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Serum soluble interleukin-2 receptor (sIL-2R) level is associated with the outcome of patients with diffuse large B cell lymphoma treated with R-CHOP regimens

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Abstract

Serum concentration of soluble interleukin-2 receptor (sIL-2R) predicts the clinical outcome of patients with aggressive non-Hodgkin's lymphoma treated with the cyclophosphamide, doxorubicin, vincristine, and prednisolone (CHOP) regimen without rituximab. In the present study, we aim to re-assess the prognostic significance of serum sIL-2R for diffuse large B cell lymphoma (DLBCL) patients treated with CHOP plus rituximab and to assess sIL-2R with subtype of DLBCL, such as GCB type and non-GCB type. Two hundred and thirty-three patients with DLBCL were enrolled between December 2002 and March 2008. To evaluate serum levels of sIL-2R, venous blood samples were drawn from patients immediately before initiation of treatment. Serum sIL-2R was determined by sandwich enzyme-linked immunosorbent assay. The 5-year overall survival (OS) rates for patients with sIL-2R levels of ≥2,000 (110 cases) and <2,000 U/mL (123 cases) were 54.2% and 89.0% (P < 0.0001), respectively. Multivariate analysis using the proportional-hazards model revealed that serum sIL-2R (P = 0.0099) and extranodal involvement sites (P = 0.0392) were independent prognostic factors for OS and that clinical stage (P = 0.0168), performance status (P = 0.0181), sIL-2R (P = 0.0232), and LDH (P = 0.0316) were independent prognostic factors for progression-free survival in sIL-2R and every factor of the International Prognostic Index. Serum sIL-2R might be a useful prognostic factor for DLBCL patients in the rituximab era.

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References

  1. The International Non-Hodgkin's Lymphoma Prognostic Factors Project (1993) A predictive model for aggressive non-Hodgkin's lymphoma. N Engl J Med 329:987–994

    Article  Google Scholar 

  2. Coiffer B, Lepage E, Briere J, Herbrecht R, Tilly H, Bouabdallah R, Morel P, Van Den Neste E, Salles G, Gaulard P, Reyes F, Lederlin P, Gisselbrecht C (2002) CHOP chemotherapy plus rituximab compared with CHOP alone in elderly patients with diVuse large-B-cell lymphoma. N Engl J Med 346:235–242

    Article  Google Scholar 

  3. Fisher RI, Shah P (2003) Current trends in large cell lymphoma. Leukemia 17:1948–1960

    Article  PubMed  CAS  Google Scholar 

  4. Pfreundschuh M, Trümper L, Osterborg A, Pettengell R, Trneny M, Imrie K, Ma D, Gill D, Walewski J, Zinzani PL, Stahel R, Kvaloy S, Shpilberg O, Jaeger U, Hansen M, Lehtinen T, López-Guillermo A, Corrado C, Scheliga A, Milpied N, Mendila M, Rashford M, Kuhnt E, Loeffler M, MabThera International Trial Group (2006) CHOP-like chemotherapy plus rituximab versus CHOP-like chemotherapy alone in young patients with good-prognosis diffuse large-B-cell lymphoma: a randomised controlled trial by the MabThera International Trial (MInT) Group. Lancet Oncol 7(5):379–391

    Article  PubMed  CAS  Google Scholar 

  5. Goto H, Tsurumi H, Takemura M, Ino-Shimomura Y, Kasahara S, Sawada M, Yamada T, Hara T, Fukuno K, Goto N, Okuno M, Takami T, Seishima M, Moriwaki H (2005) Serum-soluble interleukin-2 receptor (sIL-2R) level determines clinical outcome in patients with aggressive non-Hodgkin's lymphoma: in combination with the International Prognostic Index. J Cancer Res Clin Oncol 131(2):73–79

    Article  PubMed  CAS  Google Scholar 

  6. Rubin LA, Nelson DL (1990) The soluble interleukin-2 receptor: biology, function, and clinical application. Ann Intern Med 113(8):619–627

    PubMed  CAS  Google Scholar 

  7. Smith KA (1988) Interleukin-2: inception, impact, and implications. Science 240(4856):1169–1176, Review

    Article  PubMed  CAS  Google Scholar 

  8. Voss SD, Sondel PM, Robb RJ (1992) Characterization of the interleukin 2 receptors (IL-2R) expressed on human natural killer cells activated in vivo by IL-2: association of the p64 IL-2R gamma chain with the IL-2R beta chain in functional intermediate-affinity IL-2R. J Exp Med 176(2):531–541

    Article  PubMed  CAS  Google Scholar 

  9. Wagner DK, Kiwanuka J, Edwards BK, Rubin LA, Nelson DL, Magrath IT (1987) Soluble interleukin-2 receptor levels in patients with undifferentiated and lymphoblastic lymphomas: correlation with survival. J Clin Oncol 5(8):1262–1274

    PubMed  CAS  Google Scholar 

  10. Viviani S, Camerini E, Bonfante V, Santoro A, Balzarotti M, Fornier M, Devizzi L, Verderio P, Valagussa P, Bonadonna G (1998) Soluble interleukin-2 receptors (sIL-2R) in Hodgkin's disease: outcome and clinical implications. Br J Cancer 77(6):992–997

    Article  PubMed  CAS  Google Scholar 

  11. Semenzato G, Foa R, Agostini C, Zambello R, Trentin L, Vinante F, Benedetti F, Chilosi M, Pizzolo G (1987) High serum levels of soluble interleukin 2 receptor in patients with B chronic lymphocytic leukemia. Blood 70(2):396–400

    PubMed  CAS  Google Scholar 

  12. Yasuda N, Lai PK, Ip SH, Kung PC, Hinuma Y, Matsuoka M, Hattori T, Takatsuki K, Purtilo DT (1988) Soluble interleukin 2 receptors in sera of Japanese patients with adult T cell leukemia mark activity of disease. Blood 71(4):1021–1026

    PubMed  CAS  Google Scholar 

  13. Kitagawa J, Hara T, Tsurumi H, Goto N, Kanemura N, Yoshikawa T, Kasahara S, Yamada T, Sawada M, Takahashi T, Shimizu M, Takami T, Moriwaki H (2009) Serum-soluble interleukin-2 receptor (sIL-2R) is an extremely strong prognostic factor for patients with peripheral T-cell lymphoma, unspecified (PTCL-U). J Cancer Res Clin Oncol 135(1):53–59

    Article  PubMed  CAS  Google Scholar 

  14. Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H, Thiele J, Vardiman JW (2008) WHO classification of tumours of haematopoietic and lymphoid tissues, 4th edn. IARC Press, Lyon

    Google Scholar 

  15. Carbone PP, Kaplan HS, Musshoff K, Smithers DW, Tubiana M (1971) Report of the committee on Hodgkin's disease staging classification. Cancer Res 31:1860–1861

    PubMed  CAS  Google Scholar 

  16. Ishii Y, Takami T, Yuasa H, Takei T, Kikuchi K (1984) Two distinct antigen systems in human B lymphocytes: identification of cell surface and intracellular antigens using monoclonal antibodies. Clin Exp Immunol 58:183–192

    PubMed  CAS  Google Scholar 

  17. Hans CP, Weisenburger DD, Greiner TC, Gascoyne RD, Delabie J, Ott G, Müller-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 103:275–282

    Article  PubMed  CAS  Google Scholar 

  18. Natkunam Y, Warnke RA, Montgomery K, Falini B, van De Rijn M (2001) Analysis of MUM1/IRF4 protein expression using tissue microarrays and immunohistochemistry. Mod Pathol 14(7):686–694

    Article  PubMed  CAS  Google Scholar 

  19. Sawada M, Tsurumi H, Yamada T, Hara T, Fukuno K, Goto H, Shimizu M, Kasahara S, Yoshikawa T, Kanemura N, Oyama M, Takami T, Moriwaki H (2002) A prospective study of P-IMVP- 16/CBDCA: a novel salvage chemotherapy for patients with aggressive non-Hodgkin' s lymphoma who had previously received CHOP therapy as first-line chemotherapy. Eur J Haematol 68:354–361

    Article  PubMed  CAS  Google Scholar 

  20. Cheson BD, Horning SJ, Coiffer B, Shipp MA, Fisher RI, Connors JM, Lister TA, Vose J, Grillo-López A, Hagenbeek A, Cabanillas F, Klippensten D, Hiddemann W, Castellino R, Harris NL, Armitage JO, Carter W, Hoppe R, Canellos GP (1999) Report of an international workshop to standardize response criteria for non-Hodgkin's lymphomas. NCI Sponsored International Working Group. J Clin Oncol 17:1244–1253

    PubMed  CAS  Google Scholar 

  21. Sehn LH, Berry B, Chhanabhai M, Fitzgerald C, Gill K, Hoskins P, Klasa R, Savage KJ, Shenkier T, Sutherland J, Gascoyne RD, Connors JM (2007) 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 109:1857–1861

    Article  PubMed  CAS  Google Scholar 

  22. Nicolaides C, Dimou S, Pavlidisa N (1998) Prognostic factors in aggressive non-Hodgkin's lymphomas. Oncologist 3:189–197

    PubMed  Google Scholar 

  23. Alizadeh AA, Eisen MB, Davis RE, Ma C, Lossos IS, Rosenwald A, Boldrick JC, Sabet H, Tran T, Yu X, Powell JI, Yang L, Marti GE, Moore T, Hudson J Jr, Lu L, Lewis DB, Tibshirani R, Sherlock G, Chan WC, Greiner TC, Weisenburger DD, Armitage JO, Warnke R, Levy R, Wilson W, Grever MR, Byrd JC, Botstein D, Brown PO, Staudt LM (2000) Distinct types of diffuse large B-cell lymphoma identified by gene expression profiling. Nature 403:503–511

    Article  PubMed  CAS  Google Scholar 

  24. Wright G, Tan B, Rosenwald A, Hurt EH, Wiestner A, Staudt LM (2003) A gene expression-based method to diagnose clinically distinct subgroups of diffuse large B cell lymphoma. Proc Natl Acad Sci USA, Lyon, pp 9991–9996

    Google Scholar 

  25. Muris JJ, Meijer CJ, Vos W, van Krieken JH, Jiwa NM, Ossenkoppele GJ, Oudejans JJ (2006) Immunohistochemical profiling based on Bcl-2, CD10 and MUM1 expression improves risk stratification in patients with primary nodal diffuse large B cell lymphoma. J Pathol 208:714–723

    Article  PubMed  CAS  Google Scholar 

  26. Saito B, Shiozawa E, Usui T, Nakashima H, Maeda T, Hattori N, Shimozuma J, Adachi D, Yamochi-Onizuka T, Takimoto M, Nakamaki T, Ota H, Tomoyasu S (2007) Rituximab with chemotherapy improves survival of non-germinal center type untreated diffuse large B-cell lymphoma. Leukemia 21:2563–2566

    Article  PubMed  CAS  Google Scholar 

  27. Winter JN, Weller EA, Horning SJ, Krajewska M, Variakojis D, Habermann TM, Fisher RI, Kurtin PJ, Macon WR, Chhanabhai M, Felgar RE, Hsi ED, Medeiros LJ, Weick JK, Reed JC, Gascoyne RD (2006) Prognostic significance of Bcl-6 protein expression in DLBCL treated with CHOP or R-CHOP. A prospective correlative study. Blood 107:4207–4213

    Article  PubMed  CAS  Google Scholar 

  28. Costa LJ, Feldman AL, Micallef IN, Inwards DJ, Johnston PB, Porrata LF, Ansell SM (2008) Germinal center B (GCB) and non-GCB cell-like diffuse large B cell lymphomas have similar outcomes following autologous haematopoietic stem cell transplantation. Br J Haematol 142:404–412

    Article  PubMed  Google Scholar 

  29. Fu K, Weisenburger DD, Choi WW, Perry KD, Smith LM, Shi X, Hans CP, Greiner TC, Bierman PJ, Bociek RG, Armitage JO, Chan WC, Vose JM (2008) Addition of rituximab to standard chemotherapy improves the survival of both the germinal center B-cell-like and non-germinal center B-cell-like subtypes of diffuse large B-cell lymphoma. J Clin Oncol 26:4587–4594

    Article  PubMed  CAS  Google Scholar 

  30. Ichikawa A, Kinoshita T, Watanabe T, Kato H, Nagai H, Tsushita K, Saito H, Hotta T (1997) Mutations of the p53 gene as a prognostic factor in aggressive B-cell lymphoma. N Engl J Med 337(8):529–534

    Article  PubMed  CAS  Google Scholar 

  31. Niitsu N, Nakamine H, Okamoto M, Akamatsu H, Honma Y, Higashihara M, Okabe-Kado J, Hirano M, Adult Lymphoma Treatment Study Group, ALTSG (2003) Expression of nm23-H1 is associated with poor prognosis in peripheral T-cell lymphoma. Br J Haematol 123(4):621–630

    Article  PubMed  CAS  Google Scholar 

  32. Niitsu N, Okabe-Kado J, Kasukabe T, Yamamoto-Yamaguchi Y, Umeda M, Honma Y (1999) Prognostic implications of the differentiation inhibitory factor nm23-H1 protein in the plasma of aggressive non-Hodgkin's lymphoma. Blood 94(10):3541–3550

    PubMed  CAS  Google Scholar 

  33. Niitsu N, Okabe-Kado J, Okamoto M, Takagi T, Yoshida T, Aoki S, Hirano M, Honma Y (2001) Serum nm23-H1 protein as a prognostic factor in aggressive non-Hodgkin lymphoma. Blood 97(5):1202–1210

    Article  PubMed  CAS  Google Scholar 

  34. Hara T, Tsurumi H, Takemura M et al (2000) Serum-soluble Fas level determines clinical symptoms and outcome of patients with aggressive non-Hodgkin's lymphoma. Am J Hematol 64(4):257–261

    Article  PubMed  CAS  Google Scholar 

  35. Watanuki-Miyauchi R, Kojima Y, Tsurumi H, Hara T, Goto N, Kasahara S, Saio M, Moriwaki H, Takami T (2005) Expression of survivin and of antigen detected by a novel monoclonal antibody, T332, is associated with outcome of diffuse large B-cell lymphoma and its subtypes. Pathol Int 55(6):324–330

    Article  PubMed  CAS  Google Scholar 

  36. Goto N, Tsurumi H, Takemura M, Hara T, Sawada M, Kasahara S, Kanemura N, Yamada T, Shimizu M, Takahashi T, Tomita E, Seishima M, Takami T, Moriwaki H (2006) Serum-soluble tumor necrosis factor receptor 2 (sTNF-R2) level determines clinical outcome in patients with aggressive non-Hodgkin's lymphoma. Eur J Haematol 77(3):217–225

    Article  PubMed  CAS  Google Scholar 

  37. Ennishi D, Yokoyama M, Terui Y, Asai H, Sakajiri S, Mishima Y, Takahashi S, Komatsu H, Ikeda K, Takeuchi K, Tanimoto M, Hatake K (2009) Soluble interleukin-2 receptor retains prognostic value in patients with diffuse large B-cell lymphoma receiving rituximab plus CHOP (RCHOP) therapy. Ann Oncol 20(3):526–533

    Article  PubMed  CAS  Google Scholar 

  38. Goto N, Tsurumi H, Kasahara S, Kanemura N, Hara T, Yasuda I, Shimizu M, Murakami N, Sawada M, Yamada T, Takemura M, Seishima M, Kito Y, Takami T, Moriwaki H (2011) Serum interleukin-18 level is associated with the outcome of patients with diffuse large B-cell lymphoma treated with CHOP or R-CHOP regimens. Eur J Haematol 87:217–227

    Article  PubMed  CAS  Google Scholar 

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Correspondence to Hisashi Tsurumi.

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OS (a) and PFS (b) curves for patients with DLBCL treated with CHOP with serum sIL-2R ≥2,000 U/mL and for those with sIL-2R <2,000 U/mL (P < 0.0001 for OS; P < 0.0001 for PFS) (JPEG 78 kb)

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Goto, N., Tsurumi, H., Goto, H. et al. Serum soluble interleukin-2 receptor (sIL-2R) level is associated with the outcome of patients with diffuse large B cell lymphoma treated with R-CHOP regimens. Ann Hematol 91, 705–714 (2012). https://doi.org/10.1007/s00277-011-1363-4

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