Enrollment Criteria for Clinical Trials in Acute Myeloid Leukemia

Abstract

Emerging diagnostic and therapeutic developments give insight into the heterogeneous disease biology of acute myeloid leukemia (AML) and provide valuable prognostic information regarding response to therapies and targets for investigational treatments. Our understanding of AML has evolved from morphologic and cytochemical distinctions to cytogenetics-based classification systems. The most recent evolutionary step has been the recognition of the prognostic importance of pathobiologic variations, such as in FLT3, NPM, and c-Kit; and of clinical disease features, particularly age, de novo versus secondary disease, and remission status. Therapies designed to reverse or inhibit the mechanisms that appear to cooperate in the AML pathobiologic pathway have been developed, including those that target Bcl-2, Ras, hypermethylation, heat shock protein, multidrug resistance efflux pumps, tyrosine kinase activation, histone deacetylation, and FLT3. Despite this progress, clinical features still serve as the platform for entry into clinical trials of novel agents. As the driving mechanisms of leukemia pathogenesis become further defined, and the inhibition of said mechanisms at a molecular level are correlated to clinical response, future studies should enroll patients on the basis of these molecular features, perhaps in isolation of clinical features, as variables such as age and secondary disease are intermediate markers for underlying pathobiology.