HLA-haploidentical hematopoietic stem cell transplantation in patients with sickle cell disease: results from the phase II DREP-HAPLO trial

Abstract

We report the final analysis of the Drep-Haplo multicenter phase 2 protocol, which evaluated haploidentical transplantation after reduced-intensity conditioning regimen incorporating thiotepa, in children and adults with severe sickle cell disease (SCD). Twenty-two patients (median age: 17 years; range: 12–40) received a conditioning regimen consisting of 2 Gy total body irradiation, thymoglobulin, cyclophosphamide, fludarabine, and thiotepa, followed by T cell–replete bone marrow infusion and graft-versus-host disease (GVHD) prophylaxis based on post-transplant cyclophosphamide.

The primary endpoint, event-free survival, defined as survival without graft failure and without moderate-to-severe chronic GVHD, was 68.18% (95% CI: 51.25%–90.70%) and 61.98% (95% CI: 44.07%–87.19%) at 1 and 4 years, respectively. Overall survival and rejection-free survival at 4 years were 90.15% (95% CI: 78.03%–100%) and 85.56% (95% CI: 71.63%–100%), respectively. Six patients (27%) developed moderate-to-severe GVHD. In most cases (4/6), GVHD resolved, leaving only two patients (9%) with persistent moderate to severe GVHD at last follow-up. Eighty-five grade 2 to 4 infectious episodes were reported in 21 patients during the 24 months of follow-up, most of which were bacterial (38 cases). These data strengthen existing evidence supporting the feasibility of haploidentical transplantation in both pediatric and adult patients with severe SCD, demonstrating a very low rejection rate when thiotepa is incorporated into the conditioning regimen. Future efforts should focus on reducing chronic GVHD and infection rates.