Immunophenotyping and cytogenetics in older adults with acute myeloid leukemia: Significance of expression of the multidrug resistance gene-1 (MDR1)

One of the best hopes for improving outcome in leukemia involves identification of biologic factors that can predict response and resistance at disease presentation and that can be used to design new treatment regimens that circumvent drug resistance. Recent studies suggest that younger acute myeloid leukemia (AML) patients whose leukemic blasts express the multidrug resistance gene-1 (MDR1) have a poor prognosis. These younger MDR1+ AML patients are biologically and genetically related more to elderly MDR1+ and secondary AML patients than to younger AML patients with MDR1- true de novo AML. Data demonstrate for the first time in a large number of uniformly treated patients whose leukemic blasts were analyzed prior to therapy that MDR1 expression and functional dye/drug efflux are important independent predictors of complete response in AML in the elderly. Unexpectedly, elderly patients with de novo AML who are MDR1- have complete response rates approaching 75 percent, similar to younger AML patients, indicating that they are likely to have good outcomes with induction chemotherapy despite their age. In contrast, elderly MDR1+ de novo AML patients and elderly MDR1+ patients with secondary AML are much less likely to achieve a complete response with current regimens. These data argue for the inclusion of MDR1-modulating agents or drugs that are not MDR1 substrates in the treatment of elderly AML patients.