Allogeneic cytotoxic T-cell therapy for EBV-positive posttransplantation lymphoproliferative disease: results of a phase 2 multicenter clinical trial

Tanzina Haque, Gwen M Wilkie, Marie M Jones, Craig D Higgins, Gillian Urquhart, Phoebe Wingate, David Burns, Karen McAulay, Marc Turner, Christopher Bellamy, Peter L Amlot, Deirdre Kelly, Alastair MacGilchrist, Maher K Gandhi, Anthony J Swerdlow, Dorothy H Crawford

Research output: Contribution to journalArticlepeer-review

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.
Original languageEnglish
Pages (from-to)1123-31
Number of pages9
JournalBlood
Volume110
Issue number4
DOIs
Publication statusPublished - 15 Aug 2007

Keywords

  • Adolescent
  • Adult
  • Aged
  • Antibodies, Viral
  • Case-Control Studies
  • Child
  • Child, Preschool
  • Epstein-Barr Virus Infections
  • Female
  • HLA Antigens
  • Herpesvirus 4, Human
  • Humans
  • Immunotherapy
  • Immunotherapy, Adoptive
  • Infant
  • Lymphoproliferative Disorders
  • Male
  • Middle Aged
  • Organ Transplantation
  • Polymerase Chain Reaction
  • T-Lymphocytes, Cytotoxic
  • Transplantation Immunology
  • Transplantation, Homologous

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