Measurable Residual Disease Detection in Hematolymphoid Malignancies: Techniques and Clinical Significance

Measurable/minimal residual disease (MRD) refers to the small number of malignant cells remaining in the body of cancer patients during or after treatment. MRD detection is the best way to evaluate therapeutic response in the treatment of some hematolymphoid malignancies. Multiparametric flow cytometry and quantitative PCR are two methods commonly used for MRD detection. Recently, new techniques such as digital PCR, next-generation flow cytometry, and next-generation sequencing have been applied in MRD detection with improved sensitivity and accuracy. These methods have their advantages and limitations. MRD has been demonstrated as the strongest prognostic factor by numerous studies during the last three decades. The patients with undetectable MRD consistently demonstrate a lower risk of relapse and better survival outcomes compared with similarly treated patients with positive MRD. MRD has been used for risk stratification and guiding risk-adapted treatment for some hematolymphoid malignancies as standard patient care or in clinical trials. MRD can also be used as a surveillance biomarker with the potential to detect early relapse and a surrogate endpoint to speed up the testing and approval process for a new therapeutic product. 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 will give an overview of the MRD detection methods and the clinical implications of MRD testing in acute lymphoblastic leukemia, acute myeloid leukemia, plasma cell myeloma, chronic lymphocytic leukemia, and other hematolymphoid malignancies.