Epstein-Barr virus (EBV) load in bone marrow transplant recipients at risk to develop posttransplant lymphoproliferative disease: prophylactic infusion of EBV-specific cytotoxic T cells

Abstract

A semiquantitative polymerase chain reaction assay was used to monitor the blood levels of Epstein-Barr virus (EBV)-DNA in 9 patients receiving allogeneic bone marrow transplants (BMT). Four of 5 recipients of HLA-mismatched T-cell–depleted grafts showed a 4- to 5-log increase of EBV-DNA within 1 to 3 months after BMT. Administration of 2 to 4 infusions of 107 EBV-specific cytotoxic T-lymphocytes (CTLs)/m2 starting from the time of maximal virus load resulted in a 2- to 3-log decrease of virus titers in 3 patients. One patient, who received a T-cell culture lacking a major EBV-specific component, progressed to fatal EBV-positive lymphoma. Administration of EBV-CTLs before the onset of the EBV-DNA peak resulted in stabilization of the virus titers within 2 to 3 logs above the normal levels in the fifth patient. A moderate increase of virus titers was also detected in 3 of 4 patients receiving unmanipulated HLA-matched grafts, whereas 1 patient with Wiskott-Aldrich syndrome reached a 5-log increase of EBV-DNA load within 70 days after BMT. Our results suggest that a rapid increase of circulating EBV-DNA occurs in the absence of EBV-specific T-cell precursors or in the presence of congenital immune defects that prevent the reestablishment of virus-specific immunity. Prophylactic administration of EBV-CTLs early after BMT appears to provide the most effective protection against the development of EBV-associated lymphoproliferative disease.

Cytotoxic T lymphocytes as immune‐therapy in haematological practice

“…Thus, adoptive immunotherapy was established as an attractive therapy for the prevention and treatment of EBV-LPD in high-risk patients post-transplant. These results have been confirmed by several other groups (Imashuku et al, 1997;Gustafsson et al, 2000;Comoli et al, 2007;O'Reilly et al, 2007).…”

Preventing Stem Cell Transplantation-Associated Viral Infections Using T-Cell Therapy

“…These results have been recapitulated at numerous other centers including Memorial Sloan Kettering [88], the Karolinska Institute [89] and University of Pavia [90]. However, the rare treatment failures have also taught important lessons.…”

Adapted Treatment of Epstein–Barr Virus Infection to Prevent Posttransplant Lymphoproliferative Disorder After Heart Transplantation

“…DIS was safe and feasible, with no patients having acute rejection, but patients were treated using a range of immunosuppressive treatments, making it difficult to draw conclusions related to specific therapies. The incidence of EBV reactivation reported clearly depends on the viral-load threshold value used, and, as shown by Table 4, there are a very wide range of results (7,11,12,16,(36)(37)(38)(39)(40)(41)(42)(43)(44). Our threshold (!10 5 copies/mL)…”