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Induction treatment with SMILE and consolidation with autologous stem cell transplantation for newly diagnosed stage IV extranodal natural killer/T-cell lymphoma patients

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Abstract

The aim of this study was to investigate the impact of the induction treatment with SMILE (dexamethasone, methotrexate, ifosfamide, l-asparaginase, and etoposide) chemotherapy and consolidation with upfront autologous stem cell transplantation (ASCT) on clinical outcomes of patients with stage IV extranodal natural killer/T-cell lymphoma (ENKTL). We analyzed the treatment response to SMILE and toxicity, and explored the feasibility of upfront ASCT in 27 patients with stage IV ENKTL out of patients who were enrolled into our prospective cohort studies. The median age of patients was 45 years (range: 17–65 years), and all patients had disseminated disease. The overall response rate to SMILE induction treatment was 59 % (16/27) including nine complete responses. However, five patients died due to grade IV febrile neutropenia during SMILE and six patients did not respond to SMILE. Eleven patients could undergo ASCT, and there was no transplantation-related mortality. The survival outcome of patients underwent ASCT was better than patients who could not (P < 0.05). However, four patients relapsed even after ASCT, thus, the median overall survival was 10.6 months, and the median progression-free survival was 5.1 months. Pretreatment Epstein–Barr virus (EBV) DNA titer was only independent prognostic factor for overall survival. In conclusion, our results suggest SMILE followed by ASCT might be an effective treatment strategy for stage IV ENKTL. However, considering frequent occurrences of disease relapse and treatment-related mortality, additional efforts are required to improve treatment outcomes of stage IV ENKTL patients.

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References

  1. Yamaguchi M, Kita K, Miwa H, Nishii K, Oka K, Ohno T, Shirakawa S, Fukumoto M (1995) Frequent expression of P-glycoprotein/MDR1 by nasal T-cell lymphoma cells. Cancer 76:2351–2356

    Article  CAS  PubMed  Google Scholar 

  2. Kwong YL (2005) Natural killer-cell malignancies: diagnosis and treatment. Leukemia 19:2186–2194. doi:10.1038/sj.leu.2403955

    Article  CAS  PubMed  Google Scholar 

  3. Yamaguchi M, Tobinai K, Oguchi M, Ishizuka N, Kobayashi Y, Isobe Y, Ishizawa K, Maseki N, Itoh K, Usui N, Wasada I, Kinoshita T, Ohshima K, Matsuno Y, Terauchi T, Nawano S, Ishikura S, Kagami Y, Hotta T, Oshimi K (2009) Phase I/II study of concurrent chemoradiotherapy for localized nasal natural killer/T-cell lymphoma: Japan Clinical Oncology Group Study JCOG0211. J Clin Oncol 27:5594–5600. doi:10.1200/JCO.2009.23.8295

    Article  CAS  PubMed  Google Scholar 

  4. 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 

  5. Yamaguchi M, Suzuki R, Kwong YL, Kim WS, Hasegawa Y, Izutsu K, Suzumiya J, Okamura T, Nakamura S, Kawa K, Oshimi K (2008) Phase I study of dexamethasone, methotrexate, ifosfamide, l-asparaginase, and etoposide (SMILE) chemotherapy for advanced-stage, relapsed or refractory extranodal natural killer (NK)/T-cell lymphoma and leukemia. Cancer Sci 99:1016–1020. doi:10.1111/j.1349-7006.2008.00768.x

    Article  CAS  PubMed  Google Scholar 

  6. 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 

  7. 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, Group NK-cTS (2006) Hematopoietic stem cell transplantation for natural killer-cell lineage neoplasms. Bone Marrow Transplant 37:425–431. doi:10.1038/sj.bmt.1705244

    Article  CAS  PubMed  Google Scholar 

  8. Kwong YL (2009) High-dose chemotherapy and hematopoietic SCT in the management of natural killer-cell malignancies. Bone Marrow Transplant 44:709–714. doi:10.1038/bmt.2009.239

    Article  CAS  PubMed  Google Scholar 

  9. 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 

  10. Cheson BD, Pfistner B, Juweid ME, Gascoyne RD, Specht L, Horning SJ, Coiffier B, Fisher RI, Hagenbeek A, Zucca E, Rosen ST, Stroobants S, Lister TA, Hoppe RT, Dreyling M, Tobinai K, Vose JM, Connors JM, Federico M, Diehl V, International Harmonization Project on L (2007) Revised response criteria for malignant lymphoma. J Clin Oncol 25:579–586. doi:10.1200/JCO.2006.09.2403

    Article  PubMed  Google Scholar 

  11. Kwong YL, Kim WS, Lim ST, Kim SJ, Tang T, Tse E, Leung AY, Chim CS (2012) SMILE for natural killer/T-cell lymphoma: analysis of safety and efficacy from the Asia Lymphoma Study Group. Blood 120:2973–2980. doi:10.1182/blood-2012-05-431460

    Article  CAS  PubMed  Google Scholar 

  12. Lee J, Au WY, Park MJ, Suzumiya J, Nakamura S, Kameoka J, Sakai C, Oshimi K, Kwong YL, Liang R, Yiu H, Wong KH, Cheng HC, Ryoo BY, Suh C, Ko YH, Kim K, Lee JW, Kim WS, Suzuki R (2008) Autologous hematopoietic stem cell transplantation in extranodal natural killer/T cell lymphoma: a multinational, multicenter, matched controlled study. Biol Blood Marrow Transplant 14:1356–1364. doi:10.1016/j.bbmt.2008.09.014

    Article  PubMed  Google Scholar 

  13. Chan A, Tang T, Ng T, Shih V, Tay K, Tao M, Quek R, Lim ST (2012) To SMILE or not: supportive care matters. J Clin Oncol 30:1015–1016. doi:10.1200/JCO.2011.40.7098, author reply 1016–1017

    Article  PubMed  Google Scholar 

  14. Kim HS, Kim KH, Chang MH, Ji SH, do Lim H, Kim K, Kim SJ, Ko Y, Ki CS, Jo SJ, Lee JW, Kim WS (2009) Whole blood Epstein–Barr virus DNA load as a diagnostic and prognostic surrogate: extranodal natural killer/T-cell lymphoma. Leuk Lymphoma 50:757–763. doi:10.1080/10428190902803669

    Article  CAS  PubMed  Google Scholar 

  15. Ito Y, Kimura H, Maeda Y, Hashimoto C, Ishida F, Izutsu K, Fukushima N, Isobe Y, Takizawa J, Hasegawa Y, Kobayashi H, Okamura S, Yamaguchi M, Suzumiya J, Hyo R, Nakamura S, Kawa K, Oshimi K, Suzuki R (2012) Pretreatment EBV-DNA copy number is predictive of response and toxicities to SMILE chemotherapy for extranodal NK/T-cell lymphoma, nasal type. Clin Cancer Res 18:4183–4190. doi:10.1158/1078-0432.CCR-12-1064

    Article  CAS  PubMed  Google Scholar 

  16. Kwong YL, Pang AW, Leung AY, Chim CS, Tse E (2013) Quantification of circulating Epstein-Barr virus DNA in NK/T-cell lymphoma treated with the SMILE protocol: diagnostic and prognostic significance. Leukemia. doi:10.1038/leu.2013.212

    Google Scholar 

  17. Kwong YL (2011) The diagnosis and management of extranodal NK/T-cell lymphoma, nasal-type and aggressive NK-cell leukemia. J Clin Exp Hematop 51:21–28

    Article  PubMed  Google Scholar 

Download references

Acknowledgements

This study was supported by Samsung Medical Center grant (S-2012-0286-000) and Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology (NRF-2012R1A1A2008573).

Conflict of interest

The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Division of Hematology and Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Irwon-dong, Gangnam-gu, Seoul, 135-710, South Korea

    Seok Jin Kim, Silvia Park & Won Seog Kim

  2. Department of Laboratory Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea

    Eun Suk Kang

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

    Joon Young Choi

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

    Do Hoon Lim

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

    Young Hyeh Ko

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  1. Seok Jin Kim
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  2. Silvia Park
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  3. Eun Suk Kang
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  4. Joon Young Choi
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  5. Do Hoon Lim
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  6. Young Hyeh Ko
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  7. Won Seog Kim
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Correspondence to Won Seog Kim.

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Kim, S.J., Park, S., Kang, E.S. et al. 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 (2015). https://doi.org/10.1007/s00277-014-2171-4

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  • DOI: https://doi.org/10.1007/s00277-014-2171-4

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