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Clinical significance of serum soluble interleukin-2 receptor-α in extranodal natural killer/T-cell lymphoma (ENKTL): a predictive biomarker for treatment efficacy and valuable prognostic factor

Medical Oncology volume 30, Article number: 723 (2013) Cite this article

Abstract

Extranodal natural killer/T-cell lymphoma, nasal type (ENKTL) is an aggressive disease, and no standard treatment and validated prognostic model were established. Serum sIL-2Rα levels were measured in 94 ENKTL patients to evaluate its relationship with clinical features, treatment response, and prognosis. Serum sIL-2Rα level was 2964 ± 1613.6 ng/L in ENKTL patients, higher than in normal healthy controls (p < 0.05). Using median level (2508.5 ng/L) as cutoff, patients were divided into higher- and lower-level group (N = 47 for each). The complete remission and overall remission rate were significantly higher in lower-level group (p < 0.05). After a median follow-up time of 22.0 months, 2-year overall survival and progression-free survival rates were 60.0 and 53.0 %, respectively. Lower sIL-2Rα level significantly correlated with better progression-free survival (PFS) and overall survival (OS) (p = 0.001 and 0.002, respectively). IPI score and treatment responses after 2 cycles of chemotherapy significantly correlated with PFS and OS (p < 0.05). In a multivariate Cox regression model that included IPI score, treatment responses, and sIL-2Rα level, all three parameters were independent prognostic factors for OS (p = 0.043, 0.001, and 0.025, respectively), and the last two parameters were also independent factors for PFS (p = 0.005 and 0.005, respectively). Elevated serum sIL-2Rα level was related to poor responses to treatments and can be used as a valuable biomarker for disease activity. Moreover, serum sIL-2Rα was an independent prognostic factor for both OS and PFS. These results need to be validated in prospective trials and may support the incorporation of anti-CD25 targeted therapy into the treatment realm of ENKTL.

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References

  1. Li YX, Liu QF, Fang H, et al. Variable clinical presentations of nasal and Waldeyer ring natural killer/T-cell lymphoma. Clin Cancer Res. 2009;15:2905–12.

    Article  PubMed  Google Scholar 

  2. Vose J, Armitage J, Weisenburger D. International peripheral T-cell and natural killer/T-cell lymphoma study: pathology findings and clinical outcomes. J Clin Oncol. 2008;26:4124–30.

    Article  PubMed  Google Scholar 

  3. Wang B, Li XQ, Ma X, et al. Immunohistochemical expression and clinical significance of P-glycoprotein in previously untreated extranodal NK/T-cell lymphoma, nasal type. Am J Hematol. 2008;83:795–9.

    Article  PubMed  Google Scholar 

  4. Yamaguchi M, Kwong YL, Kim WS, et al. Phase II study of SMILE chemotherapy for newly diagnosed stage IV, relapsed, or refractory extranodal natural killer (NK)/T-cell lymphoma, nasal type: the NK-Cell tumor study group study. J Clin Oncol. 2011;29(33):4410–6.

    Article  CAS  PubMed  Google Scholar 

  5. Jaccard A, Gachard N, Marin B, et al. Efficacy of L-asparaginase with methotrexate and dexamethasone (AspaMetDex regimen) in patients with refractory or relapsing extranodal NK/T-cell lymphoma, a phase 2 study. Blood. 2011;117(6):1834–9.

    Article  CAS  PubMed  Google Scholar 

  6. Wang L, Wang ZH, Chen XQ, et al. First-line combination of gemcitabine, oxaliplatin, and L-asparaginase (GELOX) followed by involved-field radiation therapy for patients with stage IE/IIE extranodal natural killer/T-cell lymphoma. Cancer. 2013;119:348–55.

    Article  CAS  PubMed  Google Scholar 

  7. Kim TM, Park YH, Lee SY, et al. Local tumor invasiveness is more predictive of survival than international prognostic index in stage I (E)/II (E) extranodal NK/T-cell lymphoma, nasal type. Blood. 2005;106:3785–90.

    Article  CAS  PubMed  Google Scholar 

  8. Lee J, Suh C, Park YH, et al. Extranodal natural killer T-cell lymphoma, nasaltype: a prognostic model from a retrospective multicenter study. J Clin Oncol. 2006;24:612–8.

    Article  PubMed  Google Scholar 

  9. Wang L, Xia ZJ, Huang HQ, et al. Cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) in the treatment of stage IE/IIE extranodal natural killer/T cell lymphoma, nasal type: 13-year follow-up in 135 patients. Int J Hematol. 2012;96:617–23.

    Article  CAS  PubMed  Google Scholar 

  10. Kwong YL, Kim WS, Lim ST, et al. SMILE for natural killer/T-cell lymphoma: analysis of safety and efficacy from the Asia lymphoma study group. Blood. 2012;120(15):2973–80.

    Article  CAS  PubMed  Google Scholar 

  11. Suzuki R, Yamaguchi M, Izutsu K, et al. Prospective measurement of Epstein-Barr virus-DNA in plasma and peripheral blood mononuclear cells of extranodal NK/T-cell lymphoma, nasal type. Blood. 2011;118:6018–22.

    Article  CAS  PubMed  Google Scholar 

  12. Li ZM, Zhu YJ, Sun J, et al. Serum beta2-microglobin is a predictor of prognosis in patients with upper aero digestive tract NK/T-cell lymphoma. Ann Hematol. 2012;91(8):1265–70.

    Article  CAS  PubMed  Google Scholar 

  13. Bien E, Balcerska A. Serum soluble interleukin 2 receptor alpha in human cancer of adults and children: a review. Biomarkers. 2008;13(1):1–26.

    Article  CAS  PubMed  Google Scholar 

  14. Lai KN, Ho S, Leung JC, Tsao SY. Soluble interleukin-2 receptors in patients with nasopharyngeal carcinoma. Cancer. 1991;67(8):2180–5.

    Article  CAS  PubMed  Google Scholar 

  15. Berghella AM, Pellegrini P, Piancatelli D, et al. Progression mechanisms in colon cancer: soluble interleukin-2 (IL-2) receptor, IL-2 plus anti-CD3 proliferative response and tumour stage correlations. Cancer Immunol Immunother. 1994;38(3):160–6.

    CAS  PubMed  Google Scholar 

  16. Sharma S, Saha K, Shinghal RN, Malik GB. Serum soluble interleukin-2 (IL-2) receptor levels in women with breast carcinoma and its correlation with IL-2 receptor expression on blood lymphocytes and lymphocytic infiltration within the tumour. Cancer Immunol Immunother. 1991;33(3):198–202.

    Article  CAS  PubMed  Google Scholar 

  17. Barton DP, Blanchard DK, Michelini-Norris B, et al. High serum and ascitic soluble interleukin-2 receptor a levels in advanced epithelial ovarian cancer. Blood. 1993;81(2):424–9.

    CAS  PubMed  Google Scholar 

  18. Nakata B, Chung KH, Kato Y, et al. Serum soluble interleukin-2 receptor level as a prognostic indicator in gastric cancer. Br J Cancer. 1998;77(11):1820–4.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  19. Buccheri G, Marino P, Preatoni A, et al. Soluble interleukin 2 receptor in lung cancer: an indirect marker of tumor activity? Chest. 1991;99(6):1433–7.

    Article  CAS  PubMed  Google Scholar 

  20. Pui CH, Ip SH, Iflah S, et al. Serum interleukin 2 receptor levels in childhood acute lymphoblastic leukemia. Blood. 1988;71(4):1135–7.

    CAS  PubMed  Google Scholar 

  21. Janka G. Hemophagocytic syndromes. Blood Rev. 2007;21:245–53.

    Article  CAS  PubMed  Google Scholar 

  22. Falini B, Pileri S, De Solas I, et al. Peripheral T-cell lymphoma associated with hemophagocytic syndrome. Blood. 1990;75(2):434–44.

    CAS  PubMed  Google Scholar 

  23. Henter JI, Horne A, Arico M, et al. HLH-2004: diagnostic and therapeutic guidelines for hemophagocytic lymphohistiocytosis. Pediatr Blood Cancer. 2007;48:124–31.

    Article  PubMed  Google Scholar 

  24. Chan JK, Quintanilla-Martinez L, Ferry JA, Peh S-C. Extranodal NK/T-cell lymphoma, nasal type. In: Swerdlow SH, Campo E, Harris NL, et al., editors. WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues. Lyon: IARC; 2008. p. 285–8.

    Google Scholar 

  25. Huang H, Lin Z, Lin X, et al. Long-term outcomes of patients with newly diagnosed extranodal natural killer/T-cell lymphoma treated by etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin regimen: a single-institution experience. Leuk Lymphoma. 2011;52:1041–8.

    Article  CAS  PubMed  Google Scholar 

  26. Cheson BD, Horning SJ, Coiffier B, et al. Report of an international workshop to standardize response criteria for non-Hodgkin’s lymphomas. NCI sponsored international working group. J Clin Oncol. 1999;17:1244.

    CAS  PubMed  Google Scholar 

  27. Wang Liang-Shun, Chow Kuan-Chih, Li Wing-Yin, et al. Clinical significance of serum soluble interleukin 2 receptor-a in esophageal squamous cell carcinoma. Clin Cancer Res. 2000;6:1445–51.

    CAS  PubMed  Google Scholar 

  28. Talpur R, Jones DM, Alencar AJ, et al. CD25 expression is correlated with histological grade and response to denileukin diftitox in cutaneous T-cell lymphoma. J Invest Dermatol. 2006;126(3):575–83.

    Article  CAS  PubMed  Google Scholar 

  29. Smith KA. Interleukin-2: inception, impact, and implications. Science. 1988;240:1169–76.

    Article  CAS  PubMed  Google Scholar 

  30. Waldmann TA. The structure, function, and expression of interleukin-2 receptors on normal and malignant lymphocytes. Science. 1986;232:727–32.

    Article  CAS  PubMed  Google Scholar 

  31. Nakase K, Kita K, Nasu K, et al. Differential expression of interleukin-2 receptors (alpha and beta chain) in mature lymphoid neoplasms. Am J Hematol. 1994;46:179–83.

    Article  CAS  PubMed  Google Scholar 

  32. Rubin LA, Nelson DL. The soluble interleukin-2 receptor: biology, function, and clinical application. Ann Intern Med. 1990;113:619–27.

    Article  CAS  PubMed  Google Scholar 

  33. Ennishi D, Yokoyama M, Terui Y, et al. Soluble interleukin-2 receptor retains prognostic value in patients with diffuse large B-cell lymphoma receiving rituximab plus CHOP (RCHOP) therapy. Ann Oncol. 2009;20:526–33.

    Article  CAS  PubMed  Google Scholar 

  34. Yang ZZ, Grote DM, Ziesmer SC, et al. Soluble IL-2R alpha facilitates IL-2-mediated immune responses and predicts reduced survival in follicular B-cell non-Hodgkin lymphoma. Blood. 2011;118:2809–20.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  35. Niitsu N, Iijima K, Chizuka A. A high serum-soluble interleukin-2 receptor level is associated with a poor outcome of aggressive non-Hodgkin’s lymphoma. Eur J Haematol. 2001;66:24–30.

    Article  CAS  PubMed  Google Scholar 

  36. Pongpruttipan T, Sukpanichnant S, Assanasen T, et al. Extranodal NK/T-cell lymphoma, nasal type, includes cases of natural killer cell and αβ, γδ, and αβ/γδ T-cell origin: a comprehensive clinicopathologic and phenotypic study. Am J Surg Pathol. 2012;36(4):481–99.

    Article  PubMed  Google Scholar 

  37. Yoshizato T, Nannya Y, Imai Y, et al. Clinical significance of serum-soluble interleukin-2 receptor in patients with follicular lymphoma. Clin Lymphoma Myeloma Leuk. 2013;13(4):410–6.

    Article  CAS  PubMed  Google Scholar 

  38. Olin RL, Nichols KE, Naghashpour M, et al. Successful use of the anti-CD25 antibody daclizumab in an adult patient with hemophagocytic lymphohistiocytosis. Am J Hematol. 2008;83(9):747–9.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

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Acknowledgments

We thank all of the physicians at Sun Yat-sen University Cancer Center for allowing us to include their patients. We also appreciate the cooperation of all the pathologists at Sun Yat-sen University Cancer Center for their support. This work received grant support from Young Teachers’ Cultivation Project of Sun Yat-sen University (No. 12ykpy54) and National Natural Science Foundation of China (No. 81272620).

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Authors and Affiliations

  1. Department of Hematological Oncology, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, 510060, People’s Republic of China

    Wang Liang, Zhang Jing, Xia Zhong-jun, Peng Xiong-wen & Lu Yue

  2. Department of Pathology, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, People’s Republic of China

    Liao Ding-zhun

  3. State Key Laboratory of Oncology in South China, Guangzhou, Guangdong, People’s Republic of China

    Wang Liang, Liao Ding-zhun, Zhang Jing, Xia Zhong-jun, Peng Xiong-wen & Lu Yue

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  1. Wang Liang
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  2. Liao Ding-zhun
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Correspondence to Lu Yue.

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Wang Liang, Liao Ding-zhun, and Zhang Jing have contributed equally to this article.

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Liang, W., Ding-zhun, L., Jing, Z. et al. Clinical significance of serum soluble interleukin-2 receptor-α in extranodal natural killer/T-cell lymphoma (ENKTL): a predictive biomarker for treatment efficacy and valuable prognostic factor. Med Oncol 30, 723 (2013). https://doi.org/10.1007/s12032-013-0723-4

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  • DOI: https://doi.org/10.1007/s12032-013-0723-4

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