Haploidentical Bone Marrow Transplantation for Sickle Cell Disease.

Area of Science:

• Hematology
• Immunology
• Transplantation Science

Background:

• Related human leukocyte antigen (HLA)-haploidentical bone marrow transplantation (BMT) with posttransplant cyclophosphamide is a potential cure for sickle cell disease.
• Graft failure, severe graft-versus-host disease (GVHD), infections, and mortality are significant concerns.
• A novel conditioning regimen was evaluated for related HLA-haploidentical BMT in adults with sickle cell disease.

Purpose of the Study:

• To evaluate a novel conditioning regimen followed by related HLA-haploidentical BMT in adults with sickle cell disease.
• To assess the safety and efficacy of this BMT approach.
• To determine event-free survival and overall survival rates at 2 years post-transplant.

Main Methods:

• A phase 2, open-label, single-arm, multicenter study enrolled 54 participants.
• 42 participants received BMT with conditioning including antithymocyte globulin, fludarabine, cyclophosphamide, thiotepa, and total body irradiation.
• GVHD prophylaxis utilized posttransplant cyclophosphamide, mycophenolate mofetil, and sirolimus.

Main Results:

• Two-year event-free survival was 88.0% and overall survival was 95.0%.
• Graft failure occurred in 2 participants; grade 3-4 acute GVHD was 4.8% and 2-year chronic GVHD was 22.4%.
• Two of four deaths were attributed to early infectious complications.

Conclusions:

• HLA-haploidentical BMT is an accessible and potentially curative therapy for adults with sickle cell disease.
• Adverse events, including GVHD, were consistent with expectations for this procedure.
• This BMT approach demonstrates promising outcomes for sickle cell disease patients.