Infusion of cytomegalovirus (CMV)–specific T cells for the treatment of CMV infection not responding to antiviral chemotherapy

H Einsele, E Roosnek, N Rufer… - Blood, The Journal …, 2002 - ashpublications.org
H Einsele, E Roosnek, N Rufer, C Sinzger, S Riegler, J Löffler, U Grigoleit, A Moris…
Blood, The Journal of the American Society of Hematology, 2002ashpublications.org
We adoptively transferred donor-derived cytomegalovirus (CMV)-specific T-cell lines into 8
stem cell transplant recipients lacking CMV-specific T-cell proliferation. All patients, of whom
one was infected by a CMV strain that was genotypically ganciclovir resistant, had received
unsuccessful antiviral chemotherapy for more than 4 weeks. CMV-specific lines had been
prepared by repetitive stimulation with CMV antigen, which increased the percentage of
CMV-specific T cells and ablated alloreactivity completely even against patients mismatched …
We adoptively transferred donor-derived cytomegalovirus (CMV)-specific T-cell lines into 8 stem cell transplant recipients lacking CMV-specific T-cell proliferation. All patients, of whom one was infected by a CMV strain that was genotypically ganciclovir resistant, had received unsuccessful antiviral chemotherapy for more than 4 weeks. CMV-specific lines had been prepared by repetitive stimulation with CMV antigen, which increased the percentage of CMV-specific T cells and ablated alloreactivity completely even against patients mismatched for 1 to 3 HLA antigens. After transfer of 107 T cells/m2 at a median of 120 days (range, 79-479 days) after transplantation, no side effects were noticed. Despite cessation of antiviral chemotherapy, the CMV load dropped significantly in all 7 evaluable patients, with a maximal reduction after a median of 20 days (range, 5-31 days). In 2 patients with high virus load, the antiviral effect was only transient. One of these patients received a second T-cell infusion, which cleared the virus completely. At a median of 11 days after transfer, CMV-specific T-cell proliferation was demonstrated in 6 patients, and an increase in CMV-specific CD4+ T cells was demonstrated in 5 patients. In 6 patients, 1.12 to 41 CMV-specific CD8+ T cells/μL blood were detected at a median of 13 days after transfer, with an increase in all patients lacking CMV-specific CD8+ T cells prior to transfer. Hence, anti-CMV cellular therapy was successful in 5 of 7 patients, whereas in 2 of 7 patients, who received an intensified immune suppression at the time of or after T-cell therapy, only transient reductions in virus load were obtained.
ashpublications.org