Abstract
Here, we investigated for the first time the frequency and number of circulating tumor plasma cells (CTPC) in peripheral blood (PB) of newly diagnosed patients with localized and systemic plasma cell neoplasms (PCN) using next-generation flow cytometry (NGF) and correlated our findings with the distinct diagnostic and prognostic categories of the disease. Overall, 508 samples from 264 newly diagnosed PCN patients, were studied. CTPC were detected in PB of all active multiple myeloma (MM; 100%), and smoldering MM (SMM) patients (100%), and in more than half (59%) monoclonal gammopathy of undetermined significance (MGUS) cases (p <0.0001); in contrast, CTPC were present in a small fraction of solitary plasmacytoma patients (18%). Higher numbers of CTPC in PB were associated with higher levels of BM infiltration and more adverse prognostic features, together with shorter time to progression from MGUS to MM (p <0.0001) and a shorter survival in MM patients with active disease requiring treatment (p ≤ 0.03). In summary, the presence of CTPC in PB as assessed by NGF at diagnosis, emerges as a hallmark of disseminated PCN, higher numbers of PB CTPC being strongly associated with a malignant disease behavior and a poorer outcome of both MGUS and MM.
Highlights
Plasma cell neoplasms (PCN) are a heterogeneous group of diseases characterized by the clonal expansion of terminally-differentiated plasma cells (PC)[1,2,3,4]
PB peripheral blood, PC plasma cell, circulating tumor plasma cells (CTPC) circulating tumor PC, MGUS monoclonal gammopathy of undetermined significance, MM symptomatic multiple myeloma, AUC area under the curve, No number. *p
Our results showed an up to ~2-fold increased frequency of cases presenting with CTPC in PB by next-generation flow cytometry (NGF) vs. both immunocytochemistry and conventional flow cytometry, among MGUS
Summary
Plasma cell neoplasms (PCN) are a heterogeneous group of diseases characterized by the clonal expansion of terminally-differentiated plasma cells (PC)[1,2,3,4]. Represent pre-malignant phases of the disease with progressively higher degree of bone marrow (BM) involvement and relatively low rates of malignant transformation (i.e., 1 and 10% per year, respectively5–7), multiple myeloma (MM) is an active malignancy usually associated with end-organ damage requiring therapy, and potential for transformation into PC leukemia (PCL)[1,8,9]. Solitary plasmacytoma (SP) consists of a localized accumulation of tumor (mono) clonal PC (TPC) in a specific tissue area, without evidence for systemic disease[10,11], but Sanoja-Flores et al Blood Cancer Journal (2018)8:117 a rate of transformation to MM of ~ 15%–50%, depending on the primary localization of the tumor (e.g., soft-tissue vs bone plasmacytoma, respectively)[12,13]. PB involvement by circulating TPC (CTPC) increases from MGUS -19 to 37%- to MM -50 to 75%-19,24–26, and PCL (100%)[8,27], depending on whether immunocytochemistry or conventional 4–8-color flow cytometry are used, respectively
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