Early Human Leukocyte Antigen (HLA) Matched Sibling Hematopoietic Stem Cell Transplantation

The use of HLA matched sibling donor (MSD) hematopoietic stem cell transplantation (HSCT) for sickle cell disease (SCD) is evolving. Because of the low risk for graft versus host disease (GVHD) associated with younger age, HSCT is increasingly being performed prior to adolescence. The use of less gonadotoxic reduced intensity regimens (RIC) are more commonly be utilized to lessen the risk for infertility. Finally, with the recognition that most children, even those who have asymptomatic to relatively mild courses, will develop debilitating morbidities as adults and ultimately suffer an early death, HSCT is being offered to children across a wider spectrum of SCD severity. Long reserved for severely affected children, HSCT is being performed for a growing number of less severely affected children, as well as children without disease manifestation. This trial is designed to prospectively assess HSCT under these conditions. Eligibility will be limited to children less than 13 years of age who have an HLA MSD. SCD severity criteria will be broadened to include less severely affected children as well as those who are severely affected. A RIC regimen - fludarabine, alemtuzumab and melphalan (FAM) - will be employed. For GVHD prophylaxis, all patients will receive a calcineurin inhibitor and short course methotrexate. This study has the following two specific aims: Specific Aim #1: To prospectively assess the safety and efficacy of HSCT using FAM conditioning in children with SCD of varying severity who are under 13 years of age. Specific Aim #2: To address current gaps in our understanding of the long-term effects of HSCT in children with SCD, by longitudinally assessing sickle cell related cerebrovascular disease, sickle cell related nephropathy and health related quality of life.