Thiotepa-Based Regimens Are Valid Alternatives to Total Body Irradiation-Based Reduced-Intensity Conditioning Regimens in Patients with Acute Lymphoblastic Leukemia: A Retrospective Study on Behalf of the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation

Abstract

Total body irradiation (TBI) at myeloablative doses is superior to chemotherapy-based regimens in young patients with acute lymphoblastic leukemia (ALL) undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT). However, in elderly and unfit patients, in whom reduced-intensity conditioning (RIC) regimens are preferred, whether a TBI-based or a chemotherapy-based approach is better is unexplored. Thiotepa can be used as part of ALL conditioning regimens. The current study aimed to compare transplantation outcomes after RIC with TBI-based or thiotepa-based regimens in patients with ALL. The study cohort comprised patients aged ≥40 years undergoing allo-HSCT for ALL in first complete remission between 2000 and 2020 who received an RIC regimen containing either TBI (4 to 6 Gy) or thiotepa. We identified a total of 265 patients, including 117 who received a TBI-based RIC regimen and 148 who received a thiotepa-based RIC regimen. Univariate analysis revealed no significant differences in the following transplantation outcomes for TBI versus thiotepa: relapse, 23% versus 28% (P = .24); nonrelapse mortality, 20% versus 26% (P = .61); leukemia-free survival, 57% versus 46% (P = .12); overall survival, 67% versus 56% (P = .18); graft-versus-host disease (GVHD]/relapse-free survival, 45% versus 38% (P = .21); grade II-IV acute GVHD, 30% in both groups (P = .84); grade III-IV acute GVHD, 9% versus 10% (P = .89). The sole exception was the incidence of chronic GVHD, which was higher in the recipients of TBI-based regimens (43% versus 29%; P = .03). However, multivariate analysis revealed no differences in transplantation outcomes between the 2 groups. In patients aged ≥40 years receiving RIC, use of a thiotepa-based regimen may represent a valid alternative to TBI-based regimens, as no differences were observed in the main transplantation outcomes.

Keywords: Acute lymphoblastic leukemia; Thiotepa; Total body irradiation; Transplantation.