Choice of Donor Source and Conditioning Regimen for Hematopoietic Stem Cell Transplantation in Sickle Cell Disease

In the United States, one out of every 500 African American children have sickle cell disease (SCD), and SCD affects approximately 100,000 Americans. Significant advances in the treatment of this monogenetic disorder have failed to substantially extend the life expectancy of adults with SCD over the past two decades. Hematopoietic stem cell transplantation (HSCT) remains the only curative option for patients with SCD. While human leukocyte antigen (HLA) matched sibling HSCT has been successful, its availability is extremely limited. This review summarizes various conditioning regimens that are currently available. We explore recent efforts to expand the availability of allogeneic HSCT, including matched unrelated, umbilical cord blood, and haploidentical stem cell sources. We consider the use of nonmyeloablative conditioning and haploidentical donor sources as emerging strategies to expand transplant availability, particularly for SCD patients with complications and comorbidities who can undergo neither matched related transplant nor myeloablative conditioning. Finally, we show that improved conditioning agents have improved success rates not only in the HLA-matched sibling setting but also alternative donor settings.