Measurable Residual Disease Assessment in Pediatric AML

Assessment of response to induction therapy through measurable residual disease (MRD) evaluation provides pivotal prognostic information to guide clinical decision making for patients with acute myeloid leukemia (AML). An appropriate MRD assay should include specificity and stability of the MRD biomarker(s) as well as high sensitivity. Given the heterogeneity of AML, the most appropriate MRD testing approach will be dependent on the biology of the individual patient, and should be inclusive of multiple testing modalities when possible. Furthermore, pediatric AML is distinct from adult AML and should be evaluated as such. Among molecular genetic techniques, real-time quantitative polymerase chain reaction (RQ-PCR) and digital PCR (dPCR) reach 10−5–10−6 levels of sensitivity, but their application is limited to AML patients that harbor a limited set of genetic abnormalities. Conversely, morphology has insufficient sensitivity, as can next-generation sequencing (NSG) and conventional cytogenetics. Flow cytometry-based methodologies are most widely applicable and reach a sensitivity of 10−4. This chapter presents the available MRD methodologies and evaluates the appropriate use and combination of assays in different patient settings.