How to manage high-risk acute myeloid leukemia

There are three general options for management of acute myeloid leukemia (AML): standard therapy, investigational therapy or no treatment other than supportive care. Given AML's natural history and the uncertain results inherent in investigational therapy, most patients intuitively prefer standard therapy, by which is usually meant 3+7 or low-dose cytarabine. However, this preference assumes results with standard therapy are 'satisfactory'. Results with standard therapy of AML are, however, so variable that it is difficult to speak of a single result. Therefore, I review prognostic factors with standard therapy to permit physicians to better inform patients of the likely outcome with such therapy, realizing that the same data might prompt one patient/physician to prefer standard therapy and another investigational therapy under the assumption that although plausibly worse than standard the latter cannot be that much worse. Because even in patients aged >75 years, the principal cause of therapeutic failure is resistance to therapy not treatment-related mortality, I emphasize factors associated with resistance, principally a 'monosomal karyotype' and various molecular markers and extend the European Leukemia Net prognostic system. I also stress the value of waiting for cytogenetic and molecular results before beginning induction therapy and review various investigational options.