How Can We Improve on MRD Assessment by Flow Cytometry?

Abstract

Introduction Measurements of residual leukemia strongly correlate with survival, as well as relapse, in patients with acute myeloid leukemia (AML) and, therefore, when used appropriately with other prognostic variables, provide an opportunity to improve their treatment. However, the deployment and interpretation of measurable residual disease (MRD) tests in AML can be challenging, reflecting heterogeneity not only in the disease but also in the assays. Of the various technologies in use, multi-parameter flow cytometry (MFC) is arguably the most accessible and can be used to detect MRD by identification of abnormal leukemic immunophenotypes at a single-cell level in over 90% of patients, with a sensitivity of 10–3 to 10–4. MFC was the MRD methodology applied in 6,115 of the 11,151 patients in remission, as analyzed by the recently published meta-analysis of AML MRD studies.1 Since the first study in 2001,2 MFC-MRD has been extensively clinically validated, with its independent prognostic value most established after standard frontline chemotherapy and prior to allogeneic stem cell transplant. MFC-MRD has also been incorporated into trials of randomized treatment comparisons and MRD-directed therapy. Furthermore, guidelines for its use have been available since 2018,3 with an update forthcoming.