International Journal of Hematology

DOI: 10.1007/s12185-017-2381-3 Pages: 1-8

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

1. The Catholic University of Korea, Institute for Translational Research and Molecular Imaging, College of Medicine

2. The Catholic University of Korea, Catholic Institute of Cell Therapy, College of Medicine

3. The Catholic University of Korea, Catholic Hematopoietic Stem Cell Bank, Seoul St. Mary’s Hospital, College of Medicine

4. The Catholic University of Korea, Department of Nuclear Medicine, Seoul St. Mary’s Hospital, College of Medicine

5. The Catholic University of Korea, Catholic Blood and Marrow Transplantation Center, Seoul St. Mary’s Hospital, College of Medicine

6. The Catholic University of Korea, Cancer Research Institute, Seoul St. Mary’s Hospital, College of Medicine

7. The Catholic University of Korea, Division of Nephrology, Department of Internal Medicine, Seoul St. Mary’s Hospital, College of Medicine

Correspondence to:
Seok-Goo Cho
Tel: +82-2-2258-6052
Email: chosg@catholic.ac.kr

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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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