Dissecting Epstein-Barr Virus-Specific T-Cell Responses After Allogeneic EBV-Specific T-Cell Transfer for Central Nervous System Posttransplant Lymphoproliferative Disease.

Front Immunol 2018 27;9:1475. Epub 2018 Jun 27.

Pediatric Hematology and Oncology, Hannover Medical School, Hannover, Germany.

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.

Download full-text PDF

Source
http://dx.doi.org/10.3389/fimmu.2018.01475DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6030255PMC
June 2018
37 Reads

Publication Analysis

Top Keywords

lymphoproliferative disease
8
cns ptld
8
ngs tcr-profiling
8
anti-cd20 antibody
8
central nervous
8
complete remission
8
nervous system
8
posttransplant lymphoproliferative
8
achieved repeated
4
occurred suggesting
4
remission achieved
4
received infusions
4
antigens occurred
4
antibody rituximab
4
ebv antigens
4
rituximab administration
4
tcr-profiling verified
4
intrathecal anti-cd20
4
repeated intravenous
4
patient received
4

References

(Supplied by CrossRef)

Similar Publications