Strategies in the treatment of acute myelogenous leukemia.
The current treatment of acute myelogenous leukemia is far from satisfactory despite some recent advances. This review focuses on current strategies designed to improve treatment outcome. With advances in molecular biology, the definition of a complete remission should be redefined as a molecular remission where any abnormal gene rearrangement has disappeared or a clonal remission with morphologic characteristics of a complete remission, but with detectable genetics or molecular abnormalities. Abnormal gene rearrangements permit the detection of minimal residual disease, the significance of which remains to be determined. New drug development remains an important area of research and several new drugs are active in acute myelogenous leukemia. These include etoposide, idarubicin, mitoxantrone and carboplatin. Various combinations are undergoing clinical trials. Prognostic factors which predict for outcome include phenotyping, cytogenetics, cytokinetics, drug resistance and age. Proto-oncogene expression as a predictor of response is under investigation. Post-induction therapy remains controversial and approaches have included allogeneic bone marrow transplantation, autologous bone marrow transplantation with or without purging, intensive consolidation and maintenance programs. The superiority of one approach over the other has not been firmly established. Differentiating agents such as all-trans retinoic acid, and growth factors, the latter for supportive care, or recruitment of leukemic cells into the cycle are being investigated. Understanding the mechanisms of drug resistance should lead to the development of new approaches. Thus, with knowledge generated in many areas, the future should bring increasing success in treating AML.
Vogler
W R
WR
Division of Hematology/Oncology, Emory University, Atlanta, GA 30322.
D000970:Antineoplastic Agents / Q000627:therapeutic use; D001853:Bone Marrow / Q000473:pathology; D016465:Bone Marrow Purging; D016026:Bone Marrow Transplantation; D002454:Cell Differentiation / Q000187:drug effects; D004351:Drug Resistance; D006133:Growth Substances / Q000627:therapeutic use; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000097:blood / Q000401:mortality / Q000628:therapy*; D011379:Prognosis; D000090063:Proto-Oncogene Mas; D011519:Proto-Oncogenes; D012074:Remission Induction
D000970:Antineoplastic Agents; D006133:Growth Substances; C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas