Peters C, Dalle JH, Locatelli F, et al. - Despite the efficacy of total body irradiation (TBI) prior to allogeneic hematopoietic stem cell transplantation (HSCT) in pediatric patients with acute lymphoblastic leukemia (ALL), long-term side effects are concerning, therefore, researchers examined if preparative combination chemotherapy could substitute TBI in such cases. They undertook a randomized, controlled, open-label, international, multicenter, phase III, noninferiority analysis, named FORUM, wherein they randomized patients ≤ 18 years at diagnosis, 4-21 years at HSCT, in complete remission pre-HSCT, and with an HLA-compatible related or unrelated donor to receive myeloablative conditioning with fractionated 12 Gy TBI and etoposide vs fludarabine, thiotepa, and either busulfan or treosulfan. The noninferiority margin was 8%. Findings demonstrated that TBI plus etoposide, vs chemoconditioning, conferred improved overall survival and lower relapse risk. Thus, TBI plus etoposide should be used to treat patients > 4 years old with high-risk ALL receiving allogeneic HSCT.