Prognostic factors in elderly patients with AML and the implications for treatment.

The outcome of older patients with acute myeloid leukemia (AML) has not improved in the last three decades. These patients are more likely to have comorbid illness, poor performance status, and impaired organ function. These clinical features limit their ability to tolerate intensive cytotoxic chemotherapy and result in greater early mortality. The AML seen in elderly patients is also more likely to have evolved from a prior hematologic disorder, and the leukemic blasts are more likely to have poor-risk structural and numeric cytogenetic abnormalities and expression of multidrug resistance protein (MDR1). These blast features have been associated with greater resistance to therapy. Attempts to improve outcome have generally been unsuccessful. Priming of leukemic blasts with granulocyte colony-stimulating factors during cytarabine therapy, granulocyte colony-stimulating factor support to speed neutrophil recovery following induction therapy, inhibition of the MDR1 p-glycoprotein efflux pump, the use of alternative anthracyclines, and the addition of high-dose cytarabine have all been investigated in the last three decades. Further manipulation of standard cytotoxic chemotherapy alone is unlikely to improve the outcome for the majority of patients with AML. Incorporation of molecularly targeted therapies may prove to be less toxic and/or more efficacious. However, patient selection for clinical trials will continue to confound the interpretation of treatment outcomes on clinical trials of older patients with AML.