Chun K K Ma1, Emily Blyth2, Leighton Clancy3, Renee Simms3, Jane Burgess3, Rebecca Brown3, Shivashni Deo1, Kenneth P Micklethwaite2, David J Gottlieb4. 1. Faculty of Medicine, University of Sydney, Sydney, Australia; Westmead Millennium Institute, Centre for Cancer Research, Sydney, Australia. 2. Faculty of Medicine, University of Sydney, Sydney, Australia; Westmead Millennium Institute, Centre for Cancer Research, Sydney, Australia; Blood and Marrow Transplant Unit, Department of Haematology, Westmead Hospital, Sydney, Australia. 3. Faculty of Medicine, University of Sydney, Sydney, Australia; Westmead Millennium Institute, Centre for Cancer Research, Sydney, Australia; Sydney Cell and Gene Therapy Laboratory, Westmead Hospital, Sydney, Australia. 4. Faculty of Medicine, University of Sydney, Sydney, Australia; Westmead Millennium Institute, Centre for Cancer Research, Sydney, Australia; Blood and Marrow Transplant Unit, Department of Haematology, Westmead Hospital, Sydney, Australia; Sydney Cell and Gene Therapy Laboratory, Westmead Hospital, Sydney, Australia. Electronic address: david.gottlieb@sydney.edu.au.
Abstract
BACKGROUND AIMS: Virus-specific T-cell immunotherapy is emerging as a promising management strategy for virus infections in patients after hematopoietic stem cell transplant (HSCT). Here we present outcomes of 10 adult patients who received multi-virus-specific T cells prophylactically after HSCT. METHODS: Donor-derived cytomegalovirus (CMV)-, Epstein-Barr virus (EBV)-, adenoviral- and varicella zoster virus (VZV)-specific T cells were generated in a single culture and administered to HSCT patients at a dose of 2 × 10(7)/m(2) virus-specific T cells at a median of 63 days post-transplant. Patients were monitored for 12 months for evidence of viral reactivation and graft-versus-host disease. RESULTS: There was no acute infusion-related toxicity. Six patients developed CMV reactivation after T-cell infusion with a median peak CMV DNA titer of 600 copies per milliliter, and 1 received CMV-specific pharmacotherapy post-infusion. No EBV, adenoviral or VZV reactivation or disease was reported. Using interferon-γ Elispot analysis on post-infusion samples, we identified anti-viral immunity against all viruses including VZV. Three patients (30%) developed grade II-IV acute graft-versus-host disease. CONCLUSIONS: This is the first description of the use of a multi-virus-specific T-cell product containing cells specific for VZV after allogeneic HSCT. The T-cell product appears safe in the setting of HSCT and confirms our previous findings regarding CMV control and treatment. A larger study with longer follow-up is required to determine the efficacy of VZV-specific T cells given prophylactically in controlling episodes of herpes zoster and disseminated varicella infection after cessation of prophylactic anti-viral treatment.
BACKGROUND AIMS: Virus-specific T-cell immunotherapy is emerging as a promising management strategy for virus infections in patients after hematopoietic stem cell transplant (HSCT). Here we present outcomes of 10 adult patients who received multi-virus-specific T cells prophylactically after HSCT. METHODS:Donor-derived cytomegalovirus (CMV)-, Epstein-Barr virus (EBV)-, adenoviral- and varicella zoster virus (VZV)-specific T cells were generated in a single culture and administered to HSCT patients at a dose of 2 × 10(7)/m(2) virus-specific T cells at a median of 63 days post-transplant. Patients were monitored for 12 months for evidence of viral reactivation and graft-versus-host disease. RESULTS: There was no acute infusion-related toxicity. Six patients developed CMV reactivation after T-cell infusion with a median peak CMV DNA titer of 600 copies per milliliter, and 1 received CMV-specific pharmacotherapy post-infusion. No EBV, adenoviral or VZV reactivation or disease was reported. Using interferon-γ Elispot analysis on post-infusion samples, we identified anti-viral immunity against all viruses including VZV. Three patients (30%) developed grade II-IV acute graft-versus-host disease. CONCLUSIONS: This is the first description of the use of a multi-virus-specific T-cell product containing cells specific for VZV after allogeneic HSCT. The T-cell product appears safe in the setting of HSCT and confirms our previous findings regarding CMV control and treatment. A larger study with longer follow-up is required to determine the efficacy of VZV-specific T cells given prophylactically in controlling episodes of herpes zoster and disseminated varicella infection after cessation of prophylactic anti-viral treatment.
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