Acute Myeloid Leukemia Following Myelodysplastic Syndrome and Failure of Therapy with Hypomethylating Agents: An Emerging Entity With a Poor Prognosis

摘要

We assessed outcome of 63 patients with acute myeloid leukemia (AML) arising from myelodysplastic syndrome (MDS) failing hypomethylating agents (HMA). Median age was 63 years. All 63 patients received at least 1 salvage regimen for AML and 35 patients (55%) received 2 or more. Of the 31 patients (49%) who received high-dose cytarabine (HDAC) at first relapse, 2 (6%) achieved complete remission (CR) and 4 (13%) CR with incomplete platelet recovery (CRp) for an overall response rate (ORR) of 19%. Of the 32 patients (51%) who received other treatments including investigational agents, 4 (12%) achieved CR and 4 (12%) CRp, for an ORR of 24%. Median response duration was 20 weeks. With a median follow up of 42 months from AML diagnosis, median survival was similar between the 2 groups (21 weeks). The 1- and 2-year survival rates were 19% and 8%, respectively. Multivariate analysis identified low albumin, HDAC treatment, and platelet count <50×10⁹/L as independent adverse factors for CR, and platelet count <50×10⁹/L and age>65 years as independent adverse factors for survival. In conclusion, outcome of AML following MDS post HMA failure is poor, and not improved with HDAC. Novel therapies directed towards this emerging entity are urgently needed.