Future Directions in Allogeneic Stem Cell Transplantation in Acute Lymphoblastic Leukemia

Background Allogeneic stem cell transplantation (ASCT) has been a cornerstone of acute lymphoblastic leukemia (ALL) treatment for decades, with significant improvements in patient survival. These advancements are linked to better therapies, refined conditioning regimens, and minimal residual disease (MRD) monitoring. Despite progress, challenges remain in reducing relapse, treatment-related mortality, and toxicity. Summary This article explores recent advancements in ASCT for ALL, focusing on conditioning regimens, graft engineering, and post-transplant therapies. Key developments include identifying patients who benefit from reduced-intensity conditioning (RIC) over myeloablative conditioning (MAC) or reduction in dose of total body irradiation (TBI), leading to improved outcomes and lower toxicity. Innovative graft manipulation strategies, such as Orca-T and Orca-Q, aim to enhance graft-versus-leukemia (GVL) effects while minimizing graft-versus-host disease (GVHD). Additionally, post-transplant therapies, including targeted treatments, immunotherapies, and CAR-T cells, are showing promise in preventing relapse. Advances in mismatched donor use and GVHD prophylaxis are broadening donor options and reducing adverse effects, improving ASCT’s safety and effectiveness in ALL. Key Messages ASCT remains a critical treatment for high-risk ALL, with advancements in conditioning, graft engineering, and post-transplant strategies. Future focus will be on optimizing patient selection, use in post CAR-T consolidation, and refining graft manipulation, aiming to personalize ASCT and enhance survival and quality of life for ALL patients.