Detection of Minimal Residual Disease

Abstract

Complete remission for hematolymphoid neoplasms affecting the bone marrow was traditionally considered to mean absence of morphologically detectable disease in the bone marrow with restoration of normal blood findings. Minimal residual disease (MRD) is the presence of the malignant cells at very low level (typically between 1% and 0.001% of total nucleated cells) in blood and/or bone marrow, detectable only by high sensitivity ancillary technics. MRD detection is clinically used in lymphoblastic leukemia, acute myeloid leukemia, chronic lymphocytic leukemia, and plasma cell myeloma because it offers independent prognostic information, can guide additional therapy, and/or is useful as a surrogate endpoint for novel treatments for these diseases. Multiparameter flow cytometry and molecular methods are currently used, the latter including real-time quantitative PCR and next-generation sequencing assays. While molecular methods can be 1–3 logs more sensitive than flow cytometric methods, they often have technical and practical drawbacks. Flow cytometry methods can be applied more universally but require considerable experience in interpretation of results. Several case studies are presented to familiarize the reader with this testing modality.