Infusions of Epstein–Barr virus-specific cytotoxic T lymphocytes as post-remission therapy in high-risk post-transplant lymphoproliferative disorder patients: report of two cases

Abstract

Conventional therapeutic approaches to post-transplant lymphoproliferative disorder (PTLD) occurring after solid-organ transplantation have shown only limited success in achieving durable response. Key factors driving the pathogenesis of PTLD include Epstein–Barr virus (EBV) reactivation and impaired immune surveillance due to prolonged immune suppression. Thus, EBV-specific cytotoxic T lymphocytes (EBV-CTLs) have emerged as an alternative therapeutic approach for the treatment of EBV-associated PTLD by enhancing EBV-specific immunity. We evaluated the safety and efficacy of EBV latent membrane proteins (LMP)-1- and 2-specific CTLs in two PTLD patients at high risk for relapse. Following diagnosis, patients were initially treated with a combination of chemotherapy and/or radiotherapy. Patients then received a total of eight doses of 2 × 107 EBV-CTLs/m2. Following initial therapy, both patients achieved complete remission confirmed by FDG-PET/CT imaging. Post-remission therapy using adoptive transfer of EBV-CTLs was safe without immediate or late toxicities. Infusion of EBV-CTLs led to an overall reduction in plasma EBV levels in the peripheral blood, which was associated with long-term remission of both patients during a follow-up of more than 65 months. Further prospective studies with larger number of patients will be needed to confirm the role of EBV-CTLs as post-remission therapy in high-risk PTLD.

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Acknowledgements

This study was supported by a Grant from the Korea Healthcare Technology R&D Project, Ministry for Health, Welfare, and Family Affairs, Republic of Korea (H12C0718), a Research Fund of Seoul St. Mary’s Hospital, The Catholic University of Korea, and from the Catholic Institute of Cell Therapy, The Catholic University of Korea.

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Correspondence to Tai-Gyu Kim or Seok-Goo Cho.

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Tai-Gyu Kim and Seok-Goo Cho contributed equally to this work.

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Kim, N., Sohn, H., Oh, J.H. et al. Infusions of Epstein–Barr virus-specific cytotoxic T lymphocytes as post-remission therapy in high-risk post-transplant lymphoproliferative disorder patients: report of two cases. Int J Hematol 107, 596–603 (2018). https://doi.org/10.1007/s12185-017-2381-3

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Keywords

  • Adoptive T cell therapy
  • Epstein–barr virus
  • Post-remission therapy
  • Solid-organ transplantation
  • Virus-specific T cells