Effect of Two Conditionings on Relapse in Myelodysplastic Syndrome and Secondary Acute Myeloid Leukemia Undergoing Allogeneic Hematopoietic Cell Transplantation

Background The relapse rate remains high in patients with myelodysplastic syndrome (MDS)-refractory anemia with excess blasts (RAEB) and secondary acute myeloid leukemia evolving from MDS (sAML) undergoing allogeneic hematopoietic cell transplantation (allo-HCT). We investigated whether the addition of granulocyte colony-stimulating factor (G-CSF) and decitabine to busulfan plus cyclophosphamide (BuCy) conditioning would reduce relapse in this population.

Methods We did an open-label, randomised phase 3 trial at six hospitals in China. Eligible patients (aged 14-65 years) had a diagnosis of MDS-RAEB or sAML, were willing to undergo allo-HCT, and had an Eastern Cooperative Oncology Group performance status of 0-2 and HCT-comorbidity index of 0-2. Patients were randomly assigned 1:1 to receive G-CSF and decitabine plus BuCy (G-DAC-BuCy) or BuCy conditioning. Randomisation was done with permuted blocks (block size four) and implemented through an interactive web-based randomisation system. The primary endpoint was the 2-year cumulative incidence of relapse (CIR) in the intention-to-treat population. This trial is registered with ClinicalTrials.gov, NCT02744742.

Findings Between April 18, 2016 and September 30, 2019, 202 patients were enrolled and randomly assigned to receive G-DAC-BuCy (n=101) or BuCy conditioning (n=101). Median follow-up was 32.4 (range, 1.0-64.5) months after randomization. The 2-year CIR was 10.9% (95% CI: 5.8-17.9%) and 24.8% (16.8-33.5%) in the G-DAC-BuCy and BuCy groups (HR=0.387, 95% CI: 0.190-0.786; P=0.011). Within 100 days post-transplantation, the most common grade 3-4 adverse effects (AEs) in the G-DAC-BuCy and BuCy groups were infections (34 [33.7%] and 32 [31.7%]), acute graft-versus-host disease (30 [29.7%] and 30 [29.7%]), and gastrointestinal toxicity (28 [27.7%] and 29 [28.7%]). Eleven patients in the G-DAC-BuCy and 13 in the BuCy group died of AEs.

Interpretation G-DAC-BuCy conditioning can prevent relapse compared with BuCy conditioning and is well tolerated, suggesting its potential to become a standard conditioning in patients with MDS-RAEB and sAML undergoing allo-HCT.

No relevant conflicts of interest to declare.