Approach to patients with primary refractory acute myeloid leukemia

Despite successful remission induction in 60-80% of patients with newly diagnosed acute myeloid leukemia, there remain a significant number of patients who exhibit primary refractory disease. Here we examine the data for predicting likelihood of having refractory disease, available therapeutic options, and how to decide the appropriate treatment option for a patient.

Recently identified recurrent molecular mutations and early response to chemotherapy as determined by kinetics of peripheral blast clearance or nadir bone marrow biopsy assist in determining the likelihood of primary refractory disease. Newer cytotoxic agents, used as salvage chemotherapy, or in novel conditioning regimens for hematopoietic stem cell transplant may represent improvement over prior regimens. FMS-like tyrosine kinase 3 gene inhibitors and other targeted therapies currently in clinical trials show promise for select patients. Hypomethylating agents provide benefit to patients who are not candidates for other therapies.

Recent advances in understanding the pathogenesis of acute myeloid leukemia have not yet translated to a significantly improved outlook for patients with refractory disease. While there are several therapeutic options, outcomes remain poor and further studies are needed to identify and validate novel approaches.