The present and future of measurable residual disease testing in acute myeloid leukemia

Abstract

Considerable progress has been made in the past several years in the scientific understanding of, and available treatments for, acute myeloid leukemia (AML). Achievement of a conventional remission, evaluated cytomorphologically via small bone marrow samples, is a necessary but not sufficient step toward cure. It is increasingly appreciated that molecular or immunophenotypic methods to identify and quantify measurable residual disease (MRD) – populations of leukemia cells below the cytomorphological detection limit – provide refined information on the quality of response to treatment and prediction of the risk of AML recurrence and leukemia-related deaths. The principles and practices surrounding MRD remain incompletely determined however and the genetic and immunophenotypic heterogeneity of AML may prevent a one-sizefits- all approach. Here, we review the current approaches to MRD testing in AML, discuss strengths and limitations, highlight recent technological advances that may improve such testing, and summarize ongoing initiatives to generate the clinical evidence needed to advance the use of MRD testing in patients with AML.

Minimal residual disease monitoring in acute myeloid leukemia: Focus on MFC‐MRD and treatment guidance for elderly patients

“…Searches for fusion genes Genomic testing for BCR:ABL1, KMT2:MLLT3 may also be done by PCR 15 . PCR, with its capacity for amplifying copies, seems suitable for detecting low‐level AML 16 . However, due to AML's heterogeneity, 17 personalized PCR tests or panels are necessary for each patient, given the diversity of AML subtypes.…”

Bridging horizons beyond CIRCULATE-Japan: a new paradigm in molecular residual disease detection via whole genome sequencing-based circulating tumor DNA assay

“…In specific genetic mutation cases of acute myeloid leukemia patients, MRD is evaluated by PCR or NGS [ 92 , 101 ]. However, the complexity of relapsing clones and the distinction between mutations suitable for MRD evaluation and those associated with clonal hematopoiesis present challenges [ 102 ]. For leukemia patients with bone marrow fibrosis or primary myelofibrosis, MRD assessment using bone marrow biopsy specimens or ctDNA has become necessary.…”

Quantification of measurable residual disease using duplex sequencing in adults with acute myeloid leukemia

“…4,5 However, despite being well established as correlated with the antileukemic effect of treatment interventions [6][7][8][9][10][11] , clinical implementation has been limited. While no standard technique is currently used for AML MRD testing 12 , multiple methodologies exist including detection of aberrant cell surface protein expression by multiparametric flow cytometry (MFC) or detection of genetic alterations by molecular assays 13 . MFC has been widely used for AML MRD detection, but there are concerns that inter-laboratory variability and a lack of standardization could limit applicability of the technique on a broader scale.…”

“…4, 5 However, despite being well established as correlated with the antileukemic effect of treatment interventions 6-11 , clinical implementation has been limited. While no standard technique is currently used for AML MRD testing 12 , multiple methodologies exist including detection of aberrant cell surface protein expression by multiparametric flow cytometry (MFC) or detection of genetic alterations by molecular assays 13 .…”