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.
Li et al. (Fri,) studied this question.