Favorable outcomes with fludarabine, melphalan, and total-body irradiation 8-12Gy as an intensified conditioning regimen for adult allogeneic HCT.

High-dose total body irradiation (TBI)-containing conditioning regimens remain an important strategy in allogeneic hematopoietic cell transplantation (allo-HCT). We retrospectively analyzed outcomes of adult patients who received Flu/Mel80/TBI 8-12 Gy at a single center. A total of 83 patients underwent their first allo-HCT between 2002 and 2023. The median age was 54 years; acute lymphoblastic leukemia accounted for 53 % of cases, and 45 % proceeded to transplantation in non-remission. Cord blood was used in 90 % of patients. At a median follow-up of 664 days among survivors, the 3-year overall survival (OS) and relapse-free survival (RFS) were 66.5 % and 59.5 %, respectively. The 3-year cumulative incidence of relapse was 24.0 %, and that of non-relapse mortality (NRM) was 16.5 %. In multivariate analysis, disease status at transplantation was the only factor significantly associated with RFS; no variables were significantly associated with OS, relapse, or NRM. Neutrophil engraftment was achieved in all patients, with a median of 16 days. Acute GVHD grade II-IV and III-IV by day 100 occurred in 64.4 % and 15.7 % of patients, respectively. The 3-year incidence of chronic GVHD was 19.4 %. In the cord blood subgroup, pre-engraftment immune reaction (PIR) occurred in 76 % of patients. In this high-risk cohort with a large proportion of non-remission, the Flu/Mel80/TBI 8-12 Gy regimen resulted in favorable engraftment, low relapse, and acceptable toxicity. These findings suggest that this intensified TBI-based conditioning may represent a viable option for patients requiring strong antitumor activity.