Excellent Outcomes in Feasibility Study of Radiation-Free Conditioning and Transplant in Pediatric Severe Aplastic Anemia.

Severe aplastic anemia (SAA) is treated with a hematopoietic cell transplant (HCT) in the presence of an HLA-matched sibling donor (MSD) with disease-free survival (DFS) of >90%. In the absence of an MSD, immunosuppressive therapy (IST) can induce remission but concerns for relapsed/refractory disease and clonal hematopoiesis persist. IST failure is an indication for HCT. Modern HCT approaches target barriers such as graft rejection (GR), graft-versus-host disease (GVHD), and transplant-related toxicities. Traditionally, total body irradiation (TBI) inclusive HCT conditioning helps decrease GR, but the use of TBI in children increases concerns for late effects such as malignancies. To describe outcomes after HCT in children with SAA transplanted from the best available donor following a radiation-free RIC regimen in a single-center feasibility trial. The RIC regimen included alemtuzumab, fludarabine, melphalan, ±thiotepa prior to HCT GVHD prophylaxis included tacrolimus, methotrexate, or mycophenolate mofetil. Abatacept was added to GVHD prophylaxis after 2017 to decrease further or eliminate GVHD risk in patients with a non-malignant disorder. This report includes outcomes in 22 consecutive pediatric SAA recipients of HCT (11 MSD, 10 unrelated, and 1 haploidentical) between 2012 and 2023 at a single center. With a median follow-up of 48 months (range, 12-144) all recipients had sustained full myeloid donor chimerism, 100% DFS, and no grade 2 to 4 acute GVHD. One patient (4.5%) developed grade 1 acute skin GVHD, and 1 (4.5%) developed pericardial effusion attributed to chronic GVHD. Complications before day +180 were primarily transient viral reactivations. Thyroid and ovarian hypofunction were the commonest effects noted at long-term follow-up. This radiation-free RIC regimen demonstrated excellent DFS with minimal GVHD in all patients, including those from alternative donor sources. Late complications were primarily endocrine in origin.