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Icheva, V; Kayser, S; Wolff, D; Tuve, S; Kyzirakos, C; Bethge, W; Greil, J; Albert, MH; Schwinger, W; Nathrath, M; Schumm, M; Stevanovic, S; Handgretinger, R; Lang, P; Feuchtinger, T; .
Adoptive Transfer of Epstein-Barr Virus (EBV) Nuclear Antigen 1-Specific T Cells As Treatment for EBV Reactivation and Lymphoproliferative Disorders After Allogeneic Stem-Cell Transplantation.
J CLIN ONCOL. 2013; 31(1): 39-48.
Doi: 10.1200/JCO.2011.39.8495
[OPEN ACCESS]
Web of Science
PubMed
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- Co-Autor*innen der Med Uni Graz
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Schwinger Wolfgang
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- Abstract:
- Purpose Reactivation of Epstein-Barr virus (EBV) after allogeneic stem-cell transplantation (SCT) can lead to severe life-threatening infections and trigger post-transplantation lymphoproliferative disease (PTLD). Since EBV-specific T cells could prevent PTLD, cellular immunotherapy has been a promising treatment option. However, generation of antigen-specific T-cell populations has been difficult within a short time frame. Patients and Methods To improve availability in urgent clinical conditions, we developed a rapid protocol for isolation of polyclonal EBV nuclear antigen 1 (EBNA-1) -specific T cells by using an interferon gamma (IFN-gamma) capture technique. Results We report on the use of adoptive transfer of EBNA-1-specific T cells in 10 pediatric and adult patients with EBV viremia and/or PTLD after SCT. No acute toxicity or graft-versus-host disease (GVHD) of more than grade 2 occurred as a result of adoptive T-cell transfer. In vivo expansion of transferred EBNA-1-specific T cells was observed in eight of 10 patients after a median of 16 days following adoptive transfer that was associated with clinical and virologic response in seven of them (70%). None of the responders had EBV-associated mortality. Within clinical responders, three patients were disease free by the day of last follow-up (2 to 36 months), three patients died of other infectious complications, and one patient died as a result of relapse of malignancy. EBV-related mortality was observed in two of 10 patients, and another patient had ongoing viremia without clinical symptoms at last follow-up. Conclusion Adoptive ex vivo transfer of EBNA-1-specific T cells is a feasible and well-tolerated therapeutic option, representing a fast and efficient procedure to achieve reconstitution of antiviral T-cell immunity after SCT. J Clin Oncol 31:39-48. (c) 2012 by American Society of Clinical Oncology
- Find related publications in this database (using NLM MeSH Indexing)
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Adolescent -
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Adoptive Transfer -
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Adult -
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Child -
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Child, Preschool -
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Combined Modality Therapy -
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Epstein-Barr Virus Infections - immunology Epstein-Barr Virus Infections - metabolism Epstein-Barr Virus Infections - virology
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Epstein-Barr Virus Nuclear Antigens - metabolism
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Female -
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Follow-Up Studies -
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Graft vs Host Disease - immunology Graft vs Host Disease - mortality Graft vs Host Disease - prevention & control
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Herpesvirus 4, Human - physiology
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Humans -
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Interferon-gamma - metabolism
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Lymphoproliferative Disorders - etiology Lymphoproliferative Disorders - metabolism Lymphoproliferative Disorders - therapy
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Male -
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Middle Aged -
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Neoplasm Staging -
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Neoplasms - complications Neoplasms - therapy
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Prognosis -
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Stem Cell Transplantation - adverse effects
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T-Lymphocytes - immunology T-Lymphocytes - metabolism T-Lymphocytes - transplantation
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Transplantation, Homologous -
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Viral Load - immunology
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Young Adult -