Flow cytometry (FC) is a well-established method important in the diagnosis and subclassification of lymphoma. In this article, the role of FC in lymphoma prognostication will be explored, and the clinical role for FC minimal/measurable residual disease testing as a monitoring tool for mature lymphoma will be introduced. Potential pitfalls of monitoring for residual/recurrent disease following immunotherapy will be presented.
Key points
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Flow cytometry (FC) is a well-established diagnostic tool in the workup of lymphoma.
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Many prognostic immunophenotypic markers by FC have been explored in chronic lymphocytic leukemia (CLL); fewer exist for other mature lymphomas.
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Robust FC minimal/measurable residual disease assays exist for CLL but not for other mature lymphomas.
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T-cell receptor β constant region 1 evaluation by FC has the potential benefit for diagnosis and monitoring in T cell lymphomas.
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Targeted therapies introduce the potential for loss or downregulation of antigen expression; test interference from therapeutic monoclonal antibodies has been reported.
Introduction
Lymphomas comprise a heterogeneous group of diseases with variable clinical presentations, pathological features, and prognoses. In lymphoma diagnosis, flow cytometry (FC) can provide a detailed immunophenotypic profile of the lesional material and can provide a surrogate of clonality. Advantages of FC include a rapid turn-around time (within hours) and the ability to provide detailed data on subpopulations of cells. In certain lymphomas that may not have a tissue counterpart, for example, chronic lymphocytic leukemia (CLL), FC may constitute the primary diagnostic method.
Minimal/measurable residual disease (MRD) can be defined as persistent disease present posttherapy using methods more sensitive and specific than morphologic evaluation. Sensitivity levels in MRD can reach between 0.01% and 0.001% abnormal cells depending on the method utilized. In FC, the quality of MRD testing is influenced by a number of factors including the amount and quality of the specimen, the staining process (including reagent combinations used), the number of cells evaluated, and the approach to data analysis.
Recent advances in lymphoma treatment, namely targeted therapies such as therapeutic monoclonal antibodies and chimeric antigen receptor (CAR) T-cells, have practical implications for clinical FC.
This article addresses select concepts in monitoring and prognostication by FC in mature lymphomas, with information presented by lymphoma subtype.
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