Impact of Total Body Irradiation Dose in Reduced‐Intensity Conditioning for Allogeneic Hematopoietic Cell Transplantation in Acute Myeloid Leukemia

Using data from a nationwide Japanese registry, we evaluated the impact of the total body irradiation (TBI) dose in reduced-intensity conditioning (RIC) for allogeneic hematopoietic cell transplantation (allo-HCT) in patients with acute myeloid leukemia (AML). Adults undergoing their first allo-HCT with RIC between 2010 and 2021 were classified into three groups: non-TBI, low-TBI (2 to < 4 Gy), or moderate-TBI (4-8 Gy). Outcomes were analyzed separately for patients in complete remission (CR, n = 1949) and those in the non-CR group (n = 1484). Non-TBI was associated with higher overall mortality than low-TBI (hazard ratio [HR], 1.27; 95% confidence interval [CI], 1.03-1.56 in CR; HR, 1.19; 95% CI, 1.00-1.42 in non-CR). Moderate-TBI showed no significant difference in overall mortality compared to low-TBI (HR, 0.96; 95% CI, 0.80-1.15 in CR; HR, 0.89; 95% CI, 0.77-1.05 in non-CR). Among patients in the CR group with matched sibling donors, moderate-TBI reduced overall mortality (HR, 0.33; 95% CI, 0.17-0.64) and relapse (HR, 0.29; 95% CI, 0.12-0.69). In cord blood transplantation, non-TBI increased relapse in CR (HR, 2.73; 95% CI, 1.48-5.06) and overall mortality in non-CR (HR, 1.62; 95% CI, 1.19-2.19). In haploidentical transplants, non-TBI increased relapse (HR, 5.52; 95% CI, 1.72-17.72 in CR; HR, 1.54; 95% CI, 1.04-2.30 in non-CR). The incidence of secondary primary malignancies did not differ according to the use or dose of TBI. In conclusion, adding low- or moderate-TBI to RIC may improve disease control and survival without increasing non-relapse mortality.