Minimal residual disease (MRD) is the most significant independent prognostic factor in acute lymphocytic leukemia (ALL). Monitoring MRD using sensitive techniques, including multiparametric flow cytometry (MFC) and quantitative polymerase chain reaction (qPCR)-based methods, has improved the assessment of treatment response and risk stratification for clinical management. New molecular methods, such as high-throughput next-generation sequencing (NGS), have evolved into routine laboratory tools to improve the sensitivity and specificity of MRD detection. It is essential to establish standardized protocols as to the timing of assessment and methodology used, to limit inter-laboratory variability. MRD has demonstrated utility for the identification of patients with suboptimal initial response to therapy who may benefit from more intensive or novel therapies, in addition to identifying patients with an excellent response to initial therapy who may be candidates for therapeutic reduction to limit toxicity. Herein, we review the methodological approaches to MRD detection in ALL and discuss the clinical implication of MRD in risk-directed therapy and practical issues.
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