Clonal circulating cells are common in plasma cell proliferative disorders: a comparison of monoclonal gammopathy of undetermined significance, smoldering multiple myeloma, and active myeloma

Abstract

The blood of most patients with active multiple myeloma (MM) contains cells related to the bone marrow tumor. However, identifying clonal cells in the blood of patients with monoclonal gammopathy of undetermined significance (MGUS) has been difficult. In this study, we analyzed blood mononuclear cells (BMNCs) from 16 patients with MGUS, 2 with amyloidosis, 8 with smoldering MM (SMM), 2 with indolent MM (IMM), and 15 with active MM using three different methods to detect and quantitate clonal cells, ie, immunofluorescence microscopy (IM) for monoclonal plasma cells, three-color flow cytometry (FC) for CD38(+)CD45- CD45(dim) cells, and the allele-specific oligonucleotide polymerase chain reaction (ASO-PCR). Using ASO-PCR, we were able to detect clonal cells in the blood in 13 of 16 patients with MGUS, 2 of 2 with amyloid, 6 of 8 with SMM, 2 of 2 with IMM, and 13 of 15 with MM. In 9 of the 13 patients with MGUS with blood involvement, the number of clonal cells was very small ( < 0.04% of the BMNCs). The median percentage of clonal cells as determined by ASO-PCR was 0.02 for MGUS, 0.02 for SMM, and 0.24 for MM. Clonal plasma cells or CD38+CD45- CD45(dim) cells were identified by IM or FC in 6 of 16 MGUS patients, 4 of 8 with SMM, and 11 of 15 with MM. In all cases in which IM or FC detected clonal cells, the ASO-PCR was positive. This study shows that, by using ASO-PCR, clonal cells can be found at very low levels in the blood in most patients with MGUS. However, the number of clonal cells in the blood of MGUS patients is less than those with overt MM (P = .006). In contrast to MGUS, patients with active MM are more likely to have identifiable clonal circulating plasma cells (P = .05).

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

“…In these cases, ASO-PCR provided no increase in sensitivity over either IgH-PCR or flow cytometry. The results of Billadeau et al (1996) indicated that approximately 70% of patients with circulating clone will have levels within the sensitivity of the flow cytometric assay. We would therefore suggest that it is more rapid and cost-effective to assess these samples with flow cytometry and/or consensus primer-PCR first, in order to determine whether there is a requirement to develop patient-specific primers.…”

Review of phenotypic markers used in flow cytometric analysis of MGUS and MM, and applicability of flow cytometry in other plasma cell disorders

“…Some circulating B lymphocytes (CD19 + ) in MGUS and MM also carry karyotypic changes and chromosomal aberrations similar to myeloma cells. About 0AE1-1AE8% (MM) and 0.02% (MGUS) of CD19 + circulating cells carry similar chromosomal changes as BM myeloma cells (Chen & Epstein, 1996;Billadeau et al, 1996;Zojer et al, 2001).…”

Enhanced production of osteopontin in multiple myeloma: clinical and pathogenic implications

“…Multiple myeloma (MM) is a malignant disease that results from the uncontrolled proliferation of plasma cells derived from a single clone (Billadeau et al , 1996). The most common clinical problem in patients with MM is extensive bone destruction (or bone resorption), which occurs in almost all patients and is accompanied by severe and intractable pain and susceptibility to fracture (Roodman, 1997).…”