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

Summary 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.