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.

Disclosures

No relevant conflicts of interest to declare.

Author notes

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Asterisk with author names denotes non-ASH members.

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