MRD in AML: does it already guide therapy decision-making?

Prognostic factors determined at diagnosis are predictive for outcome whereas achievement of morphological complete remission (CR) is still an important end point during treatment. Residual disease after therapy may reflect the sum of all diagnosis and postdiagnosis resistance mechanisms/factors; its measurement could hypothetically be very instrumental for guiding treatment. The possibility of defining residual disease (minimal residual disease MRD) far below the level of 5% blast cells is changing the landscape of risk classification. In this manuscript, the various methods, all different in sensitivity, specificity, and phase of development, to assess MRD are discussed. Currently, the 2 methods mostly used are flow cytometry-based immune MRD (multiparameter flow cytometry MPFC) and molecular MRD assessed by real-time quantitative polymerase chain reaction. Both have advantages and disadvantages that are summarized in detail. Many studies in children as well as adults already demonstrated that MRD detection by MPFC or molecular MRD provides strong prognostic information in acute myeloid leukemia (AML) after both induction and consolidation. These studies are summarized in this review. The general conclusion of this review is that a better definition of disease burden than morphological CR is now emerging. MRD assessed by flow or molecular techniques should become standard in every clinical trial in AML. Harmonization of antibody panels, introduction of single-cell tube systems (for determination of residual leukemic stem cells), and standardized analytical programs will pave the way for individual risk assessment and become a surrogate end point for survival in studies investigating new drugs, hopefully resulting in faster drug approval in AML.