title: Cellular immunity to Epstein-Barr virus in liver transplant recipients treated with rituximab for post-transplant lymphoproliferative disease.
abstract: The evaluation of long-term cellular immunity to EBV in pediatric orthotopic liver transplant (OLT) recipients after treatment with the humanized anti-CD20 monoclonal antibody (Rituximab) has not yet been explored. At our institution, one child with EBV-related mononucleosis-like syndrome and five children with polymorphic-EBV-PTLD occurring 6-88 months after OLT were treated with Rituximab. Treatment was well tolerated. All children achieved complete remission. After Rituximab, B-lymphocytes were undetectable in the peripheral blood and EBV-load, monitored with real-time PCR, decreased to undetectable levels in all children from >4000 copies/microg DNA at diagnosis. Four to eight months after Rituximab, EBV-load increased (>4000 copies/microg DNA) in four children, and PTLD recurred in three. Their frequency of EBV-specific T-cell precursors, measured by Elispot analysis, remained lower than in healthy controls. Rituximab effectively induced regression of PTLD in OLT recipients. However, EBV-specific T-cell immunocompetence, which may be crucial for the long-term control of EBV-mediated proliferation, did not improve.
authors.affiliation: Center for Cell and Gene Therapy, Baylor College of Medicine, Texas Children's Hospital and the Methodist Hospital, Houston, Texas, USA. bsalvado@bcm.tmc.edu
authors.forename: Barbara
authors.initials: B
authors.lastname: Savoldo
authors.forename: Cliona M
authors.initials: CM
authors.lastname: Rooney
authors.forename: Ruben E
authors.initials: RE
authors.lastname: Quiros-Tejeira
authors.forename: Yvette
authors.initials: Y
authors.lastname: Caldwell
authors.forename: Hans-Joachim
authors.initials: HJ
authors.lastname: Wagner
authors.forename: Timothy
authors.initials: T
authors.lastname: Lee
authors.forename: Milton J
authors.initials: MJ
authors.lastname: Finegold
authors.forename: Gianpietro
authors.initials: G
authors.lastname: Dotti
authors.forename: Helen E
authors.initials: HE
authors.lastname: Heslop
authors.forename: John A
authors.initials: JA
authors.lastname: Goss
mesh_terms: D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D058846:Antibodies, Monoclonal, Murine-Derived; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002648:Child; D002675:Child, Preschool; D004279:DNA, Viral / Q000378:metabolism; D020031:Epstein-Barr Virus Infections / Q000276:immunology*; D005260:Female; D004854:Herpesvirus 4, Human / Q000235:genetics / Q000276:immunology*; D006801:Humans; D007111:Immunity, Cellular / Q000187:drug effects; D016031:Liver Transplantation; D008232:Lymphoproliferative Disorders / Q000188:drug therapy*; D008297:Male; D000069283:Rituximab; D013997:Time Factors
chemical_list: D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D000970:Antineoplastic Agents; D004279:DNA, Viral; D000069283:Rituximab