Enumeration and characterization of circulating multiple myeloma cells in patients with plasma cell disorders
Summary We have developed an automated assay to enumerate and characterize circulating multiple myeloma cells (CMMC) from peripheral blood of patients with plasma cell disorders. CMMC show expression of genes characteristic of myeloma and fluorescence in situ hybridisation results on CMMC correlated...
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| Veröffentlicht in: | British journal of haematology 2018-01, Vol.180 (1), p.71-81 |
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| creator | Foulk, Brad Schaffer, Mike Gross, Steve Rao, Chandra Smirnov, Denis Connelly, Mark C. Chaturvedi, Shalini Reddy, Manjula Brittingham, Greg Mata, Marielena Repollet, Madeline Rojas, Claudia Auclair, Daniel DeRome, Mary Weiss, Brendan Sasser, Amy K. |
| description | Summary
We have developed an automated assay to enumerate and characterize circulating multiple myeloma cells (CMMC) from peripheral blood of patients with plasma cell disorders. CMMC show expression of genes characteristic of myeloma and fluorescence in situ hybridisation results on CMMC correlated well with bone marrow results. We enumerated CMMC from over 1000 patient samples including separate cohorts of newly diagnosed multiple myeloma and high/intermediate risk smouldering multiple myeloma (SMM) with clinical follow‐up data. In newly diagnosed myeloma patient samples, CMMC counts correlated with other clinical measures of disease burden, including the percentage of bone marrow plasma cells, serum M protein, and International Staging System stage. CMMC counts decreased significantly from baseline when a remission was achieved due to treatment (P |
| doi_str_mv | 10.1111/bjh.15003 |
| format | Article |
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We have developed an automated assay to enumerate and characterize circulating multiple myeloma cells (CMMC) from peripheral blood of patients with plasma cell disorders. CMMC show expression of genes characteristic of myeloma and fluorescence in situ hybridisation results on CMMC correlated well with bone marrow results. We enumerated CMMC from over 1000 patient samples including separate cohorts of newly diagnosed multiple myeloma and high/intermediate risk smouldering multiple myeloma (SMM) with clinical follow‐up data. In newly diagnosed myeloma patient samples, CMMC counts correlated with other clinical measures of disease burden, including the percentage of bone marrow plasma cells, serum M protein, and International Staging System stage. CMMC counts decreased significantly from baseline when a remission was achieved due to treatment (P < 0·001). Patients with CMMC counts ≥100 at remission showed reduced survival relative to patients with CMMC counts <100. Patients with undetectable CMMC in remission showed further overall survival benefits. In the SMM cohort, there was a trend toward higher CMMC in patients with higher‐risk myeloma precursor states. Significantly higher CMMC counts were observed between intermediate/high risk SMM patients that progressed versus those without progression (P = 0·031). CMMC allow a non‐invasive means of monitoring tumour biology and may have use as a prognostic test for patients with plasma cell disorders.</description><identifier>ISSN: 0007-1048</identifier><identifier>EISSN: 1365-2141</identifier><identifier>DOI: 10.1111/bjh.15003</identifier><identifier>PMID: 29105742</identifier><language>eng</language><publisher>England: Blackwell Publishing Ltd</publisher><subject>Adult ; Aged ; biomarker ; Blood circulation ; Bone marrow ; Bone Marrow - pathology ; Cell Count ; circulating tumour cell ; Cohort Studies ; Diagnosis, Differential ; Enumeration ; Female ; Flow Cytometry - methods ; Fluorescence ; Hematology ; Humans ; In Situ Hybridization, Fluorescence ; M protein ; Male ; Middle Aged ; Multiple myeloma ; Multiple Myeloma - blood ; Multiple Myeloma - diagnosis ; Multiple Myeloma - genetics ; Multiple Myeloma - mortality ; Neoplasms, Plasma Cell - blood ; Neoplasms, Plasma Cell - diagnosis ; Neoplasms, Plasma Cell - genetics ; Neoplasms, Plasma Cell - mortality ; Neoplastic Cells, Circulating - metabolism ; Neoplastic Cells, Circulating - pathology ; Patients ; Peripheral blood ; Plasma ; plasma cell ; Plasma cells ; Prognosis ; Remission ; Reproducibility of Results ; ROC Curve ; Sensitivity and Specificity ; smouldering myeloma ; Tumors</subject><ispartof>British journal of haematology, 2018-01, Vol.180 (1), p.71-81</ispartof><rights>2017 John Wiley & Sons Ltd</rights><rights>2017 John Wiley & Sons Ltd.</rights><rights>Copyright © 2018 John Wiley & Sons Ltd</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3883-7eb7351380053026d68b9c299151237316965080dbf9f7b4c3291e40ac03b9463</citedby><cites>FETCH-LOGICAL-c3883-7eb7351380053026d68b9c299151237316965080dbf9f7b4c3291e40ac03b9463</cites><orcidid>0000-0003-2502-2399</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1111%2Fbjh.15003$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1111%2Fbjh.15003$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,776,780,1411,1427,27901,27902,45550,45551,46384,46808</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/29105742$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Foulk, Brad</creatorcontrib><creatorcontrib>Schaffer, Mike</creatorcontrib><creatorcontrib>Gross, Steve</creatorcontrib><creatorcontrib>Rao, Chandra</creatorcontrib><creatorcontrib>Smirnov, Denis</creatorcontrib><creatorcontrib>Connelly, Mark C.</creatorcontrib><creatorcontrib>Chaturvedi, Shalini</creatorcontrib><creatorcontrib>Reddy, Manjula</creatorcontrib><creatorcontrib>Brittingham, Greg</creatorcontrib><creatorcontrib>Mata, Marielena</creatorcontrib><creatorcontrib>Repollet, Madeline</creatorcontrib><creatorcontrib>Rojas, Claudia</creatorcontrib><creatorcontrib>Auclair, Daniel</creatorcontrib><creatorcontrib>DeRome, Mary</creatorcontrib><creatorcontrib>Weiss, Brendan</creatorcontrib><creatorcontrib>Sasser, Amy K.</creatorcontrib><creatorcontrib>MMRF CoMMpass Network</creatorcontrib><creatorcontrib>The MMRF CoMMpass Network</creatorcontrib><title>Enumeration and characterization of circulating multiple myeloma cells in patients with plasma cell disorders</title><title>British journal of haematology</title><addtitle>Br J Haematol</addtitle><description>Summary
We have developed an automated assay to enumerate and characterize circulating multiple myeloma cells (CMMC) from peripheral blood of patients with plasma cell disorders. CMMC show expression of genes characteristic of myeloma and fluorescence in situ hybridisation results on CMMC correlated well with bone marrow results. We enumerated CMMC from over 1000 patient samples including separate cohorts of newly diagnosed multiple myeloma and high/intermediate risk smouldering multiple myeloma (SMM) with clinical follow‐up data. In newly diagnosed myeloma patient samples, CMMC counts correlated with other clinical measures of disease burden, including the percentage of bone marrow plasma cells, serum M protein, and International Staging System stage. CMMC counts decreased significantly from baseline when a remission was achieved due to treatment (P < 0·001). Patients with CMMC counts ≥100 at remission showed reduced survival relative to patients with CMMC counts <100. Patients with undetectable CMMC in remission showed further overall survival benefits. In the SMM cohort, there was a trend toward higher CMMC in patients with higher‐risk myeloma precursor states. Significantly higher CMMC counts were observed between intermediate/high risk SMM patients that progressed versus those without progression (P = 0·031). CMMC allow a non‐invasive means of monitoring tumour biology and may have use as a prognostic test for patients with plasma cell disorders.</description><subject>Adult</subject><subject>Aged</subject><subject>biomarker</subject><subject>Blood circulation</subject><subject>Bone marrow</subject><subject>Bone Marrow - pathology</subject><subject>Cell Count</subject><subject>circulating tumour cell</subject><subject>Cohort Studies</subject><subject>Diagnosis, Differential</subject><subject>Enumeration</subject><subject>Female</subject><subject>Flow Cytometry - methods</subject><subject>Fluorescence</subject><subject>Hematology</subject><subject>Humans</subject><subject>In Situ Hybridization, Fluorescence</subject><subject>M protein</subject><subject>Male</subject><subject>Middle Aged</subject><subject>Multiple myeloma</subject><subject>Multiple Myeloma - blood</subject><subject>Multiple Myeloma - diagnosis</subject><subject>Multiple Myeloma - genetics</subject><subject>Multiple Myeloma - mortality</subject><subject>Neoplasms, Plasma Cell - blood</subject><subject>Neoplasms, Plasma Cell - diagnosis</subject><subject>Neoplasms, Plasma Cell - genetics</subject><subject>Neoplasms, Plasma Cell - mortality</subject><subject>Neoplastic Cells, Circulating - metabolism</subject><subject>Neoplastic Cells, Circulating - pathology</subject><subject>Patients</subject><subject>Peripheral blood</subject><subject>Plasma</subject><subject>plasma cell</subject><subject>Plasma cells</subject><subject>Prognosis</subject><subject>Remission</subject><subject>Reproducibility of Results</subject><subject>ROC Curve</subject><subject>Sensitivity and Specificity</subject><subject>smouldering myeloma</subject><subject>Tumors</subject><issn>0007-1048</issn><issn>1365-2141</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2018</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kctOwzAQRS0EoqWw4AeQJTawCMzEeXkJVXkJiQ2sI8dxqCvngZ2oKl-PSwoLJLyxPD46mplLyCnCFfpzXayWVxgDsD0yRZbEQYgR7pMpAKQBQpRNyJFzKwBkEOMhmYQcIU6jcErqRTPUyopetw0VTUnlUlghe2X151hsKyq1lYPxz-ad1oPpdWcUrTfKtLWgUhnjqG5o5wHV9I6udb-knRFu90tL7VpbKuuOyUEljFMnu3tG3u4Wr_OH4Pnl_nF-8xxIlmUsSFWRshhZBhAzCJMyyQouQ84xxpClDBOexJBBWVS8SotIMj-QikBIYAWPEjYjF6O3s-3HoFyf19ptWxGNageXI08QvB4jj57_QVftYBvfnacySHjEYUtdjpS0rXNWVXlndS3sJkfItxnkPoP8OwPPnu2MQ1Gr8pf8WboHrkdgrY3a_G_Kb58eRuUXt4CPWA</recordid><startdate>201801</startdate><enddate>201801</enddate><creator>Foulk, Brad</creator><creator>Schaffer, Mike</creator><creator>Gross, Steve</creator><creator>Rao, Chandra</creator><creator>Smirnov, Denis</creator><creator>Connelly, Mark C.</creator><creator>Chaturvedi, Shalini</creator><creator>Reddy, Manjula</creator><creator>Brittingham, Greg</creator><creator>Mata, Marielena</creator><creator>Repollet, Madeline</creator><creator>Rojas, Claudia</creator><creator>Auclair, Daniel</creator><creator>DeRome, Mary</creator><creator>Weiss, Brendan</creator><creator>Sasser, Amy K.</creator><general>Blackwell Publishing Ltd</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7T5</scope><scope>H94</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0003-2502-2399</orcidid></search><sort><creationdate>201801</creationdate><title>Enumeration and characterization of circulating multiple myeloma cells in patients with plasma cell disorders</title><author>Foulk, Brad ; Schaffer, Mike ; Gross, Steve ; Rao, Chandra ; Smirnov, Denis ; Connelly, Mark C. ; Chaturvedi, Shalini ; Reddy, Manjula ; Brittingham, Greg ; Mata, Marielena ; Repollet, Madeline ; Rojas, Claudia ; Auclair, Daniel ; DeRome, Mary ; Weiss, Brendan ; Sasser, Amy K.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3883-7eb7351380053026d68b9c299151237316965080dbf9f7b4c3291e40ac03b9463</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2018</creationdate><topic>Adult</topic><topic>Aged</topic><topic>biomarker</topic><topic>Blood circulation</topic><topic>Bone marrow</topic><topic>Bone Marrow - pathology</topic><topic>Cell Count</topic><topic>circulating tumour cell</topic><topic>Cohort Studies</topic><topic>Diagnosis, Differential</topic><topic>Enumeration</topic><topic>Female</topic><topic>Flow Cytometry - methods</topic><topic>Fluorescence</topic><topic>Hematology</topic><topic>Humans</topic><topic>In Situ Hybridization, Fluorescence</topic><topic>M protein</topic><topic>Male</topic><topic>Middle Aged</topic><topic>Multiple myeloma</topic><topic>Multiple Myeloma - blood</topic><topic>Multiple Myeloma - diagnosis</topic><topic>Multiple Myeloma - genetics</topic><topic>Multiple Myeloma - mortality</topic><topic>Neoplasms, Plasma Cell - blood</topic><topic>Neoplasms, Plasma Cell - diagnosis</topic><topic>Neoplasms, Plasma Cell - genetics</topic><topic>Neoplasms, Plasma Cell - mortality</topic><topic>Neoplastic Cells, Circulating - metabolism</topic><topic>Neoplastic Cells, Circulating - pathology</topic><topic>Patients</topic><topic>Peripheral blood</topic><topic>Plasma</topic><topic>plasma cell</topic><topic>Plasma cells</topic><topic>Prognosis</topic><topic>Remission</topic><topic>Reproducibility of Results</topic><topic>ROC Curve</topic><topic>Sensitivity and Specificity</topic><topic>smouldering myeloma</topic><topic>Tumors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Foulk, Brad</creatorcontrib><creatorcontrib>Schaffer, Mike</creatorcontrib><creatorcontrib>Gross, Steve</creatorcontrib><creatorcontrib>Rao, Chandra</creatorcontrib><creatorcontrib>Smirnov, Denis</creatorcontrib><creatorcontrib>Connelly, Mark C.</creatorcontrib><creatorcontrib>Chaturvedi, Shalini</creatorcontrib><creatorcontrib>Reddy, Manjula</creatorcontrib><creatorcontrib>Brittingham, Greg</creatorcontrib><creatorcontrib>Mata, Marielena</creatorcontrib><creatorcontrib>Repollet, Madeline</creatorcontrib><creatorcontrib>Rojas, Claudia</creatorcontrib><creatorcontrib>Auclair, Daniel</creatorcontrib><creatorcontrib>DeRome, Mary</creatorcontrib><creatorcontrib>Weiss, Brendan</creatorcontrib><creatorcontrib>Sasser, Amy K.</creatorcontrib><creatorcontrib>MMRF CoMMpass Network</creatorcontrib><creatorcontrib>The MMRF CoMMpass Network</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Immunology Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>British journal of haematology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Foulk, Brad</au><au>Schaffer, Mike</au><au>Gross, Steve</au><au>Rao, Chandra</au><au>Smirnov, Denis</au><au>Connelly, Mark C.</au><au>Chaturvedi, Shalini</au><au>Reddy, Manjula</au><au>Brittingham, Greg</au><au>Mata, Marielena</au><au>Repollet, Madeline</au><au>Rojas, Claudia</au><au>Auclair, Daniel</au><au>DeRome, Mary</au><au>Weiss, Brendan</au><au>Sasser, Amy K.</au><aucorp>MMRF CoMMpass Network</aucorp><aucorp>The MMRF CoMMpass Network</aucorp><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Enumeration and characterization of circulating multiple myeloma cells in patients with plasma cell disorders</atitle><jtitle>British journal of haematology</jtitle><addtitle>Br J Haematol</addtitle><date>2018-01</date><risdate>2018</risdate><volume>180</volume><issue>1</issue><spage>71</spage><epage>81</epage><pages>71-81</pages><issn>0007-1048</issn><eissn>1365-2141</eissn><abstract>Summary
We have developed an automated assay to enumerate and characterize circulating multiple myeloma cells (CMMC) from peripheral blood of patients with plasma cell disorders. CMMC show expression of genes characteristic of myeloma and fluorescence in situ hybridisation results on CMMC correlated well with bone marrow results. We enumerated CMMC from over 1000 patient samples including separate cohorts of newly diagnosed multiple myeloma and high/intermediate risk smouldering multiple myeloma (SMM) with clinical follow‐up data. In newly diagnosed myeloma patient samples, CMMC counts correlated with other clinical measures of disease burden, including the percentage of bone marrow plasma cells, serum M protein, and International Staging System stage. CMMC counts decreased significantly from baseline when a remission was achieved due to treatment (P < 0·001). Patients with CMMC counts ≥100 at remission showed reduced survival relative to patients with CMMC counts <100. Patients with undetectable CMMC in remission showed further overall survival benefits. In the SMM cohort, there was a trend toward higher CMMC in patients with higher‐risk myeloma precursor states. Significantly higher CMMC counts were observed between intermediate/high risk SMM patients that progressed versus those without progression (P = 0·031). CMMC allow a non‐invasive means of monitoring tumour biology and may have use as a prognostic test for patients with plasma cell disorders.</abstract><cop>England</cop><pub>Blackwell Publishing Ltd</pub><pmid>29105742</pmid><doi>10.1111/bjh.15003</doi><tpages>11</tpages><orcidid>https://orcid.org/0000-0003-2502-2399</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | Adult Aged biomarker Blood circulation Bone marrow Bone Marrow - pathology Cell Count circulating tumour cell Cohort Studies Diagnosis, Differential Enumeration Female Flow Cytometry - methods Fluorescence Hematology Humans In Situ Hybridization, Fluorescence M protein Male Middle Aged Multiple myeloma Multiple Myeloma - blood Multiple Myeloma - diagnosis Multiple Myeloma - genetics Multiple Myeloma - mortality Neoplasms, Plasma Cell - blood Neoplasms, Plasma Cell - diagnosis Neoplasms, Plasma Cell - genetics Neoplasms, Plasma Cell - mortality Neoplastic Cells, Circulating - metabolism Neoplastic Cells, Circulating - pathology Patients Peripheral blood Plasma plasma cell Plasma cells Prognosis Remission Reproducibility of Results ROC Curve Sensitivity and Specificity smouldering myeloma Tumors |
| title | Enumeration and characterization of circulating multiple myeloma cells in patients with plasma cell disorders |
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