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MRD is a powerful prognostic factor in AML.

Explore the molecular predictors and current management strategies for minimal residual disease (MRD) following induction chemotherapy in acute myeloid leukemia (AML). Discover how MRD detection, including PCR-based technologies and next-generation sequencing (NGS), can improve relapse prediction. Investigate the impact of MRD on post-transplant outcomes and the potential for MRD-eradicating therapies to enhance transplant success.

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MRD is a powerful prognostic factor in AML.

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  1. Molecular Predictors and Current Management of Minimal Residual Disease (MRD) Following Induction Chemotherapy for Acute Myeloid Leukemia (AML)

  2. Although most pts with AML (> 80%) achieve CR following induction therapy, relapse is common and a major cause of treatment failure • Unknown which residual leukemia-specific mutations present in bone marrow in morphologic CR contribute to impending relapse • Other persistent mutations (eg, DNMT3A, TET2, and ASXL1 mutations) may represent clonal hematopoiesis that may contribute to relapse • Molecular MRD detection by PCR-based technologies improves relapse prediction, but only used in specific genetically defined subsets of AML • NGS enables assessment of myriad disease-related gene mutations in a single assay

  3. MRD is a powerful prognostic factor in AML. • Emerging data indicate that allogeneic stem cell transplant (alloSCT) with MRD results in outcomes equivalently poor to alloSCT with morphologic AML (Araki et al., JCO 2016). • Genomic predictors of MRD are unclear, and relative efficacy of therapies for MRD remains elusive.

  4. Objectives • integrated analysis of responses for 163 patients underwent induction chemotherapy with baseline next-generation sequencing (NGS) followed by serial immunophenotypic monitoring for MRD.

  5. Methods: • 163 patients • induction chemotherapy at Memorial Sloan Kettering Cancer Center were retrospectively studied. • All received anthracycline + cytarabine, with or without investigational agents. • Immunophenotypic MRD was identified in bone marrow aspirates (BMA) by multiparameter flow cytometry. • Any level of residual disease was considered MRD+. • Molecular analysis was obtained from pre-induction BMA by NGS using 28 or 49 gene panels. • Cytogenetics/FISH were performed using standard techniques.

  6. RESULTS • AML pts with specific molecular mutations (RUNX1, SF3B1, and TP53) are unlikely to achieve MRD-CR/CRi after induction chemotherapy. • Additional therapy such as consolidation may be advantageous for some MRD+ pts to achieve MRD-CR prior to alloSCT, • Post-transplant OS is improved in pts who are MRD- at time of transplant • Our results suggest that development of MRD-eradicating therapies after AML induction has the potential to improve post-transplant outcomes.

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