Comparison of Regimens Used for Allogeneic Matched Related Donor Hematopoietic Cell Transplantation for Sickle Cell Disease

Abstract

Prior analyses have reported on the impact of different donor types and conditioning regimen intensities on outcomes for patients with sickle cell disease (SCD) who undergo hematopoietic cell transplantation (HCT), and demonstrated superior outcomes using an HLA-matched related donor (MRD). However, the impact of conditioning regimen intensity on outcomes remains unclear, with conflicting findings across studies. In addition, the lack of data on comparative outcomes of different approaches to conditioning and graft-versus-host disease (GVHD) prophylaxis for allogeneic HCT for SCD remains a gap in the field. We compared outcomes for SCD patients who have received HLA-matched related donor (MRD) HCT for SCD using different HCT regimens. We examined de-identified records of MRD HCT for SCD on patients transplanted between 1991 and 2022 in the United States and submitted to the CIBMTR. We compared the most common transplant regimens in the registry, which included TBI 300/400 cGy + sirolimus + anti-thymocyte globulin (ATG)/alemtuzumab described by Hsieh et al; Busulfan/Fludarabine + CNI/methotrexate (MTX) + ATG/alemtuzumab as described by Krishnamurti et al.; Fludarabine/Melphalan + CNI/MTX + ATG/alemtuzumab as described by King et al.; and Busulfan/Cyclophosphamide (CY) + CNI /MTX/prednisone + ATG/alemtuzumab as described by Walters et al. For pediatric MRD HCT, EFS rates were highest with the Krishnamurti et al. (3-year EFS 94%, 95% CI 88, 100) and lowest with the Hsieh et al. regimen (3-year EFS 57%, 95% CI 25, 100, p<0.001). Rates of chronic GVHD were lowest in the Hsieh et al. cohort (3-year rate 0%) and highest in the King et al. cohort (3-year rate 20.4%, 95% CI 13.2, 28.8, p=0.040). For adult MRD HCT, EFS rates were similar between the Hsieh et al. and Krishnamurti et al. regimens, while cGVHD was significantly lower in the Hsieh et al. cohort. These real-world data have the potential to inform shared decision-making in MRD HCT for SCD. Pediatric patients had the highest EFS rates using myeloablative conditioning regimens, while non-myeloablative conditioning resulted in the lowest EFS rates. Adult patients had similar event-free survival using myeloablative and non-myeloablative conditioning regimens, with less GVHD following non-myeloablative regimens.

Keywords: Conditioning regimen; Hematopoietic cell transplantation; Matched related donor; Sickle cell disease.