3710 - Outcomes and Toxicities of Total Body Irradiation-Based Conditioning for B-ALL in a Predominantly Hispanic Patient Population Undergoing Hematopoietic Stem Cell Transplantation: A Ten-Year Experience from an NCI-Designated Comprehensive Cancer Center

Purpose/Objective(s): Total body irradiation (TBI) is a key component of myeloablative conditioning for patients with B-cell acute lymphoblastic leukemia (B-ALL) undergoing hematopoietic stem cell transplantation (HSCT). While TBI-based conditioning has demonstrated better survival and lower relapse rates compared to chemotherapy-based regimens alone, data on TBI-associated toxicities remain limited. This study aims to evaluate oncologic outcomes and toxicity profiles for this patient population.

Materials/Methods: We retrospectively analyzed patients with B-ALL who underwent TBI-based conditioning between January 2015 and January 2025 at a single institution. Evaluated endpoints included overall survival (OS), disease-free survival (DFS), graft relapse-free survival (GRFS), and non-relapse mortality (NRM). Cumulative incidence of relapse (CIR) and acute (grade 3-4) and chronic (moderate to severe) graft-versus-host disease (GVHD) were calculated with death as a competing risk. Renal, pulmonary, and cardiac metrics were also assessed.

Results: 97 patients (45.4% female) with a median age of 40 years (range 28-52) were included. Ethnicity breakdown: 77.4% Hispanic, 17.5% White, 5.1% Asian. Disease: 96.9% B-type ALL, 3.1% mixed-type ALL. Philadelphia chromosome (Ph) status: 37.5% Ph+, 31.9% Ph-like, 30.6% Ph-. Donors: 39.4% haploidentical, 30.9% matched sibling, 23.4% matched unrelated, 6.3% mismatched unrelated. TBI dose was 12 Gy in 6 fractions BID (n=96) and 8 Gy in 4 fractions BID (n=1). Median follow-up time was 2.5 years. 1-year OS/DFS/CIR/GRFS were 94%/ 87%/ 9%/ 53%, respectively; 2-year outcomes were 91%/ 80%/ 15%/ 45%. 100-day NRM, aGVHD, and 1-year cGVHD were 1%, 33%, and 62%. Of the 10 deceased patients, 5 had respiratory failure with pulmonary GVHD (mean lung doses: R 829 cGy, L 762 cGy), and 2 had possible pulmonary GVHD. Renal, pulmonary, and cardiac function tests are in Table 1. Post-treatment studies were more frequent in symptomatic patients.

Conclusion: TBI-based conditioning for B-ALL patients undergoing HSCT at this single center showed superior survival and lower relapse rates than reported literature. However, higher rates of acute and chronic GVHD were noted, likely due to the high use of haploidentical donors. While renal, pulmonary, and cardiac function was preserved in most patients, minimizing TBI-related pulmonary complications may reduce mortality. Larger cohort studies with prognostic stratification are warranted to further refine toxicity management, optimize the therapeutic ratio of TBI, and ultimately improve oncologic outcomes.