2025 update on MRD in acute myeloid leukemia: a consensus document from the ELN-DAVID MRD Working Party
Jacqueline Cloos, Peter J.M. Valk, Christian Thiede, Konstanze Döhner, Gail J. Roboz, Brent L. Wood, Roland B. Walter, Sa A. Wang, Agnieszka Wierzbowska, Andrew H. Wei, David Wu, François Vergez, Adriano Venditti, Bert A. van der Reijden, Arjan A. van de Loosdrecht, Ing Soo Tiong, Felicitas Thol, Marion Subklewe, Christophe Roumier, Tom Reuvekamp, Farhad Ravandi, Claude Preudhomme, Adriana Pleșa, Jad Othman, Gert J. Ossenkoppele, Yishai Ofran, Aguirre Mimoun, Luca Maurillo, Agata Majchrzak, David C. de Leeuw, Wolfgang Kern, Dennis Dong Hwan Kim, Maura Rosane Valério Ikoma, Lukas H. Haaksma, Mónica L. Guzmán, Michaela Feuring, Barbara Depreter, Anna Czyż, Veit Bücklein, Constance Baer, Costa Bachas, Sylvie Freeman, Francesco Buccisano, Christopher S. Hourigan, Richard Dillon, Michael Heuser
Abstract
ABSTRACT: Measurable residual disease (MRD) monitoring has become a critical component in the management of acute myeloid leukemia (AML), to inform prognosis, guide therapy, and serve as a key end point in clinical trials. The 2025 update of the MRD guideline provides a comprehensive and refined framework for MRD assessment, aligned with the European LeukemiaNet (ELN) 2022 genetic risk classification. Developed by members of the ELN AML MRD Working Party, the guidelines incorporate expert consensus determined through a 2-stage Delphi round. They address the clinical implementation of MRD methodologies, technical considerations, integration into clinical trials, and future directions. Importantly, MRD recommendations are tailored to individual prognostic and genetic subgroups. A new qualitative MRD response category, designated as optimal, warning, or high risk of treatment failure, has been introduced to facilitate contextual interpretation of the MRD burden and its clinical relevance. Notably, ultrahigh-sensitivity next-generation sequencing-based MRD assessment is now recommended for FLT3 internal tandem duplication-mutated AML after intensive chemotherapy and before allogeneic hematopoietic cell transplantation. A total of 56 recommendations were formulated, with 53 achieving a high level of consensus (≥90%). These updated guidelines represent a major step forward toward harmonizing MRD assessments in AML and enhancing its clinical utility across diverse treatment settings.