Efficacy of Modified Melphalan and Busulfan-Based Conditioning Regimen for ASCT in Patients with Low- or Intermediate-Risk AML
Authors: Chen Shulian , Zhang Xiaoyu , He Yi , Feng Sizhou , Han Mingzhe , Zhao Xingli , Bai Jie , Li Lijuan , Zhang Zhihua , Ying Wang , Wang Jianxiang , Zhai Weihua , Jiang Erlie 
Published: December 2024

Backgroud:Treatment options for patients with low-risk or intermediate-risk acute myeloid leukemia (AML) patients (non-M3) who achieved complete response (CR) after one course of induction chemotherapy include consolidation chemotherapy, autologous hematopoietic stem cell transplantation (ASCT) and allogeneic hematopoietic stem cell transplantation (allo-HSCT). Compared with chemotherapy, ASCT could significantly reduce relapse rate, as was associated with significantly lower transplant-related mortality compared with allo-HSCT, but relapse rate was relatively high. The selection of conditioning regimen was crucial to reduce relapse rate after transplantation. In this study, we made refinements in the conditioning regimen with two alkylating agents, namely MCBA (the combination of melphalan, cladribine, busulfan, and cytarabine). We aim to investigate the efficacy of MCBA conditioning regimen for ASCT in low-risk or intermediate-risk AML patients who achieved CR after one course of induction chemotherapy.
Methods:This prospective multi-center clinical trial was conducted in 5 tertiary hospitals in China, and enrolled low-risk or intermediate-risk AML patients (non-M3) who achieved CR after one course of induction chemotherapy, followed by 1-2 courses of high-dose cytarabine consolidation chemotherapy, and underwent ASCT from May 2021 to January 2024 (ChiCTR Registration ID: ChiCTR2200056167). The MCBA conditioning regimen consists of melphalan 70mg/m2/d, day -6~-5, cladribine 5mg/m2/d, day -4~-2, busulfan 3.2mg/kg/d, day -8~-7, cytarabine 2g/m2/d, day -4~-2.
Results:This study included a total 26 AML patients, 18 males, 8 females, with median age 43 years (ranged 20-59 years). According to the 2017 European LeukemiaNet (ELN) criteria, there were 9 low-risk and 17 intermediate-risk patients. The median counts of infused mononuclear cells and CD34+ cells were 11.94 × 108 (range: 1.79 ×108-34.68 × 108) and 2.36 × 106/kg (range: 1.05 × 106-17.15 × 106), respectively. Neutrophil and platelet engraftment were achieved in all patients, with a median time of 12 days (range: 10-27) and 31 days (range: 12-150) respectively. On the day of reconstitution, all patients exhibited good responses, including hematologic CR and minimal residual disease (MRD) negativity rates of 100%. 18 (69.2%) patients received maintenance therapy after ASCT, with a median time of 3.25 months (range: 1-9 months). Azacytidine, venetoclax, decitabine or gilteritinib were the main maintenance therapies. Following a median follow-up of 511 days (range, 72-1048 days), the 1-year overall survival (OS) and disease-free survival (DFS) rates were 90.6% ± 6.3% and 72.0% ± 9.8%, respectively. Additionally, seven patients were reclassified as adverse risk cases based on the 2022 ELN criteria, three of whom experienced a relapse. In the univariate analysis, the absence of maintenance therapy post-ASCT and the adverse risk category based on the 2022 ELN criteria were significantly associated with worse OS.
Conclusion:The preliminary data demonstrated the efficiency of MCBA conditioning regimen for ASCT in low-risk or intermediate-risk AML patients who achieved CR after one course of induction chemotherapy. Immediate initiation of maintenance therapy post-ASCT is recommended to enhance OS. Utilizing the 2022 ELN criteria holds promise for better patient screening and improved autologous transplantation efficacy in the future.