Allogeneic Stem Cell Transplantation after Myeloablative Conditioning with Fludarabine, Thiotepa, and Cyclophosphamide in Relapsed or Refractory Aggressive B-cell and T-cell Lymphomas: Results of the Prospective ASTRAL Study.

While allogeneic stem cell transplantation (alloSCT) remains the only curative option for patients with relapsed T-cell lymphoma, its place in the treatment algorithm of aggressive B-cell lymphoma is changing. This multicentre, prospective, investigator-initiated trial investigated the efficacy and toxicity of a myeloablative conditioning regimen comprising fludarabine, thiotepa, and cyclophosphamide (FTC) prior to alloSCT in patients with relapsed/refractory (r/r) aggressive B-cell or T-cell lymphoma. Among 60 patients, PFS at one and two years was 40% (95% CI 28-52) and 36% (95% CI 24-49), OS was 43% (95% CI 31-56) and 37% (95% CI 25-50), respectively, without significant differences between 42 patients with B-cell and 18 patients with T-cell lymphoma. The primary endpoint of the study defined as 1-year PFS of 50% was not met. The cumulative incidence of progression/relapse at two years was 34% (95% CI 19-49) for B- and 11% (95% CI 0-26) for T-cell patients. Cumulative incidence of NRM was 25% (95% CI 14-36) at day 100 and 35% (95% CI 23-47) at one year. Twelve patients who had failed CAR T-cell therapy (CART) had outcomes comparable to patients without prior CART. In T-cell lymphoma, relapse after alloSCT was notably low, reflecting a strong graft-versus-lymphomaeffect. In B-cell lymphomas, our data suggest that alloSCT can be effective after CART failure, with more than one-third of patients being in remission after two years. These findings support the continued use of alloSCT in patients with aggressive lymphomas. Substantial NRM observed after FTC calls for the continued search of better tolerated conditioning regimens.