Increased circulating plasma cells detected by flow cytometry predicts poor prognosis in patients with plasma cell myeloma

Background: Flow cytometry (FC) is a reliable tool for diagnosing and monitoring of plasma cell myeloma (PCM). Recent studies used FC for quantifying plasma cells (PCs) in peripheral blood (PB) using various panels, and an adverse prognostic effect of circulating PCs (cPCs) has been reported. We investigated the prognostic implication of cPCs quantified using a simple panel in patients with PCM. Methods: Bone marrow (BM) and PB of 85 patients with PCM were analyzed by five-color FC at time of diagnosis. A serial gating strategy for quantification used CD38/CD138 to gate PCs in 100,000–200,000 acquired events, with subsequent gating for CD19, CD56, and CD45, to identify aberrant immunophenotypes. Results: cPCs were observed in 74.1% patients (63/85, median 0.067% leukocytes). Patients were grouped based on a cPC cut-off level of 0.02% derived using the receiver operating characteristic curves. Compared with patients with cPCs < 0.02% (n = 28), those with cPCs ≥ 0.02% (n = 57) showed lower hemoglobin (P = 0.003) and platelets (P = 0.014), but higher calcium, M-protein and BM PCs (P = 0.013, 0.029, and P < 0.001, respectively). Survival analysis of 74 patients showed that cPCs ≥ 0.02% predicted shorter progression-free and overall survival (P = 0.001 and 0.013, respectively), and this negative prognostic impact was retained in multivariate analysis (P = 0.023). Conclusions: Flow cytometric quantification of cPCs using five surface antigens (CD138, CD38, CD56, CD19, and CD45) is a sensitive and simple method that can be used for assessing PCM prognosis; it would allow clinical laboratories to readily adopt a risk stratification strategy based on cPC levels in PCM patients.