Multiparametric flow cytometry profiling of neoplastic plasma cells in multiple myeloma

Hans Erik Johnsen; Martin Bøgsted; Tobias W. Klausen; Peter Gimsing; Alexander Schmitz; Erik Kjærsgaard; Tina Damgaard; Pia Voss; Lene M.  Knudsen; Anne Kærsgaard Mylin; Johan Lanng Nielsen; Bo Björkstrand; Astrid Gruber; Stig Lenhoff; Kari Remes; Inger marie Dahl; Kirsten Fogd; Karen Dybkær Sørensen; Hans E Johnsen; Martin Bøgsted; Tobias Wirenfeldt Klausen; Peter Gimsing; Alexander Schmitz; Erik Kjaersgaard; Tina Damgaard; Pia Voss; Lene M Knudsen; Anne K Mylin; Johan Lanng Nielsen; Bo Björkstrand; Astrid Gruber; Stig Lenhoff; Kari Remes; Inger Marie Dahl; Kirsten Fogd; Karen Dybkaer; Nordic Myeloma Study (NMSG)

doi:10.1002/cyto.b.20523

Multiparametric flow cytometry profiling of neoplastic plasma cells in multiple myeloma

Hans Erik Johnsen, Martin Bøgsted, Tobias W. Klausen, Peter Gimsing, Alexander Schmitz, Erik Kjærsgaard, Tina Damgaard, Pia Voss, Lene M. Knudsen, Anne Kærsgaard Mylin, Johan Lanng Nielsen, Bo Björkstrand, Astrid Gruber, Stig Lenhoff, Kari Remes, Inger marie Dahl, Kirsten Fogd, Karen Dybkær Sørensen, Hans E Johnsen, Martin BøgstedTobias Wirenfeldt Klausen, Peter Gimsing, Alexander Schmitz, Erik Kjaersgaard, Tina Damgaard, Pia Voss, Lene M Knudsen, Anne K Mylin, Johan Lanng Nielsen, Bo Björkstrand, Astrid Gruber, Stig Lenhoff, Kari Remes, Inger Marie Dahl, Kirsten Fogd, Karen Dybkaer, Nordic Myeloma Study (NMSG)

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › peer review

28 Citationer (Scopus)

Abstract

The clinical impact of multiparametric flow cytometry (MFC) in multiple myeloma (MM) is still unclear and under evaluation. Further progress relies on multiparametric profiling of the neoplastic plasma cell (PC) compartment to provide an accurate image of the stage of differentiation. The primary aim of this study was to perform global analysis of CD expression on the PC compartment and subsequently to evaluate the prognostic impact. Secondary aims were to study the diagnostic and predictive impact.

DESIGN AND METHODS: The design included a retrospective analysis of MFC data generated from diagnostic bone marrow (BM) samples of 109 Nordic patients included in clinical trials within NMSG. Whole marrow were analyzed by MFC for identification of end-stage CD45(-) /CD38(++) neoplastic PC and registered the relative numbers of events and mean fluorescence intensity (MFI) staining for CD19, CD20, CD27, CD28, CD38, CD44, CD45, CD56, and isotypes for cluster analysis.

RESULTS: The median MFC-PC number was 15%, and the median light microscopy (LM)-PC number was 35%. However, the numbers were significant correlated and the prognostic value with an increased relative risk (95% CI) of 3.1 (1.7-5.5) and 2.9 (1.4-6.2), P < 0.0003 and P < 0.004 of MFC-PC and LM-PC counts, respectively. Unsupervised clustering based on global MFI assessment on PC revealed two clusters based on CD expression profiling. Cluster I with high intensity for CD56, CD38, CD45, right-angle light-scatter signal (SSC), forward-angle light-scatter signal (FSC), and low for CD28, CD19, and a Cluster II, with low intensity of CD56, CD38, CD45, SSC, FSC, and high for CD28, CD19 with a median survival of 39 months and 19 months, respectively (P = 0.02).

CONCLUSIONS: The MFC analysis of MM BM samples produces diagnostic, prognostic, and predictive information useful in clinical practice, which will be prospectively validated within the European Myeloma Network (EMN). © 2010 International Clinical Cytometry Society.

Originalsprog	Engelsk
Tidsskrift	Cytometry. Part B: Clinical Cytometry
Vol/bind	78
Udgave nummer	5
Sider (fra-til)	338-47
Antal sider	10
ISSN	1552-4949
DOI	https://doi.org/10.1002/cyto.b.20523 https://doi.org/10.1002/cyto.b.20523
Status	Udgivet - 1 sep. 2010

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Citationsformater

Johnsen, H. E., Bøgsted, M., Klausen, T. W., Gimsing, P., Schmitz, A., Kjærsgaard, E., Damgaard, T., Voss, P., Knudsen, L. M., Mylin, A. K., Nielsen, J. L., Björkstrand, B., Gruber, A., Lenhoff, S., Remes, K., Dahl, I. M., Fogd, K., Sørensen, K. D., Johnsen, H. E., ... Nordic Myeloma Study (NMSG) (2010). Multiparametric flow cytometry profiling of neoplastic plasma cells in multiple myeloma. Cytometry. Part B: Clinical Cytometry, 78(5), 338-47. https://doi.org/10.1002/cyto.b.20523, https://doi.org/10.1002/cyto.b.20523

Johnsen, HE, Bøgsted, M, Klausen, TW, Gimsing, P, Schmitz, A, Kjærsgaard, E, Damgaard, T, Voss, P, Knudsen, LM, Mylin, AK, Nielsen, JL, Björkstrand, B, Gruber, A, Lenhoff, S, Remes, K, Dahl, IM, Fogd, K, Sørensen, KD, Johnsen, HE, Bøgsted, M, Klausen, TW, Gimsing, P, Schmitz, A, Kjaersgaard, E, Damgaard, T, Voss, P, Knudsen, LM, Mylin, AK, Nielsen, JL, Björkstrand, B, Gruber, A, Lenhoff, S, Remes, K, Dahl, IM, Fogd, K, Dybkaer, K & Nordic Myeloma Study (NMSG) 2010, 'Multiparametric flow cytometry profiling of neoplastic plasma cells in multiple myeloma', Cytometry. Part B: Clinical Cytometry, bind 78, nr. 5, s. 338-47. https://doi.org/10.1002/cyto.b.20523, https://doi.org/10.1002/cyto.b.20523

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title = "Multiparametric flow cytometry profiling of neoplastic plasma cells in multiple myeloma",

abstract = "The clinical impact of multiparametric flow cytometry (MFC) in multiple myeloma (MM) is still unclear and under evaluation. Further progress relies on multiparametric profiling of the neoplastic plasma cell (PC) compartment to provide an accurate image of the stage of differentiation. The primary aim of this study was to perform global analysis of CD expression on the PC compartment and subsequently to evaluate the prognostic impact. Secondary aims were to study the diagnostic and predictive impact.DESIGN AND METHODS: The design included a retrospective analysis of MFC data generated from diagnostic bone marrow (BM) samples of 109 Nordic patients included in clinical trials within NMSG. Whole marrow were analyzed by MFC for identification of end-stage CD45(-) /CD38(++) neoplastic PC and registered the relative numbers of events and mean fluorescence intensity (MFI) staining for CD19, CD20, CD27, CD28, CD38, CD44, CD45, CD56, and isotypes for cluster analysis.RESULTS: The median MFC-PC number was 15%, and the median light microscopy (LM)-PC number was 35%. However, the numbers were significant correlated and the prognostic value with an increased relative risk (95% CI) of 3.1 (1.7-5.5) and 2.9 (1.4-6.2), P < 0.0003 and P < 0.004 of MFC-PC and LM-PC counts, respectively. Unsupervised clustering based on global MFI assessment on PC revealed two clusters based on CD expression profiling. Cluster I with high intensity for CD56, CD38, CD45, right-angle light-scatter signal (SSC), forward-angle light-scatter signal (FSC), and low for CD28, CD19, and a Cluster II, with low intensity of CD56, CD38, CD45, SSC, FSC, and high for CD28, CD19 with a median survival of 39 months and 19 months, respectively (P = 0.02).CONCLUSIONS: The MFC analysis of MM BM samples produces diagnostic, prognostic, and predictive information useful in clinical practice, which will be prospectively validated within the European Myeloma Network (EMN). {\textcopyright} 2010 International Clinical Cytometry Society.",

author = "Johnsen, {Hans Erik} and Martin B{\o}gsted and Klausen, {Tobias W.} and Peter Gimsing and Alexander Schmitz and Erik Kj{\ae}rsgaard and Tina Damgaard and Pia Voss and Knudsen, {Lene M.} and Mylin, {Anne K{\ae}rsgaard} and Nielsen, {Johan Lanng} and Bo Bj{\"o}rkstrand and Astrid Gruber and Stig Lenhoff and Kari Remes and Dahl, {Inger marie} and Kirsten Fogd and S{\o}rensen, {Karen Dybk{\ae}r} and Johnsen, {Hans E} and Martin B{\o}gsted and Klausen, {Tobias Wirenfeldt} and Peter Gimsing and Alexander Schmitz and Erik Kjaersgaard and Tina Damgaard and Pia Voss and Knudsen, {Lene M} and Mylin, {Anne K} and Nielsen, {Johan Lanng} and Bo Bj{\"o}rkstrand and Astrid Gruber and Stig Lenhoff and Kari Remes and Dahl, {Inger Marie} and Kirsten Fogd and Karen Dybkaer and Peter Gimsing",

note = "Copyright {\textcopyright} 2010 International Clinical Cytometry Society.",

year = "2010",

month = sep,

day = "1",

doi = "10.1002/cyto.b.20523",

language = "English",

volume = "78",

pages = "338--47",

journal = "Cytometry. Part B: Clinical Cytometry",

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TY - JOUR

T1 - Multiparametric flow cytometry profiling of neoplastic plasma cells in multiple myeloma

AU - Johnsen, Hans Erik

AU - Bøgsted, Martin

AU - Klausen, Tobias W.

AU - Gimsing, Peter

AU - Schmitz, Alexander

AU - Kjærsgaard, Erik

AU - Damgaard, Tina

AU - Voss, Pia

AU - Knudsen, Lene M.

AU - Mylin, Anne Kærsgaard

AU - Nielsen, Johan Lanng

AU - Björkstrand, Bo

AU - Gruber, Astrid

AU - Lenhoff, Stig

AU - Remes, Kari

AU - Dahl, Inger marie

AU - Fogd, Kirsten

AU - Sørensen, Karen Dybkær

AU - Johnsen, Hans E

AU - Bøgsted, Martin

AU - Klausen, Tobias Wirenfeldt

AU - Gimsing, Peter

AU - Schmitz, Alexander

AU - Kjaersgaard, Erik

AU - Damgaard, Tina

AU - Voss, Pia

AU - Knudsen, Lene M

AU - Mylin, Anne K

AU - Nielsen, Johan Lanng

AU - Björkstrand, Bo

AU - Gruber, Astrid

AU - Lenhoff, Stig

AU - Remes, Kari

AU - Dahl, Inger Marie

AU - Fogd, Kirsten

AU - Dybkaer, Karen

AU - Nordic Myeloma Study (NMSG)

PY - 2010/9/1

Y1 - 2010/9/1

N2 - The clinical impact of multiparametric flow cytometry (MFC) in multiple myeloma (MM) is still unclear and under evaluation. Further progress relies on multiparametric profiling of the neoplastic plasma cell (PC) compartment to provide an accurate image of the stage of differentiation. The primary aim of this study was to perform global analysis of CD expression on the PC compartment and subsequently to evaluate the prognostic impact. Secondary aims were to study the diagnostic and predictive impact.DESIGN AND METHODS: The design included a retrospective analysis of MFC data generated from diagnostic bone marrow (BM) samples of 109 Nordic patients included in clinical trials within NMSG. Whole marrow were analyzed by MFC for identification of end-stage CD45(-) /CD38(++) neoplastic PC and registered the relative numbers of events and mean fluorescence intensity (MFI) staining for CD19, CD20, CD27, CD28, CD38, CD44, CD45, CD56, and isotypes for cluster analysis.RESULTS: The median MFC-PC number was 15%, and the median light microscopy (LM)-PC number was 35%. However, the numbers were significant correlated and the prognostic value with an increased relative risk (95% CI) of 3.1 (1.7-5.5) and 2.9 (1.4-6.2), P < 0.0003 and P < 0.004 of MFC-PC and LM-PC counts, respectively. Unsupervised clustering based on global MFI assessment on PC revealed two clusters based on CD expression profiling. Cluster I with high intensity for CD56, CD38, CD45, right-angle light-scatter signal (SSC), forward-angle light-scatter signal (FSC), and low for CD28, CD19, and a Cluster II, with low intensity of CD56, CD38, CD45, SSC, FSC, and high for CD28, CD19 with a median survival of 39 months and 19 months, respectively (P = 0.02).CONCLUSIONS: The MFC analysis of MM BM samples produces diagnostic, prognostic, and predictive information useful in clinical practice, which will be prospectively validated within the European Myeloma Network (EMN). © 2010 International Clinical Cytometry Society.

AB - The clinical impact of multiparametric flow cytometry (MFC) in multiple myeloma (MM) is still unclear and under evaluation. Further progress relies on multiparametric profiling of the neoplastic plasma cell (PC) compartment to provide an accurate image of the stage of differentiation. The primary aim of this study was to perform global analysis of CD expression on the PC compartment and subsequently to evaluate the prognostic impact. Secondary aims were to study the diagnostic and predictive impact.DESIGN AND METHODS: The design included a retrospective analysis of MFC data generated from diagnostic bone marrow (BM) samples of 109 Nordic patients included in clinical trials within NMSG. Whole marrow were analyzed by MFC for identification of end-stage CD45(-) /CD38(++) neoplastic PC and registered the relative numbers of events and mean fluorescence intensity (MFI) staining for CD19, CD20, CD27, CD28, CD38, CD44, CD45, CD56, and isotypes for cluster analysis.RESULTS: The median MFC-PC number was 15%, and the median light microscopy (LM)-PC number was 35%. However, the numbers were significant correlated and the prognostic value with an increased relative risk (95% CI) of 3.1 (1.7-5.5) and 2.9 (1.4-6.2), P < 0.0003 and P < 0.004 of MFC-PC and LM-PC counts, respectively. Unsupervised clustering based on global MFI assessment on PC revealed two clusters based on CD expression profiling. Cluster I with high intensity for CD56, CD38, CD45, right-angle light-scatter signal (SSC), forward-angle light-scatter signal (FSC), and low for CD28, CD19, and a Cluster II, with low intensity of CD56, CD38, CD45, SSC, FSC, and high for CD28, CD19 with a median survival of 39 months and 19 months, respectively (P = 0.02).CONCLUSIONS: The MFC analysis of MM BM samples produces diagnostic, prognostic, and predictive information useful in clinical practice, which will be prospectively validated within the European Myeloma Network (EMN). © 2010 International Clinical Cytometry Society.

U2 - 10.1002/cyto.b.20523

DO - 10.1002/cyto.b.20523

M3 - Journal article

C2 - 20533391

SN - 1552-4949

VL - 78

SP - 338

EP - 347

JO - Cytometry. Part B: Clinical Cytometry

JF - Cytometry. Part B: Clinical Cytometry

IS - 5

ER -