Data for Nonmyeloablative Pentostatin-Cyclophosphamide Preconditioning Improves Rates of Engraftment in Adults Undergoing Haploidentical HCT for Sickle Cell Disease

Our group has implemented a nonmyeloablative haploidentical HCT protocol that adds IV pentostatin-oral cyclophosphamide (PC) preconditioning to our previous nonmyeloablative HCT regimen of alemtuzumab and total body irradiation with the goal of decreasing the graft rejection rate. This report aims to assess the impacts of the PC preconditioning.This report compares the results of NIH’s two nonmyeloablative haploidentical HCT regimens. The National Heart, Lung, and Blood Institute Institutional Review Board approved both studies. All patients gave written informed consent. Our first haploidentical protocol (haplo-1; NCT00977691) employed alemtuzumab and TBI-based conditioning with dose-escalating PT-Cy and sirolimus for GVHD prophylaxis in adults with severe SCD; the results of this study have been previously reported [23]. The second study (haplo-PC) was a prospective phase 1/2 nonmyeloablative haploidentical peripheral blood stem cell (PBSC) transplant protocol for patients with severe SCD (NCT03077542).We examined rates of graft rejection at one year post-HCT and graft failure at the last follow-up. Graft rejection refers to an acute loss of the graft, with <5% DMC and DLC. Graft failure includes those with graft rejection but also includes patients with return of acute complications of SCD, regardless of whether donor cells remained detectable. Planned follow-up occurred 1 to 2 times per week until 100 days post-HCT, every 6 months until 2 years post-HCT, and annually thereafter.