title: Multicenter study of banked third-party virus-specific T cells to treat severe viral infections after hematopoietic stem cell transplantation.
abstract: 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.
authors.affiliation: Center for Cell and Gene Therapy, Baylor College of Medicine, Texas Children's Hospital, The Methodist Hospital, Houston, TX 77030, USA.
authors.forename: Ann M
authors.initials: AM
authors.lastname: Leen
authors.forename: Catherine M
authors.initials: CM
authors.lastname: Bollard
authors.forename: Adam M
authors.initials: AM
authors.lastname: Mendizabal
authors.forename: Elizabeth J
authors.initials: EJ
authors.lastname: Shpall
authors.forename: Paul
authors.initials: P
authors.lastname: Szabolcs
authors.forename: Joseph H
authors.initials: JH
authors.lastname: Antin
authors.forename: Neena
authors.initials: N
authors.lastname: Kapoor
authors.forename: Sung-Yun
authors.initials: SY
authors.lastname: Pai
authors.forename: Scott D
authors.initials: SD
authors.lastname: Rowley
authors.forename: Partow
authors.initials: P
authors.lastname: Kebriaei
authors.forename: Bimalangshu R
authors.initials: BR
authors.lastname: Dey
authors.forename: Bambi J
authors.initials: BJ
authors.lastname: Grilley
authors.forename: Adrian P
authors.initials: AP
authors.lastname: Gee
authors.forename: Malcolm K
authors.initials: MK
authors.lastname: Brenner
authors.forename: Cliona M
authors.initials: CM
authors.lastname: Rooney
authors.forename: Helen E
authors.initials: HE
authors.lastname: Heslop
mesh_terms: D000256:Adenoviridae / Q000472:pathogenicity; D000257:Adenoviridae Infections / Q000209:etiology / Q000517:prevention & control*; D000293:Adolescent; D000328:Adult; D003587:Cytomegalovirus / Q000472:pathogenicity; D003586:Cytomegalovirus Infections / Q000209:etiology / Q000517:prevention & control*; D020031:Epstein-Barr Virus Infections / Q000209:etiology / Q000517:prevention & control*; D005260:Female; D006086:Graft vs Host Disease / Q000209:etiology / Q000517:prevention & control*; D019337:Hematologic Neoplasms / Q000150:complications* / Q000628:therapy / Q000821:virology; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects*; D004854:Herpesvirus 4, Human / Q000472:pathogenicity; D006801:Humans; D008297:Male; D011379:Prognosis; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014184:Transplantation, Homologous