HLA-identical sibling hematopoietic stem cell transplantation following reduced-toxicity myeloablative conditioning regimen in sickle cell disease

Abstract Allogeneic hematopoietic stem cell transplantation (HSCT) is the only widely available curative treatment for sickle cell disease (SCD). Myeloablative conditioning regimens are associated with excellent outcomes in children with HLA-identical sibling donors but are limited by organ toxicity in adults. Here we report 48 children and adults who underwent HLA-identical sibling HSCT for SCD using a reduced toxicity conditioning (RTC) regimen (fludarabine, busulfan, and anti-thymocyte globulin), followed by cyclosporine plus methotrexate for graft-versus-host disease (GVHD) prophylaxis. Median (range) age at transplant and duration of follow-up were 16.5 (7–35) years and 77.5 (1-169) months, respectively. Indication for HSCT included neurological complications in 25 (52.1%) patients and 10 (20.8%) were alloimmunized against red blood cell antigens. All patients achieved engraftment, except one who died before engraftment period. Secondary graft failure, grade ≥ 2 acute GHVD and chronic GVHD were present in 7 (14.6%), 10 (20.8%) and 7 (14.6%) patients, respectively. Five-year overall survival (OS) and event-free survival (EFS) (95% CI) were 91% (77.8–96.5) and 80.3% (65.5–89.2), respectively. Survival curves were not different between children and adults (p = 0.37 and p = 0.33, respectively). RTC regimen is safe and effective, with acceptable toxicity and incidence of GVHD, in children and adults with SCD.