Advertisement

Annals of Hematology

, Volume 91, Issue 5, pp 705–714 | Cite as

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

  • Naoe Goto
  • Hisashi Tsurumi
  • Hideko Goto
  • Yoriko Ino Shimomura
  • Senji Kasahara
  • Takeshi Hara
  • Ichiro Yasuda
  • Masahito Shimizu
  • Nobuo Murakami
  • Takeshi Yoshikawa
  • Kenji Fukuno
  • Takeshi Takahashi
  • Yusuke Kito
  • Tsuyoshi Takami
  • Hisataka Moriwaki
Original Article

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.

Keywords

Soluble interleukin-2 receptor (sIL-2R) R-CHOP DLBCL 

Supplementary material

277_2011_1363_Fig4_ESM.jpg (78 kb)
Supplementary figure

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)

277_2011_1363_MOESM1_ESM.tif (1.5 mb)
High-resolution image (TIFF 1,520 kb)

References

  1. 1.
    The International Non-Hodgkin's Lymphoma Prognostic Factors Project (1993) A predictive model for aggressive non-Hodgkin's lymphoma. N Engl J Med 329:987–994CrossRefGoogle Scholar
  2. 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 346:235–242CrossRefGoogle Scholar
  3. 3.
    Fisher RI, Shah P (2003) Current trends in large cell lymphoma. Leukemia 17:1948–1960PubMedCrossRefGoogle Scholar
  4. 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):379–391PubMedCrossRefGoogle Scholar
  5. 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):73–79PubMedCrossRefGoogle Scholar
  6. 6.
    Rubin LA, Nelson DL (1990) The soluble interleukin-2 receptor: biology, function, and clinical application. Ann Intern Med 113(8):619–627PubMedGoogle Scholar
  7. 7.
    Smith KA (1988) Interleukin-2: inception, impact, and implications. Science 240(4856):1169–1176, ReviewPubMedCrossRefGoogle Scholar
  8. 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):531–541PubMedCrossRefGoogle Scholar
  9. 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):1262–1274PubMedGoogle Scholar
  10. 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):992–997PubMedCrossRefGoogle Scholar
  11. 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):396–400PubMedGoogle Scholar
  12. 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):1021–1026PubMedGoogle Scholar
  13. 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):53–59PubMedCrossRefGoogle Scholar
  14. 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, LyonGoogle Scholar
  15. 15.
    Carbone PP, Kaplan HS, Musshoff K, Smithers DW, Tubiana M (1971) Report of the committee on Hodgkin's disease staging classification. Cancer Res 31:1860–1861PubMedGoogle Scholar
  16. 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 58:183–192PubMedGoogle Scholar
  17. 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 103:275–282PubMedCrossRefGoogle Scholar
  18. 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):686–694PubMedCrossRefGoogle Scholar
  19. 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 68:354–361PubMedCrossRefGoogle Scholar
  20. 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 17:1244–1253PubMedGoogle Scholar
  21. 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 109:1857–1861PubMedCrossRefGoogle Scholar
  22. 22.
    Nicolaides C, Dimou S, Pavlidisa N (1998) Prognostic factors in aggressive non-Hodgkin's lymphomas. Oncologist 3:189–197PubMedGoogle Scholar
  23. 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 403:503–511PubMedCrossRefGoogle Scholar
  24. 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 9991–9996Google Scholar
  25. 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 208:714–723PubMedCrossRefGoogle Scholar
  26. 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 21:2563–2566PubMedCrossRefGoogle Scholar
  27. 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 107:4207–4213PubMedCrossRefGoogle Scholar
  28. 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 142:404–412PubMedCrossRefGoogle Scholar
  29. 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 26:4587–4594PubMedCrossRefGoogle Scholar
  30. 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):529–534PubMedCrossRefGoogle Scholar
  31. 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):621–630PubMedCrossRefGoogle Scholar
  32. 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):3541–3550PubMedGoogle Scholar
  33. 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):1202–1210PubMedCrossRefGoogle Scholar
  34. 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):257–261PubMedCrossRefGoogle Scholar
  35. 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):324–330PubMedCrossRefGoogle Scholar
  36. 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):217–225PubMedCrossRefGoogle Scholar
  37. 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):526–533PubMedCrossRefGoogle Scholar
  38. 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 87:217–227PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2011

Authors and Affiliations

  • Naoe Goto
    • 1
    • 4
  • Hisashi Tsurumi
    • 1
  • Hideko Goto
    • 2
  • Yoriko Ino Shimomura
    • 1
  • Senji Kasahara
    • 1
  • Takeshi Hara
    • 1
  • Ichiro Yasuda
    • 1
  • Masahito Shimizu
    • 1
  • Nobuo Murakami
    • 1
  • Takeshi Yoshikawa
    • 3
  • Kenji Fukuno
    • 2
  • Takeshi Takahashi
    • 2
  • Yusuke Kito
    • 4
  • Tsuyoshi Takami
    • 4
  • Hisataka Moriwaki
    • 1
  1. 1.First Department of Internal MedicineGifu University Graduate School of MedicineGifuJapan
  2. 2.Second Department of Internal MedicineGifu Municipal HospitalGifuJapan
  3. 3.Department of Internal MedicineKisogawa HospitalAichiJapan
  4. 4.Department of ImmunopathologyGifu University Graduate School of MedicineGifuJapan

Personalised recommendations