Haploidentical Peripheral Blood Stem Cell Transplantation Demonstrates Stable Engraftment in Adults with Sickle Cell Disease

We report on the screening and development of haploidentical hematopoietic stem cell transplantation (HSCT) for adult patients with clinically aggressive sickle cell disease (SCD) at our institution. Of 50 adult SCD patients referred for HSCT between 1/2014–3/2017, 20% were denied by insurance. Of 41 patients initially screened, 10% lacked an available haploidentical donor, 29% had elevated donor specific antibodies (DSA) and 34% declined to proceed to HSCT. All 10 patients who were transplanted received peripheral blood stem cells (PBSC). The initial two were conditioned with alemtuzumab/total body irradiation (TBI) 3Gy followed by post-transplant cyclophosphamide and failed to engraft. The next 8 patients received the regimen developed at Johns Hopkins University (Bolaños-Meade J, Blood 2012) with TBI 3Gy. G-CSF was administered from day+12 in those with HbS 0.5 x10(9)/L of 22 days (range, 18–23 days). One patient subsequently lost the graft and 7 (87.5%) maintained >95% donor cell chimerism at 1-year post-HSCT. Two patients developed acute GVHD ≥ grade 2. One had chronic GVHD and died >1 year after HSCT of unknown causes. With a median follow up of 16 months (range, 11–29 months), 7 patients (87.5%) are alive. Our findings suggest that limited insurance coverage, high rate of DSA and patient declining HSCT, may limit the availability of haploidentical HSCT in adult SCD patients. The modified Hopkins regimen used here demonstrates high engraftment and low morbidity rates and should be tested in larger, multicenter prospective clinical trials.