Clinical outcome after failure of hypomethylating therapy for myelodysplastic syndrome.

Around half of patients with myelodysplastic syndrome (MDS) fail to respond to hypomethylating therapy (HMT) and most responders progress within 2 yr. Retrospective studies report poor outcomes after HMT failure. Here, we analyzed the outcomes of patients suffering HMT failure. Of 149 patients with MDS treated with either azacitidine or decitabine, 91 who experienced HMT failure were included in the study. Median overall survival (OS) was 12.1 months: 16.2 months for lower-risk MDS and 9.3 months for higher-risk MDS. Disease status and progression to acute myeloid leukemia (AML) at the time of HMT failure were independent prognostic factors for OS. Fifty-four patients received one or more treatment modalities, and 23 received allogeneic hematopoietic cell transplantation (HCT). The objective response to non-transplant treatments was poor (11-17%), whereas 17 transplanted patients showed a complete response. OS probability at 2 yr post-HCT was 60.9%: 78.6% for patients receiving HCT during MDS and 33.3% for those receiving HCT after developing AML. In conclusion, the clinical outcome of patients after HMT failure was poor. Long-term disease-free survival was observed in approximately 50% of patients who received allogeneic HCT. Therefore, allogeneic HCT should be performed early in appropriate patients, and particularly before progression to AML.