Journal of Leukemia
Open Access

The Role of Minimal Residual Disease Monitoring in Acute Myeloid Leukemia: Redefining Treatment Success

Chris Zhang^{* *}Correspondence: Chris Zhang, Department of Pharmacy, University of Sao Paulo, Butanta, Sao Paulo, Brazil, Email:

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Description

The paradigm of treatment response assessment in Acute Myeloid Leukemia (AML) has undergone profound evolution with the widespread implementation of Minimal Residual Disease (MRD) monitoring. Traditional morphologic Complete Remission (CR), defined as <5% bone marrow blasts with recovery of peripheral blood counts, has served as the cornerstone of response evaluation for decades [1]. However, this criterion has proven inadequate in identifying patients with persistent submicroscopic disease who remain at high risk for relapse despite achieving apparent remission. The integration of sensitive MRD detection techniques has fundamentally altered our understanding of disease kinetics and transformed clinical decision-making algorithms [2].

Contemporary MRD assessment in AML primarily employs two complementary modalities: Multiparameter Flow Cytometry (MFC) and molecular techniques including Real-Time Quantitative Polymerase Chain Reaction (RT-qPCR) and Next- Generation Sequencing (NGS) [3]. Each approach offers distinct advantages and limitations that must be considered in clinical implementation. MFC detects leukemia-associated immunophenotypes with sensitivity typically reaching 10^-3 to 10^-4, while molecular techniques targeting specific mutations or fusion transcripts can achieve sensitivity of 10^-4 to 10^-6. The recent development of standardized panels and reporting formats through collaborative efforts such as the European LeukemiaNet MRD Working Group has enhanced reproducibility across centers [4].

The prognostic significance of MRD status has been robustly demonstrated across multiple studies. A landmark meta-analysis encompassing 81 studies and 11,151 patients revealed that MRD negativity was associated with substantially improved relapse-free survival (hazard ratio 0.36, 95% CI 0.29-0.44) and overall survival (hazard ratio 0.42, 95% CI 0.34-0.54) across all age groups and genetic risk categories. This predictive value persists independent of other established prognostic factors including cytogenetics and mutation status, suggesting that MRD represents the most powerful single predictor of outcomes in AML [5].

Despite these compelling data, several critical challenges remain in optimizing MRD-guided therapy. First, the optimal timing of assessment remains controversial, with different protocols evaluating MRD after induction, consolidation, or at multiple timepoints. The kinetics of MRD clearance appear particularly informative, with early negativity carrying superior prognostic implications compared to delayed clearance [6]. Second, the threshold defining MRD positivity varies across studies and techniques, complicating cross-trial comparisons. Third, not all patients have trackable markers, particularly those with normal karyotype and without established molecular lesions [7].

Perhaps most fundamentally, the transition from MRD as a prognostic tool to a guide for therapeutic intervention remains incompletely defined. The RELAZA2 trial provided promising evidence for preemptive therapy based on molecular MRD detection, demonstrating that azacitidine in patients with molecular relapse significantly reduced the incidence of morphologic relapse. Similarly, the GIMEMA AML1310 trial demonstrated that MRD-guided consolidation with allogeneic Hematopoietic Stem Cell Transplantation (HSCT) improved outcomes in intermediate-risk AML. These findings suggest that MRD status should inform treatment intensification, maintenance strategies, and immunotherapeutic approaches [8].

Several emerging strategies show promise in enhancing the utility of MRD assessment. Digital droplet PCR offers enhanced sensitivity and quantitative precision compared to conventional RT-qPCR. Mass cytometry enables simultaneous assessment of over 40 parameters, potentially uncovering previously undetectable leukemic populations. Cell-free DNA analysis in peripheral blood represents an attractive non-invasive alternative to bone marrow sampling, particularly for serial monitoring. Integration of artificial intelligence algorithms to identify complex immunophenotypic patterns may further improve discrimination between residual leukemia and regenerating normal hematopoiesis [9].

The ongoing refinement of detection techniques, standardization of reporting, and development of MRD-guided interventional studies will further solidify the central role of MRD monitoring in optimizing outcomes for patients with AML. The future lies in personalized treatment algorithms that dynamically adapt to evolving MRD status, ultimately transforming AML from a typically fatal disease to a potentially curable malignancy for a growing proportion of patients [10].

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