Thiotepa and busulfan combined with cyclophosphamide conditioning regimen plus maintenance therapy improved the disease-free survival of patients with relapsed/refractory haematologic malignancies after undergoing allogeneic transplantation

Abstract Objective: Conditioning regimens are critical for patients with relapsed/refractory (R/R) malignant haematologic diseases. Thiotepa, an alkylating agent with excellent cytotoxicity and blood‒brain barrier permeability, has been widely used in conditioning regimens for lymphoma and has recently been used in patients with acute leukaemia with central nervous system involvement. Methods: The aim of this retrospective study was to observe the efficacy and safety of a conditioning regimen comprising thiotepa, busulfan, and cyclophosphamide (TBC) for allogeneic haematopoietic stem cell transplantation (allo-HSCT) in patients with R/R haematologic diseases. The TBC regimen consists of thiotepa 5 mg/kg/day for 2 days, busulfan 3.2mg/kg/d for 2 days, cyclophosphamide 40mg/kg/d for 2 days. Rabbit ATG was added in haploid-identical and unrelated-matched donor transplantation. Results: Between July 2022 and December 2023, 27 patients were selected. Among them, 23 patients (85.2%) were diagnosed with lymphoma and acute leukemia. Central nervous system leukemia or extramedullary infiltration was present in 7 patients of acute leukemia. 6 patients recurred after autologous transplantation and 1 patient recurred after allo-HSCT. 4 patients had received chimeric antigen receptor T-cell (CAR-T cell) therapy before transplantation due to disease recurrence or persistent nonremission. With a median follow-up of 609 (243-954) days, the 1-year and estimated 2-year overall survival (OS) rates were 85.2% ± 6.8% and 76.5% ± 8.5%, respectively. The 1-year and estimated 2-year disease-free survival (DFS) rates were 81.5% ± 7.5% and 62.8% ± 12.2%, respectively. Six patients experienced relapse, and the 1-year and estimated 2-year cumulative incidence of relapse (CIR) rates were 14.8% ± 6.8% and 31.0% ± 12.6%, respectively. Two patients died from graft-versus-host disease (GVHD) or infection. The 1-year and estimated 2-year nonrelapse mortality (NRM) rates were 4.2% ± 4.1% and 8.5% ± 5.8%, respectively. 14 (51.9%) patients received maintenance therapy after allo-HSCT. Regimen-related toxicities were mostly well tolerated. Multivariate analysis revealed that failure to achieve first complete remission (CR1) before HSCT and previous treatment with CAR-T cell were predictors of poor DFS. Conclusion: This study suggests that the TBC conditioning regimen may be a promising option for patients with R/R haematologic diseases undergoing allo-HSCT.