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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.
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CLINICAL TRIALS AND OBSERVATIONS
Allogeneic cytotoxic T-cell therapy for EBV-positive posttransplantation lymphoproliferative disease: results of a phase 2 multicenter clinical trial
Tanzina Haque1,
Gwen M. Wilkie1,
Marie M. Jones1,
Craig D. Higgins2,
Gillian Urquhart1,
Phoebe Wingate1,
David Burns1,
Karen McAulay1,
Marc Turner3,
Christopher Bellamy4,
Peter L. Amlot5,
Deirdre Kelly6,
Alastair MacGilchrist7,
Maher K. Gandhi8,
Anthony J. Swerdlow2, and
Dorothy H. Crawford1
1 Clinical and Molecular Virology Laboratory, University of Edinburgh, Edinburgh, United Kingdom;
2 Sir Richard Doll Building, Institute of Cancer Research, Sutton, United Kingdom;
3 Scottish National Blood Transfusion Service, Royal Infirmary, Edinburgh, United Kingdom;
4 Department of Pathology, Royal Infirmary, Edinburgh, United Kingdom;
5 Department of Immunology, Royal Free Hospital and University College Medical School, London, United Kingdom;
6 Liver Unit, Birmingham Children's Hospital, Birmingham, United Kingdom;
7 Liver Transplant Unit, Edinburgh Royal Infirmary, Edinburgh, United Kingdom,
8 Immunohaematology Laboratory, Queensland Institute of Medical Research, Brisbane, Australia
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.

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