More than 95 percent of plasma cell neoplasms show loss of CD19, making it one of the most consistent immunophenotypic abnormalities detected by flow cytometry, according to a recent study.
Flow cytometry is an established method for the diagnosis and monitoring of multiple myeloma. It provides a sensitive approach to distinguishing normal plasma cells from neoplastic plasma cells by assessing both clonality through immunoglobulin light chain restriction and immunophenotypic patterns. Published in Seminars in Diagnostic Pathology, researchers reviewed its applications in the evaluation of plasma cell neoplasms.
Normal plasma cells typically demonstrate bright CD38 expression, dim CD45, positivity for CD19 and CD138, and negativity for CD20 and CD56. In contrast, neoplastic plasma cells frequently exhibit loss of CD19, reduced or absent CD45, and aberrant expression of markers such as CD56 and CD117. Other markers, including CD27 and CD81, may also be altered, and these changes have been associated with prognostic differences. Treatment with anti-CD38 agents such as daratumumab may interfere with CD38 detection, requiring the use of additional markers such as CD138, CD319, or nanobody-based reagents to reliably identify plasma cells.
Flow cytometry is useful for identifying abnormal plasma cell populations even when admixed with normal cells, making it applicable for measurable residual disease (MRD) testing. Studies have demonstrated that the persistence of MRD after therapy, including following autologous stem cell transplantation, is associated with inferior progression-free survival. These findings informed the International Myeloma Working Group’s inclusion of MRD negativity by flow cytometry in its response criteria.
Technical aspects of MRD testing include appropriate panel design, collection of sufficient total events to reach sensitivity of at least 10-5, and gating strategies to ensure accurate separation of plasma cell populations. Panels developed by groups such as EuroFlow and Memorial Sloan Kettering Cancer Center illustrate standardized approaches for distinguishing normal from abnormal plasma cells.
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