title: Treatment of Epstein-Barr-virus-positive post-transplantation lymphoproliferative disease with partly HLA-matched allogeneic cytotoxic T cells.
abstract: BACKGROUND
  Epstein-Barr virus (EBV)-associated post-transplantation lymphoproliferative disease (PTLD) is a common, often fatal, complication of bone-marrow and solid-organ transplantation. Since tumour growth results from inadequate T-cell control of latent EBV, new immunotherapeutic approaches to treatment are being pioneered.
  
  
  METHODS
  In a phase 1/2 trial, eight patients with progressive PTLD unresponsive to conventional treatment were given one to six infusions of partly HLA-matched allogeneic EBV-specific cytotoxic T lymphocytes (CTLs) from a frozen bank of CTLs derived from healthy blood donors.
  
  
  RESULTS
  Of the five patients who completed treatment, three had complete remission and two had no clinical response. One patient partly responded after two infusions. No graft-versus-host disease or allo-specific antibodies were detected, and graft function improved in three cases. Tumour responses were mainly seen in those with early, localised, polyclonal disease. EBV load in peripheral blood fell to undetectable levels in all patients who responded to treatment, but was more variable in those who did not.
  
  
  CONCLUSIONS
  Treatment of EBV-associated PTLD with partly HLA-matched CTLs grown from unrelated donors is effective. Spontaneous remission is very unlikely to account for tumour regression in our patients; however, a larger, controlled trial is needed to assess this treatment further. The frozen bank of allogeneic CTLs is less prohibitively labour intensive and expensive for wide scale use than treatment with autologous CTLs. Such banks could be established to treat other infectious and neoplastic diseases in many patients.
authors.affiliation: Laboratory for Clinical and Molecular Virology, University of Edinburgh, Edinburgh EH9 1QH, UK. t.haque@ed.ac.uk
authors.forename: Tanzina
authors.initials: T
authors.lastname: Haque
authors.forename: Gwen M
authors.initials: GM
authors.lastname: Wilkie
authors.forename: Clare
authors.initials: C
authors.lastname: Taylor
authors.forename: Peter L
authors.initials: PL
authors.lastname: Amlot
authors.forename: Parvez
authors.initials: P
authors.lastname: Murad
authors.forename: Angela
authors.initials: A
authors.lastname: Iley
authors.forename: Dilani
authors.initials: D
authors.lastname: Dombagoda
authors.forename: Kate M
authors.initials: KM
authors.lastname: Britton
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Swerdlow
authors.forename: Dorothy H
authors.initials: DH
authors.lastname: Crawford
mesh_terms: D000914:Antibodies, Viral / Q000097:blood; D002648:Child; D002675:Child, Preschool; D020031:Epstein-Barr Virus Infections / Q000150:complications* / Q000635:transmission; D006680:HLA Antigens / Q000276:immunology*; D004854:Herpesvirus 4, Human / Q000276:immunology; D006650:Histocompatibility Testing; D006801:Humans; D008232:Lymphoproliferative Disorders / Q000209:etiology* / Q000628:therapy*; D008875:Middle Aged; D016377:Organ Transplantation / Q000009:adverse effects*; D013602:T-Lymphocytes, Cytotoxic / Q000637:transplantation*; D014184:Transplantation, Homologous; D016896:Treatment Outcome
chemical_list: D000914:Antibodies, Viral; D006680:HLA Antigens