What is the optimal induction strategy for older patients?

Prognoses of older patients (age ≥60 years) vary greatly following use of standard therapy, such as 3 + 7: 3 days of daunorubicin or idarubicin + 7 days of cytarabine (ara-C). Although most older patients receive only supportive care, the principal prognostic factor among the presumably healthier treated patients is cytogenetics, with a monosomal karyotype conferring a particularly poor prognosis. However other factors are also informative and several systems incorporating multiple factors have been devised to help guide the fundamental decision as to whether a patient should receive standard therapy or, much more frequently, investigational therapy. Although physicians may be reluctant to await results of cytogenetic analysis and molecular markers (NPM, FLT3), data suggest no harm is done by waiting for these results to become available; certainly the risk of delaying therapy is less than the risk of giving a patient 3 + 7 when the risk of treatment-related mortality (TRM) is greater than the chance of a beneficial response. Nonetheless, in general the risk of TRM is less than that of resistance to therapy, even in patients aged ≥75 years. Perhaps, however, focusing on the former, there is an increasing tendency to administer azacitidine or decitabine to older patients. However there is little to suggest that on average these drugs by themselves convey what many patients would consider medically meaningful improvements in survival. Hence these drugs should not reduce the imperative of putting older patients on trials involving new drugs. Finally, confirming everyday observation, age alone is a very inadequate predictor of outcome and is likely a surrogate for other covariates. Accordingly, the common practice of assigning patients to treatment protocols based solely on age leaves much to be desired.