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Epstein–Barr virus-related diffuse large B-cell lymphoma in mogamulizumab-treated adult T-cell leukemia with incomplete T-cell reconstitution

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Abstract

Adult T-cell leukemia (ATL) is an aggressive mature T-cell malignancy with a poor prognosis. The anti-C–C motif chemokine receptor 4 (CCR4) antibody mogamulizumab (moga) reduces ATL cells and induces reconstitution of polyclonal T cells; however, ATL cases often remain resistant and moga sometimes causes fatal immunopathology. Epstein–Barr virus (EBV)-related B-cell lymphoma develops in severely immunocompromised subjects, and is particularly associated with impaired T-cell immunity. Here, we report an ATL patient who had received conventional chemotherapy plus moga, and subsequently developed EBV-related diffuse large B-cell lymphoma (DLBCL) of the central nervous system. Next-generation sequencing-based T-cell receptor repertoire analyses identified residual abnormal clones and revealed that reconstitution of polyclonal T cells was incomplete, even after moga treatment. Furthermore, a skin rash that developed after moga treatment was found to contain ATL clones. This case suggests that the limited therapeutic effects of moga and incomplete T-cell reconstitution are associated with severely impaired T-cell immunity and subsequent development of EBV-related DLBCL.

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References

  1. Verdonck K, Gonzalez E, Van Dooren S, Vandamme AM, Vanham G, Gotuzzo E. Human T-lymphotropic virus 1: recent knowledge about an ancient infection. Lancet Infect Dis. 2007;7(4):266–81.

    Article  CAS  PubMed  Google Scholar 

  2. Katsuki T, Katsuki K, Imai J, Hinuma Y. Immune suppression in healthy carriers of adult T-cell leukemia retrovirus (HTLV-I): impairment of T-cell control of Epstein-Barr virus-infected B-cells. Jpn J Cancer Res. 1987;78(7):639–42.

    CAS  PubMed  Google Scholar 

  3. Sadahira Y, Nishihara H, Shimizu M, Hirokawa M, Wada H, Yamada O, et al. Epstein-Barr virus-associated Hodgkin’s disease in HTLV-I seropositive patients: a report of two cases. Pathol Int. 1998;48(1):67–73.

    Article  CAS  PubMed  Google Scholar 

  4. Yasunaga J, Sakai T, Nosaka K, Etoh K, Tamiya S, Koga S, et al. Impaired production of naive T lymphocytes in human T-cell leukemia virus type I-infected individuals: its implications in the immunodeficient state. Blood. 2001;97(10):3177–83.

    Article  CAS  Google Scholar 

  5. Chen S, Ishii N, Ine S, Ikeda S, Fujimura T, Ndhlovu LC, et al. Regulatory T cell-like activity of Foxp3 + adult T cell leukemia cells. Int Immunol. 2006;18(2):269–77.

    Article  CAS  PubMed  Google Scholar 

  6. 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(8):837–42.

    Article  CAS  PubMed  Google Scholar 

  7. Fuji S, Shindo T. Friend or foe? Mogamulizumab in allogeneic hematopoietic stem cell transplantation for adult T-cell leukemia/lymphoma. Stem Cell Investig. 2016;3:70.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Ureshino H, Shindo T, Nishikawa H, Watanabe N, Watanabe E, Satoh H, et al. Effector regulatory T cells reflect the equilibrium between antitumor immunity and autoimmunity in adult T-cell leukemia. Cancer Immunol Res. 2016;4(8):644–9.

    Article  CAS  PubMed  Google Scholar 

  9. Shindo T, Kitaura K, Ureshino H, Kamachi K, Miyahara M, Doi K, et al. Deep sequencing of the T cell receptor visualizes reconstitution of T cell immunity in mogamulizumab-treated adult T cell leukemia. Oncoimmunol. 2017;7(3):e1405204.

    Article  Google Scholar 

  10. Ellman MH, Hurwitz H, Thomas C, Kozloff M. Lymphoma developing in a patient with rheumatoid arthritis taking low dose weekly methotrexate. J Rheumatol. 1991;18(11):1741–3.

    CAS  PubMed  Google Scholar 

  11. Castillo JJ, Beltran BE, Miranda RN, Young KH, Chavez JC, Sotomayor EM. EBV-positive diffuse large B-cell lymphoma of the elderly: 2016 update on diagnosis, risk-stratification, and management. Am J Hematol. 2016;91(5):;529–37.

    Article  PubMed  Google Scholar 

  12. Ohyama Y, Kumode T, Eguchi G, Yamaguchi T, Maeda Y. Induction of molecular remission by using anti-CC-chemokine receptor 4 (anti-CCR4) antibodies for adult T cell leukemia: a risk of opportunistic infection after treatment with anti-CCR4 antibodies. Ann Hematol. 2014;93:169–71.

    Article  PubMed  Google Scholar 

  13. Totani H, Kusumoto S, Ishida T, Masuda A, Yoshida T, Ito A, et al. Reactivation of hepatitis B virus (HBV) infection in adult T-cell leukemia-lymphoma patients with resolved HBV infection following systemic chemotherapy. Int J Hematol. 2015;101:398–404.

    Article  CAS  PubMed  Google Scholar 

  14. Tanaka H, Aoki H, Sugita Y, Shimizu R, Kiko K, Mochida H, et al. Development of Epstein-Barr Virus-related primary diffuse large B-cell lymphoma of the central nervous system in a patient with peripheral T-cell lymphoma, not otherwise specified after mogamulizumab treatment. Intern Med. 2017;56(20):2759–63.

    Article  PubMed  PubMed Central  Google Scholar 

  15. Kitaura K, Shini T, Matsutani T, Suzuki R. A new high-throughput sequencing method for determining diversity and similarity of T cell receptor (TCR) α and β repertoires and identifying potential new invariant TCR α chains. BMC Immunol. 2016;17(1):38.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Teshima T, Akashi K, Shibuya T, Taniguchi S, Okamura T, Harada M, et al. Central nervous system involvement in adult T-cell leukemia/lymphoma. Cancer. 1990;15(65):327–32.

    Article  Google Scholar 

  17. Kawasaki C, Ikeda H, Fukumoto T. Cerebral mass lesions associated with adult T-cell leukemia/lymphoma. Int J Hematol. 1995;61:97–102.

    Article  CAS  PubMed  Google Scholar 

  18. Beltran B, Salas R, Quinons P, Morales D, Hurtado F, Cotrina E, et al. EBV-positive diffuse large B-cell lymphoma in a human T-lymphotropic virus type 1 carrier. Infect Agent Cancer. 2009;4:10.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Tobinai K, Ohtsu T, Hayashi M, Kinoshita T, Matsuno Y, Mukai K, et al. Epstein-Barr virus (EBV) genome carrying monoclonal B-cell lymphoma in a patient with adult T-cell leukemia-lymphoma. Leuk Res. 1991;15:837–46.

    Article  CAS  PubMed  Google Scholar 

  20. Amano M, Marutsuka K, Sugimoto T, Todaka T, Setoyama M. Epstein-Barr virus-associated primary central nervous system lymphoma in a patient with adult T-cell leukemia/lymphoma. J Dermatol. 2011;38:575–80.

    Article  PubMed  Google Scholar 

  21. Talvensaari K, Clave E, Douay C, Rabian C, Garderet L, Busson M, et al. A broad T-cell repertoire diversity and an efficient thymic function indicate a favorable long-term immune reconstitution after cord blood stem cell transplantation. Blood. 2002;99(4):;1458–64.

    Article  PubMed  Google Scholar 

  22. Britanova OV, Putintseva EV, Shugay M, Merzlyak EM, Turchaninova MA, Staroverov DB, et al. Age-related decrease in TCR repertoire diversity measured with deep and normalized sequence profiling. J Immunol. 2014;192:2689–98.

    Article  CAS  PubMed  Google Scholar 

  23. Tu W, Rao S. Mechanisms Underlying T cell immunosenescence: aging and cytomegalovirus infection. Front Microbiol. 2016;7:2111.

    Article  PubMed  PubMed Central  Google Scholar 

  24. Yager EJ, Ahmed M, Lanzer K, Randall TD, Woodland DL, Blackman MA. Age-associated decline in T cell repertoire diversity leads to holes in the repertoire and impaired immunity to influenza virus. J Exp Med. 2008;205:711–23.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Sugita Y, Furuta T, Ohshima K, Komaki S, Miyoshi J, Morioka M, et al. The perivascular microenvironment in Epstein-Barr virus positive primary central nervous system lymphoma: the role of programmed cell death 1 and programmed cell death ligand 1. Neuropathology. 2018;38:125–34.

    Article  CAS  PubMed  Google Scholar 

  26. Hashimoto A, Chiba N, Tsuno H, Komiya A, Furukawa H, Matsui T, et al. Incidence of malignancy and the risk of lymphoma in Japanese patients with rheumatoid arthritis compared to the general population. J Rheumatol. 2015;42:564–71.

    Article  CAS  PubMed  Google Scholar 

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Correspondence to Takero Shindo.

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Kamachi, K., Shindo, T., Miyahara, M. et al. Epstein–Barr virus-related diffuse large B-cell lymphoma in mogamulizumab-treated adult T-cell leukemia with incomplete T-cell reconstitution. Int J Hematol 109, 221–227 (2019). https://doi.org/10.1007/s12185-018-2552-x

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  • DOI: https://doi.org/10.1007/s12185-018-2552-x

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