Hematopoietic stem cell transplantation for sickle cell disease: The changing landscape

Allogeneic hematopoietic stem cell transplantation (HSCT) remains the only curative therapy for sickle cell disease (SCD); however, its use is limited by lack of suitable human leukocyte antigen (HLA)-matched donors and decreased application in older patients with significant morbidity. Myeloablative, HLA-identical sibling transplantation in children with SCD offers excellent long-term survival, with overall and event-free survival rates of 95% and 92%, respectively. However, the risk of graft-versus-host-disease, infections, infertility, and other long-term transplant complications, further limits its widespread use. Recent approaches using reduced intensity conditioning (RIC) are associated with lower toxicity, allowing extension of this modality to children and adults with significant morbidity; however, these approaches are also associated with increased risk of graft failure. The optimal RIC regimen that strikes the optimal balance between maximizing the rate of stable engraftment while minimizing transplant-related morbidity and mortality is unknown. Alternative donor transplants, most prominently, partial HLA-mismatched related transplants (haploidentical), are being investigated with promising initial results. This review will discuss long-term results of HLA-matched sibling HSCT for SCD, and recent updates on HLA-matched unrelated donor and unrelated umbilical cord blood HSCT for SCD.