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Immunophenotype of normal vs. myeloma plasma cells: Toward antibody panel specifications for MRD detection in multiple myeloma.
Cytometry B Clin Cytom. 2016 Jan; 90(1):61-72.CB

Abstract

In recent years, several studies on large series of multiple myeloma (MM) patients have demonstrated the clinical utility of flow cytometry monitoring of minimal residual disease (flow-MRD) in bone marrow (BM), for improved assessment of response to therapy and prognostication. However, disturbing levels of variability exist regarding the specific protocols and antibody panels used in individual laboratories. Overall, consensus exists about the utility of combined assessment of CD38 and CD138 for the identification of BM plasma cells (PC); in contrast, more heterogeneous lists of markers are used to further distinguish between normal/reactive PCs and myeloma PCs in the MRD settings. Among the later markers, CD19, CD45, CD27, and CD81, together with CD56, CD117, CD200, and CD307, have emerged as particularly informative; however, no single marker provides enough specificity for clear discrimination between clonal PCs and normal PCs. Accordingly, multivariate analyses of single PCs from large series of normal/reactive vs. myeloma BM samples have shown that combined assessment of CD138 and CD38, together with CD45, CD19, CD56, CD27, CD81, and CD117 would be ideally suited for MRD monitoring in virtually every MM patient. However, the specific antibody clones, fluorochrome conjugates and sources of the individual markers determines its optimal (vs. suboptimal or poor) performance in an eight-color staining. Assessment of clonality, via additional cytoplasmic immunoglobulin (CyIg) κ vs. CyIgλ evaluation, may contribute to further establish the normal/reactive vs. clonal nature of small suspicious PC populations at high sensitivity levels, provided that enough cells are evaluated.

Authors+Show Affiliations

Centro de Investigación del Cáncer (Instituto de Biología Molecular y Celular del Cáncer, CSIC-USAL), Instituto Biosanitario de Salamanca (IBSAL), Servicio de Citometría y Departamento de Medicina-NUCLEUS, Universidad de Salamanca (Salamanca), Spain.Haematological Malignancy Diagnostic Service, St James Institute of Oncology, Leeds Teaching Hospitals, Leeds, United Kingdom.Clínica Universidad de Navarra, Centro de Investigaciones Médicas Aplicadas (CIMA), Pamplona, Spain.Department of Hematology, Hospital Universitario de Salamanca, Instituto Biosanitario de Salamanca (IBSAL), Centro de Investigación del Cáncer (Instituto de Biología Molecular y Celular del Cáncer, CSIC-USAL), Salamanca, Spain.Second Department of Medicine, University Hospital of Schleswig Holstein, Campus Kiel (UNIKIEL), Kiel, Germany.Department of Immunology, Erasmus MC, University Medical Center Rotterdam (Erasmus MC), Rotterdam, The Netherlands.Centro de Investigación del Cáncer (Instituto de Biología Molecular y Celular del Cáncer, CSIC-USAL), Instituto Biosanitario de Salamanca (IBSAL), Servicio de Citometría y Departamento de Medicina-NUCLEUS, Universidad de Salamanca (Salamanca), Spain.Department of Hematology, Hospital Universitario de Salamanca, Instituto Biosanitario de Salamanca (IBSAL), Centro de Investigación del Cáncer (Instituto de Biología Molecular y Celular del Cáncer, CSIC-USAL), Salamanca, Spain.Centro de Investigación del Cáncer (Instituto de Biología Molecular y Celular del Cáncer, CSIC-USAL), Instituto Biosanitario de Salamanca (IBSAL), Servicio de Citometría y Departamento de Medicina-NUCLEUS, Universidad de Salamanca (Salamanca), Spain.Department of Hematology, Hospital Universitario de Salamanca, Instituto Biosanitario de Salamanca (IBSAL), Centro de Investigación del Cáncer (Instituto de Biología Molecular y Celular del Cáncer, CSIC-USAL), Salamanca, Spain.Department of Immunology, Erasmus MC, University Medical Center Rotterdam (Erasmus MC), Rotterdam, The Netherlands.Centro de Investigación del Cáncer (Instituto de Biología Molecular y Celular del Cáncer, CSIC-USAL), Instituto Biosanitario de Salamanca (IBSAL), Servicio de Citometría y Departamento de Medicina-NUCLEUS, Universidad de Salamanca (Salamanca), Spain.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Review

Language

eng

PubMed ID

26100534

Citation

Flores-Montero, Juan, et al. "Immunophenotype of Normal Vs. Myeloma Plasma Cells: Toward Antibody Panel Specifications for MRD Detection in Multiple Myeloma." Cytometry. Part B, Clinical Cytometry, vol. 90, no. 1, 2016, pp. 61-72.
Flores-Montero J, de Tute R, Paiva B, et al. Immunophenotype of normal vs. myeloma plasma cells: Toward antibody panel specifications for MRD detection in multiple myeloma. Cytometry B Clin Cytom. 2016;90(1):61-72.
Flores-Montero, J., de Tute, R., Paiva, B., Perez, J. J., Böttcher, S., Wind, H., Sanoja, L., Puig, N., Lecrevisse, Q., Vidriales, M. B., van Dongen, J. J., & Orfao, A. (2016). Immunophenotype of normal vs. myeloma plasma cells: Toward antibody panel specifications for MRD detection in multiple myeloma. Cytometry. Part B, Clinical Cytometry, 90(1), 61-72. https://doi.org/10.1002/cyto.b.21265
Flores-Montero J, et al. Immunophenotype of Normal Vs. Myeloma Plasma Cells: Toward Antibody Panel Specifications for MRD Detection in Multiple Myeloma. Cytometry B Clin Cytom. 2016;90(1):61-72. PubMed PMID: 26100534.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Immunophenotype of normal vs. myeloma plasma cells: Toward antibody panel specifications for MRD detection in multiple myeloma. AU - Flores-Montero,Juan, AU - de Tute,Ruth, AU - Paiva,Bruno, AU - Perez,José Juan, AU - Böttcher,Sebastian, AU - Wind,Henk, AU - Sanoja,Luzalba, AU - Puig,Noemí, AU - Lecrevisse,Quentin, AU - Vidriales,María Belén, AU - van Dongen,Jacques J M, AU - Orfao,Alberto, Y1 - 2015/07/31/ PY - 2015/01/28/received PY - 2015/05/25/revised PY - 2015/06/17/accepted PY - 2015/6/24/entrez PY - 2015/6/24/pubmed PY - 2016/11/12/medline KW - EuroFlow KW - antibody panels KW - high sensitivity KW - markers KW - minimal residual disease KW - multiple myeloma SP - 61 EP - 72 JF - Cytometry. Part B, Clinical cytometry JO - Cytometry B Clin Cytom VL - 90 IS - 1 N2 - In recent years, several studies on large series of multiple myeloma (MM) patients have demonstrated the clinical utility of flow cytometry monitoring of minimal residual disease (flow-MRD) in bone marrow (BM), for improved assessment of response to therapy and prognostication. However, disturbing levels of variability exist regarding the specific protocols and antibody panels used in individual laboratories. Overall, consensus exists about the utility of combined assessment of CD38 and CD138 for the identification of BM plasma cells (PC); in contrast, more heterogeneous lists of markers are used to further distinguish between normal/reactive PCs and myeloma PCs in the MRD settings. Among the later markers, CD19, CD45, CD27, and CD81, together with CD56, CD117, CD200, and CD307, have emerged as particularly informative; however, no single marker provides enough specificity for clear discrimination between clonal PCs and normal PCs. Accordingly, multivariate analyses of single PCs from large series of normal/reactive vs. myeloma BM samples have shown that combined assessment of CD138 and CD38, together with CD45, CD19, CD56, CD27, CD81, and CD117 would be ideally suited for MRD monitoring in virtually every MM patient. However, the specific antibody clones, fluorochrome conjugates and sources of the individual markers determines its optimal (vs. suboptimal or poor) performance in an eight-color staining. Assessment of clonality, via additional cytoplasmic immunoglobulin (CyIg) κ vs. CyIgλ evaluation, may contribute to further establish the normal/reactive vs. clonal nature of small suspicious PC populations at high sensitivity levels, provided that enough cells are evaluated. SN - 1552-4957 UR - https://www.unboundmedicine.com/medline/citation/26100534/Immunophenotype_of_normal_vs__myeloma_plasma_cells:_Toward_antibody_panel_specifications_for_MRD_detection_in_multiple_myeloma_ L2 - https://doi.org/10.1002/cyto.b.21265 DB - PRIME DP - Unbound Medicine ER -