Abatacept Prevents Severe Acute Graft‐Versus‐Host Disease Without Increasing Graft Failure Risk in Pediatric Bone Marrow Failure Syndromes

Background Pediatric patients with inherited or acquired bone marrow failure syndromes (BMFS) often require an allogeneic hematopoietic stem cell transplant (HSCT) to cure the hematological manifestations. Amongst these, those without a matched sibling donor (MSD), are at increased risk for graft failure and are known to tolerate graft‐versus‐host disease (GVHD) poorly. Abatacept (ABA) is Food and Drug Administration (FDA)‐approved for the prevention of acute GVHD. Objectives Our primary objective was to investigate the cumulative incidence (CI) of severe acute (Grade III–IV) GVHD in patients with BMFS undergoing a matched unrelated donor (MUD) or mismatched related or unrelated donor (MMRD/MMUD) HSCT with ABA added to standard GVHD prophylaxis of calcineurin inhibitor and methotrexate or mycophenolate mofetil, and evaluate the incidence of graft failure. Secondary outcomes included overall survival (OS) and acute and chronic GVHD‐free graft failure‐free overall survival (GFS) at 1 year. Study Design We compared the CI of severe acute GVHD and graft failure by Day 180 in patients who received ABA ( n = 26), against a historical cohort of HSCT BMFS patients who did not receive ABA ( n = 21) in a combined retrospective review from two centers. Results None of the patients in the ABA cohort experienced severe (Grade III–IV) acute GVHD compared to 14% in our historical cohort (CI 0% vs. 14%, p = 0.05). All patients in our ABA cohort successfully engrafted, with one patient experiencing poor graft function. In the historical cohort, one patient experienced primary graft failure. The rates of chronic GVHD were comparable between the historical and ABA groups, 28.6% versus 19.2% ( p = 0.51). The OS (95.2% vs. 96.0%, p = 0.3) and GFS at 1 year (64.3% vs. 65.3%, p = 0.5) were similar in the ABA group compared to the historical group. Conclusion ABA was well tolerated in patients with BMFS and prevented severe acute GVHD without increasing the incidence of graft failure. Rates of chronic GVHD and GFS at 1 year were similar, but analysis was limited due to sample size and variability in ABA dosing.