Skip to main content

Advertisement

SpringerLink
Log in

Persistent complete remission of acute leukemic-phase CCR4-positive gamma–delta peripheral T-cell lymphoma by autologous stem cell transplantation with mogamulizumab

  • Case Report
  • Published:
International Journal of Hematology Aims and scope Submit manuscript

An Erratum to this article was published on 11 June 2015

Abstract

Peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS), frequently shows a poor outcome. Especially, expressions of CC chemokine receptor 4 (CCR4) and γδ T-cell receptor (TCR) are associated with worse prognosis in PTCL-NOS. We here report successful treatment with autologous peripheral blood stem cell transplantation (auto-PBSCT) combined with anti-CCR4 antibody mogamulizumab for a very rare case of CCR4+γδTCR+ PTCL-NOS that coexisted with Hodgkin’s lymphoma. PTCL-NOS in this patient progressed to leukemic phase, whereas Hodgkin’s lymphoma disappeared with standard chemotherapies within 4 years of the initial diagnosis. Leukemic-phase PTCL-NOS was refractory to several chemotherapies. However, auto-PBSCT following high-dose chemotherapy combined with pre- and post-transplant mogamulizumab, which is a humanized monoclonal antibody to CCR4, provided persistent complete remission of PTCL-NOS, despite residual γδTCR+ in the transplanted stem cell product, suggesting a purging effect of mogamulizumab. At 15 months after transplantation, we also found markedly fewer effector regulatory T cells, which may have contributed to prolonged remission. This case suggests that autologous stem cell transplantation combined with mogamulizumab may have a potential to cure T-cell neoplasms that express CCR4 including leukemic-phase PTCL-NOS.

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
Fig. 4
Fig. 5

Similar content being viewed by others

References

  1. The non-Hodgkin’s lymphoma classification project. A clinical evaluation of the international lymphoma study group classification of non-hodgkin’s lymphoma. Blood. 1997;89:3909–18.

    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. Weisenburger DD, Savage KJ, Harris NL, Gascoyne RD, Jaffe ES, MacLennan KA, et al. Peripheral T-cell lymphoma, not otherwise specified: a report of 340 cases from the International Peripheral T-cell Lymphoma Project. Blood. 2011;117:3402–8.

    Article  CAS  PubMed  Google Scholar 

  4. Niedobitek G, Baumann I, Brabletz T, Lisner R, Winkelmann C, Helm G, et al. Hodgkin’s disease and peripheral T-cell lymphoma: composite lymphoma with evidence of epstein-barr virus infection. J Pathol. 2000;191:394–9.

    Article  CAS  PubMed  Google Scholar 

  5. Sanchez S, Holmes H, Katabi N, Newman J, Domiatti-Saad R, Stone M, et al. Composite lymphocyte-rich Hodgkin lymphoma and peripheral T-cell lymphoma associated with Epstein-Barr virus: a case report and review of the literature. Arch Pathol Lab Med. 2006;130:107–12.

    PubMed  Google Scholar 

  6. Pajor L, Kajtár B, Jáksó P, Lacza Á, László R, Radványi G, et al. Epstein-Barr virus-induced B-cell proliferation of Hodgkin’s and Reed-Sternberg cell pheno- and genotype may develop in peripheral T-cell lymphomas. Histopathology. 2006;49:553–7.

    Article  CAS  PubMed  Google Scholar 

  7. Foss FM, Zinzani PL, Vose JM, Gascoyne RD, Rosen ST, Tobinai K. Peripheral T-cell lymphoma. Blood. 2011;117:6756–67.

    Article  CAS  PubMed  Google Scholar 

  8. Ishida T, Inagaki H, Utsunomiya A, Takatsuka Y, Komatsu H, Iida S, et al. CXC chemokine receptor 3 and CC chemokine receptor 4 expression in T-cell and NK-cell lymphomas with special reference to clinicopathological significance for peripheral T-cell lymphoma, unspecified. Clin Cancer Res. 2004;10:5494–500.

    Article  CAS  PubMed  Google Scholar 

  9. Ito A, Ishida T, Utsunomiya A, Sato F, Mori F, Yano H, et al. Defucosylated anti-CCR4 monoclonal antibody exerts potent ADCC against primary ATLL cells mediated by autologous human immune cells in NOD/Shi-scid, IL-2R gamma (null) mice in vivo. J Immunol. 2009;183:4782–91.

    Article  CAS  PubMed  Google Scholar 

  10. Yamamoto K, Utsunomiya A, Tobinai K, Tsukasaki K, Uike N, Uozumi K, et al. Phase I study of KW-0761, a defucosylated humanized anti-CCR4 antibody, in relapsed patients with adult T-cell leukemia-lymphoma and peripheral T-cell lymphoma. J Clin Oncol. 2010;28:1591–8.

    Article  CAS  PubMed  Google Scholar 

  11. Ogura M, Ishida T, Hatake K, Taniwaki M, Ando K, Tobinai K, et al. Multicenter phase II study of mogamulizumab (KW-0761), a defucosylated anti-CC chemokine receptor 4 antibody, in patients with relapsed peripheral T-cell lymphoma and cutaneous T-cell lymphoma. J Clin Oncol. 2014;32:1157–63.

    Article  CAS  PubMed  Google Scholar 

  12. Arcaini L, Morello L, Tucci A, Rusconi C, Ladetto M, Rattotti S, et al. Autologous stem cell transplantation with in vivo purged progenitor cells shows long-term efficacy in relapsed/refractory follicular lymphoma. Am J Hematol. 2015;90:230–4.

    Article  CAS  PubMed  Google Scholar 

  13. Ikeda K, Ohto H, Kanno T, Gonda K, Suzuki Y, Ono T, et al. Peripheral blood progenitor cell collection by two programs for autologous and allogeneic transplantation. Transfusion. 2014;54:1235–42.

    Article  CAS  PubMed  Google Scholar 

  14. Numata A, Miyamoto T, Ohno Y, Kamimura T, Kamezaki K, Tanimoto T, et al. Long-term outcomes of autologous PBSCT for peripheral T-cell lymphoma: retrospective analysis of the experience of the Fukuoka BMT group. Bone Marrow Transplant. 2010;45:311–6.

    Article  CAS  PubMed  Google Scholar 

  15. Nishikawa H, Sakaguchi S. Regulatory T cells in tumor immunity. Int J Cancer. 2010;127:759–67.

    CAS  PubMed  Google Scholar 

  16. Sugiyama D, Nishikawa H, Maeda Y, Nishioka M, Tanemura A, Katayama I, et al. Anti-CCR4 mAb selectively depletes effector-type FoxP3+CD4+ regulatory T cells, evoking antitumor immune responses in humans. Proc Natl Acad Sci USA. 2013;110:17945–50.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  17. Ngoma AM, Ikeda K, Hashimoto Y, Mochizuki K, Takahashi H, Sano H, et al. Impaired regulatory T cell reconstitution in patients with acute graft-versus-host disease and cytomegalovirus infection after allogeneic bone marrow transplantation. Int J Hematol. 2012;95:86–94.

    Article  PubMed  Google Scholar 

  18. Saito T, Matsuno Y, Tanosaki R, Watanabe T, Kobayashi Y, Tobinai K. gammadelta T-cell neoplasms: a clinicopathological study of 11 cases. Ann Oncol. 2002;13:1792–8.

    Article  CAS  PubMed  Google Scholar 

  19. Ishida T, Jo T, Takemoto S, Suzushima H, Uozumi K, Yamamoto K, et al. Dose-intensified chemotherapy alone or in combination with mogamulizumab in newly diagnosed aggressive adult T-cell leukaemia-lymphoma: a randomized phase II study. Br J Haematol. 2015. [Epub ahead of print].

  20. d’Amore F, Relander T, Lauritzsen GF, Jantunen E, Hagberg H, Anderson H, et al. Up-front autologous stem-cell transplantation in peripheral T-cell lymphoma: NLG-T-01. J Clin Oncol. 2012;30:3093–9.

    Article  PubMed  Google Scholar 

  21. Gui L, Shi Y, He X, Lei Y, Zhang H, Han X, et al. High-dose therapy and autologous stem cell transplantation in peripheral T-cell lymphoma: treatment outcome and prognostic factor analysis. Int J Hematol. 2014;99:69–78.

    Article  CAS  PubMed  Google Scholar 

  22. Skarbnik AP, Burki M, Pro B. Peripheral T-cell lymphomas: a review of current approaches and hopes for the future. Front Oncol. 2013;3:138.

    Article  PubMed Central  PubMed  Google Scholar 

  23. Ito Y, Miyamoto T, Chong Y, Aoki T, Kato K, Akashi K, et al. Successful treatment with anti-CC chemokine receptor 4 MoAb of relapsed adult T-cell leukemia/lymphoma after umbilical cord blood transplantation. Bone Marrow Transplant. 2013;48:998–9.

    Article  CAS  PubMed  Google Scholar 

  24. Belhadj K, Reyes F, Farcet J-P, Tilly H, Bastard C, Angonin R, et al. Hepatosplenic gammadelta T-cell lymphoma is a rare clinicopathologic entity with poor outcome: report on a series of 21 patients. Blood. 2003;102:4261–9.

    Article  CAS  PubMed  Google Scholar 

Download references

Conflict of interest

The authors declare no conflict of interest.

Author information

Author notes

    Authors and Affiliations

    1. Department of Cardiology and Hematology, Fukushima Medical University, 1 Hikariga-oka, Fukushima, Fukushima, 960-1295, Japan

      Miki Furukawa, Kazuhiko Ikeda, Hiroshi Ohkawara, Hiroshi Takahashi, Koki Udea, Hayato Matsumoto, Kazuei Ogawa & Yasuchika Takeishi

    2. Department of Transfusion and Transplantation Immunology, Fukushima Medical University, Fukushima, Japan

      Kazuhiko Ikeda, Shunichi Saito & Hitoshi Ohto

    3. Department of Pathology and Diagnostic Pathology, Fukushima Medical University, Fukushima, Japan

      Yuko Hashimoto

    Authors
    1. Miki Furukawa
      View author publications

      You can also search for this author in PubMed Google Scholar

    2. Kazuhiko Ikeda
      View author publications

      You can also search for this author in PubMed Google Scholar

    3. Hiroshi Ohkawara
      View author publications

      You can also search for this author in PubMed Google Scholar

    4. Shunichi Saito
      View author publications

      You can also search for this author in PubMed Google Scholar

    5. Hiroshi Takahashi
      View author publications

      You can also search for this author in PubMed Google Scholar

    6. Koki Udea
      View author publications

      You can also search for this author in PubMed Google Scholar

    7. Hayato Matsumoto
      View author publications

      You can also search for this author in PubMed Google Scholar

    8. Yuko Hashimoto
      View author publications

      You can also search for this author in PubMed Google Scholar

    9. Hitoshi Ohto
      View author publications

      You can also search for this author in PubMed Google Scholar

    10. Kazuei Ogawa
      View author publications

      You can also search for this author in PubMed Google Scholar

    11. Yasuchika Takeishi
      View author publications

      You can also search for this author in PubMed Google Scholar

    Corresponding author

    Correspondence to Kazuhiko Ikeda.

    Additional information

    M. Furukawa and K. Ikeda equally contributed to this work.

    About this article

    Check for updates. Verify currency and authenticity via CrossMark

    Cite this article

    Furukawa, M., Ikeda, K., Ohkawara, H. et al. Persistent complete remission of acute leukemic-phase CCR4-positive gamma–delta peripheral T-cell lymphoma by autologous stem cell transplantation with mogamulizumab. Int J Hematol 102, 498–505 (2015). https://doi.org/10.1007/s12185-015-1805-1

    Download citation

    • Received:

    • Revised:

    • Accepted:

    • Published:

    • Issue Date:

    • DOI: https://doi.org/10.1007/s12185-015-1805-1

    Keywords

    Search

    Navigation