Fludarabine-treosulfan compared with fludarabine-melphalan conditioning for adult acute lymphoblastic leukemia

The optimal conditioning strategy for adult acute lymphoblastic leukemia (ALL) undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains undefined, particularly in older or medically vulnerable patients. Reduced-intensity regimens lower non-relapse mortality (NRM) but increase relapse risk. Treosulfan-based conditioning may represent an intermediate-intensity alternative, though comparative data in ALL are limited. We conducted a retrospective registry-based study including 967 adult patients with B- or T-ALL undergoing first allo-HSCT in complete remission (CR1 or CR2+) between 2012 and 2024. Patients received fludarabine-melphalan (Flu/Mel, n=778) or fludarabine-treosulfan (Flu/Treo, n=189). The primary endpoint was leukemia-free survival (LFS); secondary endpoints included overall survival (OS), relapse incidence (RI), NRM, and graft-versus-host disease. Outcomes were censored at 2 years. Multivariable Cox models adjusted for clinical and transplant-related variables. Flu/Treo recipients were transplanted more recently, more often received haploidentical donors, and were more frequently beyond CR1. Median age was slightly higher in the Flu/Treo group. At 2 years, OS was 65.6% with Flu/Treo versus 60.5% with Flu/Mel, and LFS 57.2% versus 49.7%. RI was lower with Flu/Treo (24.1% vs 31.5%), while NRM was similar (18.6% vs 18.8%). In multivariable analysis, conditioning regimen did not significantly affect OS or LFS, but Flu/Treo was associated with reduced RI (HR 0.61, p=0.011) without differences in NRM. Similar results were observed in B-ALL, while no differences emerged in T-ALL. Flu/Treo was associated with a lower relapse incidence compared with Flu/Mel, particularly in patients with B-cell ALL, without an increase in non-relapse mortality. However, no significant differences were observed in overall survival or leukemia-free survival. These findings support Flu/Treo as a reasonable alternative conditioning platform for adult patients with ALL and warrant prospective validation.