Addition of thiotepa to total body irradiation-based conditioning in allogeneic hematopoietic stem cell transplantation for relapsed/refractory acute leukemia and lymphoma: a propensity score-matched retrospective study

Background: Relapsed/refractory (R/R) acute leukemia (AL) carries a poor prognosis, with allogeneic hematopoietic stem cell transplantation (allo-HSCT) the primary curative option. Total body irradiation (TBI)-based conditioning is a cornerstone, but optimizing intensity remains challenging. Thiotepa, a bifunctional alkylating agent, may enhance disease control when added to TBI, but data in R/R AL are lacking. Methods: This single-center retrospective study (2020–2025) included R/R AL and lymphoma patients receiving TBI-based conditioning with (TBI + TT) or without (TBI) thiotepa. Propensity score matching (1:2, caliper = 0.2) used 9 covariates. Primary endpoints were overall survival (OS) and disease-free survival (DFS). Secondary endpoints included relapse, non-relapse mortality (NRM), engraftment, GVHD, CMV infection, and mucositis. Kaplan-Meier, Fine-Gray competing risk, and inverse probability of treatment weighting (IPTW) analyses were employed. Results: After matching, 48 TBI + TT and 86 TBI patients were analyzed. OS (HR = 0.901, 95% CI 0.569–1.425, P = 0.655) and DFS (HR = 0.809, 95% CI 0.504–1.299, P = 0.380) were comparable. The 1-year relapse cumulative incidence was lower with TBI + TT (6.7% vs. 17.8%, Gray’s P = 0.035; multivariable sHR = 0.280, 95% CI 0.083–0.942, P = 0.040), though hypothesis-generating given only 3 relapse events. NRM was comparable (Gray’s P = 0.374). Mucositis was significantly higher with TBI + TT (81.2% vs. 64.0%, P = 0.049). IPTW confirmed comparable OS ( P = 0.690) and DFS ( P = 0.975). Conclusion: Adding thiotepa to TBI-based conditioning for R/R AL is associated with lower relapse incidence without compromising OS, DFS, engraftment, or GVHD, at the cost of increased mucosal toxicity. The relapse finding requires cautious interpretation and prospective validation.