International Journal of Hematology

, Volume 96, Issue 5, pp 617–623 | Cite as

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

  • Liang Wang
  • Zhong-jun Xia
  • Hui-qiang Huang
  • Yue Lu
  • Yu-jing Zhang
Original Article


We conducted a retrospective study of 135 patients of stage IE/IIE extranodal natural killer/T cell lymphoma, nasal type (ENKTL) treated with CHOP as induction chemotherapy to find some valuable prognostic factors and analyze the usefulness of International Prognostic Index (IPI) and Korean Prognostic Index (KPI) in predicting prognosis. Most of the patients were in the low-risk group (IPI score 0–1). Complete remission (CR) after induction chemotherapy was achieved in 31.8 % of the patients, which increased to 69.6 % after radiotherapy. The 2-, 5-, and 10-year overall survival (OS) rates were 60, 48, and 43 %, respectively. Patients with better performance status (ECOG 0-1), normal serum LDH level, without local invasiveness, low KPI scores, and IPI score of 0 had significantly better overall survival (P < 0.05) in univariate analysis. Using multivariate analysis, we identified serum LDH level, ECOG PS score and local invasiveness to be independent prognostic factors. In conclusion, ENKTL is an aggressive lymphoma that shows heterogeneity. The IPI and KPI score systems should be improved further to classify patients into different groups, and should be validated in larger prospective trials. Due to the multi-drug resistance mechanism of ENKTL, CHOP is no longer the state of art and novel drugs should be incorporated into future treatments.


Extranodal natural killer/T cell lymphoma International Prognostic Index Korean Prognostic Index Overall survival 



We would like to thank all of the doctors of the Cancer center, Sun-Yat Sen University for allowing us to include their patients. In addition, we appreciate the cooperation of all the pathologists of the Cancer center, Sun-Yat Sen University for their support. The authors have declared no conflicts of interest, and this work did not receive any fundings.


  1. 1.
    Li YX, Liu QF, Fang H, Qi SN, Wang H, Wang WH, et al. Variable clinical presentations of nasal and Waldeyer ring natural killer/T-cell lymphoma. Clin Cancer Res. 2009;15(8):2905–12.PubMedCrossRefGoogle Scholar
  2. 2.
    Au WY, Weisenburger DD, Intragumtornchai T, Nakamura S, Kim WS, Sng I, et al. Clinical differences between nasal and extranasal natural killer/T-cell lymphoma: a study of 136 cases from the International Peripheral T-Cell Lymphoma Project. Blood. 2009;113(17):3931–7.PubMedCrossRefGoogle Scholar
  3. 3.
    Jaffe ES, Chan JK, Su IJ, Frizzera G, Mori S, Feller AC, et al. Report of the workshop on nasal and related extranodal angiocentric T/natural killer cell lymphomas. Definitions, differential diagnosis, and epidemiology. Am J Surg Pathol. 1996;20:103–11.PubMedCrossRefGoogle Scholar
  4. 4.
    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
  5. 5.
    Lee J, Park YH, Kim WS, Lee SS, Ryoo BY, Yang SH, et al. Extranodal nasal type NK/T-cell lymphoma: elucidating clinical prognostic factors for risk-based stratification of therapy. Eur J Cancer. 2005;41:1402–8.PubMedCrossRefGoogle Scholar
  6. 6.
    Miller TP, Dahlberg S, Cassady JR, Adelstein DJ, Spier CM, Grogan TM, et al. Chemotherapy alone compared with chemotherapy plus radiotherapy for localized intermediate- and high-grade non-Hodgkin’s lymphoma. N Engl J Med. 1998;339:21–6.PubMedCrossRefGoogle Scholar
  7. 7.
    Fisher RI, Gaynor ER, Dahlberg S, Oken MM, Grogan TM, Mize EM, et al. Comparison of a standard regimen (CHOP) with three intensive chemotherapy regimens for advanced non-Hodgkin’s lymphoma. N Engl J Med. 1993;328:1002–6.PubMedCrossRefGoogle Scholar
  8. 8.
    Li YX, Yao B, Jin J, Wang WH, Liu YP, Song YW, et al. Radiotherapy as primary treatment for stage IE and IIE nasal natural killer/T-cell lymphoma. J Clin Oncol. 2006;24:181–9.PubMedCrossRefGoogle Scholar
  9. 9.
    Huang MJ, Jiang Y, Liu WP, Li ZP, Li M, Zhou L, et al. Early or up-front radiotherapy improved survival of localized extranodal NK/T-cell lymphoma, nasal-type in the upper aerodigestive tract. Int J Radiat Oncol Biol Phys. 2008;70:166–74.PubMedCrossRefGoogle Scholar
  10. 10.
    Kim TM, Park YH, Lee SY, Kim JH, Kim DW, Im SA, 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.PubMedCrossRefGoogle Scholar
  11. 11.
    Lee J, Suh C, Park YH, Ko YH, Bang SM, Lee JH, et al. Extranodal natural killer T-cell lymphoma, nasaltype: a prognostic model from a retrospective multicenter study. J Clin Oncol. 2006;24:612–8.PubMedCrossRefGoogle Scholar
  12. 12.
    Tae Min Kim, Dae Seog Heo. Extranodal NK/T-cell lymphoma, nasal type: new staging system and treatment strategies. Cancer Sci. 2009;100:2242–8.Google Scholar
  13. 13.
    Miller AA, Salewski E. Prospects for pirarubicin. Med Pediatr Oncol. 1994;22:261–8.PubMedCrossRefGoogle Scholar
  14. 14.
    Tsurumi H, Yamada T, Sawada M, Kasahara S, Kanemura N, Kojima Y, et al. Biweekly CHOP or THP-COP regimens in the treatment of newly diagnosed aggressive non-Hodgkin’s lymphoma. A comparison of doxorubicin and pirarubicin: a randomized phase II study. J Cancer Res Clin Oncol. 2004;130:107–13.PubMedCrossRefGoogle Scholar
  15. 15.
    Cheson BD, Horning SJ, Coiffier B, Shipp MA, Fisher RI, Connors JM, 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.PubMedGoogle Scholar
  16. 16.
    Yamaguchi M, Tobinai K, Oguchi M, Ishizuka N, Kobayashi Y, Isobe Y, et al. Phase I/II study of concurrent chemoradiotherapy for localized nasal natural killer/T-cell lymphoma: Japan Clinical Oncology Group Study JCOG0211. J Clin Oncol. 2009;27(33):5594–600.PubMedCrossRefGoogle Scholar
  17. 17.
    Cheung MM, Chan JK, Wong KF. Natural killer cell neoplasms: a distinctive group of highly aggressive lymphomas/leukemias. Semin Hematol. 2003;40(3):221–32.PubMedCrossRefGoogle Scholar
  18. 18.
    Wu X, Li P, Zhao J, Yang X, Wang F, Yang YQ, et al. A clinical study of 115 patients with extranodal natural killer/T-cell lymphoma, nasal type. Clin Oncol (R Coll Radiol). 2008;20(8):619–25.CrossRefGoogle Scholar
  19. 19.
    Kwong, YL, Liang R Chapter 76: leukaemia and lymphoma of NK cell origin. In: Magrath I, Rohatiner A, editors. The lymphoid neoplasms. 3rd edn. London: Hodder Arnold (in press).Google Scholar
  20. 20.
    Ribrag V, Ell Hajj M, Janot F, Girinsky T, Domenge C, Schwaab G et al. Early locoregional high-dose chemotherapy is associated with long-term disease control in localized primary angiocentric lymphoma of the nose and nasopharynx. Leukemia. 2001;15(7):1123–6.Google Scholar
  21. 21.
    Yamaguchi M, Kwong YL, Kim WS, Maeda Y, Hashimoto C, Suh C, 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.PubMedCrossRefGoogle Scholar
  22. 22.
    Jaccard A, Gachard N, Marin B, Rogez S, Audrain M, Suarez F, 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.PubMedCrossRefGoogle Scholar
  23. 23.
    Kim HS, Kim KH, Kim KH, et al. Whole blood Epstein–Barr virus DNA load as a diagnostic and prognostic surrogate: extranodal natural killer/T-cell lymphoma. Leuk Lymphoma. 2009;50(5):757–63.PubMedCrossRefGoogle Scholar
  24. 24.
    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(23):6018–22.PubMedCrossRefGoogle Scholar

Copyright information

© The Japanese Society of Hematology 2012

Authors and Affiliations

  • Liang Wang
    • 1
  • Zhong-jun Xia
    • 1
  • Hui-qiang Huang
    • 2
  • Yue Lu
    • 1
  • Yu-jing Zhang
    • 3
  1. 1.Department of Hematologic Oncology, State Key Laboratory of Oncology in South ChinaSun Yat-sen University Cancer CenterGuangzhouPeople’s Republic of China
  2. 2.Department of Medical OncologyState Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer CenterGuangzhouPeople’s Republic of China
  3. 3.Department of Radiation OncologyState Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer CenterGuangzhouPeople’s Republic of China

Personalised recommendations