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Dissecting Epstein-Barr virus-specific T-cell responses after allogeneic EBV-specific T-cell transfer for central nervous system posttransplant lymphoproliferative disease

: Schultze-Florey, R.E.; Tischer, S.; Kuhlmann, L.; Hundsdoerfer, P.; Koch, A.; Anagnostopoulos, I.; Ravens, S.; Goudeva, L.; Schultze-Florey, C.; Koenecke, C.; Blasczyk, R.; Koehl, U.; Heuft, H.-G.; Prinz, I.; Eiz-Vesper, B.; Maecker-Kolhoff, B.

Fulltext ()

Frontiers in Immunology 9 (2018), Art. 1475, 9 pp.
ISSN: 1664-3224 (online)
Journal Article, Electronic Publication
Fraunhofer IZI ()

Epstein–Barr virus (EBV)-associated posttransplant lymphoproliferative disease (PTLD) with central nervous system (CNS) involvement is a severe complication after solid organ transplantation. Standard treatment with reduction of immunosuppression and anti-CD20 antibody application often fails leading to poor outcome. Here, we report the case of an 11-year-old boy with multilocular EBV-positive CNS PTLD 10 years after liver transplantation. Complete remission was achieved by repeated intravenous and intrathecal anti-CD20 antibody rituximab administration combined with intrathecal chemotherapy (methotrexate, cytarabine, prednisone) over a time period of 3 months. Due to the poor prognosis of CNS PTLD and lack of EBV-specific T-cells (EBV-CTLs) in patient’s blood, we decided to perform EBV-directed T-cell immunotherapy as a consolidating treatment. The patient received five infusions of allogeneic EBV-CTLs from a 5/10 HLA-matched unrelated third-party donor. No relevant acute toxicity was observed. EBV-CTLs became detectable after first injection and increased during the treatment course. Next-generation sequencing (NGS) TCR-profiling verified the persistence and expansion of donor-derived EBV-specific clones. After two transfers, epitope spreading to unrelated EBV antigens occurred suggesting onset of endogenous T-cell production, which was supported by detection of recipient-derived clones in NGS TCR-profiling. Continuous complete remission was confirmed 27 months after initial diagnosis.