Multicenter study of banked third-party virus-specific T cells to treat severe viral infections after hematopoietic stem cell transplantation

Virus-specific T cell (VST) lines could provide useful antiviral prophylaxis and treatment of immune-deficient patients if it were possible to avoid the necessity of generating a separate line for each patient, often on an emergency basis. We prepared a bank of 32 virus-specific lines from individua...

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Bibliographic Details
Published in:Blood 2013-06, Vol.121 (26), p.5113-5123
Main Authors: Leen, Ann M., Bollard, Catherine M., Mendizabal, Adam M., Shpall, Elizabeth J., Szabolcs, Paul, Antin, Joseph H., Kapoor, Neena, Pai, Sung-Yun, Rowley, Scott D., Kebriaei, Partow, Dey, Bimalangshu R., Grilley, Bambi J., Gee, Adrian P., Brenner, Malcolm K., Rooney, Cliona M., Heslop, Helen E.
Format: Article
Language:English
Subjects:
Adenoviridae - pathogenicity
Adenoviridae Infections - etiology
Adenoviridae Infections - prevention & control
Adenovirus
Adolescent
Adult
Cytomegalovirus
Cytomegalovirus - pathogenicity
Cytomegalovirus Infections - etiology
Cytomegalovirus Infections - prevention & control
Epstein-Barr virus
Epstein-Barr Virus Infections - etiology
Epstein-Barr Virus Infections - prevention & control
Female
Graft vs Host Disease - etiology
Graft vs Host Disease - prevention & control
Hematologic Neoplasms - complications
Hematologic Neoplasms - therapy
Hematologic Neoplasms - virology
Hematopoietic Stem Cell Transplantation - adverse effects
Herpesvirus 4, Human - pathogenicity
Humans
Male
Plenary Paper
Prognosis
T-Lymphocytes, Cytotoxic - immunology
Transplantation, Homologous
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Summary:Virus-specific T cell (VST) lines could provide useful antiviral prophylaxis and treatment of immune-deficient patients if it were possible to avoid the necessity of generating a separate line for each patient, often on an emergency basis. We prepared a bank of 32 virus-specific lines from individuals with common HLA polymorphisms who were immune to Epstein-Barr virus (EBV), cytomegalovirus, or adenovirus. A total of 18 lines were administered to 50 patients with severe, refractory illness because of infection with one of these viruses after hematopoietic stem cell transplant. The cumulative rates of complete or partial responses at 6 weeks postinfusion were 74.0% (95% CI, 58.5%-89.5%) for the entire group (n = 50), 73.9% (95% CI, 51.2% -96.6%) for cytomegalovirus (n = 23), 77.8% for adenovirus (n = 18), and 66.7% (95% CI, 36.9%-96.5%) for EBV (n = 9). Only 4 responders had a recurrence or progression. There were no immediate infusion-related adverse events, and de novo graft-versus-host disease developed in only 2 patients. Despite the disparity between the lines and their recipients, the mean frequency of VSTs increased significantly postinfusion, coincident with striking decreases in viral DNA and resolution of clinical symptoms. The use of banked third-party VSTs is a feasible and safe approach to rapidly treat severe or intractable viral infections after stem cell transplantation. This study is registered at www.clinicaltrials.gov as NCT00711035. • Banked third-party virus-specific T cells can safely and rapidly treat severe or intractable viral infections after HSCT.
ISSN:0006-4971
1528-0020
1528-0020
DOI:10.1182/blood-2013-02-486324