Background Total body irradiation (TBI) is commonly used in conditioning regimens for allogeneic hematopoietic stem cell transplantation (allo-HSCT), especially in acute lymphoblastic leukemia (ALL). Its efficacy depends on dose and fractionation: myeloablative regimens provide disease control and engraftment, while lower-dose TBI in reduced-intensity conditioning (RIC) supports graft-versus-tumor effects with reduced toxicity. This study evaluates real-world clinical outcomes of TBI-based conditioning in allo-HSCT.

Methods All adult patients (pts) who received TBI-based conditioning at the Bone Marrow Transplantation Unit of Spedali Civili of Brescia between 2007–2025 were retrospectively included. Written informed consent was obtained. Pts were stratified by TBI dose: myeloablative (800–1000–1200 cGy) vs. RIC (200–400 cGy). A subgroup analysis was performed in pts with ALL, comparing 800, 1000, and 1200 cGy. Overall survival (OS) and time-to-event outcomes were analyzed via Kaplan–Meier method. Cumulative incidences were calculated using Gray's method to account for competing risks.

Results We analyzed 111 pts (median age 47 years, range 18–75) who consecutively underwent allo-HSCT with TBI-based conditioning regimens. Diagnoses included ALL (49 pts, 44%), Lymphomas or Chronic Lymphoproliferative Disorders (19%), Acute Myeloid Leukemia (17%), and Multiple Myeloma (13%). The overall cohort showed favorable outcomes, with a median OS of 83 months (5-year OS: 59%), a 2-year cumulative incidence of relapse (CIR) of 23.9%, and a 2-year non-relapse mortality (NRM) of 22.3%. The cumulative incidence (CI) of grade III-IV acute GVHD (aGVHD) at day +100 was 8.2%, while the 2-year CI of moderate-to-severe chronic GVHD (cGVHD) was 21.9%. Mucositis was the most common complication (63%) and was significantly associated with TBI dose (p<0.001).

Among the 49 pts with ALL, the median age was 41 years (18–62), with a male predominance (61%). Most pts were in first complete remission (CR1) at transplant (71%) and received peripheral blood stem cells (80%). Donors were unrelated in 45% of cases, matched related in 29%, and haploidentical in 22%. All pts underwent myeloablative TBI-based conditioning at doses of 800, 1000, or 1200 cGy. Baseline characteristics were comparable across dose groups.

Pts treated with 1200 cGy had the most favorable outcomes, with a 2-year OS of 80.1% (95%CI 62.7-90.0), compared to 60% with 1000 cGy and 50% with 800 cGy (p=0.04). The 1-year CIR was lowest in the 1200 cGy group (12.5%) versus 40% with 800 cGy. Although the 2-year NRM was higher with 1200 cGy (14.2%), this difference did not reach statistical significance. Similarly, a higher CI of grade III–IV aGVHD (14%, 95%CI: 5–27) and 2-year moderate-to-severe cGVHD (37%, 95%CI: 21–53) were observed in the 1200 cGy group, though without statistical significance. The 1-year GVHD-Free Relapse-Free Survival (GRFS) also favored 1200 cGy (60%), compared to 50% with 1000 cGy and 40% with800 cGy. When stratified by disease status, pts in CR1 had significantly better outcomes than those beyond CR1, with a 1-year OS of 88.6% versus 31.4% (p<0.001). Within the CR1 subgroup, 1200 cGy was associated with the most favorable results, achieving a 1-year OS of 96.2% (95%CI 75.7-99.4), compared to 66.7% in pts receiving 800 and 1000 cGy. In contrast, among pts beyond CR1, TBI dose did not influence survival. These findings suggest that intensification of conditioning with 1200 cGy TBI may benefit pts with ALL in CR1, while no clear advantage is seen in more advanced disease stages. Further studies on larger cohorts are needed to confirm these results.

Multivariate analysis confirmed disease status and TBI dose as independent predictors of OS. Treatment with 1200 cGy was significantly associated with improved survival (HR 0.12, 95%CI: 0.02–0.47; p=0.003), as was undergoing allo-HSCT in CR1 (HR 0.17, 95%CI: 0.05–0.52; p=0.001).

Conclusion This study confirms the central role of TBI-based conditioning in the allo-HSCT setting for a broad range of hematologic malignancies, demonstrating favorable survival outcomes and an acceptable toxicity profile. In the ALL subgroup, our data support the use of 1200 cGy TBI in pts undergoing transplant in first complete remission, where it was associated with excellent survival. Conversely, no specific TBI dose showed a clear benefit in pts beyond CR1, highlighting the need for individualized, risk-adapted strategies in this high-risk population.

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2025
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