PTCy-based allo-BMT platform as a curative, accessible alternative for pediatric and young adult severe aplastic anemia

Severe aplastic anemia (SAA) is a life-threatening bone marrow failure syndrome. Allogeneic bone marrow transplantation (allo-BMT) is the most definitive curative treatment for SAA and is prioritized when matched sibling donors (MSDs) are available. Haploidentical BMT (haplo-BMT) with posttransplant cyclophosphamide (PTCy) has emerged as a promising alternative, expanding donor access while mitigating historically high rates of graft failure and graft-versus-host disease (GVHD). We report the outcomes of 31 consecutive pediatric, adolescent, and young adult patients (aged ≤21 years) with acquired SAA who underwent allo-BMT at a single institution (2014-2024). Patients with treatment-naïve (TN) and relapsed/refractory (R/R) SAA were included. Patients received reduced-intensity conditioning (RIC) haplo-BMT or MSD-BMT with PTCy, mycophenolate mofetil, and tacrolimus (PTCy cohort, n = 23), or standard-of-care (SOC) MSD-BMT with cyclophosphamide/antithymocyte globulin conditioning and calcineurin inhibitor/methotrexate–based GVHD prophylaxis (SOC cohort, n = 8). Overall survival was 97% (PTCy, 96%; SOC, 100%). GVHD rates were low, with only 1 case of grade 2 acute GVHD and 1 case of extensive chronic GVHD (cGVHD) in the PTCy group, and 1 case of extensive cGVHD in the SOC group. No patients developed clonal hematopoiesis. Late effects were infrequent, and limited to menstrual dysfunction and BK virus–associated nephropathy in 1 patient. Robust donor chimerism was achieved in the PTCy cohort, in contrast to uniformly mixed chimerism in the SOC group. These findings demonstrate that RIC haplo-BMT with PTCy is a safe and effective curative approach for pediatric patients with both R/R and TN SAA, supporting its use as a frontline option even when MSDs are available.