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Blood, 1 April 2002, Vol. 99, No. 7, pp. 2592-2598
TRANSPLANTATION
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
Patrizia Comoli,
Massimo Labirio,
Sabrina Basso,
Fausto Baldanti,
Paolo Grossi,
Milena Furione,
Mario Viganò,
Roberto Fiocchi,
Giorgio Rossi,
Fabrizio Ginevri,
Bruno Gridelli,
Antonia Moretta,
Daniela Montagna,
Franco Locatelli,
Giuseppe Gerna, and
Rita Maccario
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,
Università 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.
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.
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