Severe aplastic anemia (SAA) is a marrow failure disorder with high morbidity and mortality. It is treated with bone marrow transplantation (BMT) for those with fully matched donors or immunosuppressive therapy (IST) for those who lack such a donor, which is often the case for underrepresented minorities. We conducted a prospective phase II trial of reduced-intensity conditioning HLA-haplo BMT and post-transplantation cyclophosphamide (PTCy)-based graft-versus-host (GVHD) prophylaxis as initial therapy for patients with SAA. The median age was 25 (range 3-63) years and the median follow-up was 40.9 months (95% CI: 29.4, 55.7 mos). Over 35% of enrollment was from underrepresented racial/ethnic groups. The cumulative incidence of grade II-IV aGVHD at day 100 is 7% (95% CI: NA, 17%) and chronic GVHD at 2 years is 4% (95% CI: NA, 11%). The overall survival for 27 patients is 92% (95% CI: 83,100%) at one, two, and three years. The first 7 patients received lower dose total body irradiation (200 versus 400 cGY), but these patients were more likely to have graft failure, 3 of 7, compared to 0 out of 20 patients in the higher dose group (p=0.01, Fisher exact). HLA-haploidentical BMT with PTCy using 400cGY total body irradiation resulted in 100% overall survival with minimal GVHD in 20 consecutive patients. Not only does this approach avoid the ramifications of IST and its low failure-free survival, but also the use of haploidentical donors expands access to BMT across all populations. Clinical trial: NCT02833805.
