title: Treatment of EBV-related post-renal transplant lymphoproliferative disease with a tailored regimen including EBV-specific T cells.
abstract: The treatment of EBV-associated post-transplant lymphoproliferative disease (PTLD) poses a considerable challenge. Efforts have been made to define regimens based on combination of the available therapeutic agents, chosen and tailored on a patient-by-patient basis, with the aim of augmenting event-free patient and graft survival. Recently, autologous EBV-specific cytotoxic T-lymphocytes (CTL) have proved effective in enhancing EBV-specific immune responses and reducing viral load in organ transplant recipients with active infection. We investigated the use of a tailored combined approach including autologous EBV-specific CTL for the treatment of EBV-related PTLD developing after pediatric kidney transplantation. Five patients with disseminated monoclonal (n = 3) or localized polyclonal (n = 2) PTLD unresponsive to reduction of immunosuppression were enrolled. The patients with disseminated PTLD received 4-5 courses of reduced-dosage polychemotherapy, accompanied by rituximab on the first day of each course, while localized disease was removed surgically. At treatment completion, autologous EBV-specific CTL were infused. All patients showed a complete response to treatment, without therapy-related toxicity or rejection, and persist in remission with good renal function at a median follow-up of 31 months. These preliminary results suggest that a combined chemoimmunotherapy regimen including virus-specific T-cells is well tolerated and potentially effective as first-line treatment of EBV-related PTLD.
authors.affiliation: Laboratory of Transplant Immunology and Pediatric Hematology/Oncology, IRCCS Policlinico S. Matteo, Pavia, Italy. pcomoli@smatteo.pv.it
authors.forename: Patrizia
authors.initials: P
authors.lastname: Comoli
authors.forename: Rita
authors.initials: R
authors.lastname: Maccario
authors.forename: Franco
authors.initials: F
authors.lastname: Locatelli
authors.forename: Umberto
authors.initials: U
authors.lastname: Valente
authors.forename: Sabrina
authors.initials: S
authors.lastname: Basso
authors.forename: Alberto
authors.initials: A
authors.lastname: Garaventa
authors.forename: Paolo
authors.initials: P
authors.lastname: Tomà
authors.forename: Gerardo
authors.initials: G
authors.lastname: Botti
authors.forename: Giovanni
authors.initials: G
authors.lastname: Melioli
authors.forename: Fausto
authors.initials: F
authors.lastname: Baldanti
authors.forename: Arcangelo
authors.initials: A
authors.lastname: Nocera
authors.forename: Francesco
authors.initials: F
authors.lastname: Perfumo
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Ginevri
mesh_terms: D000293:Adolescent; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D058846:Antibodies, Monoclonal, Murine-Derived; D002648:Child; D002675:Child, Preschool; D003131:Combined Modality Therapy; D020031:Epstein-Barr Virus Infections / Q000628:therapy* / Q000821:virology; D005260:Female; D006085:Graft Survival; D004854:Herpesvirus 4, Human / Q000502:physiology*; D006801:Humans; D007155:Immunologic Factors / Q000627:therapeutic use*; D016030:Kidney Transplantation / Q000009:adverse effects*; D017710:Lymphocyte Transfusion; D008232:Lymphoproliferative Disorders / Q000628:therapy* / Q000821:virology; D008297:Male; D011183:Postoperative Complications; D000069283:Rituximab; D016176:T-Lymphocyte Subsets / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D016896:Treatment Outcome; D014779:Virus Replication / Q000187:drug effects
chemical_list: D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D007155:Immunologic Factors; D000069283:Rituximab