Thiotepa, busulfan and fludarabine conditioning regimen for adult patients with lymphoid malignancies undergoing allogeneic stem cell transplantation: a study on behalf of GETH-TC

Abstract

The efficacy of thiotepa, busulfan, and fludarabine (TBF) conditioning in lymphoproliferative disorders remains under investigation. We analyzed outcomes in 157 patients with lymphoid malignancies who underwent a first allogeneic hematopoietic stem cell transplantation (alloHCT) following TBF conditioning. Non-relapse mortality (NRM) at 3 years reached 32%, while the cumulative incidence of relapse (CIR) was 19%. At 3 years, progression-free survival (PFS), overall survival (OS), and graft-versus-host disease (GVHD)-free/relapse-free survival (GRFS) were 49.7%, 58.0%, and 44.2%, respectively. The cumulative incidences of grade III-IV acute GVHD at 100 days and moderate-to-severe chronic GVHD at 3 years were 8.3% and 12%, respectively. On multivariate analysis, patients receiving high-dose thiotepa (10 mg/kg) demonstrated a significantly lower CIR than those receiving low-dose thiotepa (5 mg/kg) (HR 2.95 [95% CI, 1.37-6.33], p = 0.006), with no significant effect on NRM. Female donor-to-male recipient transplants were associated with reduced OS (HR 2.0 [95% CI, 1.17-3.44], p = 0.011) and increased NRM (HR 2.43 [95% CI, 1.29-4.35], p = 0.005). TBF conditioning demonstrated a substantial anti-tumor effect, counterbalanced by elevated toxicity. Careful patient selection and effective toxicity mitigation strategies are essential to ensure individuals can tolerate TBF's toxicity while maximizing its benefits in disease control.