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Myeloma

Multiparameter flow cytometry for the identification of the Waldenström’s clone in IgM-MGUS and Waldenström’s Macroglobulinemia: new criteria for differential diagnosis and risk stratification

Leukemia volume 28, pages 166–173 (2014)Cite this article

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Abstract

Although multiparameter flow cytometry (MFC) has demonstrated clinical relevance in monoclonal gammopathy of undetermined significance (MGUS)/myeloma, immunophenotypic studies on the full spectrum of Waldenström’s Macroglobulinemia (WM) remain scanty. Herein, a comprehensive MFC analysis on bone marrow samples from 244 newly diagnosed patients with an immunoglobulin M (IgM) monoclonal protein was performed, including 67 IgM-MGUS, 77 smoldering and 100 symptomatic WM. Our results show a progressive increase on the number and light-chain-isotype-positive B-cells from IgM-MGUS to smoldering and symptomatic WM (P<.001), with only 1% of IgM-MGUS patients showing >10% B cells or 100% light-chain-isotype-positive B-cells (P<.001). Complete light-chain restriction of the B-cell compartment was an independent prognostic factor for time-to progression in smoldering WM (median 26 months; HR: 19.8, P=0.001) and overall survival in symptomatic WM (median 44 months; HR: 2.6, P=0.004). The progressive accumulation of light-chain-isotype-positive B-cells accompanied the emergence of a characteristic Waldenstrom’s phenotype (CD22+dim/CD25+/CD27+/IgM+) that differed from other B-NHL by negative expression of CD5, CD10, CD11c or CD103. In contrast to myeloma, light-chain-isotype-positive plasma cells in IgM monoclonal gammopathies show otherwise normal antigenic expression. Our results highlight the potential value of MFC immunophenotyping for the characterization of the Waldenström’s clone, as well as for the differential diagnosis, risk of progression and survival in WM.

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Acknowledgements

This work was supported by the Cooperative Research Thematic Network (RTICC) RD06/0020/0006, Instituto de Salud Carlos III/Subdirección General de Investigación Sanitaria (FIS: PI060339; 06/1354; 02/0905; 01/0089/01-02; PS09/01897/01370) and Consejería de Sanidad, Junta de Castilla y León, Valladolid, Spain (557/A/10).

Author contributions

JFSM and BP conceived the idea and together with RGS, EMO, AO and MBV designed the study protocol; BP, MCM, JJP and MBV analyzed the flow cytometry data; RGS, EMO, JA, NdH, FE, RC, AGdC, JG, JH, MS, AM, EP, AB, JA, LS, TJGL and JFSM contributed with provision of study material or patients; BP and JFSM analyzed and interpreted data; BP performed statistical analysis; BP and JFSM wrote the manuscript. All authors reviewed and approved the manuscript.

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Authors and Affiliations

  1. Department of Hematology, Hospital Universitario de Salamanca, Salamanca, Spain

    B Paiva, M C Montes, R García-Sanz, E M Ocio, J Alonso, A Martin, J J Perez, M-B Vidríales & J F San Miguel

  2. IBSAL IBMCC (USAL-CSIC), Salamanca, Spain

    B Paiva, R García-Sanz, E M Ocio, A Orfao, M-B Vidríales & J F San Miguel

  3. Complejo Hospitalario de León, León, Spain

    N de las Heras & F Escalante

  4. Hospital Clínico Universitario de Valladolid, Valladolid, Spain

    R Cuello & A G de Coca

  5. Hospital Comarcal del Bierzo, Ponferrada, León, Spain

    J Galende

  6. Hospital General de Segovia, Segovia, Spain

    J Hernández

  7. Hospital Virgen de la Concha, Zamora, Spain

    M Sierra

  8. Hospital Virgen del Puerto, Plasencia, Spain

    E Pardal

  9. Hospital Nuestra Señora de Sonsoles, Ávila, Spain

    A Bárez

  10. Hospital Rio Carrión, Palencia, Spain

    J Alonso

  11. Hospital Santos Reyes, Aranda de Duero, Spain

    L Suarez

  12. Complejo Asistencial Universitario de Burgos, Burgos, Spain

    T J González-López

  13. Servicio General de Citometría and Departamento de Medicina, Universidad de Salamanca, Salamanca, Spain

    A Orfao

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Paiva, B., Montes, M., García-Sanz, R. et al. Multiparameter flow cytometry for the identification of the Waldenström’s clone in IgM-MGUS and Waldenström’s Macroglobulinemia: new criteria for differential diagnosis and risk stratification. Leukemia 28, 166–173 (2014). https://doi.org/10.1038/leu.2013.124

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