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Hyperfibrinogenemia is a poor prognostic factor in diffuse large B cell lymphoma

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Abstract

Diffuse large B cell lymphoma (DLBCL) is the most common subtype of non-Hodgkin lymphomas worldwide. Previous studies indicated that hyperfibrinogenemia was a poor predictor in various tumors. The purpose of our study was to evaluate the prognostic effect of hyperfibrinogenemia in DLBCL. Data of 228 patients, who were diagnosed with DLBCL in our hospital between May 2009 and February 2016, were analyzed retrospectively. The Kaplan-Meier method and Cox regression were performed to find prognostic factors associated with progression-free survival (PFS) and overall survival (OS). Receiver operator characteristic (ROC) curve and the areas under the curve were used to evaluate the predictive accuracy of predictors. Comparison of characters between groups indicated that patients with high National Comprehensive Cancer Network-International Prognostic Index (NCCN-IPI) score (4–8) and advanced stage (III–IV) were more likely to suffer from hyperfibrinogenemia. The Kaplan-Meier method revealed that patients with hyperfibrinogenemia showed inferior PFS (P < 0.001) and OS (P < 0.001) than those without hyperfibrinogenemia. Multivariate analysis showed that hyperfibrinogenemia was an independent prognostic factor associated with poor outcomes (HR = 1.90, 95% CI: 1.15–3.16 for PFS, P = 0.013; HR = 2.65, 95% CI: 1.46–4.79 for OS, P = 0.001). We combined hyperfibrinogenemia and NCCN-IPI to build a new prognostic index (NPI). The NPI was demonstrated to have a superior predictive effect on prognosis (P = 0.0194 for PFS, P = 0.0034 for OS). Hyperfibrinogenemia was demonstrated to be able to predict poor outcome in DLBCL, especially for patients with advanced stage and high NCCN-IPI score. Adding hyperfibrinogenemia to NCCN-IPI could significantly improve the predictive effect of NCCN-IPI.

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References

  1. Martelli M, Ferreri AJ, Agostinelli C, Di Rocco A, Pfreundschuh M, Pileri SA (2013) Diffuse large B-cell lymphoma. Crit Rev Oncol Hematol 87(2):146–171. https://doi.org/10.1016/j.critrevonc.2012.12.009

    Article  PubMed  Google Scholar 

  2. Falduto A, Cimino F, Speciale A, Musolino C, Gangemi S, Saija A, Allegra A (2017) How gene polymorphisms can influence clinical response and toxicity following R-CHOP therapy in patients with diffuse large B cell lymphoma. Blood Rev 31:235–249. https://doi.org/10.1016/j.blre.2017.02.005

    Article  CAS  PubMed  Google Scholar 

  3. Hans CP, Weisenburger DD, Greiner TC, Gascoyne RD, Delabie J, Ott G, Muller-Hermelink HK, Campo E, Braziel RM, Jaffe ES, Pan Z, Farinha P, Smith LM, Falini B, Banham AH, Rosenwald A, Staudt LM, Connors JM, Armitage JO, Chan WC (2004) Confirmation of the molecular classification of diffuse large B-cell lymphoma by immunohistochemistry using a tissue microarray. Blood 103(1):275–282. https://doi.org/10.1182/blood-2003-05-1545

    Article  CAS  PubMed  Google Scholar 

  4. Zhou Z, Sehn LH, Rademaker AW, Gordon LI, Lacasce AS, Crosby-Thompson A, Vanderplas A, Zelenetz AD, Abel GA, Rodriguez MA, Nademanee A, Kaminski MS, Czuczman MS, Millenson M, Niland J, Gascoyne RD, Connors JM, Friedberg JW, Winter JN (2014) An enhanced International Prognostic Index (NCCN-IPI) for patients with diffuse large B-cell lymphoma treated in the rituximab era. Blood 123(6):837–842. https://doi.org/10.1182/blood-2013-09-524108

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Weisel JW (2005) Fibrinogen and fibrin. Adv Protein Chem 70:247–299. https://doi.org/10.1016/S0065-3233(05)70008-5

    Article  CAS  PubMed  Google Scholar 

  6. Davalos D, Akassoglou K (2012) Fibrinogen as a key regulator of inflammation in disease. Semin Immunopathol 34(1):43–62. https://doi.org/10.1007/s00281-011-0290-8

    Article  CAS  PubMed  Google Scholar 

  7. Steinbrecher KA, Horowitz NA, Blevins EA, Barney KA, Shaw MA, Harmel-Laws E, Finkelman FD, Flick MJ, Pinkerton MD, Talmage KE, Kombrinck KW, Witte DP, Palumbo JS (2010) Colitis-associated cancer is dependent on the interplay between the hemostatic and inflammatory systems and supported by integrin alpha(M)beta(2) engagement of fibrinogen. Cancer Res 70(7):2634–2643. https://doi.org/10.1158/0008-5472.CAN-09-3465

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Mantovani A, Allavena P, Sica A, Balkwill F (2008) Cancer-related inflammation. Nature 454(7203):436–444. https://doi.org/10.1038/nature07205

    Article  CAS  PubMed  Google Scholar 

  9. Machlus KR, Cardenas JC, Church FC, Wolberg AS (2011) Causal relationship between hyperfibrinogenemia, thrombosis, and resistance to thrombolysis in mice. Blood 117(18):4953–4963. https://doi.org/10.1182/blood-2010-11-316885

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Tennent GA, Brennan SO, Stangou AJ, O'Grady J, Hawkins PN, Pepys MB (2007) Human plasma fibrinogen is synthesized in the liver. Blood 109(5):1971–1974. https://doi.org/10.1182/blood-2006-08-040956

    Article  CAS  PubMed  Google Scholar 

  11. Jiang HG, Li J, Shi SB, Chen P, Ge LP, Jiang Q, Tang XP (2014) Value of fibrinogen and D-dimer in predicting recurrence and metastasis after radical surgery for non-small cell lung cancer. Med Oncol 31(7):22. https://doi.org/10.1007/s12032-014-0022-8

    Article  CAS  PubMed  Google Scholar 

  12. Perisanidis C, Psyrri A, Cohen EE, Engelmann J, Heinze G, Perisanidis B, Stift A, Filipits M, Kornek G, Nkenke E (2015) Prognostic role of pretreatment plasma fibrinogen in patients with solid tumors: a systematic review and meta-analysis. Cancer Treat Rev 41(10):960–970. https://doi.org/10.1016/j.ctrv.2015.10.002

    Article  CAS  PubMed  Google Scholar 

  13. Wakatsuki K, Matsumoto S, Migita K, Ito M, Kunishige T, Nakade H, Nakatani M, Kitano M, Sho M (2017) Preoperative plasma fibrinogen is associated with lymph node metastasis and predicts prognosis in resectable esophageal cancer. World J Surg 41:2068–2077. https://doi.org/10.1007/s00268-017-3991-x

    Article  PubMed  Google Scholar 

  14. Sahni A, Simpson-Haidaris PJ, Sahni SK, Vaday GG, Francis CW (2008) Fibrinogen synthesized by cancer cells augments the proliferative effect of fibroblast growth factor-2 (FGF-2). J Thromb Haemost 6(1):176–183. https://doi.org/10.1111/j.1538-7836.2007.02808.x

    Article  CAS  PubMed  Google Scholar 

  15. Kijima T, Arigami T, Uchikado Y, Uenosono Y, Kita Y, Owaki T, Mori S, Kurahara H, Kijima Y, Okumura H, Maemura K, Ishigami S, Natsugoe S (2017) Combined fibrinogen and neutrophil-lymphocyte ratio as a prognostic marker of advanced esophageal squamous cell carcinoma. Cancer Sci 108(2):193–199. https://doi.org/10.1111/cas.13127

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Cushman M, Folsom AR, Wang L, Aleksic N, Rosamond WD, Tracy RP, Heckbert SR (2003) Fibrin fragment D-dimer and the risk of future venous thrombosis. Blood 101(4):1243–1248. https://doi.org/10.1182/blood-2002-05-1416

    Article  CAS  PubMed  Google Scholar 

  17. Sase T, Wada H, Yamaguchi M, Ogawa S, Kamikura Y, Nishikawa M, Kaneko T, Abe Y, Nishioka J, Nobori T, Shiku H (2005) Haemostatic abnormalities and thrombotic disorders in malignant lymphoma. Thromb Haemost 93(1):153–159. https://doi.org/10.1160/TH04-04-0260

    Article  CAS  PubMed  Google Scholar 

  18. Troppan KT, Melchardt T, Wenzl K, Schlick K, Deutsch A, Bullock MD, Reitz D, Beham-Schmid C, Weiss L, Neureiter D, Trankenschuh W, Greil R, Neumeister P, Egle A, Pichler M (2016) The clinical significance of fibrinogen plasma levels in patients with diffuse large B cell lymphoma. J Clin Pathol 69(4):326–330. https://doi.org/10.1136/jclinpath-2015-203356

    Article  CAS  PubMed  Google Scholar 

  19. Kamphuisen PW, Beyer-Westendorf J (2014) Bleeding complications during anticoagulant treatment in patients with cancer. Thromb Res 133(Suppl 2):S49–S55. https://doi.org/10.1016/S0049-3848(14)50009-6

    Article  CAS  PubMed  Google Scholar 

  20. Prandoni P, Lensing AW, Piccioli A, Bernardi E, Simioni P, Girolami B, Marchiori A, Sabbion P, Prins MH, Noventa F, Girolami A (2002) Recurrent venous thromboembolism and bleeding complications during anticoagulant treatment in patients with cancer and venous thrombosis. Blood 100(10):3484–3488. https://doi.org/10.1182/blood-2002-01-0108

    Article  CAS  PubMed  Google Scholar 

  21. Short NJ, Connors JM (2014) New oral anticoagulants and the cancer patient. Oncologist 19(1):82–93. https://doi.org/10.1634/theoncologist.2013-0239

    Article  CAS  PubMed  Google Scholar 

  22. van Es N, Coppens M, Schulman S, Middeldorp S, Buller HR (2014) Direct oral anticoagulants compared with vitamin K antagonists for acute venous thromboembolism: evidence from phase 3 trials. Blood 124(12):1968–1975. https://doi.org/10.1182/blood-2014-04-571232

    Article  CAS  PubMed  Google Scholar 

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Funding

This study was supported by the National Natural Science Foundation of China (81370657, 81470328, 81600130, 81770166, 81720108002), Jiangsu Province’s Medical Elite Programme (ZDRCA2016022), Project of National Key Clinical Specialty, National Science & Technology Pillar Program (2014BAI09B12), Jiangsu Provincial Special Program of Medical Science (BL2014086 and BE2017751), and National Science and Technology Major Project (2017ZX09304032).

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Author notes

  1. Jun-Ying Niu and Tian Tian contributed equally to this work.

Authors and Affiliations

  1. Department of Hematology, the First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Nanjing, 210029, China

    Jun-Ying Niu, Tian Tian, Hua-Yuan Zhu, Jin-Hua Liang, Wei Wu, Lei Cao, Rui-Nan Lu, Li Wang, Jian-Yong Li & Wei Xu

  2. Key Laboratory of Hematology, Nanjing Medical University, Nanjing, 210029, China

    Jun-Ying Niu, Tian Tian, Hua-Yuan Zhu, Jin-Hua Liang, Wei Wu, Lei Cao, Rui-Nan Lu, Li Wang, Jian-Yong Li & Wei Xu

  3. Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing, 210029, China

    Jun-Ying Niu, Tian Tian, Hua-Yuan Zhu, Jin-Hua Liang, Wei Wu, Lei Cao, Rui-Nan Lu, Li Wang, Jian-Yong Li & Wei Xu

Authors
  1. Jun-Ying Niu
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  2. Tian Tian
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  3. Hua-Yuan Zhu
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  5. Wei Wu
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  8. Li Wang
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  9. Jian-Yong Li
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Correspondence to Wei Xu.

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The authors declare that they have no conflict of interest.

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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. For this type of study, formal consent is not required.

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Informed consent was obtained from all individual participants included in the study.

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Niu, JY., Tian, T., Zhu, HY. et al. Hyperfibrinogenemia is a poor prognostic factor in diffuse large B cell lymphoma. Ann Hematol 97, 1841–1849 (2018). https://doi.org/10.1007/s00277-018-3382-x

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  • DOI: https://doi.org/10.1007/s00277-018-3382-x

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