Transplant versus no transplant outcome in adolescents and adults with sickle cell disease eligible for allogeneic hematopoietic stem cell transplantation.

Hematopoietic stem cell transplantation (HSCT) remains the only curative option for sickle cell disease (SCD), but its use in adolescents and adults is limited by toxicity concerns. We evaluated the risk-benefit profile of HSCT in this population through a comparative analysis of transplant versus nontransplant strategies. HSCT was analyzed as a time-dependent variable in consecutive adolescents and adults with an indication for transplantation who were referred for HSCT counseling. At the last follow-up, patients had either undergone HSCT or not. HSCT procedures involved matched related donor (MRD) transplants after myeloablative or non-myeloablative conditioning, and haploidentical transplants after reduced-intensity conditioning. The primary endpoints were overall survival (OS) and composite event-free survival (cEFS), calculated from the initial consultation. Events included death, grade III-IV acute or moderate-to-severe chronic graft-versus-host disease (GVHD), graft rejection, overt stroke, third hospitalized painful crises within two years, acute chest syndrome (ACS), delayed hemolytic transfusion reaction, or initiation of new SCD modifying therapy. Ninety-four patients were included (median follow-up: 2.9 years), of whom 58 underwent HSCT. The 2-year OS was 98% with HSCT versus (vs.) 97% without HSCT (P = 0.55). cEFS was significantly higher post-transplant (72% vs. 28%, P < 0.0001), with marked reduction in painful crises and ACS. Among patients who underwent transplantation, the 2-year rejection-free survival from the time of transplant was 91% for MRD and 82% for haploidentical HSCT (P = 0.40). HSCT substantially improves cEFS without excess short-term mortality, supporting its broader use in adolescents and adults with SCD, particularly when an MRD is available.