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Blood, 15 August 2005, Vol. 106, No. 4, pp. 1154-1163.
Prepublished online as a Blood First Edition Paper on May 3, 2005; DOI 10.1182/blood-2005-01-0178.
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REVIEWS IN TRANSLATIONAL HEMATOLOGY
Drug therapy for acute myeloid leukemia
Martin S. Tallman,
D. Gary Gilliland, and
Jacob M. Rowe
From the Division of Hematology/Oncology, Department of Medicine, Northwestern University Feinberg School of Medicine, Robert H. Lurie Comprehensive Cancer Center, Chicago IL; the Division of Hematology/Oncology, Brigham and Women's Hospital, Howard Hughes Medical Institute, Harvard Medical School, Boston, MA; and the Department of Hematology and Bone Marrow Transplantation, Rambam Medical Center, Technion Israel Institute of Technology, Haifa, Israel.
Abstract
Although improvement in outcomes has occurred in younger adults with acute myeloid leukemia (AML) during the past 4 decades, progress in older adults has been much less conspicuous, if at all. Approximately 50% to 75% of adults with AML achieve complete remission (CR) with cytarabine and an anthracycline such as daunorubicin or idarubicin or the anthracenedione mitoxantrone. However, only approximately 20% to 30% of the patients enjoy long-term disease survival. Various postremission strategies have been explored to eliminate minimal residual disease. The optimal dose, schedule, and number of cycles of postremission chemotherapy for most patients are not known. A variety of prognostic factors can predict outcome and include the karyotype of the leukemic cells and the presence of transmembrane transporter proteins, which extrude certain chemotherapy agents from the cell and confer multidrug resistance and mutations in or over expressions of specific genes such as WT1, CEBPA, BAX and the ratio of BCL2 to BAX, BAALC, EVI1, KIT, and FLT3. Most recently, insights into the molecular pathogenesis of AML have led to the development of more specific targeted agents and have ushered in an exciting new era of antileukemia therapy. Such agents include the immunoconjugate gemtuzumab ozogamicin, multidrug resistance inhibitors, farnesyl transferase inhibitors, histone deacetylase and proteosome inhibitors, antiangiogenesis agents, Fms-like tyrosine kinase 3 (FLT3) inhibitors, and apoptosis inhibitors.
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