International Cross-Age Consensus Guideline on Measurable Residual Disease Assessment in Acute Lymphoblastic Leukemia.
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Measurable residual disease (MRD) assessment is central to risk stratification, response evaluation, and relapse detection in acute lymphoblastic leukemia (ALL). However, substantial global variability in its methodology and implementation persists. Differences in sampling strategies, detection methods, reporting thresholds, and interpretation criteria hinder cross-trial comparability and clinical standardization. To address this, an international expert panel representing major pediatric and adult study groups and reference laboratories developed consensus recommendations, using a structured current-practices survey followed by a multi-round Delphi process. Consensus was achieved on 38 of 41 statements. Recommendations span three domains: pre-analytical requirements, technical and nomenclature standards, and MRD-based remission and relapse definitions. Bone marrow was endorsed as the reference specimen for MRD assessment, and MRD was prioritized over cytomorphology in cases of discordance. Principles for risk- and actionability-guided late MRD monitoring, confirmation of MRD reappearance, and MRD-informed relapse assessment were also defined. Among the key technical consensus statements, a standardized MRD assay nomenclature was adopted. Areas without consensus-namely, anticoagulant choice for PCR-based MRD, interpretation of isolated BCR::ABL1 reconversion, and the exclusive use of MRD to define remission-highlight ongoing biological and clinical complexity. This guideline, applicable across all ages, provides a practical framework to standardize MRD assessment in ALL and support MRD-guided clinical decision-making.