Skip to main content
SpringerLink
Log in

Multiple myeloma, gammopathies

Prognostic significance of circulating plasma cells by multi-parametric flow cytometry in light chain amyloidosis

  • Article
  • Published:
Leukemia Submit manuscript

Abstract

We evaluated the prognostic impact of clonal circulating plasma cells (cPCs) detected by six-color multi-parametric flow cytometry (MFC) in light chain (AL) amyloidosis at diagnosis. Of the 154 patients who underwent MFC, cPCs were detected in 42% (n = 65) patients. Median number of cPCs was 81 per 150,000 events (range: 6–17,844). High bone marrow plasma cell percentage was an independent predictor of presence of cPCs. Presence of cPCs at diagnosis was associated with inferior overall survival (OS) (90 vs. 98 months, p = 0.003) and inferior progression free survival (PFS) (31 vs. 52 months, p = 0.02). Estimated 1, 2 and 5 year OS in the two groups was: 74, 64 and 57 and 89, 87, and 80%, respectively. Estimated PFS at 1, 2, and 5 years was: 69, 56, and 23% and 80, 74, and 37%, respectively. Furthermore, the presence of cPCs at diagnosis was an independent adverse predictor of OS in multivariable analysis. Achieving a very-good partial response, or better, was able to overcome the adverse impact of cPCs at diagnosis. Patients with cPCs at diagnosis may warrant closer monitoring post-treatment, especially if they do not achieve a deep hematologic response.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Gertz MA. Immunoglobulin light chain amyloidosis: 2016 update on diagnosis, prognosis, and treatment. Am J Hematol. 2016;91:947–56.

    Article  PubMed  CAS  Google Scholar 

  2. Wechalekar A, Wechalekar AD, Mahmood SA, Youngstein T, Coyne M, Foard D. et al. Interim analysis of ALCHemy—a prospective study of 1000 patients with Systemic AL amyloidosis. Clin Lymp Myel Leuk. 2015;15:e60

    Article  Google Scholar 

  3. Mahmood S, Palladini G, Sanchorawala V, Wechalekar A. Update on treatment of light chain amyloidosis. Haematologica . 2014;99:209–21.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  4. Merlini G, Stone MJ. Dangerous small B-cell clones. Blood . 2006;108:2520–30.

    Article  PubMed  CAS  Google Scholar 

  5. Kourelis TV, Kumar SK, Gertz MA, Lacy MQ, Buadi FK, Hayman SR, et al. Coexistent multiple myeloma or increased bone marrow plasma cells define equally high-risk populations in patients with immunoglobulin light chain amyloidosis. J Clin Oncol: Off J Am Soc Clin Oncol. 2013;31:4319–24.

    Article  CAS  Google Scholar 

  6. Kyle RA, Rajkumar SV. Criteria for diagnosis, staging, risk stratification and response assessment of multiple myeloma. Leukemia . 2009;23:3–9.

    Article  PubMed  CAS  Google Scholar 

  7. Morice WG, Hanson CA, Kumar S, Frederick LA, Lesnick CE, Greipp PR. Novel multi-parameter flow cytometry sensitively detects phenotypically distinct plasma cell subsets in plasma cell proliferative disorders. Leukemia . 2007;21:2043–6.

    Article  PubMed  CAS  Google Scholar 

  8. Lisenko K, Schonland SO, Jauch A, Andrulis M, Rocken C, Ho AD, et al. Flow cytometry-based characterization of underlying clonal B and plasma cells in patients with light chain amyloidosis. Cancer Med. 2016;5:1464–72.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  9. Gonsalves WI, Rajkumar SV, Dispenzieri A, Dingli D, Timm MM, Morice WG, et al. Quantification of circulating clonal plasma cells via multiparametric flow cytometry identifies patients with smoldering multiple myeloma at high risk of progression. Leukemia . 2017;31:130–5.

    Article  PubMed  CAS  Google Scholar 

  10. Gonsalves WI, Rajkumar SV, Gupta V, Morice WG, Timm MM, Singh PP, et al. Quantification of clonal circulating plasma cells in newly diagnosed multiple myeloma: implications for redefining high-risk myeloma. Leukemia . 2014;28:2060–5.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  11. Gonsalves WI, Morice WG, Rajkumar V, Gupta V, Timm MM, Dispenzieri A, et al. Quantification of clonal circulating plasma cells in relapsed multiple myeloma. Br J Haematol. 2014;167:500–5.

    Article  PubMed  PubMed Central  Google Scholar 

  12. Paiva B, Perez-Andres M, Vidriales MB, Almeida J, de las Heras N, Mateos MV. et al. Competition between clonal plasma cells and normal cells for potentially overlapping bone marrow niches is associated with a progressively altered cellular distribution in MGUS vs myeloma. Leukemia . 2011;25:697–706.

    Article  PubMed  CAS  Google Scholar 

  13. Bianchi G, Kyle RA, Larson DR, Witzig TE, Kumar S, Dispenzieri A, et al. High levels of peripheral blood circulating plasma cells as a specific risk factor for progression of smoldering multiple myeloma. Leukemia . 2013;27:680–5.

    Article  PubMed  CAS  Google Scholar 

  14. Chakraborty R, Muchtar E, Kumar SK, Jevremovic D, Buadi FK, Dingli D, et al. Risk stratification in myeloma by detection of circulating plasma cells prior to autologous stem cell transplantation in the novel agent era. Blood Cancer J. 2016;6:e512.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  15. Pardanani A, Witzig TE, Schroeder G, McElroy EA, Fonseca R, Dispenzieri A, et al. Circulating peripheral blood plasma cells as a prognostic indicator in patients with primary systemic amyloidosis. Blood . 2003;101:827–30.

    Article  PubMed  CAS  Google Scholar 

  16. Kumar S, Dispenzieri A, Lacy MQ, Hayman SR, Buadi FK, Colby C, et al. Revised prognostic staging system for light chain amyloidosis incorporating cardiac biomarkers and serum free light chain measurements. J Clin Oncol. 2012;30:989–95.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  17. Kumar S, Kimlinger T, Morice W. Immunophenotyping in multiple myeloma and related plasma cell disorders. Best Pract & Res Clin Haematol. 2010;23:433–51.

    Article  CAS  Google Scholar 

  18. Muchtar E, Jevremovic D, Dispenzieri A, Dingli D, Buadi FK, Lacy MQ, et al. The prognostic value of multiparametric flow cytometry in AL amyloidosis at diagnosis and at the end of first-line treatment. Blood . 2017;129:82–7.

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgements

The Mayo Clinic Hematological Malignancies Program and in part by grants K23CA218742, CA107476, CA168762, and CA186781 from the National Cancer Institute, Rockville, MD, USA. It is also supported in part by the Jabbs Foundation, Birmingham, United Kingdom, the Henry J. Predolin Foundation, USA, and the Marion Schwartz Foundation for Multiple Myeloma.

Authors contritbutions

S.S, S.K.K., and W.I.G. designed the study, collected the data, analyzed the data, and wrote the manuscript; N.T. collected the data and contributed to writing and reviewing the manuscript. A.D., M.A.G., D.D., D.J., W.J.M., P.K., T.V.K., M.Q.L., S.R.H., F.K.B., N.L., R.S.G., Y.L., S.J.R., J.A.L., S.R.Z., R.W., Y.L.H., M.A.H., A.L.F., R.A.K., and S.V.R. contributed to writing and reviewing the manuscript.

Author information

Authors and Affiliations

  1. Division of Hematology, Department of Internal Medicine, Mayo Clinic, Rochester, MN, USA

    Surbhi Sidana, Nidhi Tandon, Angela Dispenzieri, Morie A. Gertz, David Dingli, Prashant Kapoor, Taxiarchis V. Kourelis, Martha Q. Lacy, Suzanne R. Hayman, Francis K. Buadi, Nelson Leung, Ronald S. Go, Yi Lin, Stephen J. Russell, John A. Lust, Steven R. Zeldenrust, Rahma Warsame, Yi L. Hwa, Miriam Hobbs, Amie Fonder, Robert A. Kyle, S. Vincent Rajkumar, Shaji K. Kumar & Wilson I. Gonsalves

  2. Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA

    Dragan Jevremovic & William G. Morice

  3. Division of Nephrology, Department of Internal Medicine, Mayo Clinic, Rochester, MN, USA

    Nelson Leung

Authors
  1. Surbhi Sidana
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Nidhi Tandon
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Angela Dispenzieri
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Morie A. Gertz
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. David Dingli
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Dragan Jevremovic
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. William G. Morice
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Prashant Kapoor
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Taxiarchis V. Kourelis
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Martha Q. Lacy
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Suzanne R. Hayman
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Francis K. Buadi
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Nelson Leung
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. Ronald S. Go
    View author publications

    You can also search for this author in PubMed Google Scholar

  15. Yi Lin
    View author publications

    You can also search for this author in PubMed Google Scholar

  16. Stephen J. Russell
    View author publications

    You can also search for this author in PubMed Google Scholar

  17. John A. Lust
    View author publications

    You can also search for this author in PubMed Google Scholar

  18. Steven R. Zeldenrust
    View author publications

    You can also search for this author in PubMed Google Scholar

  19. Rahma Warsame
    View author publications

    You can also search for this author in PubMed Google Scholar

  20. Yi L. Hwa
    View author publications

    You can also search for this author in PubMed Google Scholar

  21. Miriam Hobbs
    View author publications

    You can also search for this author in PubMed Google Scholar

  22. Amie Fonder
    View author publications

    You can also search for this author in PubMed Google Scholar

  23. Robert A. Kyle
    View author publications

    You can also search for this author in PubMed Google Scholar

  24. S. Vincent Rajkumar
    View author publications

    You can also search for this author in PubMed Google Scholar

  25. Shaji K. Kumar
    View author publications

    You can also search for this author in PubMed Google Scholar

  26. Wilson I. Gonsalves
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Wilson I. Gonsalves.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Electronic supplementary material

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Sidana, S., Tandon, N., Dispenzieri, A. et al. Prognostic significance of circulating plasma cells by multi-parametric flow cytometry in light chain amyloidosis. Leukemia 32, 1421–1426 (2018). https://doi.org/10.1038/s41375-018-0063-7

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41375-018-0063-7

  • Springer Nature Limited

This article is cited by

Search

Navigation