{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T12:05:15Z","timestamp":1791288315217,"version":"4.3.0"},"reference-count":32,"publisher":"American Society of Hematology","issue":"7","content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2002,4,1]]},"abstract":"<jats:p>Epstein-Barr virus (EBV)\u2013associated 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.<\/jats:p>","DOI":"10.1182\/blood.v99.7.2592","type":"journal-article","created":{"date-parts":[[2002,10,11]],"date-time":"2002-10-11T14:33:52Z","timestamp":1034346832000},"page":"2592-2598","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":217,"title":["Infusion of autologous Epstein-Barr virus (EBV)\u2013specific cytotoxic T cells for prevention of EBV-related lymphoproliferative disorder in solid organ transplant recipients with evidence of active virus replication"],"prefix":"10.1182","volume":"99","author":[{"given":"Patrizia","family":"Comoli","sequence":"first","affiliation":[{"name":"From the Department of Pediatrics, Viral Diagnostic Service, and Department of Heart Surgery, IRCCS Policlinico S. Matteo, Pavia, Italy; the Department of Medicine and Public Health, Universita\u0300 dell' Insubria, Varese, Italy; the Cardiovascular Department and Liver Transplant Center, Ospedali Riuniti, Bergamo, Italy; the Liver Transplant Center, Ospedale Maggiore, Milano, Italy; and the Department of Pediatric Nephrology, Istituto G. Gaslini, Genova, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Massimo","family":"Labirio","sequence":"additional","affiliation":[{"name":"From the Department of Pediatrics, Viral Diagnostic Service, and Department of Heart Surgery, IRCCS Policlinico S. Matteo, Pavia, Italy; the Department of Medicine and Public Health, Universita\u0300 dell' Insubria, Varese, Italy; the Cardiovascular Department and Liver Transplant Center, Ospedali Riuniti, Bergamo, Italy; the Liver Transplant Center, Ospedale Maggiore, Milano, Italy; and the Department of Pediatric Nephrology, Istituto G. Gaslini, Genova, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sabrina","family":"Basso","sequence":"additional","affiliation":[{"name":"From the Department of Pediatrics, Viral Diagnostic Service, and Department of Heart Surgery, IRCCS Policlinico S. Matteo, Pavia, Italy; the Department of Medicine and Public Health, Universita\u0300 dell' Insubria, Varese, Italy; the Cardiovascular Department and Liver Transplant Center, Ospedali Riuniti, Bergamo, Italy; the Liver Transplant Center, Ospedale Maggiore, Milano, Italy; and the Department of Pediatric Nephrology, Istituto G. Gaslini, Genova, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fausto","family":"Baldanti","sequence":"additional","affiliation":[{"name":"From the Department of Pediatrics, Viral Diagnostic Service, and Department of Heart Surgery, IRCCS Policlinico S. Matteo, Pavia, Italy; the Department of Medicine and Public Health, Universita\u0300 dell' Insubria, Varese, Italy; the Cardiovascular Department and Liver Transplant Center, Ospedali Riuniti, Bergamo, Italy; the Liver Transplant Center, Ospedale Maggiore, Milano, Italy; and the Department of Pediatric Nephrology, Istituto G. Gaslini, Genova, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paolo","family":"Grossi","sequence":"additional","affiliation":[{"name":"From the Department of Pediatrics, Viral Diagnostic Service, and Department of Heart Surgery, IRCCS Policlinico S. Matteo, Pavia, Italy; the Department of Medicine and Public Health, Universita\u0300 dell' Insubria, Varese, Italy; the Cardiovascular Department and Liver Transplant Center, Ospedali Riuniti, Bergamo, Italy; the Liver Transplant Center, Ospedale Maggiore, Milano, Italy; and the Department of Pediatric Nephrology, Istituto G. Gaslini, Genova, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Milena","family":"Furione","sequence":"additional","affiliation":[{"name":"From the Department of Pediatrics, Viral Diagnostic Service, and Department of Heart Surgery, IRCCS Policlinico S. Matteo, Pavia, Italy; the Department of Medicine and Public Health, Universita\u0300 dell' Insubria, Varese, Italy; the Cardiovascular Department and Liver Transplant Center, Ospedali Riuniti, Bergamo, Italy; the Liver Transplant Center, Ospedale Maggiore, Milano, Italy; and the Department of Pediatric Nephrology, Istituto G. Gaslini, Genova, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mario","family":"Vigano\u0300","sequence":"additional","affiliation":[{"name":"From the Department of Pediatrics, Viral Diagnostic Service, and Department of Heart Surgery, IRCCS Policlinico S. Matteo, Pavia, Italy; the Department of Medicine and Public Health, Universita\u0300 dell' Insubria, Varese, Italy; the Cardiovascular Department and Liver Transplant Center, Ospedali Riuniti, Bergamo, Italy; the Liver Transplant Center, Ospedale Maggiore, Milano, Italy; and the Department of Pediatric Nephrology, Istituto G. Gaslini, Genova, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberto","family":"Fiocchi","sequence":"additional","affiliation":[{"name":"From the Department of Pediatrics, Viral Diagnostic Service, and Department of Heart Surgery, IRCCS Policlinico S. Matteo, Pavia, Italy; the Department of Medicine and Public Health, Universita\u0300 dell' Insubria, Varese, Italy; the Cardiovascular Department and Liver Transplant Center, Ospedali Riuniti, Bergamo, Italy; the Liver Transplant Center, Ospedale Maggiore, Milano, Italy; and the Department of Pediatric Nephrology, Istituto G. Gaslini, Genova, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giorgio","family":"Rossi","sequence":"additional","affiliation":[{"name":"From the Department of Pediatrics, Viral Diagnostic Service, and Department of Heart Surgery, IRCCS Policlinico S. Matteo, Pavia, Italy; the Department of Medicine and Public Health, Universita\u0300 dell' Insubria, Varese, Italy; the Cardiovascular Department and Liver Transplant Center, Ospedali Riuniti, Bergamo, Italy; the Liver Transplant Center, Ospedale Maggiore, Milano, Italy; and the Department of Pediatric Nephrology, Istituto G. Gaslini, Genova, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabrizio","family":"Ginevri","sequence":"additional","affiliation":[{"name":"From the Department of Pediatrics, Viral Diagnostic Service, and Department of Heart Surgery, IRCCS Policlinico S. Matteo, Pavia, Italy; the Department of Medicine and Public Health, Universita\u0300 dell' Insubria, Varese, Italy; the Cardiovascular Department and Liver Transplant Center, Ospedali Riuniti, Bergamo, Italy; the Liver Transplant Center, Ospedale Maggiore, Milano, Italy; and the Department of Pediatric Nephrology, Istituto G. Gaslini, Genova, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruno","family":"Gridelli","sequence":"additional","affiliation":[{"name":"From the Department of Pediatrics, Viral Diagnostic Service, and Department of Heart Surgery, IRCCS Policlinico S. Matteo, Pavia, Italy; the Department of Medicine and Public Health, Universita\u0300 dell' Insubria, Varese, Italy; the Cardiovascular Department and Liver Transplant Center, Ospedali Riuniti, Bergamo, Italy; the Liver Transplant Center, Ospedale Maggiore, Milano, Italy; and the Department of Pediatric Nephrology, Istituto G. Gaslini, Genova, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonia","family":"Moretta","sequence":"additional","affiliation":[{"name":"From the Department of Pediatrics, Viral Diagnostic Service, and Department of Heart Surgery, IRCCS Policlinico S. Matteo, Pavia, Italy; the Department of Medicine and Public Health, Universita\u0300 dell' Insubria, Varese, Italy; the Cardiovascular Department and Liver Transplant Center, Ospedali Riuniti, Bergamo, Italy; the Liver Transplant Center, Ospedale Maggiore, Milano, Italy; and the Department of Pediatric Nephrology, Istituto G. Gaslini, Genova, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniela","family":"Montagna","sequence":"additional","affiliation":[{"name":"From the Department of Pediatrics, Viral Diagnostic Service, and Department of Heart Surgery, IRCCS Policlinico S. Matteo, Pavia, Italy; the Department of Medicine and Public Health, Universita\u0300 dell' Insubria, Varese, Italy; the Cardiovascular Department and Liver Transplant Center, Ospedali Riuniti, Bergamo, Italy; the Liver Transplant Center, Ospedale Maggiore, Milano, Italy; and the Department of Pediatric Nephrology, Istituto G. Gaslini, Genova, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Franco","family":"Locatelli","sequence":"additional","affiliation":[{"name":"From the Department of Pediatrics, Viral Diagnostic Service, and Department of Heart Surgery, IRCCS Policlinico S. Matteo, Pavia, Italy; the Department of Medicine and Public Health, Universita\u0300 dell' Insubria, Varese, Italy; the Cardiovascular Department and Liver Transplant Center, Ospedali Riuniti, Bergamo, Italy; the Liver Transplant Center, Ospedale Maggiore, Milano, Italy; and the Department of Pediatric Nephrology, Istituto G. Gaslini, Genova, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giuseppe","family":"Gerna","sequence":"additional","affiliation":[{"name":"From the Department of Pediatrics, Viral Diagnostic Service, and Department of Heart Surgery, IRCCS Policlinico S. Matteo, Pavia, Italy; the Department of Medicine and Public Health, Universita\u0300 dell' Insubria, Varese, Italy; the Cardiovascular Department and Liver Transplant Center, Ospedali Riuniti, Bergamo, Italy; the Liver Transplant Center, Ospedale Maggiore, Milano, Italy; and the Department of Pediatric Nephrology, Istituto G. Gaslini, Genova, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rita","family":"Maccario","sequence":"additional","affiliation":[{"name":"From the Department of Pediatrics, Viral Diagnostic Service, and Department of Heart Surgery, IRCCS Policlinico S. Matteo, Pavia, Italy; the Department of Medicine and Public Health, Universita\u0300 dell' Insubria, Varese, Italy; the Cardiovascular Department and Liver Transplant Center, Ospedali Riuniti, Bergamo, Italy; the Liver Transplant Center, Ospedale Maggiore, Milano, Italy; and the Department of Pediatric Nephrology, Istituto G. 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disorder.","volume":"71","author":"Schaar","year":"2001","journal-title":"Transplantation."},{"key":"2020021300132294000_B13","doi-asserted-by":"crossref","first-page":"1770","DOI":"10.1097\/00007890-199812270-00035","article-title":"Interferon-alpha treatment of posttransplant lymphoproliferative disorder in recipients of solid organ transplants.","volume":"9","author":"Davis","year":"1998","journal-title":"Transplantation."},{"key":"2020021300132294000_B14","doi-asserted-by":"crossref","first-page":"1334","DOI":"10.1056\/NEJM198805193182013","article-title":"Treatment of B-cell lymphoproliferative disorders with interferon \u03b1 and intravenous gammaglobulin.","volume":"318","author":"Shapiro","year":"1988","journal-title":"N Engl J Med."},{"key":"2020021300132294000_B15","doi-asserted-by":"crossref","first-page":"1451","DOI":"10.1056\/NEJM199105233242102","article-title":"Anti-B-cell monoclonal antibodies in the treatment of severe B-cell lymphoproliferative syndrome following bone 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