Skip to main content

Advertisement

SpringerLink
Log in

Successful treatment with mogamulizumab followed by allogeneic hematopoietic stem-cell transplantation in adult T-cell leukemia/lymphoma: a report of two cases

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

Abstract

A humanized anti-CC chemokine receptor 4 (CCR4) monoclonal antibody, mogamulizumab (MOG), has been shown to be safe and effective in the treatment of relapsed/refractory adult T-cell leukemia/lymphoma (ATLL). MOG depletes ATLL cells as well as regulatory T cells (Tregs), as CCR4 is expressed on these cells as well. In this context, pretransplant treatment with MOG may induce severe graft-versus-host disease (GVHD) in allogeneic hematopoietic stem-cell transplantation (HSCT). However, the influence of MOG on allogeneic HSCT, including its induction of GVHD, is unclear. In this report, we describe two patients treated with MOG who subsequently underwent allogeneic HSCT. They did not develop severe GVHD or treatment-related complications. In addition, we examined the kinetics of Tregs in the second case. Finally, we suggest that the detrimental effects of MOG can be avoided, which should be prospectively evaluated in future studies.

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

Similar content being viewed by others

References

  1. 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;77:164–70.

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  3. Itoh K, Ohtsu T, Fukuda H, Sasaki Y, Ogura M, Morishima Y, et al. Randomized phase II study of biweekly CHOP and dose-escalated CHOP with prophylactic use of lenograstim (glycosylated G-CSF) in aggressive non-Hodgkin’s lymphoma: Japan Clinical Oncology Group Study 9505. Ann Oncol. 2002;13:1347–55.

    Article  CAS  PubMed  Google Scholar 

  4. Tsukasaki K, Utsunomiya A, Fukuda H, Shibata T, Fukushima T, Takatsuka Y, 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  CAS  PubMed  Google Scholar 

  5. Ishida T, Hishizawa M, Kato K, Tanosaki R, Fukuda T, Takatsuka Y, et al. Impact of graft-versus-host disease on allogeneic hematopoietic cell transplantation for adult T cell leukemia-lymphoma focusing on preconditioning regimens: nationwide retrospective study. Biol Blood Marrow Transpl. 2013;19:1731–9.

    Article  Google Scholar 

  6. Ishii T, Ishida T, Utsunomiya A, Inagaki A, Yano H, Komatsu H, et al. Defucosylated humanized anti-CCR4 monoclonal antibody KW-0761 as a novel immunotherapeutic agent for adult T-cell leukemia/lymphoma. Clin Cancer Res. 2010;16:1520–31.

    Article  CAS  PubMed  Google Scholar 

  7. 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  CAS  PubMed  Google Scholar 

  8. Kurose K, Ohue Y, Sato E, Yamauchi A, Eikawa S, Isobe M, et al. Increase in activated Treg in TIL in lung cancer and in vitro depletion of Treg by ADCC using an antihuman CCR4 mAb (KM2760). J Thorac Oncol. 2015;10:74–83.

    Article  CAS  PubMed  Google Scholar 

  9. Kurose K, Ohue Y, Wada H, Iida S, Ishida T, Kojima T, et al. Phase Ia study of FoxP3 + CD4 Treg depletion by infusion of a humanized anti-CCR4 antibody, KW-0761, in cancer patients. Clin Cancer Res. 2015;21:4327–36.

    Article  CAS  PubMed  Google Scholar 

  10. Cohen JL, Trenado A, Vasey D, Klatzmann D, Salomon BL. CD4(+)CD25(+) immunoregulatory T cells: new therapeutics for graft-versus-host disease. J Exp Med. 2002;196:401–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Edinger M, Hoffmann P, Ermann J, Drago K, Fathman CG, Strober S, et al. CD4 + CD25 + regulatory T cells preserve graft-versus-tumor activity while inhibiting graft-versus-host disease after bone marrow transplantation. Nat Med. 2003;9:1144–50.

    Article  CAS  PubMed  Google Scholar 

  12. Hoffmann P, Ermann J, Edinger M, Fathman CG, Strober S. Donor-type CD4(+)CD25(+) regulatory T cells suppress lethal acute graft-versus-host disease after allogeneic bone marrow transplantation. J Exp Med. 2002;196:389–99.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Brunstein CG, Miller JS, Cao Q, McKenna DH, Hippen KL, Curtsinger J, et al. Infusion of ex vivo expanded T regulatory cells in adults transplanted with umbilical cord blood: safety profile and detection kinetics. Blood. 2010;117:1061–70.

    Article  PubMed  Google Scholar 

  14. Di Ianni M, Falzetti F, Carotti A, Terenzi A, Castellino F, Bonifacio E, et al. Tregs prevent GVHD and promote immune reconstitution in HLA-haploidentical transplantation. Blood. 2011;117:3921–8.

    Article  PubMed  Google Scholar 

  15. Haji S, Kiyasu J, Choi I, Suehiro Y, Toyoda K, Tsuda M, et al. Administration of an anti-CC chemokine receptor 4 monoclonal antibody, mogamulizumab, before allogeneic bone marrow transplantation for adult T-cell leukemia/lymphoma. Bone Marrow Transpl. 2016;51:432–4.

    Article  CAS  Google Scholar 

  16. Sugio T, Kato K, Aoki T, Ohta T, Saito N, Yoshida S, et al. Mogamulizumab treatment prior to allogeneic hematopoietic stem cell transplantation induces severe acute graft-versus-host disease. Biol Blood Marrow Transpl. 2016;9:1608–14.

    Article  Google Scholar 

  17. Inoue Y, Fuji S, Tanosaki R, Fukuda T. Pretransplant mogamulizumab against ATLL might increase the risk of acute GVHD and non-relapse mortality. Bone Marrow Transpl. 2015;51:725–7.

    Article  Google Scholar 

  18. Motohashi K, Suzuki T, Kishimoto K, Numata A, Nakajima Y, Tachibana T, et al. Successful treatment of a patient with adult T cell leukemia/lymphoma using anti-CC chemokine receptor 4 monoclonal antibody mogamulizumab followed by allogeneic hematopoietic stem cell transplantation. Int J Hematol. 2013;98:258–60.

    Article  PubMed  Google Scholar 

  19. 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  CAS  PubMed  Google Scholar 

  20. 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;169:672–82.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. First Department of Internal Medicine, Kansai Medical University, 2-5-1 Shinmachi, Hirakata City, Osaka, 573-1010, Japan

    Yukie Tsubokura, Atsushi Satake, Masaaki Hotta, Hideaki Yoshimura, Shinya Fujita, Yoshiko Azuma, Takahisa Nakanishi, Aya Nakaya, Tomoki Ito, Kazuyoshi Ishii & Shosaku Nomura

Authors
  1. Yukie Tsubokura
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Atsushi Satake
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Masaaki Hotta
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Hideaki Yoshimura
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Shinya Fujita
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Yoshiko Azuma
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Takahisa Nakanishi
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Aya Nakaya
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Tomoki Ito
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Kazuyoshi Ishii
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Shosaku Nomura
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Atsushi Satake.

Ethics declarations

Conflict of interest

The authors have declared that no competing interests exist.

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Tsubokura, Y., Satake, A., Hotta, M. 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 104, 744–748 (2016). https://doi.org/10.1007/s12185-016-2087-y

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12185-016-2087-y

Keywords

Search

Navigation