title: Allogeneic cytotoxic T-cell therapy for EBV-positive posttransplantation lymphoproliferative disease: results of a phase 2 multicenter clinical trial.
abstract: We present the results of a multicenter clinical trial using Epstein-Barr virus (EBV)-specific cytotoxic T lymphocytes (CTLs) generated from EBV-seropositive blood donors to treat patients with EBV-positive posttransplantation lymphoproliferative disease (PTLD) on the basis of the best HLA match and specific in vitro cytotoxicity. Thirty-three PTLD patients who had failed on conventional therapy were enrolled. No adverse effects of CTL infusions were observed and the response rate (complete or partial) in 33 patients was 64% at 5 weeks and 52% at 6 months. Fourteen patients achieved a complete remission, 3 showed a partial response, and 16 had no response at 6 months (5 died before completing treatment). At 5 weeks, there was a significant trend toward better responses with higher numbers of CD4(+) cells in infused CTL lines (P = .001) that were maintained at 6 months (P = .001). Patients receiving CTLs with closer HLA matching responded better at 6 months (P = .048). Female patients responded better than male patients, but the differences were not statistically significant. Our results show that allogeneic CTLs are a safe and rapid therapy for PTLD, bypassing the need to grow CTLs for individual patients. The response rate in this poor prognosis patient group is encouraging.
authors.affiliation: Clinical and Molecular Virology Laboratory, University of Edinburgh, Edinburgh, United Kingdom. t.haque@medsch.ucl.ac.uk
authors.forename: Tanzina
authors.initials: T
authors.lastname: Haque
authors.forename: Gwen M
authors.initials: GM
authors.lastname: Wilkie
authors.forename: Marie M
authors.initials: MM
authors.lastname: Jones
authors.forename: Craig D
authors.initials: CD
authors.lastname: Higgins
authors.forename: Gillian
authors.initials: G
authors.lastname: Urquhart
authors.forename: Phoebe
authors.initials: P
authors.lastname: Wingate
authors.forename: David
authors.initials: D
authors.lastname: Burns
authors.forename: Karen
authors.initials: K
authors.lastname: McAulay
authors.forename: Marc
authors.initials: M
authors.lastname: Turner
authors.forename: Christopher
authors.initials: C
authors.lastname: Bellamy
authors.forename: Peter L
authors.initials: PL
authors.lastname: Amlot
authors.forename: Deirdre
authors.initials: D
authors.lastname: Kelly
authors.forename: Alastair
authors.initials: A
authors.lastname: MacGilchrist
authors.forename: Maher K
authors.initials: MK
authors.lastname: Gandhi
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Swerdlow
authors.forename: Dorothy H
authors.initials: DH
authors.lastname: Crawford
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000914:Antibodies, Viral / Q000097:blood; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D020031:Epstein-Barr Virus Infections / Q000628:therapy* / Q000821:virology; D005260:Female; D006680:HLA Antigens / Q000276:immunology; D004854:Herpesvirus 4, Human / Q000276:immunology*; D006801:Humans; D007167:Immunotherapy; D016219:Immunotherapy, Adoptive; D007223:Infant; D008232:Lymphoproliferative Disorders / Q000628:therapy* / Q000821:virology; D008297:Male; D008875:Middle Aged; D016377:Organ Transplantation; D016133:Polymerase Chain Reaction; D013602:T-Lymphocytes, Cytotoxic / Q000637:transplantation*; D014181:Transplantation Immunology; D014184:Transplantation, Homologous
chemical_list: D000914:Antibodies, Viral; D006680:HLA Antigens