 2 years AE reporting was conducted according to the BMT CTN's Manual of Operating Procedures. Unexpected, serious AEs (SAEs) were reported through an expedited AE reporting system. Expected AEs were reported using National Cancer Institute (NCI)'s Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0 at regular intervals.
Renal and urinary disorders Renal function compromise	17.9% 5/28 • Number of events 7 • Adverse event reporting requirements become effective at the time of the participant's biologic assignment, and up to 2 years AE reporting was conducted according to the BMT CTN's Manual of Operating Procedures. Unexpected, serious AEs (SAEs) were reported through an expedited AE reporting system. Expected AEs were reported using National Cancer Institute (NCI)'s Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0 at regular intervals.	12.9% 11/85 • Number of events 14 • Adverse event reporting requirements become effective at the time of the participant's biologic assignment, and up to 2 years AE reporting was conducted according to the BMT CTN's Manual of Operating Procedures. Unexpected, serious AEs (SAEs) were reported through an expedited AE reporting system. Expected AEs were reported using National Cancer Institute (NCI)'s Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0 at regular intervals.
Musculoskeletal and connective tissue disorders Avascular necrosis	14.3% 4/28 • Number of events 4 • Adverse event reporting requirements become effective at the time of the participant's biologic assignment, and up to 2 years AE reporting was conducted according to the BMT CTN's Manual of Operating Procedures. Unexpected, serious AEs (SAEs) were reported through an expedited AE reporting system. Expected AEs were reported using National Cancer Institute (NCI)'s Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0 at regular intervals.	11.8% 10/85 • Number of events 11 • Adverse event reporting requirements become effective at the time of the participant's biologic assignment, and up to 2 years AE reporting was conducted according to the BMT CTN's Manual of Operating Procedures. Unexpected, serious AEs (SAEs) were reported through an expedited AE reporting system. Expected AEs were reported using National Cancer Institute (NCI)'s Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0 at regular intervals.
Skin and subcutaneous tissue disorders Leg ulceration	3.6% 1/28 • Number of events 1 • Adverse event reporting requirements become effective at the time of the participant's biologic assignment, and up to 2 years AE reporting was conducted according to the BMT CTN's Manual of Operating Procedures. Unexpected, serious AEs (SAEs) were reported through an expedited AE reporting system. Expected AEs were reported using National Cancer Institute (NCI)'s Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0 at regular intervals.	3.5% 3/85 • Number of events 4 • Adverse event reporting requirements become effective at the time of the participant's biologic assignment, and up to 2 years AE reporting was conducted according to the BMT CTN's Manual of Operating Procedures. Unexpected, serious AEs (SAEs) were reported through an expedited AE reporting system. Expected AEs were reported using National Cancer Institute (NCI)'s Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0 at regular intervals.
Respiratory, thoracic and mediastinal disorders Acute chest syndrome with hospitalization	10.7% 3/28 • Number of events 3 • Adverse event reporting requirements become effective at the time of the participant's biologic assignment, and up to 2 years AE reporting was conducted according to the BMT CTN's Manual of Operating Procedures. Unexpected, serious AEs (SAEs) were reported through an expedited AE reporting system. Expected AEs were reported using National Cancer Institute (NCI)'s Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0 at regular intervals.	14.1% 12/85 • Number of events 18 • Adverse event reporting requirements become effective at the time of the participant's biologic assignment, and up to 2 years AE reporting was conducted according to the BMT CTN's Manual of Operating Procedures. Unexpected, serious AEs (SAEs) were reported through an expedited AE reporting system. Expected AEs were reported using National Cancer Institute (NCI)'s Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0 at regular intervals.
Blood and lymphatic system disorders Vaso-occlusive pain with hospitalization or parenteral opioid drugs in outpatient setting	35.7% 10/28 • Number of events 11 • Adverse event reporting requirements become effective at the time of the participant's biologic assignment, and up to 2 years AE reporting was conducted according to the BMT CTN's Manual of Operating Procedures. Unexpected, serious AEs (SAEs) were reported through an expedited AE reporting system. Expected AEs were reported using National Cancer Institute (NCI)'s Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0 at regular intervals.	76.5% 65/85 • Number of events 161 • Adverse event reporting requirements become effective at the time of the participant's biologic assignment, and up to 2 years AE reporting was conducted according to the BMT CTN's Manual of Operating Procedures. Unexpected, serious AEs (SAEs) were reported through an expedited AE reporting system. Expected AEs were reported using National Cancer Institute (NCI)'s Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0 at regular intervals.
Infections and infestations Bacterial, Fungal, and Viral Infections	50.0% 14/28 • Number of events 33 • Adverse event reporting requirements become effective at the time of the participant's biologic assignment, and up to 2 years AE reporting was conducted according to the BMT CTN's Manual of Operating Procedures. Unexpected, serious AEs (SAEs) were reported through an expedited AE reporting system. Expected AEs were reported using National Cancer Institute (NCI)'s Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0 at regular intervals.	11.8% 10/85 • Number of events 12 • Adverse event reporting requirements become effective at the time of the participant's biologic assignment, and up to 2 years AE reporting was conducted according to the BMT CTN's Manual of Operating Procedures. Unexpected, serious AEs (SAEs) were reported through an expedited AE reporting system. Expected AEs were reported using National Cancer Institute (NCI)'s Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0 at regular intervals.