The Korean journal of internal medicine

The Korean Association of Internal Medicine (대한내과학회)
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Myeloma prognostic index at diagnosis might be a prognostic marker in patients newly diagnosed with multiple myeloma

  • Kim, Dae Sik (Division of Oncology and Hematology, Department of Internal Medicine, Korea University School of Medicine) ;
  • Yu, Eun Sang (Division of Oncology and Hematology, Department of Internal Medicine, Korea University School of Medicine) ;
  • Kang, Ka-Won (Division of Oncology and Hematology, Department of Internal Medicine, Korea University School of Medicine) ;
  • Lee, Se Ryeon (Division of Oncology and Hematology, Department of Internal Medicine, Korea University School of Medicine) ;
  • Park, Yong (Division of Oncology and Hematology, Department of Internal Medicine, Korea University School of Medicine) ;
  • Sung, Hwa Jung (Division of Oncology and Hematology, Department of Internal Medicine, Korea University School of Medicine) ;
  • Choi, Chul Won (Division of Oncology and Hematology, Department of Internal Medicine, Korea University School of Medicine) ;
  • Kim, Byung Soo (Division of Oncology and Hematology, Department of Internal Medicine, Korea University School of Medicine)
  • Received : 2016.03.01
  • Accepted : 2016.04.17
  • Published : 2017.07.01
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Abstract

Background/Aims: The aims of this study were to identify the value of inflammatory markers as pretreatment prognostic factors for patients with multiple myeloma (MM) and to estimate the value of a prognostic index including these markers at diagnosis. Methods: A total of 273 newly diagnosed MM patients undergoing active treatment were analyzed in this study. The prognostic values for survival of the pretreatment inflammatory markers were investigated. A myeloma prognostic index (MPI) was derived using prognostic factors determined to be independently significant on multivariate analysis. Results: A high pretreatment neutrophil-lymphocyte ratio (NLR), low platelet count, and high C-reactive protein (CRP) level had independently unfavorable significance for overall survival (OS). The MPI was derived based on these factors. Per the MPI, 1 point each was assigned to high NLR, low platelet count, and high CRP. Risk categories were stratified into low- (score 0), intermediate- (score 1), and high-risk (score 2 or 3) groups. The MPI demonstrated independent statistical significance for OS on multivariate analysis ([intermediate: hazard ratio (HR), 1.91; 95% confidence interval (CI), 1.12 to 3.24] and [high: HR, 3.37; 95% CI, 2.00 to 5.69]; p < 0.001). Moreover, this significance could be observed regardless of age, renal function, and exposure to novel agents. In addition, the International Staging System risk group could be further significantly stratified using the MPI. Conclusions: The MPI, consisting of pretreatment inflammatory markers, NLR, platelet count, and CRP, might be effective in predicting the survival of newly diagnosed MM patients undergoing active treatment.

Keywords

Acknowledgement

Supported by : Korea Health Industry Development Institute (KHIDI)

References

  1. Kyle RA, Rajkumar SV. Multiple myeloma. Blood 2008;111:2962-2972. https://doi.org/10.1182/blood-2007-10-078022
  2. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2015. CA Cancer J Clin 2015;65:5-29. https://doi.org/10.3322/caac.21254
  3. Greipp PR, San Miguel J, Durie BG, et al. International Staging System for multiple myeloma. J Clin Oncol 2005;23:3412-3420. https://doi.org/10.1200/JCO.2005.04.242
  4. Balkwill F, Mantovani A. Inflammation and cancer: back to Virchow? Lancet 2001;357:539-545. https://doi.org/10.1016/S0140-6736(00)04046-0
  5. Coussens LM, Werb Z. Inflammation and cancer. Nature 2002;420:860-867. https://doi.org/10.1038/nature01322
  6. Templeton AJ, Ace O, McNamara MG, et al. Prognostic role of platelet to lymphocyte ratio in solid tumors: a systematic review and meta-analysis. Cancer Epidemiol Biomarkers Prev 2014;23:1204-1212. https://doi.org/10.1158/1055-9965.EPI-14-0146
  7. Zahorec R. Ratio of neutrophil to lymphocyte counts: rapid and simple parameter of systemic inflammation and stress in critically ill. Bratisl Lek Listy 2001;102:5-14.
  8. McMillan DC. The systemic inflammation-based Glasgow Prognostic Score: a decade of experience in patients with cancer. Cancer Treat Rev 2013;39:534-540. https://doi.org/10.1016/j.ctrv.2012.08.003
  9. Templeton AJ, McNamara MG, Seruga B, et al. Prognostic role of neutrophil-to-lymphocyte ratio in solid tumors: a systematic review and meta-analysis. J Natl Cancer Inst 2014;106:dju124.
  10. Keam B, Ha H, Kim TM, et al. Neutrophil to lymphocyte ratio improves prognostic prediction of International Prognostic Index for patients with diffuse large B-cell lymphoma treated with rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone. Leuk Lymphoma 2015;56:2032-2038. https://doi.org/10.3109/10428194.2014.982642
  11. Kelkitli E, Atay H, Cilingir F, et al. Predicting survival for multiple myeloma patients using baseline neutrophil/lymphocyte ratio. Ann Hematol 2014;93:841-846. https://doi.org/10.1007/s00277-013-1978-8
  12. Koh YW, Kang HJ, Park C, et al. Prognostic significance of the ratio of absolute neutrophil count to absolute lymphocyte count in classic Hodgkin lymphoma. Am J Clin Pathol 2012;138:846-854. https://doi.org/10.1309/AJCPO46GFKGNXCBR
  13. Shrotriya S, Walsh D, Bennani-Baiti N, Thomas S, Lorton C. C-reactive protein is an important biomarker for prognosis tumor recurrence and treatment response in adult solid tumors: a systematic review. PLoS One 2015;10:e0143080. https://doi.org/10.1371/journal.pone.0143080
  14. Bataille R, Boccadoro M, Klein B, Durie B, Pileri A. C-reactive protein and beta-2 microglobulin produce a simple and powerful myeloma staging system. Blood 1992;80:733-737.
  15. Palumbo A, Avet-Loiseau H, Oliva S, et al. Revised International Staging System for multiple myeloma: a report from International Myeloma Working Group. J Clin Oncol 2015;33:2863-2869. https://doi.org/10.1200/JCO.2015.61.2267
  16. Chng WJ, Dispenzieri A, Chim CS, et al. IMWG consensus on risk stratification in multiple myeloma. Leukemia 2014;28:269-277. https://doi.org/10.1038/leu.2013.247
  17. Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Cell 2011;144:646-674. https://doi.org/10.1016/j.cell.2011.02.013
  18. Barlogie B, Bolejack V, Schell M, Crowley J. Prognostic factor analyses of myeloma survival with intergroup trial S9321 (INT 0141): examining whether different variables govern different time segments of survival. Ann Hematol 2011;90:423-428. https://doi.org/10.1007/s00277-010-1130-y
  19. Black S, Kushner I, Samols D. C-reactive protein. J Biol Chem 2004;279:48487-48490. https://doi.org/10.1074/jbc.R400025200
  20. Wang CS, Sun CF. C-reactive protein and malignancy: clinico-pathological association and therapeutic implication. Chang Gung Med J 2009;32:471-482.
  21. Kim SJ, Kim K, Kim BS, et al. Clinical features and survival outcomes in patients with multiple myeloma: analysis of web-based data from the Korean Myeloma Registry. Acta Haematol 2009;122:200-210. https://doi.org/10.1159/000253027
  22. Jung SH, Kim JS, Lee WS, et al. Prognostic value of the inverse platelet to lymphocyte ratio (iPLR) in patients with multiple myeloma who were treated up front with a novel agent-containing regimen. Ann Hematol 2016;95:55-61. https://doi.org/10.1007/s00277-015-2521-x
  23. Cook G, Campbell JD, Carr CE, Boyd KS, Franklin IM. Transforming growth factor beta from multiple myeloma cells inhibits proliferation and IL-2 responsiveness in T lymphocytes. J Leukoc Biol 1999;66:981-988. https://doi.org/10.1002/jlb.66.6.981
  24. Sakamaki S, Hirayama Y, Matsunaga T, et al. Transforming growth factor-beta1 (TGF-beta1) induces thrombopoietin from bone marrow stromal cells, which stimulates the expression of TGF-beta receptor on megakaryocytes and, in turn, renders them susceptible to suppression by TGF-beta itself with high specificity. Blood 1999;94:1961-1970.
  25. Fritz E, Ludwig H, Scheithauer W, Sinzinger H. Shortened platelet half-life in multiple myeloma. Blood 1986;68:514-520.

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