Hypomethylating agents as maintenance therapy following allogeneic hematopoietic cell transplantation for myeloid malignancies

With improved safety of the procedure, disease recurrence is now the leading cause of treatment failure when allogeneic hematopoietic cell transplantation is used to treat acute myeloid leukemia (AML). Recent studies suggest that maintenance therapy with hypomethylating agents after standard induction and consolidation chemotherapy prolongs disease-free and possibly overall survival in older patients with AML. While these results argue that hypomethylating agents should likewise prolong remission duration if used as maintenance after allogeneic transplantation for AML, trials to date have failed to show a benefit. This failure may be due, in part, to difficulties in administering the drugs in this setting, and in part, because of an inability to identify those patients most likely to benefit. Realizing the full potential of hypomethylating agents in the management of patients with AML will likely require both improved drug formulations as well as an increased understanding of their mechanism of action in the complex postallogeneic transplant environment.