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Poor prognostic impact of high serum ferritin levels in patients with a lower risk of diffuse large B cell lymphoma

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Abstract

The International Prognostic Index (IPI) and other prognostic models cannot accurately classify risks in patients with lower-risk diffuse large B cell lymphoma (DLBCL). This study retrospectively analyzed serum levels of ferritin (500 and ≥ 500 ng/mL) and other reported risk factors for survival in 312 patients. High and high-intermediate risk IPI scores (hazard ratio (HR) [95% confidence interval (CI)] 2.22 [1.33, 3.72], P = 0.002 and 2.29 [1.33, 3.93], P = 0.003, respectively) and ferritin concentration ≥ 500 ng/mL (HR [95% CI] 2.22 [1.37, 3.60], P = 0.001 and 2.18 [1.31, 3.63], P = 0.003, respectively) were independent poor prognostic factors for 5-year progression-free survival (PFS) and overall survival (OS) rates in all patients. Additionally, high ferritin level (≥ 500 ng/mL) was an independent poor prognostic factor for PFS and OS in patients with lower-risk IPI (HR [95% CI] 3.37 [1.36, 8.33], P = 0.009 and 3.29 [1.23, 8.83], P = 0.0018, respectively). In conclusion, serum ferritin levels may be helpful in predicting survival in patients with DLBCL, especially in those with lower-risk IPI scores.

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References

  1. Sehn LH. Optimal use of prognostic factors in non-Hodgkin lymphoma. Hematology Am Soc Hematol Educ Program. 2006;2006:295–302.

    Article  Google Scholar 

  2. Shipp M. International non-Hodgkin’s lymphoma prognostic factors project. A predictive model for aggressive non-Hodgkin’s lymphoma. N Engl J Med. 1993;329:987–94.

    Article  Google Scholar 

  3. Sehn LH, Berry B, Chhanabhai M, Fitzgerald C, Gill K, Hoskins P, et al. The revised International Prognostic Index (R-IPI) is a better predictor of outcome than the standard IPI for patients with diffuse large B-cell lymphoma treated with R-CHOP. Blood. 2007;109:1857–61.

    Article  CAS  Google Scholar 

  4. Zhou Z, Sehn LH, Rademaker AW, Gordon LI, LaCasce AS, Crosby-Thompson A, et al. An enhanced International Prognostic Index (NCCN-IPI) for patients with diffuse large B-cell lymphoma treated in the rituximab era. Blood. 2014;123:837–42.

    Article  CAS  Google Scholar 

  5. Bari A, Marcheselli L, Sacchi S, Marcheselli R, Pozzi S, Ferri P, et al. Prognostic models for diffuse large B-cell lymphoma in the rituximab era: a never-ending story. Ann Oncol. 2009;21:1486–91.

    Article  Google Scholar 

  6. Rosenwald A, Wright G, Chan WC, Connors JM, Campo E, Fisher RI, et al. The use of molecular profiling to predict survival after chemotherapy for diffuse large-B-cell lymphoma. N Engl J Med. 2002;346:1937–47.

    Article  Google Scholar 

  7. Schmitz R, Wright GW, Huang DW, Johnson CA, Phelan JD, Wang JQ, et al. Genetics and pathogenesis of diffuse large B-cell lymphoma. N Engl J Med. 2018;378:1396–407.

    Article  CAS  Google Scholar 

  8. Riedell PA, Smith SM. Double hit and double expressors in lymphoma: definition and treatment. Cancer. 2018;124:4622–32.

    Article  Google Scholar 

  9. Rosenwald A, Bens S, Advani R, Barrans S, Copie-Bergman C, Elsensohn M, et al. Prognostic significance of MYC rearrangement and translocation partner in diffuse large B-cell lymphoma: a study by the lunenburg lymphoma biomarker consortium. J Clin Oncol. 2019; JCO1900743.

  10. Matzner Y, Konijn A, Hershko C. Serum ferritin in hematologic malignancies. Am J Hematol. 1980;9:13–22.

    Article  CAS  Google Scholar 

  11. Aulbert E, Steffens O. Serum ferritin—a tumor marker in malignant lymphomas? Onkologie. 1990;13:102–8.

    CAS  PubMed  Google Scholar 

  12. Eshhar Z, Order SE, Katz DH. Ferritin, a Hodgkin’s disease associated antigen. Proc Natl Acad Sci USA. 1974;71:3956–60.

    Article  CAS  Google Scholar 

  13. Koyama S, Fujisawa S, Watanabe R, Itabashi M, Ishibashi D, Ishii Y, et al. Serum ferritin level is a prognostic marker in patients with peripheral T-cell lymphoma. Int J Lab Hematol. 2017;39:112–7.

    Article  CAS  Google Scholar 

  14. Yoh KA, Lee HS, Park LC, Lee EM, Shin SH, Park DJ, et al. The prognostic significance of elevated levels of serum ferritin before chemotherapy in patients with non-Hodgkin lymphoma. Clin Lymphoma Myeloma Leuk. 2014;14:43–9.

    Article  Google Scholar 

  15. Mahindra A, Bolwell B, Sobecks R, Rybicki L, Pohlman B, Dean R, et al. Elevated ferritin is associated with relapse after autologous hematopoietic stem cell transplantation for lymphoma. Biol Blood Marrow Transpl. 2008;14:1239–44.

    Article  Google Scholar 

  16. Verbsky JW, Grossman WJ. Hemophagocytic lymphohistiocytosis: diagnosis, pathophysiology, treatment, and future perspectives. Ann Med. 2006;38:20–31.

    Article  CAS  Google Scholar 

  17. Fardet L, Coppo P, Kettaneh A, Dehoux M, Cabane J, Lambotte O. Low glycosylated ferritin, a good marker for the diagnosis of hemophagocytic syndrome. Arthritis Rheum. 2008;58:1521–7.

    Article  CAS  Google Scholar 

  18. Pfreundschuh M, Ho AD, Cavallin-Stahl E, Wolf M, Pettengell R, Vasova I, et al. Prognostic significance of maximum tumour (bulk) diameter in young patients with good-prognosis diffuse large-B-cell lymphoma treated with CHOP-like chemotherapy with or without rituximab: an exploratory analysis of the MabThera International Trial Group (MInT) study. Lancet Oncol. 2008;9:435–44.

    Article  Google Scholar 

  19. Müller C, Murawski N, Wiesen MH, Held G, Poeschel V, Zeynalova S, et al. The role of sex and weight on rituximab clearance and serum elimination half-life in elderly patients with DLBCL. Blood. 2012;119:3276–84.

    Article  Google Scholar 

  20. Bittenbring JT, Neumann F, Altmann B, Achenbach M, Achenbach M, Ziepert M, et al. Vitamin D deficiency impairs rituximab-mediated cellular cytotoxicity and outcome of patients with diffuse large B-cell lymphoma treated with but not without rituximab. J Clin Oncol. 2014;32:3242–8.

    Article  CAS  Google Scholar 

  21. Carson KR, Bartlett NL, McDonald JR, Luo S, Zeringue A, Liu J, et al. Increased body mass index is associated with improved survival in United States veterans with diffuse large B-cell lymphoma. J Clin Oncol. 2012;30:3217–22.

    Article  Google Scholar 

  22. Maurer MJ, Micallef IN, Cerhan JR, Katzmann JA, Link BK, Colgan JP, et al. Elevated serum free light chains are associated with event-free and overall survival in two independent cohorts of patients with diffuse large B-cell lymphoma. J Clin Oncol. 2011;29:1620–6.

    Article  Google Scholar 

  23. Cox MC, Nofroni I, Ruco L, Amodeo R, Ferrari A, La Verde G, et al. Low absolute lymphocyte count is a poor prognostic factor in diffuse-large-B-cell-lymphoma. Leuk Lymphoma. 2008;49:1745–51.

    Article  Google Scholar 

  24. Porrata LF, Ristow KM, Habermann TM, Witzig TE, Colgan JP, Inwards DJ, et al. Peripheral blood absolute lymphocyte/monocyte ratio during rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone treatment cycles predicts clinical outcomes in diffuse large B-cell lymphoma. Leuk Lymphoma. 2014;55:2728–38.

    Article  CAS  Google Scholar 

  25. Cao Y, Shi Y-X, Chen J-O, Tan Y-T, Cai Y-C, Luo H-Y, et al. Serum C-reactive protein as an important prognostic variable in patients with diffuse large B cell lymphoma. Tumour Biol. 2012;33:1039–44.

    Article  Google Scholar 

  26. Swan F Jr, Velasquez WS, Tucker S, Redman JR, Rodriguez MA, McLaughlin P, et al. A new serologic staging system for large-cell lymphomas based on initial beta 2-microglobulin and lactate dehydrogenase levels. J Clin Oncol. 1989;7:1518–27.

    Article  Google Scholar 

  27. Dayer E, Dayer J-M, Roux-Lombard P. Primer: the practical use of biological markers of rheumatic and systemic inflammatory diseases. Nat Clin Pract Rheumatol. 2007;3:512–20.

    Article  CAS  Google Scholar 

  28. Hazard JT, Drysdale JW. Ferritinaemia in cancer. Nature. 1977;265:755–6.

    Article  CAS  Google Scholar 

  29. Aulbert E, Fromm H, Hornemann H. Ferritin in acute leukemia. Serum ferritin concentration as a nonspecific tumor marker for M1 and M2 myeloid leukemia. Med Klin (Munich). 1991;86:297–304.

    CAS  Google Scholar 

  30. Armand P, Kim HT, Cutler CS, Ho VT, Koreth J, Alyea EP, et al. Prognostic impact of elevated pretransplantation serum ferritin in patients undergoing myeloablative stem cell transplantation. Blood. 2007;109:4586–8.

    Article  CAS  Google Scholar 

  31. Maxim PE, Veltri RW. Serum ferritin as a tumor marker in patients with squamous cell carcinoma of the head and neck. Cancer. 1986;57:305–11.

    Article  CAS  Google Scholar 

  32. Kalousová M, Krechler T, Jáchymová M, Kuběna AA, Žák A, Zima T. Ferritin as an independent mortality predictor in patients with pancreas cancer Results of a pilot study. Tumour Biol. 2012;33:1695–700.

    Article  Google Scholar 

Download references

Acknowledgements

This study was supported in part by Korean National Research Foundation (KNRF) grants 2015M3A9B6073646 and 2017M3A9G7072564 (both to Ho Sup Lee and Jee-Yeong Jeong) as well as a Korean National Research Foundation (KNRF) grant to Dajung Kim (2019R1G1A1010388).

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Authors and Affiliations

  1. Division of Hematology/Oncology, Department of Internal Medicine, Kosin University College of Medicine, Kosin University Gospel Hospital, 262 Gamcheon-ro, Seo-gu, Busan, 49267, South Korea

    Da Jung Kim, Taeyun Kim & Ho Sup Lee

  2. Department of Biochemistry Cancer Research Institute, Kosin University College of Medicine, Busan, South Korea

    Jee-Yeong Jeong

  3. Department of Hematology and Oncology, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan, South Korea

    Jae-Cheol Jo

  4. Department of Internal Medicine, Busan Paik Hospital, Busan, South Korea

    Won Sik Lee

  5. Department of Internal Medicine, Busan National University Hospital, Busan, South Korea

    Ho-Jin Shin

  6. Department of Internal Medicine, Dong-A University College of Medicine, Busan, South Korea

    Ji Hyun Lee

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  1. Da Jung Kim
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Correspondence to Ho Sup Lee.

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Ethical standards

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and national research committee and with the Declaration of Helsinki (1964) and its later amendments or comparable ethical standards. According to the Declaration of Helsinki, the trial was approved by the Institutional Research Ethics Board of Kosin University Gospel Hospital, which waived the requirement for informed consent given the retrospective nature of this study.

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Supplementary material 1 (DOCX 29 kb)

12185_2019_2816_MOESM2_ESM.tiff

Five-year progression-free survival (PFS) (A) and overall survival (OS) (B) curves according to serum ferritin level in patients with higher-risk International Prognostic Index (IPI) scores (TIFF 250 kb)

Supplementary material 3 (TIFF 255 kb)

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Kim, D.J., Kim, T., Jeong, JY. et al. Poor prognostic impact of high serum ferritin levels in patients with a lower risk of diffuse large B cell lymphoma. Int J Hematol 111, 559–566 (2020). https://doi.org/10.1007/s12185-019-02816-6

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  • DOI: https://doi.org/10.1007/s12185-019-02816-6

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