International Journal of Hematology

, Volume 107, Issue 5, pp 596–603 | Cite as

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

  • Nayoun Kim
  • Hyun-Jung Sohn
  • Joo Hyun Oh
  • Young-Woo Jeon
  • Hyun-Joo Lee
  • Hyun-Il Cho
  • Byung Ha Chung
  • Chul-Woo Yang
  • Tai-Gyu Kim
  • Seok-Goo Cho
Case Report

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.

Keywords

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

Notes

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.

Compliance with ethical standards

Conflicts of interest

The authors declare that there are no conflicts of interest.

Supplementary material

12185_2017_2381_MOESM1_ESM.docx (13 kb)
Supplementary material 1 (DOCX 13 kb)

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Copyright information

© The Japanese Society of Hematology 2017

Authors and Affiliations

  1. 1.Institute for Translational Research and Molecular Imaging, College of MedicineThe Catholic University of KoreaSeoulSouth Korea
  2. 2.Catholic Institute of Cell Therapy, College of MedicineThe Catholic University of KoreaSeoulSouth Korea
  3. 3.Catholic Hematopoietic Stem Cell Bank, Seoul St. Mary’s Hospital, College of MedicineThe Catholic University of KoreaSeoulSouth Korea
  4. 4.Department of Nuclear Medicine, Seoul St. Mary’s Hospital, College of MedicineThe Catholic University of KoreaSeoulSouth Korea
  5. 5.Catholic Blood and Marrow Transplantation Center, Seoul St. Mary’s Hospital, College of MedicineThe Catholic University of KoreaSeoulSouth Korea
  6. 6.Cancer Research Institute, Seoul St. Mary’s Hospital, College of MedicineThe Catholic University of KoreaSeoulSouth Korea
  7. 7.Division of Nephrology, Department of Internal Medicine, Seoul St. Mary’s Hospital, College of MedicineThe Catholic University of KoreaSeoulSouth Korea

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