AML in the Elderly: a Biologically Distinct Disease in which MDR1 Expression and Unfavorable Cytogenetics Contribute to Poor Clinical Response. Studies of the Southwest Oncology Group

摘要: Elderly patients with acute myeloid leukemia (AML) respond poorly to chemotherapy compared younger cohorts. To determine the contribution of biologic factors this poor response, we studied 211 (161 de novo, 50 secondary AML) over 55 years age (median: 68 years) registered a single clinical trial for previously untreated AML (SWOG 9031: Phase III randomized standard dose cytosine arabinoside and daunomycin +/− rhG-CSF). Pretreatment blasts were karyotyped, analyzed MDR1 expression functional efflux by multiparameter flow cytometry. In addition, pre-treatment marrows trilineage dyspoiesis. was very high (71%) in these cases, distinctly different from frequency about 35% detected group similar methods. Functional (58% cases +) unfavorable karyotype (e.g. −5/5q−, −7/7q−, complex abn; present 32% cases) also frequent both novo cases. Over 80% evaluable showed erythroid or megakaryocyte dyspoiesis while 68% Secondary AML, CD34 expression, efflux, cytogenetics all associated lower complete remission (CR) rates univariate analysis. Dyspoiesis, cytogenetics, not clearly predictive CR. multivariate analysis, three independent predictors CR found: secondaryAML (p= 0.0035),MDR1 (p = 0.0041) 0.0031). Resistant disease 0.0007) 0.017). elderly is dyspoiesis, thus more closely resembles myelodysplasia related than patients. Analysis parameters at diagnosis may help identify likelihood achieving current therapies. Biologic studies can MDR1+ where benefit therapies which include modulators, non-MDR1 transported drugs. Other are likely important elderly, await further investigation.