Sensitivity of minimal residual disease in acute myeloid leukaemia in first remission--methodologies in relation to their clinical situation.

The concept of minimal residual disease in acute myeloid leukaemia has been steadily developed pre-clinically, with quantitative polymerase chain reaction (qPCR) leading the way with highly validated assays for patient-based risk stratification at post-treatment time points, which are being integrated in clinical trials both at evaluation of first complete remission (CR1) and after attaining CR1. Moreover, multicolour flow cytometry (MFC) has been increasingly employed in identifying leukaemia-associated immunophenotypes (LAIPs) with significant progress being made in standardization. In translating these widely varying methodologies to parameters useful for individualized patient decision-making, one of the obstacles has been that the assays entail varying sensitivities dependent on a number of variables. For qPCR, sensitivity depends on target type (i.e. fusion transcript, mutated gene or even overexpressed gene) and - in the case of overexpressed genes - on expression in healthy haematopoiesis. For MFC, sensitivity is likewise largely a function on whether the same phenotype is seen in normal immature cells and, in addition, antigen drift/shift with LAIPs changing at relapse is a well-known problem. In considering which sensitivity to opt for, a further variable is the situation of patient, most importantly the level of cytoreduction intended. Here we will attempt to give an overview of these pertinent questions intended for the practicing haematologist, focusing on where the field is heading at the clinical level.