Role of minimal residual disease in the management of acute myeloid leukemia—a case-based discussion

Abstract

AML is stratified into risk-categories based on cytogenetic and molecular features that prognosticate survival and facilitate treatment algorithms, though there is still significant heterogeneity within risk groupings with regard to risk of relapse and prognosis. The ambiguity regarding prognosis is due in large part to the relatively outdated criteria used to determine response to therapy. Whereas risk assessment has evolved to adopt cytogenetic and molecular profiling, response criteria are still largely determined by bone marrow morphologic assessment and peripheral cell count recovery. Minimal residual disease refers to the detection of a persistent population of leukemic cells below the threshold for morphologic CR determination. MRD assessment represents standard of care for ALL and PML, but concerns over prognostic capability and standardization have limited its use in AML. However, recent advancements in MRD assessment and research supporting the use of MRD assessment in AML require the reconsideration and review of this clinical tool in this disease entity. This review article will first compare and contrast the major modalities used to assess MRD in AML, such as RQ-PCR and flow cytometry, as well as touching upon newer technologies such as next-generation sequencing and digital droplet PCR. The majority of the article will discuss the evidence supporting the use of MRD assessment to prognosticate disease at various time points during treatment, and review the limited number of studies that have incorporated MRD assessment into novel treatment algorithms for AML. The article concludes by discussing the current major limitations to the implementation of MRD assessment in this disease. The manuscript is bookended by a clinical vignette that highlights the need for further research and refinement of this clinical tool.

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