Skip to main content

EPOCH regimen as salvage therapy for adult T-cell leukemia–lymphoma

Abstract

Adult T-cell leukemia–lymphoma (ATL) is an intractable hematopoietic malignancy with a very poor prognosis. Although improved responses have been achieved through intensive chemotherapy in newly diagnosed patients with aggressive ATL, most patients suffer from relapse or disease recurrence, and an effective salvage therapy, especially for candidates for allogeneic hematopoietic stem cell transplantation (allo-HSCT), is yet to be established. The efficacy of the EPOCH regimen has been reported for several lymphoid malignancies; however, its efficacy for ATL has not been sufficiently evaluated. Here, we report results of a study of the EPOCH regimen as a salvage therapy for ATL. We retrospectively analyzed patients with relapsed or refractory ATL treated in our institution, with EPOCH as a first salvage therapy. Fourteen patients with a median age of 58 years were analyzed, among whom eight achieved a response, including a complete response in one patient and partial responses in seven. Seven patients underwent allo-HSCT after EPOCH therapy; however, the median overall survival (OS) could not be determined, whereas OS at 2 years after allo-HSCT was estimated to be 85.7%. These results suggest that EPOCH is an option for salvage therapy in patients with ATL, including candidates for allo-HSCT.

This is a preview of subscription content, access via your institution.

Fig. 1
Fig. 2
Fig. 3

References

  1. Uchiyama T, Yodoi J, Sagawa K, Takatsuki K, Uchino H. Adult T-cell leukemia: clinical and hematologic features of 16 cases. Blood. 1977;50(3):481–92.

    PubMed  CAS  Google Scholar 

  2. Poiesz BJ, Ruscetti FW, Gazdar AF, Minna JD, Gallo RC. Detection and isolation of type C retrovirus particles from fresh and cultured lymphocytes of a patient with cutaneous T-cell lymphoma. Proc Natl Acad Sci USA. 1980;77(12):7415–9.

    Article  PubMed  CAS  Google Scholar 

  3. Hinuma Y, Nagata K, Hanaoka M, Nakai M, Matsumoto T, Kinoshita KI, et al. Adult T-cell leukemia: Antigen in an ATL cell line and detection of antibodies to the antigen in human sera. Proc Natl Acad Sci USA. 1981;78:6476–80.

    Article  PubMed  CAS  Google Scholar 

  4. Yoshida M, Miyoshi I, Hinuma Y. Isolation and characterization of retrovirus from cell lines of human adult T cell leukemia and its implication in the disease. Proc Natl Acad Sci USA. 1982;79:2031–5.

    Article  PubMed  CAS  Google Scholar 

  5. Shimoyama M. Diagnostic criteria and classification of clinical subtypes of adult T-cell leukaemia-lymphoma. A report from the Lymphoma Study Group (1984–87). Br J Haematol. 1991;79:428–37.

    Article  PubMed  CAS  Google Scholar 

  6. Tsukasaki K, Hermine O, Bazarbachi A, Ratner L, Ramos JC, Harrington W Jr, et al. Definition, prognostic factors, treatment, and response criteria of adult T-cell leukemia–lymphoma: a proposal from an international consensus meeting. J Clin Oncol. 2009;27(3):453–9.

    Article  PubMed  PubMed Central  Google Scholar 

  7. Tsukasaki K, Utsunomiya A, Fukuda H, Shibata T, Fukushima T, Takatsuka Y, Ikeda S, et al. VCAP-AMP-VECP compared with biweekly CHOP for adult T-cell leukemia–lymphoma: Japan Clinical Oncology Group Study JCOG9801. J Clin Oncol. 2007;25:5458–64.

    Article  PubMed  CAS  Google Scholar 

  8. Taniguchi H, Imaizumi Y, Makiyama J, Itonaga H, Ando K, Sawayama Y, et al. Outcome of patients with relapsed/refractory adult T-cell leukemia–lymphoma after salvage therapy. Rinsho Ketsueki. 2013;54(12):2159–66.

    PubMed  Google Scholar 

  9. Katsuya H, Ishitsuka K, Utsunomiya A, Hanada S, Eto T, Moriuchi Y, et al. Treatment and survival among 1594 patients with ATL. Blood. 2015;126(24):2570–7.

    Article  PubMed  CAS  Google Scholar 

  10. Gutierrez M, Chabner BA, Pearson D, Steinberg SM, Jaffe ES, Cheson BD, et al. Role of a doxorubicin-containing regimen in relapsed and resistant lymphomas: an 8-year follow-up study of EPOCH. J Clin Oncol. 2000;18(21):3633–42.

    Article  PubMed  CAS  Google Scholar 

  11. Wilson WH, Bryant G, Bates S, Fojo A, Wittes RE, Steinberg SM, et al. EPOCH chemotherapy: toxicity and efficacy in relapsed and refractory non-Hodgkin’s lymphoma. J Clin Oncol. 1993;11(8):1573–82.

    Article  PubMed  CAS  Google Scholar 

  12. Jermann M, Jost LM, Taverna Ch, Jacky E, Honegger HP, Betticher DC, et al. Rituximab-EPOCH, an effective salvage therapy for relapsed, refractory or transformed B-cell lymphomas: results of a phase II study. Ann Oncol. 2004;15:511–6.

    Article  PubMed  CAS  Google Scholar 

  13. Dobashi N, Usui N, Kobayashi T, Yamazaki H, Asai O, Yano S, et al. EPOCH therapy for relapsed/refractory lymphoid malignancies. Rinsho Ketsueki. 1998;39(4):267–72.

    PubMed  CAS  Google Scholar 

  14. Wilder DD, Ogden JL, Jain VK. A multicenter trial of infusional etoposide, doxorubicin, and vincristine with cyclophosphamide and prednisone (EPOCH) in patients with relapsed non-Hodgkin’s lymphoma. Clin Lymphoma. 2001;1(4):285–92.

    Article  PubMed  CAS  Google Scholar 

  15. Nagajothi N, Dham SK, Gelfand Y, Sanmugarajah J. Treatment of AIDS-associated anaplastic large-cell lymphoma with dose-adjusted EPOCH chemotherapy. J Natl Med Assoc. 2007;99(7):799–801.

    PubMed  PubMed Central  Google Scholar 

  16. Pejša V, Prka Z, Lucijanić M, Mitrović Z, Piršić M, Jakšić O, et al. Rituximab with dose-adjusted EPOCH as first-line treatment in patients with highly aggressive diffuse large B-cell lymphoma and autologous stem cell transplantation in selected patients. Croat Med J. 2017;58(1):40–8.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  17. Lamar ZS, Fino N, Palmer J, Gruber L, Morris BB, Raetskaya-Solntseva O, et al. Dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin (EPOCH) with or without rituximab as first-line therapy for aggressive non-Hodgkin’s lymphoma. Clin Lymphoma Myeloma Leuk. 2016;16(2):76–81.

    Article  PubMed  Google Scholar 

  18. Dunleavy K, Pittaluga S, Shovlin M, Steinberg SM, Cole D, Grant C, et al. Low-intensity therapy in adults with Burkitt’s lymphoma. N Engl J Med. 2013;369(20):1915–25.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  19. Ikeda K, Oka M, Yamada Y, Soda H, Fukuda M, Kinoshita A, et al. Adult T-cell leukemia cells over-express the multidrug-resistance-protein (MRP) and lung-resistance-protein (LRP) genes. Int J Cancer. 1999;82:599–604.

    Article  PubMed  CAS  Google Scholar 

  20. Ratner L, Harrington W, Feng X, Grant C, Jacobson S, Noy A, et al. Human T cell leukemia virus reactivation with progression of adult T-cell leukemia–lymphoma. PLoS ONE. 2009;4(2):e4420.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  21. Tsukasaki K, Tobinai K, Shimoyama M, Kozuru M, Uike N, Yamada Y, et al. Deoxycoformycin-containing combination chemotherapy for adult T-cell leukemia–lymphoma: Japan Clinical Oncology Group Study (JCOG9109). Int J Hematol. 2003;77(2):164–70.

    Article  PubMed  CAS  Google Scholar 

  22. Yamada Y, Tomonaga M, Fukuda H, Hanada S, Utsunomiya A, Tara M, et al. A new G-SCF-supported combination chemotherapy, LSG15, for adult T-cell leukemia–lymphoma: Japan Clinical Oncology Group Study 9303. Br J Haematol. 2001;113:375–82.

    Article  PubMed  CAS  Google Scholar 

  23. Katsuya H, Yamanaka T, Ishitsuka K, Utsunomiya A, Sasaki H, Hanada S, et al. Prognostic index for acute- and lymphoma-type adult T-cell leukemia/lymphoma. J Clin Oncol. 2012;30:1635–40.

    Article  PubMed  CAS  Google Scholar 

  24. Maeda Y, Nishimori H, Yoshida I, Hiramatsu Y, Uno M, Masaki Y, et al. Dose-adjusted EPOCH chemotherapy for untreated peripheral T-cell lymphomas: a multicenter phase II trial of West-JHOG PTCL0707. Haematologica. 2017;102:2097–103.

    Article  PubMed  PubMed Central  Google Scholar 

  25. Ishida T, Utsunomiya A, Iida S, Inagaki H, Takatsuka Y, Kusumoto S, et al. Clinical significance of CCR4 expression in adult T-cell leukemia/lymphoma: Its close association with skin involvement and unfavorable outcome. Clin Cancer Res. 2003;9:3625–34.

    PubMed  CAS  Google Scholar 

  26. Ishida T, Joh T, Uike N, Yamamoto K, Utsunomiya A, Yoshida S, et al. Defucosylated anti-CCR4 monoclonal antibody (KW-0761) for relapsed adult T-cell leukemia–lymphoma: a multicenter phase II study. J Clin Oncol. 2012;30:837–42.

    Article  PubMed  CAS  Google Scholar 

  27. Ishida T, Fujiwara H, Nosaka K, Taira N, Abe Y, Imaizumi Y, et al. Multicenter phase II study of lenalidomide in relapsed or recurrent adult T-cell leukemia/lymphoma: ATLL-002. J Clin Oncol. 2016;34:4086–93.

    Article  PubMed  CAS  Google Scholar 

  28. Tobinai K, Uike N, Saburi Y, Chou T, Etoh T, Masuda M, et al. Phase II study of cladribine (2-chlorodeoxyadenosine) in R/r adult T-cell leukemia–lymphoma. Int J Hematol. 2003;77:512–7.

    Article  PubMed  CAS  Google Scholar 

  29. Tsuda H, Takatsuki K, Ohno R, Masaoka T, Okada K, Shirakawa S, et al. Treatment of adult T-cell leukaemia-lymphoma with irinotecan hydrochloride (CPT-11). Br J Cancer. 1994;70:771–4.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  30. Ishitsuka K, Utsunomiya A, Katsuya H, Takeuchi S, Takatsuka Y, Hidaka M, et al. A phase II study of bortezomib in patients with r/r aggressive adult T-cell leukemia/lymphoma. Cancer Sci. 2015;106:1219–23.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  31. Hermine O, Dombret H, Poupon J, Arnulf B, Lefrere F, Rousselot P, et al. Phase II trial of arsenic trioxide and alpha interferon in patients with relapsed/refractory adult T-cell leukemia/lymphoma. Hematol J. 2004;5:130–4.

    Article  PubMed  CAS  Google Scholar 

  32. Berkowitz JL, Janik JE, Stewart DM, Jaffe ES, Stetler-Stevenson M, Shih JH, et al. Safety, efficacy, and pharmacokinetics/pharmacodynamics of daclizumab (anti-CD25) in patients with adult T-cell leukemia/lymphoma. Clin Immunol. 2014;155:176–87.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  33. Kawano N, Yoshida S, Kuriyama T, Tahara Y, Yamashita K, Nagahiro Y, et al. Clinical features and treatment outcomes of 81 patients with aggressive type adult T-cell leukemia–lymphoma at a single institution over a 7-year period (2006-2012). Intern Med. 2015;54:1489–98.

    Article  PubMed  Google Scholar 

  34. Fuji S, Inoue Y, Utsunomiya A, Moriuchi Y, Uchimaru K, Choi I, et al. Pretransplantation anti-CCR4 antibody mogamulizumab against adult T-cell leukemia/lymphoma is associated with significantly increased risks of severe and corticosteroid-refractory graft-versus-host disease, nonrelapse mortality, and overall mortality. J Clin Oncol. 2016;34:3426–33.

    Article  PubMed  Google Scholar 

  35. Tsubokura Y, Satake A, Hotta M, Yoshimura H, Fujita S, Azuma Y, et al. Successful treatment with mogamulizumab followed by allogeneic hematopoietic stem-cell transplantation in adult T-cell leukemia/lymphoma: a report of two cases. Int J Hematol. 2016;104:744–8.

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgements

We thank the hematologists in the Department of Hematology, Nagasaki University Hospital, for diagnosis and treatment of patients with ATL. We would like to thank Editage (www.editage.jp) for English language editing.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Yoshitaka Imaizumi.

Ethics declarations

Conflict of interest

The authors have no conflict of interest to declare.

About this article

Verify currency and authenticity via CrossMark

Cite this article

Toriyama, E., Imaizumi, Y., Taniguchi, H. et al. EPOCH regimen as salvage therapy for adult T-cell leukemia–lymphoma. Int J Hematol 108, 167–175 (2018). https://doi.org/10.1007/s12185-018-2455-x

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12185-018-2455-x

Keywords

  • Adult T-cell leukemia–lymphoma (ATL)
  • EPOCH regimen
  • Salvage therapy