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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

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 leadin...

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Autores principales: Schultze-Florey, Rebecca E., Tischer, Sabine, Kuhlmann, Leonie, Hundsdoerfer, Patrick, Koch, Arend, Anagnostopoulos, Ioannis, Ravens, Sarina, Goudeva, Lilia, Schultze-Florey, Christian, Koenecke, Christian, Blasczyk, Rainer, Koehl, Ulrike, Heuft, Hans-Gert, Prinz, Immo, Eiz-Vesper, Britta, Maecker-Kolhoff, Britta
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6030255/
https://www.ncbi.nlm.nih.gov/pubmed/29997626
http://dx.doi.org/10.3389/fimmu.2018.01475
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author Schultze-Florey, Rebecca E.
Tischer, Sabine
Kuhlmann, Leonie
Hundsdoerfer, Patrick
Koch, Arend
Anagnostopoulos, Ioannis
Ravens, Sarina
Goudeva, Lilia
Schultze-Florey, Christian
Koenecke, Christian
Blasczyk, Rainer
Koehl, Ulrike
Heuft, Hans-Gert
Prinz, Immo
Eiz-Vesper, Britta
Maecker-Kolhoff, Britta
author_facet Schultze-Florey, Rebecca E.
Tischer, Sabine
Kuhlmann, Leonie
Hundsdoerfer, Patrick
Koch, Arend
Anagnostopoulos, Ioannis
Ravens, Sarina
Goudeva, Lilia
Schultze-Florey, Christian
Koenecke, Christian
Blasczyk, Rainer
Koehl, Ulrike
Heuft, Hans-Gert
Prinz, Immo
Eiz-Vesper, Britta
Maecker-Kolhoff, Britta
author_sort Schultze-Florey, Rebecca E.
collection PubMed
description 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.
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spelling pubmed-60302552018-07-11 Dissecting Epstein-Barr Virus-Specific T-Cell Responses After Allogeneic EBV-Specific T-Cell Transfer for Central Nervous System Posttransplant Lymphoproliferative Disease Schultze-Florey, Rebecca E. Tischer, Sabine Kuhlmann, Leonie Hundsdoerfer, Patrick Koch, Arend Anagnostopoulos, Ioannis Ravens, Sarina Goudeva, Lilia Schultze-Florey, Christian Koenecke, Christian Blasczyk, Rainer Koehl, Ulrike Heuft, Hans-Gert Prinz, Immo Eiz-Vesper, Britta Maecker-Kolhoff, Britta Front Immunol Immunology 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. Frontiers Media S.A. 2018-06-27 /pmc/articles/PMC6030255/ /pubmed/29997626 http://dx.doi.org/10.3389/fimmu.2018.01475 Text en Copyright © 2018 Schultze-Florey, Tischer, Kuhlmann, Hundsdoerfer, Koch, Anagnostopoulos, Ravens, Goudeva, Schultze-Florey, Koenecke, Blasczyk, Koehl, Heuft, Prinz, Eiz-Vesper and Maecker-Kolhoff. https://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
Schultze-Florey, Rebecca E.
Tischer, Sabine
Kuhlmann, Leonie
Hundsdoerfer, Patrick
Koch, Arend
Anagnostopoulos, Ioannis
Ravens, Sarina
Goudeva, Lilia
Schultze-Florey, Christian
Koenecke, Christian
Blasczyk, Rainer
Koehl, Ulrike
Heuft, Hans-Gert
Prinz, Immo
Eiz-Vesper, Britta
Maecker-Kolhoff, Britta
Dissecting Epstein-Barr Virus-Specific T-Cell Responses After Allogeneic EBV-Specific T-Cell Transfer for Central Nervous System Posttransplant Lymphoproliferative Disease
title Dissecting Epstein-Barr Virus-Specific T-Cell Responses After Allogeneic EBV-Specific T-Cell Transfer for Central Nervous System Posttransplant Lymphoproliferative Disease
title_full Dissecting Epstein-Barr Virus-Specific T-Cell Responses After Allogeneic EBV-Specific T-Cell Transfer for Central Nervous System Posttransplant Lymphoproliferative Disease
title_fullStr Dissecting Epstein-Barr Virus-Specific T-Cell Responses After Allogeneic EBV-Specific T-Cell Transfer for Central Nervous System Posttransplant Lymphoproliferative Disease
title_full_unstemmed Dissecting Epstein-Barr Virus-Specific T-Cell Responses After Allogeneic EBV-Specific T-Cell Transfer for Central Nervous System Posttransplant Lymphoproliferative Disease
title_short Dissecting Epstein-Barr Virus-Specific T-Cell Responses After Allogeneic EBV-Specific T-Cell Transfer for Central Nervous System Posttransplant Lymphoproliferative Disease
title_sort dissecting epstein-barr virus-specific t-cell responses after allogeneic ebv-specific t-cell transfer for central nervous system posttransplant lymphoproliferative disease
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6030255/
https://www.ncbi.nlm.nih.gov/pubmed/29997626
http://dx.doi.org/10.3389/fimmu.2018.01475
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