Flow cytometric analysis in the diagnosis and prognostication of plasma cell neoplasms

Flow cytometry immunophenotyping (FCM) has become an integral part of diagnosis and management of patients with plasma cell neoplasms (PCN) and related diseases. Immunophenotypic profiles of neoplastic plasma cells (PCs) in PCN are distinct from that of benign or reactive PCs, and differs from that of B cell neoplasms with plasmacytic differentiation. Progression of monoclonal gammopathy of undetermined significance (MGUS) or smoldering myeloma to myeloma is usually accompanied by expansion of neoplastic fraction of the total PCs quantifiable by FCM. The most powerful application of FCM concerns monitoring of minimal residual disease (MRD). FCM is sensitive, quantitative, fast, and widely applicable. Absence of MRD by a sensitive multicolor FCM assay has been shown to correlate with a better progression free survival and overall survival. MRD assessment by FCM may serve as a surrogate for therapeutic efficacy, and in turn the endpoint of clinical trials, allowing speedier approval of newer drugs by regulatory bodies. With the emerging immunotherapy, FCM also allows rapid identification of potential markers for targeted therapy. The chapter begins with an overview of immunophenotypic features of neoplastic PCs and their distinction from normal PCs. This is followed by discussion of immmunophenotypic profiles that may help distinguish PCs from B cell lymphoma versus those from PCN. The principles and a practical approach to assessing MRD by FCM are emphasized and illustrated. The chapter concludes with a summary of clinical utilities and future outlook of FCM as a powerful tool for diagnostic and prognostication of PCN.