Skip to main content

Advertisement

SpringerLink
Log in

Extra-nodal natural killer/T cell lymphoma in elderly patients: the impact of aging on clinical outcomes and treatment tolerability

  • Original Article
  • Published:
Annals of Hematology Aims and scope Submit manuscript

Abstract

Extra-nodal natural killer/T cell lymphoma (ENKTL) is rare in elderly patients, and its clinical course is unclear. The efficacy and tolerability of non-anthracycline-based treatments as a standard regimen in elderly patients have not been fully investigated. This study assessed the impact of aging on clinical outcomes and treatment tolerability. We retrospectively analyzed 51 patients aged ≥60 years who were diagnosed with ENKTL from January 1998 to December 2012. We defined new treatments as non-anthracycline regimens (etoposide, ifosfamide, mesna, cisplatin, and dexamethasone (VIPD); etoposide, ifosfamide, mesna, dexamethasone, and l-asparaginase (VIDL); methotrexate, leucovorin, etoposide, ifosfamide, mesna, dexamethasone, and l-asparaginase (MIDLE); ifosfamide, methotrexate, etoposide, and prednisolone (IMVP16/PD); or methotrexate, leucovorin, etoposide, ifosfamide, mesna, dexamethasone, and l-asparaginase (SMILE), with or without radiation therapy). The median age was 66 years (60–83 years). Twenty patients were diagnosed at advanced stage, and 18 had poor performance status. The overall survival and progression-free survival were 6.7 and 5.2 months, respectively. Clinical outcomes of patients with early disease were superior to those of patients with advanced disease. Among patients who received new treatments, concurrent chemoradiation therapy (CCRT) for localized disease was tolerable, although 37.5 % of patients with advanced disease who received SMILE discontinued chemotherapy due to intolerability. Elderly patients with ENKTL have poor prognostic factors compared to younger patients. In particular, patients with advanced disease have extremely poor prognosis due to inability to tolerate treatment and rapid progression of disease.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Cai Q, Luo X, Zhang G, Huang H, Huang H, Lin T, Jiang W, Xia Z, Young KH (2014) New prognostic model for extranodal natural killer/T cell lymphoma, nasal type. Ann Hematol 93:1541–1549. doi:10.1007/s00277-014-2089-x

    Article  PubMed  Google Scholar 

  2. Ma Q, Zhang HL, Liu X, Zhou SY, Qian ZZ, Zhai QL, Fu K, Wang HQ (2013) Prognostic factors of nasal NK/T-cell lymphoma. Zhonghua Er Bi Yan Hou Tou Jing Wai Ke Za Zhi 48:1011–1016

    PubMed  Google Scholar 

  3. William BM, Armitage JO (2013) International analysis of the frequency and outcomes of NK/T-cell lymphomas. Best Pract Res Clin Haematol 26:23–32. doi:10.1016/j.beha.2013.04.003

    Article  CAS  PubMed  Google Scholar 

  4. Kim SJ, Yang DH, Kim JS, Kwak JY, Eom HS, Hong DS, Won JH, Lee JH, Yoon DH, Cho J, Nam TK, Lee SW, Ahn YC, Suh C, Kim WS (2014) Concurrent chemoradiotherapy followed by L-asparaginase-containing chemotherapy, VIDL, for localized nasal extranodal NK/T cell lymphoma: CISL08-01 phase II study. Ann Hematol 93:1895–1901. doi:10.1007/s00277-014-2137-6

    Article  CAS  PubMed  Google Scholar 

  5. Au WY, Weisenburger DD, Intragumtornchai T, Nakamura S, Kim WS, Sng I, Vose J, Armitage JO, Liang R (2009) 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 113:3931–3937. doi:10.1182/blood-2008-10-185256

    Article  CAS  PubMed  Google Scholar 

  6. Lee J, Suh C, Park YH, Ko YH, Bang SM, Lee JH, Lee DH, Huh J, Oh SY, Kwon HC, Kim HJ, Lee SI, Kim JH, Park J, Oh SJ, Kim K, Jung C, Park K, Kim WS (2006) Extranodal natural killer T-cell lymphoma, nasal-type: a prognostic model from a retrospective multicenter study. J Clin Oncol 24:612–618. doi:10.1200/jco.2005.04.1384

    Article  PubMed  Google Scholar 

  7. Thyss A, Saada E, Gastaud L, Peyrade F, Re D (2014) Hodgkin’s lymphoma in older patients: an orphan disease? Mediterr J Hematol Infect Dis 6:e2014050. doi:10.4084/mjhid.2014.050

    Article  PubMed  PubMed Central  Google Scholar 

  8. Sato A, Nakamura N, Kojima M, Ohmachi K, Carreras J, Kikuti YY, Numata H, Ohgiya D, Tazume K, Amaki J, Moriuchi M, Miyamoto M, Aoyama Y, Kawai H, Ichiki A, Hara R, Kawada H, Ogawa Y, Ando K (2014) Clinical outcome of Epstein-Barr virus-positive diffuse large B-cell lymphoma of the elderly in the rituximab era. Cancer Sci 105:1170–1175. doi:10.1111/cas.12467

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Wang ZY, Li YX, Wang H, Wang WH, Jin J, Liu YP, Song YW, Wang SL, Liu XF, Yu ZH (2011) Unfavorable prognosis of elderly patients with early-stage extranodal nasal-type NK/T-cell lymphoma. Ann Oncol 22:390–396. doi:10.1093/annonc/mdq347

    Article  CAS  PubMed  Google Scholar 

  10. Kim SJ, Kim WS (2010) Treatment of localized extranodal NK/T cell lymphoma, nasal type. Int J Hematol 92:690–696. doi:10.1007/s12185-010-0720-8

    Article  CAS  PubMed  Google Scholar 

  11. Lee J, Kim WS, Park YH, Park SH, Park KW, Kang JH, Lee SS, Lee SI, Lee SH, Kim K, Jung CW, Ahn YC, Ko YH, Park K (2005) Nasal-type NK/T cell lymphoma: clinical features and treatment outcome. Br J Cancer 92:1226–1230. doi:10.1038/sj.bjc.6602502

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Lee J, Park YH, Kim WS, Lee SS, Ryoo BY, Yang SH, Park KW, Kang JH, Park JO, Lee SH, Kim K, Jung CW, Park YS, Im YH, Kang WK, Lee MH, Ko YH, Ahn YC, Park K (2005) Extranodal nasal type NK/T-cell lymphoma: elucidating clinical prognostic factors for risk-based stratification of therapy. Eur J Cancer 41:1402–1408. doi:10.1016/j.ejca.2005.03.010

    Article  PubMed  Google Scholar 

  13. Oshimi K, Kawa K, Nakamura S, Suzuki R, Suzumiya J, Yamaguchi M, Kameoka J, Tagawa S, Imamura N, Ohshima K, Kojya S, Iwatsuki K, Tokura Y, Sato E, Sugimori H (2005) NK-cell neoplasms in Japan. Hematology 10:237–245. doi:10.1080/10245330400026162

    Article  PubMed  Google Scholar 

  14. Lee SH, Ahn YC, Kim WS, Ko YH, Kim K, Park K (2006) The effect of pre-irradiation dose intense CHOP on anthracyline resistance in localized nasal NK/T-cell lymphoma. Haematologica 91:427–428

    PubMed  Google Scholar 

  15. Kim SJ, Kim K, Kim BS, Kim CY, Suh C, Huh J, Lee SW, Kim JS, Cho J, Lee GW, Kang KM, Eom HS, Pyo HR, Ahn YC, Ko YH, Kim WS (2009) Phase II trial of concurrent radiation and weekly cisplatin followed by VIPD chemotherapy in newly diagnosed, stage IE to IIE, nasal, extranodal NK/T-cell lymphoma: consortium for improving survival of lymphoma study. J Clin Oncol 27:6027–6032. doi:10.1200/jco.2009.23.8592

    Article  CAS  PubMed  Google Scholar 

  16. Kim SJ, Yoon DH, Jeong SH, Shin D-Y, Bae SH, Hong J, Park EK, Kim SH, Yhim H-Y, Yang D-H, Lee HW, Lee J-J, Lee M, Eom HS, Kwak J-Y, Lee JH, Hong DS, Suh C, Kim WS (2013) Phase II trial of L-asparaginase plus concurrent chemoradiotherapy followed by Midle (methotrexate, ifosfamide, etoposide, dexamethasone, and L-asparaginase) chemotherapy for patients with newly diagnosed stage I/II extranodal NK/T-cell lymphoma, nasal type. Blood 122:3037

    Google Scholar 

  17. Kim SJ, Park S, Kang ES, Choi JY, Lim do H, Ko YH, Kim WS (2015) Induction treatment with SMILE and consolidation with autologous stem cell transplantation for newly diagnosed stage IV extranodal natural killer/T-cell lymphoma patients. Ann Hematol 94:71–78. doi:10.1007/s00277-014-2171-4

    Article  CAS  PubMed  Google Scholar 

  18. Yamaguchi M, Kwong YL, Kim WS, Maeda Y, Hashimoto C, Suh C, Izutsu K, Ishida F, Isobe Y, Sueoka E, Suzumiya J, Kodama T, Kimura H, Hyo R, Nakamura S, Oshimi K, Suzuki R (2011) 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 29:4410–4416. doi:10.1200/jco.2011.35.6287

    Article  CAS  PubMed  Google Scholar 

  19. Cabanillas F, Hagemeister FB, Bodey GP, Freireich EJ (1982) IMVP-16: an effective regimen for patients with lymphoma who have relapsed after initial combination chemotherapy. Blood 60:693–697

    CAS  PubMed  Google Scholar 

  20. Park BB, Kim WS, Lee J, Park KW, Kang JH, Lee SH, Park JO, Kim K, Jung CW, Park YS, Im YH, Kang WK, Ko YH, Lee MH, Park K (2005) IMVP-16/Pd followed by high-dose chemotherapy and autologous stem cell transplantation as a salvage therapy for refractory or relapsed peripheral T-cell lymphomas. Leuk Lymphoma 46:1743–1748. doi:10.1080/10428190500178266

    Article  CAS  PubMed  Google Scholar 

  21. Palumbo A, Bringhen S, Ludwig H, Dimopoulos MA, Blade J, Mateos MV, Rosinol L, Boccadoro M, Cavo M, Lokhorst H, Zweegman S, Terpos E, Davies F, Driessen C, Gimsing P, Gramatzki M, Hajek R, Johnsen HE, Leal Da Costa F, Sezer O, Spencer A, Beksac M, Morgan G, Einsele H, San Miguel JF, Sonneveld P (2011) Personalized therapy in multiple myeloma according to patient age and vulnerability: a report of the European Myeloma Network (EMN). Blood 118:4519–4529. doi:10.1182/blood-2011-06-358812

    Article  CAS  PubMed  Google Scholar 

  22. Mileshkin L, Prince HM (2005) The adverse prognostic impact of advanced age in multiple myeloma. Leuk Lymphoma 46:951–966. doi:10.1080/10428190500085024

    Article  PubMed  Google Scholar 

  23. Lee J, Kim CY, Park YJ, Lee NK (2013) Sequential chemotherapy followed by radiotherapy versus concurrent chemoradiotherapy in patients with stage I/II extranodal natural killer/T-cell lymphoma, nasal type. Blood Res 48:274–281. doi:10.5045/br.2013.48.4.274

    Article  PubMed  PubMed Central  Google Scholar 

  24. Tsai HJ, Lin SF, Chen CC, Chen TY, Su WC, Hwang WL, Lin JC, Chiou TJ, Kao WY, Chiu CF, Chang YF, Chang JS, Chang MC, Su IJ (2015) Long-term results of a phase II trial with frontline concurrent chemoradiotherapy followed by consolidation chemotherapy for localized nasal natural killer/T-cell lymphoma. Eur J Haematol 94:130–137. doi:10.1111/ejh.12405

    Article  CAS  PubMed  Google Scholar 

  25. Tse E, Kwong YL (2013) How I treat NK/T-cell lymphomas. Blood 121:4997–5005. doi:10.1182/blood-2013-01-453233

    Article  CAS  PubMed  Google Scholar 

  26. Wang C, Bai H, Xi R, Pan Y, Xu S, Zhang Q, Chen Y, Zhou J (2013) [Curative effect of nasal type extranodal NK/T-cell lymphoma by sequential chemotherapy combined radiotherapy compared with chemotherapy]. Lin Chung Er Bi Yan Hou Tou Jing Wai Ke Za Zhi 27:1283–1286, 1290

    PubMed  Google Scholar 

  27. Kim GE, Lee SW, Chang SK, Park HC, Pyo HR, Kim JH, Moon SR, Lee HS, Choi EC, Kim KM (2001) Combined chemotherapy and radiation versus radiation alone in the management of localized angiocentric lymphoma of the head and neck. Radiother Oncol 61:261–269. doi:10.1016/S0167-8140(01)00428-5

    Article  CAS  PubMed  Google Scholar 

  28. Suzuki R (2012) NK/T-cell lymphomas: pathobiology, prognosis and treatment paradigm. Curr Oncol Rep 14:395–402. doi:10.1007/s11912-012-0245-9

    Article  CAS  PubMed  Google Scholar 

  29. Tse E, Kwong YL (2014) Management of advanced NK/T-cell lymphoma. Curr Hematol Malig Rep 9:233–242. doi:10.1007/s11899-014-0216-3

    Article  PubMed  Google Scholar 

  30. Yang L, Liu H, Xu XH, Wang XF, Huang HM, Shi WY, Jiang SH (2013) Retrospective study of modified SMILE chemotherapy for advanced-stage, relapsed, or refractory extranodal natural killer (NK)/T cell lymphoma, nasal type. Med Oncol 30:720. doi:10.1007/s12032-013-0720-7

    Article  PubMed  Google Scholar 

  31. Tse E, Chan TS, Koh LP, Chng WJ, Kim WS, Tang T, Lim ST, Lie AK, Kwong YL (2014) Allogeneic haematopoietic SCT for natural killer/T-cell lymphoma: a multicentre analysis from the Asia Lymphoma Study Group. Bone Marrow Transplant 49:902–906. doi:10.1038/bmt.2014.65

    Article  CAS  PubMed  Google Scholar 

  32. Yong W, Zheng W, Zhu j, Zhang Y, Wang X, Xie Y, Lin N, Xu B, Lu A, Li J (2009) L-asparaginase in the treatment of refractory and relapsed extranodal NK/T-cell lymphoma, nasal type. Ann Hematol 88:647–652. doi:10.1007/s00277-008-0669-3

    Article  CAS  PubMed  Google Scholar 

  33. Yong W, Zheng W, Zhu J, Zhang Y, Wei Y, Wang X, Lin N, Xie Y, Xu B, Li J (2006) Midline NK/T- cell lymphoma nasal-type: treatment outcome, the effect of L-asparaginase based regimen, and prognostic factors. Hematol Oncol 24:28–33

    Article  CAS  PubMed  Google Scholar 

  34. Yong W, Zheng W, Zhang Y, Zhu J, Wei Y, Zhu D, Li J (2003) L-asparaginase-based regimen in the treatment of refractory midline nasal/nasal-type T/NK-cell lymphoma. Int J Hematol 78:163–167

    Article  CAS  PubMed  Google Scholar 

  35. Murashige N, Kami M, Kishi Y, Kim SW, Takeuchi M, Matsue K, Kanda Y, Hirokawa T, Kusumi E, Hirabayashi N, Nagafuji K, Suzuki R, Takeuchi K, Oshimi K (2005) Allogeneic haematopoietic stem cell transplantation as a promising treatment for natural killer-cell neoplasm. Br J Haematol 130:561–567

    Article  PubMed  Google Scholar 

  36. Suzuki R, Suzumiya J, Nakamura S, Kagami Y, Kameoka JI, Sakai C, Mukai H, Takenaka K, Yoshino T, Tsuzuki T, Sugimori H, Kawa K, Kodera Y, Oshimi K (2006) Haematopoietic stem cell transplantation for natural killer-cell lineage neoplasm. Bone Marrow Transplant 37:425–431

    Article  CAS  PubMed  Google Scholar 

  37. Yokohama H, Yamamoto J, Tohmiya Y, Yamada MF, Ohguchi H, Ohnishi Y, Okitsu Y, Fukuhara N, Ohbaohtsuka R, Kohata J, Ishizawa K, Kameoka J, Harigae H (2010) Allogeneic hematopoietic stem cell transplant following chemotherapy containing l-asparaginase as a promising treatment for patients with relapsed or refractory extranodal natural killer/T cell lymphoma, nasal type. Leuk Lymphoma 51:1509–1512

    Article  Google Scholar 

  38. Ennish D, Maeda Y, Fujii M, Kondo E, Shinagawa K, Ikeda K, Ichimura K, Yoshino T, Tanimoto M (2011) Allogeneic hematopoietic stem cell transplantation for advanced extranodal natural killer/T-cell lymphoma, nasal type. Leuk Lymphoma 52:1255–1261

    Article  Google Scholar 

Download references

Acknowledgments

This study was not supported by any funding groups.

Author information

Authors and Affiliations

  1. Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul, 135-710, Korea

    Sung Min Kim, Silvia Park, Seok Jin Kim & Won Seog Kim

  2. Department of Radiation Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea

    Dong Ryul Oh & Yong Chan Ahn

  3. Department of Pathology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea

    Young Hyeh Ko

Authors
  1. Sung Min Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Silvia Park
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Dong Ryul Oh
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Yong Chan Ahn
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Young Hyeh Ko
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Seok Jin Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Won Seog Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Won Seog Kim.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Kim, S.M., Park, S., Oh, D.R. et al. Extra-nodal natural killer/T cell lymphoma in elderly patients: the impact of aging on clinical outcomes and treatment tolerability. Ann Hematol 95, 581–591 (2016). https://doi.org/10.1007/s00277-015-2581-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00277-015-2581-y

Keywords

Search

Navigation