The Use of a Reduced-Intensity Conditioning (RIC) Regimen in Patients Ages 2-30 Undergoing Allogeneic Transplantation for Sickle Cell Disease

Background: Sickle cell disease (SCD) affects 72,000 individuals in the United States and causes considerable morbidity and mortality. Hematopoietic stem cell transplantation (HSCT) is the only cure for patients with SCD. Multiple studies show matched sibling transplants after myeloablative (MAB) conditioning have acceptable results, but with potential long-term complications, like endocrine and fertility issues. Only 14% of SCD patients will have acceptable sibling donors, and results have been less promising with higher rates of transplant related mortality (TRM) using alternative donors after MAB conditioning. Historically, only pediatric patients were considered candidates for HSCT, but a recent study demonstrated that young adult SCD patients may be able to tolerate a RIC HSCT with minimal complications. In an attempt to minimize the risk of TRM while still maximizing the available donors, this study examines the use of a RIC regimen for either matched sibling or alternative donor HSCT in SCD patients ages 2-30.

Methods: Patients were deemed eligible for matched sibling HSCT if they had SCD, and for alternative donor HSCT if they had SCD with severe features with a 9-10/10 unrelated donor or 5-6/6 UCB in the donor registry. The conditioning regimen consisted of Alemtuzumab, Fludarabine, and Melphalan. Post-HCST, donor chimerism and hemoglobin S (HbS) percentages were followed closely, and there was strict monitoring for post-HSCT complications, including graft rejection, graft vs. host disease (GVHD), infectious complications, and other post-HSCT issues.

Results: 11 patients (8 related donors, 3 unrelated donors) with median age of 8.1 years (range: 2.3-23 years) were enrolled. For related HSCT, the probabilities of primary neutrophil & platelet engraftment, grade II-IV acute GVHD, chronic GVHD, and graft rejection were 100%, 27%, 12.5%, and 0%, respectively. Donor chimerisms ranged from 96-100% with HbS% between 0-43%, with median follow-up of 19 months (range: 3-24 months). Probability of 1-yr DFS and OS were 100% & 100%. For alternative donor HSCT, the probabilities of primary neutrophil & platelet engraftment, grade II-IV GVHD, chronic GVHD, and graft rejection were 100%, 33%, 33%, and 33%, respectively. Donor chimerisms ranged from 0-100% with HbS% between 0-18%, with median follow-up of 8 months (range: 2-25 months). Probability of 1-yr DFS and OS were 33% & 66%.

Conclusions: Our results show that this RIC regimen followed by matched sibling HSCT is well tolerated, but the results were discouraging for alternative donor HSCT. Because of this, we are currently developing a protocol using post-transplant cyclophosphamide in alternative donor HSCT for SCD.