Dissecting Epstein-Barr Virus-Specific T-Cell Responses After Allogeneic EBV-Specific T-Cell Transfer for Central Nervous System Posttransplant Lymphoproliferative Disease
Standard
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.
in: FRONT IMMUNOL, Jahrgang 9, 27.06.2018, S. 1475.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
Harvard
APA
Vancouver
Bibtex
}
RIS
TY - JOUR
T1 - Dissecting Epstein-Barr Virus-Specific T-Cell Responses After Allogeneic EBV-Specific T-Cell Transfer for Central Nervous System Posttransplant Lymphoproliferative Disease
AU - Schultze-Florey, Rebecca E
AU - Tischer, Sabine
AU - Kuhlmann, Leonie
AU - Hundsdoerfer, Patrick
AU - Koch, Arend
AU - Anagnostopoulos, Ioannis
AU - Ravens, Sarina
AU - Goudeva, Lilia
AU - Schultze-Florey, Christian
AU - Koenecke, Christian
AU - Blasczyk, Rainer
AU - Koehl, Ulrike
AU - Heuft, Hans-Gert
AU - Prinz, Immo
AU - Eiz-Vesper, Britta
AU - Maecker-Kolhoff, Britta
PY - 2018/6/27
Y1 - 2018/6/27
N2 - 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.
AB - 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.
U2 - 10.3389/fimmu.2018.01475
DO - 10.3389/fimmu.2018.01475
M3 - SCORING: Journal article
C2 - 29997626
VL - 9
SP - 1475
JO - FRONT IMMUNOL
JF - FRONT IMMUNOL
SN - 1664-3224
ER -