Conditioning regimen of 5-day decitabine administration for allogeneic stem cell transplantation in patients with myelodysplastic syndrome and myeloproliterative neoplasms

Abstract Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a potentially curative treatment for patients with myelodysplastic syndromes (MDS) and myelodysplastic/myeloproliferative neoplasms (MDS/MPN). However, post-HSCT relapse remains a major cause of treatment failure. Here, we assessed the efficacy of a new conditioning regimen comprising decitabine (Dec), busulfan (Bu), cyclophosphamide (Cy), fludarabine (Flu), and cytarabine (Ara-c) for allo-HSCT in patients with MDS and MDS/MPN. In total, 48 patients were enrolled, including 44 with MDS and 4 with chronic myelomonocytic leukemia (CMML). Patients received Dec 20 mg/m2/day on days -9 to -5, combined with a Bu/Cy/ Flu/ Ara-c modified preparative regimen. At a median follow-up of 522 (range: 15-1313) days, the overall survival (OS) was 86%, relapse incidence was 12%, and non-relapse mortality was 12%. The incidence of severe acute (grade III/IV) graft-versus-host disease (GVHD) was 23% and that of chronic GVHD was 15%. At 2 years, OS was 74% and 86%, respectively, for MDS patients with high risk and very high risk. Survival was promising in patients with poor-risk mutations, such as TP53 and ASXL1 (88%), and in those with ≥3 gene mutations (79%). Results of immunomonitoring studies revealed that proper natural killer cell cells made essential contributions to these favorable clinical outcomes. Overall, this new regimen was associated with a low relapse rate, low incidence and severity of GVHD, and satisfactory survival for allo-HSCT patients with MDS and MDS/MPN.