Monitoring minimal residual disease in acute myeloid leukaemia: a review of the current evolving strategies

Abstract

Several disease-monitoring techniques are available for the physician treating acute myeloid leukaemia (AML). Besides immunohistochemistry assisted light microscopy, the past 20 years have seen the development and preclinical perfection of a number of techniques, most notably quantitative polymerase chain reaction (PCR) and multicolor flow cytometry. Late additions to the group of applicable assays include next generation sequencing and digital PCR. In this review the principles of use of these modalities at three different time points during the AML disease course are discussed, namely at the time of treatment evaluation, pretransplantation and postconsolidation. The drawbacks and pitfalls of each different technique are delineated. The evidence or lack of evidence for minimal residual disease guided treatment decisions is discussed. Lastly, future strategies in the MRD field are suggested and commented upon.

Keywords: AML; Minimal residual disease; NGS; Preemotive treatment; flow cytometry; qPCR.

Figure 1.

Relapse kinetics of different AML subtypes and relation to treatment onset. Relapse kinetics from Ommen and colleagues (several papers) [Ommen et al. 2010, 2014, 2015] and Yin et al. [2012]. Time to treatment onset for azacitidine from Silverman et al. [2011]. Time to treatment onset for chemotherapy and GvL effect based on common clinical observations (disappearance of blasts after first course of chemotherapy, full chimerism often 3 months post transplantation). AML, acute myeloid leukaemia; GvL, graft versus leukaemia.