title: Infusion of autologous Epstein-Barr virus (EBV)-specific cytotoxic T cells for prevention of EBV-related lymphoproliferative disorder in solid organ transplant recipients with evidence of active virus replication.
abstract: Epstein-Barr virus (EBV)-associated posttransplantation lymphoproliferative disorders (PTLDs) are a well-recognized complication of immunosuppression in solid organ transplant recipients. The reported therapeutic approaches are frequently complicated by rejection, toxicity, and other infectious pathologies, and overall mortality in patients with unresponsive PTLD remains high. Thus, low-toxicity treatment options or, preferably, some form of prophylactic/preemptive intervention are warranted to improve PTLD outcome in this setting. We assessed whether transfer of EBV-specific cytotoxic T lymphocytes (CTLs) generated in vitro from the peripheral blood of allograft recipients receiving immunosuppression could increase EBV-specific killing in vivo without augmenting the probability of graft rejection. Autologous EBV-specific CTLs were generated for 23 patients who were identified as being at risk of developing PTLD through the finding of elevated EBV DNA load. Of the 23 patients, 7 received 1 to 5 infusions of EBV-specific CTLs. CTL transfer was well tolerated, and none of the patients showed any evidence of rejection. An increase of the EBV-specific cytotoxicity was observed after infusion, notwithstanding continuation of immunosuppressive therapy. EBV DNA levels had a 1.5- to 3-log decrease in 5 patients, whereas in the other 2 graft recipients CTL transfer had no apparent stable effect on EBV load. Our data suggest that the infusion of autologous EBV-specific CTLs obtained from peripheral blood mononuclear cells recovered at the time of viral reactivation is able to augment virus-specific immune response and to reduce viral load in organ transplant recipients. This approach may, therefore, be safely used as prophylaxis of EBV-related lymphoproliferative disorders in these patients, following a strategy of preemptive therapy guided by EBV DNA levels.
authors.affiliation: Department of Pediatrics, Immunology Laboratory, IRCCS Policlinico S. Matteo, P.le Golgi 2, 27100 Pavia, Italy. pcomoli@smatteo.pv.it
authors.forename: Patrizia
authors.initials: P
authors.lastname: Comoli
authors.forename: Massimo
authors.initials: M
authors.lastname: Labirio
authors.forename: Sabrina
authors.initials: S
authors.lastname: Basso
authors.forename: Fausto
authors.initials: F
authors.lastname: Baldanti
authors.forename: Paolo
authors.initials: P
authors.lastname: Grossi
authors.forename: Milena
authors.initials: M
authors.lastname: Furione
authors.forename: Mario
authors.initials: M
authors.lastname: Viganò
authors.forename: Roberto
authors.initials: R
authors.lastname: Fiocchi
authors.forename: Giorgio
authors.initials: G
authors.lastname: Rossi
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Ginevri
authors.forename: Bruno
authors.initials: B
authors.lastname: Gridelli
authors.forename: Antonia
authors.initials: A
authors.lastname: Moretta
authors.forename: Daniela
authors.initials: D
authors.lastname: Montagna
authors.forename: Franco
authors.initials: F
authors.lastname: Locatelli
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Gerna
authors.forename: Rita
authors.initials: R
authors.lastname: Maccario
mesh_terms: D017252:CD3 Complex / Q000097:blood; D016827:CD8 Antigens / Q000097:blood; D002648:Child; D002675:Child, Preschool; D005260:Female; D005434:Flow Cytometry; D004854:Herpesvirus 4, Human / Q000502:physiology*; D006801:Humans; D017710:Lymphocyte Transfusion; D008232:Lymphoproliferative Disorders / Q000628:therapy* / Q000821:virology; D008297:Male; D008875:Middle Aged; D016377:Organ Transplantation; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000097:blood; D013601:T-Lymphocytes / Q000145:classification / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014779:Virus Replication
chemical_list: D017252:CD3 Complex; D016827:CD8 Antigens; D016692:Receptors, Antigen, T-Cell, gamma-delta