Flow-Cytometric Monitoring of Minimal Residual Disease in Pediatric Patients With Acute Myeloid Leukemia: Recent Advances and Future Strategies

Minimal residual disease (MRD) by multiparametric flow cytometry (MFC) has been recently shown as a strong and independent prognostic marker of relapse in pediatric AML (pedAML) when measured at specific time points during Induction and/or Consolidation therapy. Hence, MFC-MRD has the potential to refine the current strategies of pedAML risk stratification, traditionally based on the cytogenetic and molecular genetic aberrations at diagnosis. Consequently, it may guide the modulation of therapy intensity and clinical decision making. However, the use of non-standardized protocols, including different staining panels, analysis, and gating strategies, may hamper a broad implementation of MFC-MRD monitoring in clinical routine. Besides, the thresholds of MRD positivity still need to be validated in large, prospective and multi-center clinical studies, as well as optimal time points of MRD assessment during therapy, to better discriminate patients with different prognosis. In the present review, we summarize the most relevant findings on MFC-MRD testing in pedAML. We examine the clinical significance of MFC-MRD and the recent advances in its standardization, including innovative approaches with an automated analysis of MFC-MRD data. We also touch upon other technologies for MRD assessment in AML, such as quantitative genomic breakpoint PCR, current challenges and future strategies to enable full incorporation of MFC-MRD into clinical practice.