Treatment of Epstein-Barr-virus-positive post-transplantation lymphoproliferative disease with partly HLA-matched allogeneic cytotoxic T cells.
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.
Haque
Tanzina
T
Laboratory for Clinical and Molecular Virology, University of Edinburgh, Edinburgh EH9 1QH, UK. t.haque@ed.ac.uk
Wilkie
Gwen M
GM
Taylor
Clare
C
Amlot
Peter L
PL
Murad
Parvez
P
Iley
Angela
A
Dombagoda
Dilani
D
Britton
Kate M
KM
Swerdlow
Anthony J
AJ
Crawford
Dorothy H
DH
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
D000914:Antibodies, Viral; D006680:HLA Antigens