Peripheral Blood Involvement with Minimal Disease Is Common in Multiple Myeloma but Not in Smoldering Myeloma

Plasma cell dyscrasias (PCD) are characterized by the accumulation of clonal abnormal plasma cells (APC) in the bone marrow (BM) and excessive monoclonal proteins in the serum and/or urine that ultimately leads to end-organ damage. BM evaluation of plasma cells (PC) is an important criterion for the diagnosis and risk stratification schemes in patient with PCD. The percent APCs in BM determined by flow cytometry (FC) has been shown to be an independent risk factor for progression from myeloma precursor disease (monoclonal gammopathy of uncertain significance, MGUS; smoldering multiple myeloma, SMM) to multiple myeloma (MM). However, the role of FC evaluation of APC in peripheral blood (PB) is not well studied. In this study we evaluate FC characterization of circulating PCs in the PB from patients with SMM and MM.

Both PB & BM aspirate specimens from 27 patients (15 SMM & 12 MM) were analyzed with 8-color multiparametric FC using a panel of antibodies (CD138, CD38, CD19, CD20, CD27, CD28, CD45, CD56, CD117, CD13, CD14, CD16, CD3, CD34 and intracellular kappa & lambda light chains) and acquiring over 3 million events. The pattern of surface antigen and intracellular light chain expression was utilized to determine the percent of all PCs that are APC (defined as monoclonal with aberrant antigen expression). The percentages of PB APCs were correlated with percentages of BM APCs and BM biopsy findings.

Of the 27 cases, PCs were detected in PB from 20 patients (10 SMM & 10 MM). Mean percentage of total PCs in PB from SMM was 0. 011% (range 0. 002–0. 01) and from MM patients 0. 099% (range 0. 006–0. 5). APCs were detected in 4/15 (26%) SMM cases (mean APC 34. 8% of PCs, range 7–99%) and 10/12 (83%) MM cases (mean APC 97. 6% of PC, range 90–99%). We assessed the immunophenotypic features of APCs from PB with APCs of BM and no immunophenotypic statistical differences were detected.

FC evaluation of PB PCs from patients is useful in the differentiation between MM and the precursor disease SMM. Greater than 95% APC was observed in PB in some MM patients. Extent of PB involvement with APC may be an independent prognostic indicator in monitoring progression of SMM to MM.

No relevant conflicts of interest to declare.