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Blood, 15 August 2007, Vol. 110, No. 4, pp. 1123-1131.
Prepublished online as a Blood First Edition Paper on April 27, 2007; DOI 10.1182/blood-2006-12-063008.
 Previous Article | Next Article 
Submitted December 13, 2006
Accepted April 26, 2007
Allogeneic cytotoxic T cell therapy for EBV-positive post transplant lymphoproliferative disease: results of a phase II multicentre 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, and Dorothy H Crawford
Clinical and Molecular Virology Laboratory, University of Edinburgh, Edinburgh, United Kingdom
Sir Richard Doll Building, Institute of Cancer Research, Sutton, United Kingdom
Scottish National Blood Transfusion Services, Royal Infirmary, Edinburgh, United Kingdom
Department of Pathology, Royal Infirmary, Edinburgh, United Kingdom
Department of Immunology, Royal Free Hospital and University College Medical School, London, United Kingdom
Liver Unit, Birmingham Children's Hospital, Birmingham, United Kingdom
Liver Transplant Unit, Royal Infirmary, Edinburgh, United Kingdom
Immunohaematology Laboratory, Queensland Institute of Medical Research, Brisbane, Australia
* Corresponding author; email: t.haque{at}medsch.ucl.ac.uk.
We present the results of a multicentre clinical trial using Epstein-Barr virus (EBV)-specific cytotoxic T lymphocytes (CTL) generated from EBV seropositive blood donors to treat patients with EBV-positive post transplant 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 towards better responses with higher numbers of CD4 positive cells in infused CTL lines (p=0.001) that was maintained at 6 months (p=0.001). Patients receiving CTL with closer HLA matching responded better at 6 months (p=0.048). Female patients responded better than male patients but the differences were not statistically significant. Our results show that allogeneic CTL are a safe and rapid therapy for PTLD bypassing the need to grow CTL for individual patients. The response rate in this poor prognosis patient group is encouraging.
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