Acute myeloid leukemia in adults: where do we go from here?

Although 30-40% of newly diagnosed younger patients with acute myeloid leukemia (AML) can be cured with current approaches, the overall outcome has not improved in recent years. In addition, the outcome in adults > 60 years of age remains dismal with < 10% of patients achieving remission remaining alive and disease free. Results of randomized clinical trials in AML evaluating high-dose cytosine arabinoside, changes in anthracyclines, the use of hematopoietic growth factors, stem cell transplantation in first remission, and modulation of the multidrug resistance phenotype are reviewed. New directions for clinical trials include the use of nonmyeloablative allogeneic stem cell transplantation as a form of "immunotherapy", refinements in autologous stem cell transplantation, and possibly manipulations of neoangiogenesis in the bone marrow and incorporation of newer agents, such as gemtuzumab zogamicin into treatment regimens. It is likely, however, that future advances will be a consequence of a better understanding of the biology of leukemic stem cells, and issues related to such studies are discussed.