Allogeneic cytotoxic T-cell therapy for EBV-positive posttransplantation lymphoproliferative disease: results of a phase 2 multicenter clinical trial.
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.
Haque
Tanzina
T
Clinical and Molecular Virology Laboratory, University of Edinburgh, Edinburgh, United Kingdom. t.haque@medsch.ucl.ac.uk
Wilkie
Gwen M
GM
Jones
Marie M
MM
Higgins
Craig D
CD
Urquhart
Gillian
G
Wingate
Phoebe
P
Burns
David
D
McAulay
Karen
K
Turner
Marc
M
Bellamy
Christopher
C
Amlot
Peter L
PL
Kelly
Deirdre
D
MacGilchrist
Alastair
A
Gandhi
Maher K
MK
Swerdlow
Anthony J
AJ
Crawford
Dorothy H
DH
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
D000914:Antibodies, Viral; D006680:HLA Antigens