Clonal circulating cells are common in plasma cell proliferative disorders

A comparison of monoclonal gammopathy of undetermined significance, smoldering multiple myeloma, and active myeloma

Daniel D Billadeau, Brian Van Ness, Terry Kimlinger, Robert A. Kyle, Terry M Therneau, Philip R. Greipp, Thomas Elmer Witzig

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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 patientswith 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) celts 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).

Original languageEnglish (US)
Pages (from-to)289-296
Number of pages8
JournalBlood
Volume88
Issue number1
StatePublished - Jul 1 1996

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Monoclonal Gammopathy of Undetermined Significance
Plasma Cells
Multiple Myeloma
Blood
Polymerase chain reaction
Plasmas
Blood Cells
Flow cytometry
Alleles
Polymerase Chain Reaction
Fluorescence Microscopy
Microscopic examination
Flow Cytometry
Cell Count
Amyloid
Tumors
Bone
ribonucleotide polymerase
Color
Bone Marrow

ASJC Scopus subject areas

  • Hematology

Cite this

Clonal circulating cells are common in plasma cell proliferative disorders : A comparison of monoclonal gammopathy of undetermined significance, smoldering multiple myeloma, and active myeloma. / Billadeau, Daniel D; Van Ness, Brian; Kimlinger, Terry; Kyle, Robert A.; Therneau, Terry M; Greipp, Philip R.; Witzig, Thomas Elmer.

In: Blood, Vol. 88, No. 1, 01.07.1996, p. 289-296.

Research output: Contribution to journalArticle

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title = "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 patientswith 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) celts 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).",
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