The Efficacy of Modified Melphalan and Busulfan-Based Conditioning Regimen for Autologous-HSCT in Low-Risk and Intermediate-Risk AML Patients

Topic: 4. Acute myeloid leukemia - Clinical Background: Treatment options for patients with low-risk and 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 (auto-HSCT) and allogeneic hematopoietic stem cell transplantation (allo-HSCT). Compared with chemotherapy, auto-HSCT 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. Aims: 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 auto-HSCT in low-risk and 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 and intermediate-risk AML patients (non-M3) who achieved CR after one course of induction chemotherapy, followed by 1-3 courses of high-dose cytarabine consolidation chemotherapy, and underwent auto-HSCT from May 2021 to January 2023 (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 16 AML patients, 10 males, 6 females, with median age 40.5 years (ranged 20–52 years). There were 5 of low-risk and 11 of intermediate-risk. The median infused mononuclear cell and CD34+ cell counts were 11.21×108/kg (ranged 1.79–34.68×108/kg) and 2.24×106/kg (ranged 1.05–17.15×106/kg) respectively. Neutrophil and platelet engraftment were achieved in all patients, with a median time of 13 days (ranged 11-27 days) and 34 days (ranged 12-150 days) respectively. On the day of reconstitution, all patients exhibited good responses, including hematologic CR and minimal residual disease (MRD) negativity rates of 100%. 7 (43.8%) patients received maintenance therapy after auto-HSCT, with a median time of 3.5 months (ranged 1–9 months). Azacytidine, venetoclax or geritinib were the main maintenance therapies. With a median follow-up of 192.5 days（ranged 28-648 days）, minimal residual disease (MRD) turned positive in one patient at 6.5 months after auto-HSCT, the remained 15 patients consistently negative. The most common regimen-related toxicity mainly included grade Ⅰ liver damage (37.5%), grade Ⅰ-Ⅱ oral mucositis (37.5%) and grade Ⅰ-Ⅲ diarrhea (87.5%), which were all well tolerated. Summary/Conclusion: The preliminary data demonstrated the efficiency of MCBA conditioning regimen for auto-HSCT in low-risk and intermediate-risk AML patients who achieved CR after one course of induction chemotherapy. The regimen-related toxicity was well tolerated.Keywords: Busulfan-melphalan, Conditioning, Acute myeloid leukemia, Autologous hematopoietic stem cell transplantation