Measurable Residual Disease Testing in Acute Leukemia: Technology and Clinical Significance

ABSTRACT

Measurable/minimal residual disease (MRD) is the strongest independent prognostic predictor in acute leukemia. Patients with undetectable MRD or good MRD response consistently demonstrate a lower risk of relapse and better survival outcomes compared with similarly treated patients with positive MRD or poor MRD response. MRD has already been used to guide risk-adapted therapies in routine care of patients with acute leukemia or in clinical trials in many countries. MRD can also be used as a surveillance biomarker with the potential to detect early relapse, and as a surrogate endpoint to speed up the testing and approval process for a new therapeutic agent. Multi-parametric flow cytometry and quantitative PCR are two methods commonly used for MRD detection. Recently, new techniques, such as digital PCR, next-generation sequencing, and next-generation flow cytometry, have also been applied in MRD detection and showed improved sensitivity and accuracy. These methods have their own advantages and limitations. Despite tremendous advances in this field, there are still issues and questions regarding MRD testing methods and how to translate MRD information accurately into clinical and therapeutic applications. This chapter gives an overview of the methods and the clinical implications of MRD testing in acute lymphoblastic leukemia and acute myeloid leukemia.