Maintenance therapy with low‐dose azacitidine after allogeneic hematopoietic stem cell transplantation for recurrent acute myelogenous leukemia or myelodysplastic syndrome

BACKGROUND: Recurrence is a major cause of treatment failure after allogeneic transplantation for acute myelogenous leukemia (AML) and myelodysplastic syndrome (MDS), and treatment options are very limited. Azacitidine is a DNA methyltransferase inhibitor with activity in myeloid disease. The authors hypothesized that low‐dose azacitidine administered after transplant would reduce recurrence rates, and conducted a study to determine a safe dose/schedule combination. METHODS: Forty‐five high‐risk patients were treated. Median age was 60 years; median number of comorbidities was 3; 67% were not in remission. By using a Bayesian adaptive method to determine the best dose/schedule combination based on time to toxicity, the authors investigated combinations of 5 daily azacitidine doses, 8, 16, 24, 32, and 40 mg/m2, and 4 schedules: 1, 2, 3, or 4 cycles, each with 5 days of drug and 25 days of rest. Cycle 1 started on Day +40. RESULTS: Reversible thrombocytopenia was the dose‐limiting toxicity. The optimal combination was 32 mg/m2 given for 4 cycles. Median follow‐up was 20.5 months. One‐year event‐free and overall survival were 58% and 77%, justifying further studies to estimate long‐term clinical benefit. No dose significantly affected DNA global methylation. CONCLUSIONS: Azacitidine at 32 mg/m2 given for 5 days is safe and can be administered after allogeneic transplant for at least 4 cycles to heavily pretreated AML/MDS patients. The trial also suggested that this treatment may prolong event‐free and overall survival, and that more cycles may be associated with greater benefit. Cancer 2010. © 2010 American Cancer Society. Azacitidine may decrease the disease recurrence rate after allogeneic transplants for advanced acute myelogenous leukemia or myelodysplastic syndrome. The authors determined that the maximum tolerated dose is 32 mg/m2 for 5 days, in monthly cycles.