[Guideline development for MRD diagnostics in AML as a blueprint for solid tumors]

In acute myeloid leukemia (AML), the monitoring of measurable residual disease (MRD) has evolved over the past two decades from predominantly prognostic supplementary information to a central tool for risk stratification, treatment planning, and study endpoint definition. This development has been closely linked to advances in diagnostic technologies (multiparameter flow cytometry, qPCR/dPCR, next-generation sequencing) and international standardization initiatives.

This review aims to assess the evolution of MRD recommendations for AML over the past decade, identify key developmental milestones, and evaluate their relevance for cfDNA/ctDNA-based MRD approaches in solid tumors.

This is a narrative review article.

The 2018 European LeukemiaNet (ELN) recommendations for the first time established a widely accepted framework for minimum technical standards and reporting for measurable disease monitoring in AML. The 2021 update further integrated these technical recommendations into clinical decision-making and established consistent definitions, including those for MRD response and MRD relapse. The 2025 update of the ELN-DAVID network represents a comprehensive revision, as MRD recommendations are now systematically formulated along the lines of the genetic ELN 2022 risk groups and AML subtypes. In parallel, ultrahigh-sensitivity, error-corrected NGS approaches (UHS-NGS) have opened up new applications for MRD. For pathological diagnostics, AML can be seen as a model disease, since the standards established over many years for pre-analytics, analytical validation, cut-offs, longitudinal interpretation, quality assurance, and interdisciplinary implementation represent a blueprint for current cfDNA/ctDNA-based MRD strategies in solid tumors.