Objectives

The primary objective was to compare overall survival rates between hematopoietic cell transplantation (HCT) and Standard of Care (SOC) treatments in adolescents and young adults with severe sickle cell disease (SCD).

Background

Sickle cell disease (SCD) is associated with significant morbidity, health care utilization, impaired quality of life, and early mortality. Retrospective reports suggest excellent survival in patients younger than 13 years who were treated with HLA-matched sibling transplantation. A pilot trial, using the HCT regimen utilized in this trial, conducted from 2012-2016 reported a 1-year survival of 91% and an event-free survival of 82%. The BMT CTN 1503 study was designed to investigate 2-year overall survival rates in adolescents and young adults who received HCT from an HLA-matched donor sibling or unrelated donor compared to participants who received standard treatment.

Participants

A total of 113 participants enrolled in the study. Of these, 28 participants were enrolled in the HCT arm (donor arm) and 85 participants were enrolled in the standard treatment arm (no donor arm). All participants were between 15-41 years of age with severe sickle cell disease, adequate physical health, and hepatic function.

The donor search was conducted after confirmation of eligibility. Only those participants with an HLA-matched sibling or HLA-matched unrelated donor were eligible for the donor arm. Donor arm participation required a liver MRI to document hepatic iron content and lack of clinical or radiologic evidence of a recent neurologic event. Individuals with previous HLA typing of both related and unrelated potential donors were not eligible for this study.

Design

Participants assigned to the donor arm were intended to receive a bone marrow graft and a myeloablative conditioning regimen of busulfan (12.8 mg/kg), fludarabine (105 mg/m²), and rabbit antithymocyte globulin (6 mg/kg). Graft-versus-host disease (GVHD) prophylaxis included tacrolimus and methotrexate. Two additional regimens (B and C) were approved in an amendment. Regimen B was an alternative for HLA-matched sibling transplantation and included alemtuzumab and low-dose total body irradiation (TBI), peripheral blood graft, and sirolimus for GVHD prophylaxis. Regimen C consisted of alemtuzumab, fludarabine, and melphalan, a marrow graft, and tacrolimus and methotrexate for GVHD prophylaxis.

The primary end point was overall 2-year survival between the two groups. Secondary end points included quarterly assessment of sickle-related events. Annual assessments included health-related quality of life scores, pain intensity, 6-minute walk, tricuspid regurgitant jet velocity, albuminuria, and pulmonary function testing. Additional end points such as occurrence of HCT-related complications were assessed for donor arm participants.

Conclusions

The study did not meet the enrollment criteria required to perform a comparative analysis; however, point estimates were generated with 95% confidence interval (CI). The estimate of overall survival for 2 years after biologic assignment was 89% in the transplant treatment arm (95% CI, 78-100) and 93% (95% CI, 87-99) in standard care treatment arm. Furthermore, HCT led to improvements in vaso-occlusive crisis, fatigue, and social function.

Walters MC, Eapen M, Liu Y, et al. Hematopoietic cell transplant compared with standard care in adolescents and young adults with sickle cell disease. Blood Adv. 2025;9(5):955-965. doi:10.1182/bloodadvances.2024013926

Request Data

Please note that researchers must be registered on this site to submit a request, and you will be prompted to log in. If you are not registered on this site, you can do so via the Request button. Registration is quick, easy and free.