Science

EBV-specific cytotoxic T cells prevent lymphoproliferative disease after transplant

Last Updated: 2006-12-07 17:36:28 -0400 (Reuters Health)

NEW YORK (Reuters Health) - For solid organ transplant patients at risk of Epstein Barr virus (EBV) complications, infusions of ex vivo-expanded autologous EBV-specific cytotoxic T cells prevent and treat EBV-associated posttransplantation lymphoproliferative disease, investigators in Germany and the US report.

Immunosuppressive regimens used to prevent allograft rejection increase the incidence of EBV-associated lymphoproliferative disease, as well as other viral infections and tumors, Dr. Barbara Savoldo and her team note in the November issue of Blood.

Current options for patients with EBV-associated posttransplantation lymphoproliferative disease -- antiviral agents, cytotoxic drugs, or monoclonal antibodies -- are limited, as the disease recurs once the drug or antibody are discontinued. The alternative of reducing medical immunosuppressive increases the risk of graft rejection.

Dr. Savoldo, from Baylor College of Medicine in Houston, and her team evaluated a new approach in a cohort of solid-organ transplant recipients --11 children below age 4 years and one 40-year old adult -- considered to be at high risk for development of EBV-associated posttransplantation lymphoproliferative disease.

They drew blood from the recipients without altering their immunosuppressant regimen, then stimulated peripheral-blood mononuclear cells to expand the numbers of EBV-specific cytotoxic T lymphocytes. The median time was 41 days for generating enough cells for two doses at 50 million cells/m�. Testing showed the cytotoxic T cells to be reactive to a broad array of EBV antigens.

Two patients had localized EBV-associated posttransplantation lymphoproliferative disease, one in the liver and the other in an eye. The tumor in the liver completely resolved, and the tumor in the eye had a 50% decrease in size that remained stable over one year, suggesting that the cells were "able to expand in vivo, to be able to traffic to and infiltrate tumor sites, and to control emergent disease."

The remaining 10 patients, who had persisting high levels of EBV, also experienced in vivo cytotoxic activity, as evidenced by "a rise in plasma EBV-DNA, suggesting lysis of infected target cells."

Dr. Savoldo and her associates suggest treating patients with rituximab while the autologous EBV-CTL line is being prepared. She and her associates predict that "the treatment combination we propose, which is based not only on EBV disease cytoreduction but also on using cytotoxic T lymphocytes to restore the immune response to the underlying oncogenic virus, will prove to be highly cost effective, since it should spare both the allograft and the patient."

Blood 2006;108:2942-2949.