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Myeloma

High levels of peripheral blood circulating plasma cells as a specific risk factor for progression of smoldering multiple myeloma

Leukemia volume 27, pages 680–685 (2013)Cite this article

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Abstract

Smoldering multiple myeloma (SMM) carries a 50% risk of progression to multiple myeloma (MM) or related malignancy within the first 5 years following diagnosis. The goal of this study was to determine if high levels of circulating plasma cells (PCs) are predictive of SMM transformation within the first 2–3 years from diagnosis. Ninety-one patients diagnosed with SMM at Mayo Clinic from January 1994 through January 2007, who had testing for circulating PCs using an immunofluorescent assay and adequate follow-up to ascertain disease progression, were studied. High level of circulating PCs was defined as absolute peripheral blood PCs >5 × 106/l and/or >5% PCs per 100 cytoplasmic immunoglobulin (Ig)-positive peripheral blood mononuclear cells. Patients with high circulating PCs (14 of 91 patients, 15%) were significantly more likely to progress to active disease within 2 years compared with patients without high circulating PCs, 71% versus 24%, respectively, P=0.001. Corresponding rates for progression within 3 years were 86% versus 34%, respectively, P<0.001. Overall survival (OS) after both SMM diagnosis and MM diagnosis was also significantly different. High levels of circulating PCs identify SMM patients with an elevated risk of progression within the first 2–3 years following diagnosis.

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References

  1. International Myeloma Working Group. Criteria for the classification of monoclonal gammopathies, multiple myeloma and related disorders: a report of the International Myeloma Working Group. Br J Haematol 2003; 121: 749–757.

    Google Scholar 

  2. Bianchi G, Ghobrial IM . Does my patient with a serum monoclonal spike have multiple myeloma? Hematol oncol clin North Am 2012; 26: 383–393.

    Article  Google Scholar 

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

    Article  CAS  Google Scholar 

  4. Blade J, Dimopoulos M, Rosinol L, Rajkumar SV, Kyle RA . Smoldering (asymptomatic) multiple myeloma: current diagnostic criteria, new predictors of outcome, and follow-up recommendations. J clin oncol 2010; 28: 690–697.

    Article  CAS  Google Scholar 

  5. Kyle RA, Remstein ED, Therneau TM, Dispenzieri A, Kurtin PJ, Hodnefield JM et al. Clinical course and prognosis of smoldering (asymptomatic) multiple myeloma. N Engl J Med 2007; 356: 2582–2590.

    Article  CAS  Google Scholar 

  6. Kyle RA, Buadi F, Rajkumar SV . Management of monoclonal gammopathy of undetermined significance (MGUS) and smoldering multiple myeloma (SMM). Oncology 2011; 25: 578–586.

    PubMed  Google Scholar 

  7. Korde N, Kristinsson SY, Landgren O . Monoclonal gammopathy of undetermined significance (MGUS) and smoldering multiple myeloma (SMM): novel biological insights and development of early treatment strategies. Blood 2011; 117: 5573–5581.

    Article  CAS  Google Scholar 

  8. Detweiler-Short K, Hayman S, Gertz MA, Lacy MQ, Dispenzieri A, Kumar S et al. Long-term results of single-agent thalidomide as initial therapy for asymptomatic (smoldering or indolent) myeloma. Am J Hematol 2010; 85: 737–740.

    Article  CAS  Google Scholar 

  9. Witzig TE, Mandrekar S, Detweiler-Short K, Lacy MQ, Laumann K, Dispenzieri A et al. A phase III randomized trial of Thalidomide (THAL) plus Zoledronic Acid (ZLD) versus Zoledronic Acid alone in patients with early stage multiple myeloma (MC0289). Blood 2010; 116: 1259–1260.

    Google Scholar 

  10. Kyle RA, Durie BG, Rajkumar SV, Landgren O, Blade J, Merlini G et al. Monoclonal gammopathy of undetermined significance (MGUS) and smoldering (asymptomatic) multiple myeloma: IMWG consensus perspectives risk factors for progression and guidelines for monitoring and management. Leukemia 2010; 24: 1121–1127.

    Article  CAS  Google Scholar 

  11. Dispenzieri A, Kyle RA, Katzmann JA, Therneau TM, Larson D, Benson J et al. Immunoglobulin free light chain ratio is an independent risk factor for progression of smoldering (asymptomatic) multiple myeloma. Blood 2008; 111: 785–789.

    Article  CAS  Google Scholar 

  12. Nowakowski GS, Witzig TE, Dingli D, Tracz MJ, Gertz MA, Lacy MQ et al. Circulating plasma cells detected by flow cytometry as a predictor of survival in 302 patients with newly diagnosed multiple myeloma. Blood 2005; 106: 2276–2279.

    Article  CAS  Google Scholar 

  13. Kumar S, Rajkumar SV, Kyle RA, Lacy MQ, Dispenzieri A, Fonseca R et al. Prognostic value of circulating plasma cells in monoclonal gammopathy of undetermined significance. J Clin Oncol 2005; 23: 5668–5674.

    Article  Google Scholar 

  14. Witzig TE, Kyle RA, Greipp PR . Circulating peripheral blood plasma cells in multiple myeloma. Curr Top Microbiol Immunol 1992; 182: 195–199.

    CAS  PubMed  Google Scholar 

  15. Witzig TE, Kyle RA, Ofallon WM, Greipp PR . Detection of peripheral-blood plasma-cells as a predictor of disease course in patients with smoldering multiple-myeloma. Br J Haematol 1994; 87: 266–272.

    Article  CAS  Google Scholar 

  16. Witzig TE, Dhodapkar MV, Kyle RA, Greipp PR . Quantitation of circulating peripheral blood plasma cells and their relationship to disease activity in patients with multiple myeloma. Cancer 1993; 72: 108–113.

    Article  CAS  Google Scholar 

  17. Rajkumar SV . Prevention of progression in monoclonal gammopathy of undetermined significance. Clin cancer res 2009; 15: 5606–5608.

    Article  Google Scholar 

  18. Rajkumar SV . Preventive strategies in monoclonal gammopathy of undetermined significance and smoldering multiple myeloma. Am J Hematol 2012; 87: 453–454.

    Article  Google Scholar 

  19. Bianchi G, Kyle RA, Colby CL, Larson DR, Kumar S, Katzmann JA et al. Impact of optimal follow-up of monoclonal gammopathy of undetermined significance on early diagnosis and prevention of myeloma-related complications. Blood 2010; 116: 2019–2025, quiz 2197.

    Article  CAS  Google Scholar 

  20. Rajkumar SV . Treatment of multiple myeloma. Nat rev Clin oncol 2011; 8: 479–491.

    Article  CAS  Google Scholar 

  21. Rajkumar SV, Larson D, Kyle RA . Diagnosis of smoldering multiple myeloma. N Engl J Med 2011; 365: 474–475.

    Article  CAS  Google Scholar 

  22. Billadeau D, Van Ness B, Kimlinger T, Kyle RA, Therneau TM, Greipp PR et al. Clonal circulating cells are common in plasma cell proliferative disorders: a comparison of monoclonal gammopathy of undetermined significance, smoldering multiple myeloma, and active myeloma. Blood 1996; 88: 289–296.

    CAS  PubMed  Google Scholar 

  23. Witzig TE, Gonchoroff NJ, Katzmann JA, Therneau TM, Kyle RA, Greipp PR . Peripheral blood B cell labeling indexes are a measure of disease-activity in patients with monoclonal gammopathies. J Clin Oncol 1988; 6: 1041–1046.

    Article  CAS  Google Scholar 

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Acknowledgements

This work was supported in part by the National Cancer Institute, National Institutes of Health, Bethesda, MD (CA107476, CA168762, CA100707, CA 83724) and by the NIH/NCRR CTSA Grant Number TL1 RR024152. Also supported in part by the Jabbs Foundation, Birmingham, United Kingdom and the Henry J Predolin Foundation, USA.

Author Contributions

GB and SVR were involved in the concept and design of the study, data collection, data analysis, and wrote the manuscript; RAK, DRL, TEW, SK, WGM, and AD were involved with data interpretation, critical review, and critical edits to the manuscript. All authors gave final approval to the manuscript.

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Authors and Affiliations

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

    G Bianchi

  2. Division of Hematology, Mayo Clinic, Rochester, MN, USA

    R A Kyle, T E Witzig, S Kumar, A Dispenzieri & S V Rajkumar

  3. Division of Biostatistics, Mayo Clinic, Rochester, MN, USA

    D R Larson

  4. Division of Hematopathology, Mayo Clinic, Rochester, MN, USA

    W G Morice

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  1. G Bianchi
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  2. R A Kyle
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  6. A Dispenzieri
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Correspondence to S V Rajkumar.

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Bianchi, G., Kyle, R., Larson, D. et al. High levels of peripheral blood circulating plasma cells as a specific risk factor for progression of smoldering multiple myeloma. Leukemia 27, 680–685 (2013). https://doi.org/10.1038/leu.2012.237

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