The modified melphalan and busulfan-based regimen combined with maintenance therapy improved the survival of patients with refractory/relapsed AML after allogeneic transplantation: middle-term outcome of a multicenter trial.

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) maintains the only promising curative option for patients with refractory/relapsed (R/R) acute myeloid leukemia (AML). However, the long-term survival results are suboptimal. Optimization of the conditioning regimen aims to eradicate leukemia blasts and reduce early relapse. Here we reported of the preliminary result of the prospective multicenter single arm study to evaluate the efficacy and safety of a modified dual alkylator-conditioning regimen, MCBC (regimen including Melphalan, Cladribine, Busulfan and Cyclophosphamide) (ChiCTR Registration ID: ChiCTR2000029936). This trial enrolled 56 patients from July 2020 to January 2022. With a median follow-up of 854 days (range 48 to 1343), the 2-year overall survival (OS) and relapse-free survival (RFS) were 60.7 ± 6.5% (95% CI 47.5-73.9) and 57.1 ± 6.6% (95% CI 43.8-70.5), respectively, the estimated 3-year OS and RFS rates were 58.9 ± 6.6% (95% CI 45.6-72.2) and 55.4 ± 6.6% (95% CI 41.9-68.8), respectively. A total of 19 patients experienced relapse, the 2-year cumulative incidence relapse (CIR) rate was 34.2 ± 6.6% (95% CI 19.5-44.8), the estimated 3-year CIR rate was 36.3 ± 6.7% (95% CI 21.1-46.7). Six patients died of severe infection or graft-versus-host disease (GVHD). The non-relapse mortality (NRM) rate was 11.8 ± 4.5% (95% CI 2.4-19.1). Mucositis was the main reported regimen-related toxicity, and it was well controlled. Subgroup analyses illustrated that blasts count ≥ 20% before HSCT and the absence of maintenance treatment after HSCT were poor predictors. Our study confirmed the excellent anti-leukemia activity and acceptable toxicity of the MCBC conditioning regimen in R/R AML. Opportune maintenance treatment after HSCT led to significantly improved OS and RFS.