Circulating plasma cells in multiple myeloma: characterization and correlation with disease stage

Abstract

Summary. The aim of this study was to develop a flow cytometric test to quantitate low levels of circulating myeloma plasma cells, and to determine the relationship of these cells with disease stage. Cells were characterized using five-parameter flow cytometric analysis with a panel of antibodies, and results were evaluated by comparison with fluorescent consensus-primer IgH-PCR.Bone marrow myeloma plasma cells, defined by high CD38 and Syndecan-1 expression, did not express CD10, 23, 30, 34 or 45RO, and demonstrated weak expression of CD37 and CD45. 65% of patients had CD19 ¹ 56 þ plasma cells, 30% CD19 ¹ 56 low , and 5% CD19 þ 56 þ , and these two antigens discriminated myeloma from normal plasma cells, which were all CD19 þ 56 low .Peripheral blood myeloma plasma cells had the same composite phenotype, but expressed significantly lower levels of CD56 and Syndecan-1, and were detected in 75% (38/51) of patients at presentation, 92% (11/12) of patients in relapse, and 40% (4/10) of stem cell harvests. Circulating plasma cells were not detectable in patients in CR (n ¼ 9) or normals (n ¼ 10), at a sensitivity of up to 1 in 10 000 cells. There was good correlation between the flow cytometric test and IgH-PCR results: myeloma plasma cells were detectable by flow cytometry in all PCR positive samples, and samples with no detectable myeloma plasma cells were PCR negative. Absolute numbers decreased in patients responding to treatment, remained elevated in patients with refractory disease, and increased in patients undergoing relapse. We conclude that flow cytometry can provide an effective aternative to IgH-PCR that will allow quantitative assessment of low levels of residual disease.

The absence of CD56 (NCAM) on malignant plasma cells is a hallmark of plasma cell leukemia and of a special subset of multiple myeloma

“…Clearly, their CD56 − MM patients (45% of their patients) did not overlap our CD56 − population of patients. On the other hand, our data are in complete agreement with those of Rawstron et al, 12 showing a weaker expression of CD56 on circulating myeloma cells in MM lacking overt PCL. A last point deserves some comment.…”

“…The interest in using CD138 to define plasma cells has been validated by ourselves 8 and recently confirmed by others. 12 CD138 plasma cell identification was controlled by coexpression of CD38 and intracytoplasmic / immunofluorescence, in a three-color assay. 13 The mean fluorescence ratio (MFR) was calculated as follows: mean of specific fluorescence/mean of control fluorescence.…”

Utility of flow cytometry immunophenotyping in multiple myeloma and other clonal plasma cell‐related disorders

“…Circulating aberrant PC have been detected at diagnosis in a relatively high percentage of MM cases (46-75%) (122,123) and in patients with MGUS and smoldering MM (25 and 50%, respectively) (124). However, contradictory results exist concerning the relationship between frequency of PB clonal PC and tumor burden, disease stage or cytogenetic abnormalities (39,(122)(123)(124); in addition, the clinic-biological significance of PC trafficking still remains to be clarified. Circulating aberrant PC have been found in PB-derived leukaphaeresis products after mobilization (16-41%) (72,125) and prior to ASCT (39%) (125).…”

Competition between clonal plasma cells and normal cells for potentially overlapping bone marrow niches is associated with a progressively altered cellular distribution in MGUS vs myeloma

“…5,6 Despite the different tumor mass [7][8][9][10][11][12][13][14] and clinical behavior of the disease, clonal PC from MGUS, SMM and MM patients show highly similar and largely overlapping genetic profiles. [15][16][17] In addition, no clear phenotypic differences have been reported so far among clonal PC from MGUS, SMM and MM, 18 except for a few molecules involved in the interaction between PC and their microenvironment.…”