Treosulfan/fludarabine versus thiotepa/busulfan/fludarabine for allogeneic haematopoietic cell transplantation in lymphoma in the post‐transplant cyclophosphamide era: A GETH ‐ TC study

Allogeneic haematopoietic cell transplantation (alloHCT) remains a potentially curative strategy for relapsed or refractory lymphoid malignancies, even in the post-chimeric antigen receptor T-cell and bispecific antibody era. While reduced-intensity conditioning regimens offer lower non-relapse mortality (NRM), relapse rates remain high, and optimal conditioning strategies in the setting of post-transplant cyclophosphamide (PTCy) prophylaxis remain undefined. In this retrospective, international multicentre study, the primary end-point was NRM. We compared treosulfan/fludarabine (Treo/Flu) versus thiotepa/busulfan/fludarabine (TBF) in 178 adults with lymphoid malignancies undergoing first alloHCT with PTCy and peripheral blood grafts. Three-year NRM was 14.0% with Treo/Flu versus 33.0% with TBF. On multivariate analysis, Treo/Flu was associated with significantly lower 3-year NRM (hazard ratio [HR] 0.44; 95% confidence interval [CI], 0.22-0.87; p = 0.018). Conditioning regimen was not independently associated with overall survival (OS) or progression-free survival (PFS), and relapse incidence was similar between regimens. Moderate to severe chronic graft-versus-host disease (GVHD) was higher with Treo/Flu (26.0% vs. 9.9%; HR 2.43; 95% CI, 1.09-5.43; p = 0.03), while GVHD-free/relapse-free survival (GFRS) was comparable. Findings were consistent in a prespecified propensity score-matched sensitivity analysis. These findings support Treo/Flu as a potentially safer reduced-toxicity conditioning option than TBF in the context of PTCy-based GVHD prophylaxis for lymphoid malignancies and warrant prospective validation.