DAC-Based Conditioning Regimen Versus Standard Conditioning Regimen for Myelodysplastic Syndrome

Background: Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is the only curable way for Myelodysplastic syndromes (MDS). There are still some patients have a poor prognosis after transplantation, including high frequency of relapse, poor response to salvage therapy and short overall survival. This study aimed to investigate whether DAC-based conditioning regimen improves survival compared with standard conditioning regimen for MDS patients.

Methods: One hundred and forty-seven patients with MDS were enrolled in this prospective multicenter study. Eligible patients were randomly assigned to DAC-based conditioning regimen or standard conditioning regimen before allo-HSCT in a 1:1 ratio. Patients in standard conditioning regimen group received busulfan (3.2 mg/kg/day on days -7 to -4) and cyclophosphamide (60 mg/kg/day on days -3 and -2) for allo-HSCT. DAC-based conditioning regimen comprising decitabine (20 mg/m2/day on days -14 to -10), busulfan (3.2 mg/kg/day on days -7 to -4), and cyclophosphamide (60 mg/kg/day on days -3 and -2). The primary endpoint was overall survival after randomization. This trial was registered at ClinicalTrials.gov (NCT 02744742).

Results: The median time to neutrophil reconstitution was 12 (8-35) days and 12 (9-34) days in the DAC-based conditioning regimen and standard conditioning regimen groups, respectively (P=0.577). The median platelet reconstitution time was 14 (9-68) days and 14 (10-90) days in the DAC-based conditioning regimen and standard conditioning regimen groups, respectively (P=0.017). Median follow-up was 419 (range, 1-1697) days. Overall survival was longer for DAC-based conditioning regimen than for standard conditioning regimen (P=0.034). 3-year OS was 62% (95%CI 46-98%) in the DAC-based conditioning regimen group and 43% (95%CI 29-64%) in the standard conditioning regimen group. 3-year GRFS was 50% (95%CI 34-74%) and 39% (95%CI 26-58%) in the DAC-based conditioning regimen and standard conditioning regimen groups, respectively (P=0.183). 3-year relapse incidence was 12% (95%CI 3-11%) and 25% (95%CI 11-29%) in the DAC-based conditioning regimen and standard conditioning regimen groups, respectively (P=0.209). There were no significant differences in the incidence of graft-versus-host disease, the incidence of infections, and other adverse events between two groups. The treatment-related mortality rate at 3 years was 30% (95% CI 13-34%) and 45% (95% CI 30-67%) in DAC conditioning and standard conditioning group, respectively(P=0.061). Stratified and multivariable logistic regression analysis showed that DAC-based conditioning regimen is an independent favorable factor for OS for very poor risk patients (HR 0.42, 95% CI, 0.19-0.93, P= 0.03) and a protective factor for CIR for patients with high-risk karyotype(HR 0.56, 95% CI, 0.18-1.36, P=0.04).

Conclusions: Our study demonstrates that DAC-based conditioning regimen had a survival benefit versus standard conditioning regimen in MDS patients, especially for very poor risk cases according to IPSS-R. DAC conditioning also has lower relapse for patients with high-risk karyotypes, shorter platelet reconstitution and tolerable toxicity. These results may contribute to improving the management of MDS patients for better survival.