MRD monitoring in AML: ELN 2025 guideline updates

A 2025 update to the measurable residual disease (MRD) guidelines from the European LeukemiaNet (ELN) acute myeloid leukemia (AML) MRD working party (ELN-DAVID) was recently published in Blood by Cloos et al. The update provides a comprehensive framework for MRD assessment in AML, aligned with the ELN 2022 genetic risk classification. Developed through a two-stage Delphi consensus process involving experts from 29 international centers, the guidelines address clinical implementation, technical considerations, and integration into clinical trials. A total of 56 recommendations were formulated, including seven key updates.

Key data: The update introduces detailed MRD guidance tailored to genetic subgroups, qualitative MRD response categories (optimal, warning, or high risk of treatment failure), and MRD burden categorization (negative, low-level positive, or positive). Additionally, the percentage cutoffs for each assay and target have been updated to reflect biological heterogeneity and differences of MRD assays, including lowered NPM1 cutoffs. Multiparameter flow cytometry (MFC)-MRD assessment is recommended during the first year of follow-up after allogeneic hematopoietic stem cell transplantation (allo-HSCT), while quantitative polymerase chain reaction (qPCR) or ultrahigh-sensitivity next-generation sequencing (UHS-NGS) is recommended after 2 years. Mutation testing for FLT3-ITD using UHS-NGS is also recommended after 2 cycles of chemotherapy and prior to allo-HSCT. 

Key learning: These updated guidelines represent the harmonization of MRD assessments in AML, enhancing clinical utility across diverse treatment settings through standardized methodologies, target-specific cutoffs, and contextual interpretation frameworks.