Update on MRD in acute myeloid leukemia: a consensus document
Measurable residual disease monitoring is an evolving area in the care, treatment, and study of acute myeloid leukemia patients. Complete remission for acute myeloid leukemia (AML) patients post-treatment (defined as fewer than five percent blasts in bone marrow by morphological evaluation in addition to other blood count recovery and clinical metrics) has been the gold standard for gauging response to therapy. With advancements in flow cytometry, cytogenetic, and molecular assessments of AML, investigators are working to identify better predictors of response using measurable residual disease (MRD) methodologies. ELN-DAVID (the European LeukemiaNet international working group for MRD assessment and validation in AML) recently published a 2025 update to its AML MRD recommendations guideline. While the working group noted improved standardization of MRD applications and nomenclature across laboratories, recommendations for clinical decision-making according to MRD results remain limited. One notable issue is that thresholds for MRD positivity may differ between laboratories and assays. Therefore, clinicians are advised to discuss the interpretation of individual MRD results with their laboratory colleagues. The working group also highlighted that negative MRD results do not necessarily indicate eradication of disease and, conversely, a fraction of patients with MRD positivity after treatment may never experience clinical disease relapse. Among the molecular-specific MRD recommendations highlighted in the update are the following. Techniques for molecular MRD assessment should be validated for a limit of detection of 10-4 to 10-5, and qualitative polymerase chain reaction (qPCR), digital PCR (dPCR), or ultrahigh-sensitivity next-generation sequencing (UHS-NGS) are recommended. Validated leukemia-specific MRD assays, such as those for NPM1, FLT3-ITD, PML::RARA, RUNX1::RUNX1T1, CBFB::MYH11, and KMT2A rearrangements, are preferred over less specific markers, such as WT1 or EVI1 expression. Digital PCR is an alternative to qPCR, and validated assays are available. Assays for KMT2A-rearranged AML MRD testing are being developed, but the role of clinical intervention in the setting of fusion-gene persistence in remission at specific thresholds and treatment timepoints remains to be established. Important considerations for UHS-NGS assays for FLT3-internal tandem duplication (ITD) MRD include the ability to detect FLT3-ITDs up to 200 base pairs in length and that at least 500 ng of input DNA are recommended to confidently call MRD negativity. Mutations in genes associated with germline predisposition or age-related clonal hematopoiesis are not prognostic at the time of remission assessment after intensive chemotherapy and before allogeneic hematopoietic cell transplantation and should not be taken into account at these time points. Emerging variants detected by UHS-NGS in remission that were not previously detected at diagnosis should be reported only if confidently detected above background noise and if donor origin has been excluded. Although single-cell sequencing and cell-free DNA are being explored for MRD assessment, their clinical use as prognostic MRD markers are not yet recommended. A full review of the updated ELN-DAVID recommendations in the context of other recommendations, such as the November 2025 National Comprehensive Cancer Network AML guideline update, is sure to spark discussions in the molecular-testing and clinical-management realms.
Cloos J, Valk PJM, Thiede C, et al. 2025 update on MRD in acute myeloid leukemia: a consensus document from the ELN-DAVID MRD Working Party. Blood. 2026;147:1147–1167.
Correspondence: Dr. Michael Heuser at michael.heuser@uk-halle.de