Role of Minimal Residual Disease Testing in Acute Myeloid Leukemia

Key points

Introduction

Pediatric acute myeloid leukemia (AML) is a heterogeneous disease with different morphologic, phenotypic, and genetic features, and variable clinical outcomes. ^1 , 2 Over the past few decades, outcomes for pediatric AML have improved substantially, with overall survival reaching 60% to 70% and event-free survival exceeding 50%. 34567 The improvement in outcomes has been achieved with implementation of risk stratification based on genetic features and response to therapy, intensification of chemotherapy with improved supportive care, and application of hematopoietic stem cell transplant (HCT). Minimal or, more accurately, measurable residual disease (MRD), the presence of persistent leukemic blasts after therapy, represents the integrated effect of leukemia genetics, patient characteristics, and chemotherapy regimens, which together determine a patient’s response to therapy. There is growing evidence that MRD is a robust independent prognostic factor in pediatric AML. 89101112 Therefore, MRD has emerged as an essential factor for risk stratification and guiding risk-directed therapy.

Given the independent prognostic value of MRD, it is crucial to develop standardized, sensitive, and accurate methods to detect and monitor MRD. With rapidly improving technology, the assessment of MRD has evolved substantially. At present, MRD in AML is most commonly measured by multiparametric flow cytometry and reverse transcriptase (RT) quantitative polymerase chain reaction (qPCR)–based methods. New molecular methods, such as high-throughput next-generation sequencing (HTS), have evolved into routine laboratory tools for identification of mutations at diagnosis and become promising in MRD detection. Common methods for MRD assessment in AML are compared in Table 1 .