Hypomethylating agents for patients with myelodysplastic syndromes prior to hematopoietic stem cell transplantation: a systematic review and meta-analysis

The use of hypomethylating agents (HMAs) prior to hematopoietic stem cell transplantation (HSCT) in patients with myelodysplastic syndromes (MDS) was still controversial. Therefore, we sought to evaluate the impact of hypomethylation therapy before HSCT, with a special focus on long-term outcome. Databases, including PubMed, Embase Ovid, and the Cochrane Library, were searched for studies published up to 4 November 2018. Overall survival (OS) was selected as the primary endpoint, and relapse-free survival (RFS) was the secondary endpoint. A total of 6 cohort studies were included in the final meta-analysis. Our results showed that the outcome of patients with MDS using HMAs prior to HSCT was similar compared to those who did not with OS (HR = 0.81, 95% CI 0.63-1.04, p = 0.104) and RFS (HR = 0.96, 95% CI 0.72-1.26, p = 0.749). The pooled HR of OS in the older patients was 0.75 (95% CI 0.57-0.98, p = 0.035). No evidence showed that patients with MDS will benefit from using HMAs before HSCT in long-term survival (OS and RFS) compared to chemotherapy or best supportive therapy, though older patients were more likely to benefit from pre-transplantation HMAs treatment in terms of long-term survival. Our conclusions await further validation by prospective studies with larger sample size and randomized-controlled design. Particularly, to clarify whether the older patients who are candidates for HSCT could benefit from this bridging treatment will be of great interest.