Test Then Erase? Current Status and Future Opportunities for Measurable Residual Disease Testing in Acute Myeloid
Amanda L Blackmon1, Christopher S Hourigan2
1Department of Hematology and Hematopoietic Cell Transplantation, City of Hope National Medical Center, Duarte, California, USA.
Background:
Measurable residual disease (MRD) test positivity during and after treatment in patients with acute myeloid leukemia (AML) has been associated with higher rates of relapse and worse overall survival. Current approaches for MRD testing are not standardized leading to inconsistent results and poor prognostication of disease. Pertinent studies evaluating AML MRD testing at specific times points, with various therapeutics and testing methods are presented.
Summary:
AML is a set of diseases with different molecular and cytogenetic characteristics and is often polyclonal with evolution over time. This genetic diversity poses a great challenge for a single AML MRD testing approach. The current ELN 2021 MRD guidelines recommend MRD testing by quantitative polymerase chain reaction in those with a validated molecular target or multiparameter flow cytometry (MFC) in all other cases. The benefit of MFC is the ability to use this method across disease subsets, at the relative expense of suboptimal sensitivity and specificity. AML MRD detection may be improved with molecular methods. Genetic characterization at AML diagnosis and relapse is now standard of care for appropriate therapeutic assignment, and future initiatives will provide the evidence to support testing in remission to direct clinical interventions.
Key Messages:
The treatment options for patients with AML have expanded for specific molecular subsets such as FLT3 and IDH1/2 mutated AML, with development of novel agents for NPM1 mutated or KMT2A rearranged AML ongoing, but also due to effective venetoclax-combinations. Evidence regarding highly sensitive molecular MRD detection methods for specific molecular subgroups, in the context of these new treatment approaches, will likely shape the future of AML care.
Insights
Measurable residual disease (MRD) testing in acute myeloid leukemia (AML) is crucial but lacks standardization. Improved, sensitive molecular MRD detection methods are needed to guide future AML treatment strategies and improve patient outcomes.
Area of Science:
- Hematology
- Molecular Diagnostics
- Oncology
Background:
- Measurable residual disease (MRD) positivity in acute myeloid leukemia (AML) correlates with increased relapse rates and decreased survival.
- Current MRD testing methods for AML are not standardized, leading to inconsistent results and unreliable prognostication.
- The genetic heterogeneity of AML presents challenges for a universal MRD testing strategy.
Purpose of the Study:
- To review studies evaluating acute myeloid leukemia (AML) measurable residual disease (MRD) testing.
- To discuss various therapeutic approaches and testing methodologies for AML MRD.
- To highlight the need for standardized and sensitive MRD detection in AML management.
Main Methods:
- Review of pertinent studies on AML MRD testing.
- Evaluation of different time points, therapeutics, and testing methods for MRD detection.
- Discussion of current European LeukemiaNet (ELN) 2021 guidelines for MRD testing.
Main Results:
- Existing MRD testing approaches, including quantitative polymerase chain reaction (qPCR) and multiparameter flow cytometry (MFC), have limitations in sensitivity and specificity.
- Molecular methods show promise for improving AML MRD detection accuracy.
- Genetic characterization at diagnosis and relapse is standard, with future focus on MRD testing in remission.
Conclusions:
- Standardization of AML MRD testing is essential for accurate prognostication and clinical decision-making.
- Advancements in sensitive molecular MRD detection methods are critical, especially with evolving AML therapeutics.
- Future research should focus on validating sensitive MRD assays to guide targeted interventions in AML care.
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