Alternative donor hematopoietic stem cell transplantation for sickle cell disease

Area of Science:

• Hematology
• Transplantation Immunology
• Pediatric Hematology

Background:

• Sickle cell disease (SCD) is a debilitating genetic disorder.
• Curative stem cell transplantation is limited by the lack of matched sibling donors.
• Alternative donors are crucial for expanding access to potentially curative therapies for SCD.

Purpose of the Study:

• To evaluate the efficacy and safety of reduced-intensity conditioning followed by CD34+ cell-selected, T-cell-depleted peripheral blood stem cell transplantation from alternative donors in patients with symptomatic SCD.
• To assess engraftment, graft-versus-host disease (GVHD), and survival outcomes.

Main Methods:

• Ten patients with symptomatic SCD received CD34+ selected, T-cell-depleted peripheral blood stem cells from mismatched family or unrelated donors.
• A reduced-intensity conditioning regimen included melphalan, thiotepa, fludarabine, and rabbit anti-thymocyte globulin.
• A companion study monitored immune reconstitution, including donor lymphocyte infusions and methotrexate for GVHD prophylaxis.

Main Results:

• Nine of 10 patients survived with a median follow-up of 49 months and stable donor engraftment (mean chimerism 99.1%).
• No sickle cell complications occurred post-transplant.
• Low incidence of acute (2/7) and chronic (1/7) GVHD was observed, but 3 patients developed Epstein-Barr virus-related posttransplant lymphoproliferative disorder (PTLD), with one death.
• Two-year overall survival was 90% and event-free survival was 80%.

Conclusions:

• Reduced-intensity conditioning with CD34+ selected, T-cell-depleted alternative donor stem cell transplantation achieves engraftment in all SCD patients.
• This approach offers a viable curative option for most SCD patients lacking matched donors.
• While GVHD is minimized, PTLD remains a significant concern requiring careful management.