title: Donor-derived CMV-specific T cells reduce the requirement for CMV-directed pharmacotherapy after allogeneic stem cell transplantation.
abstract: We investigated the use of adoptively transferred donor-derived cytomegalovirus (CMV) specific cytotoxic T lymphocytes (CTL) as immune reconstitution postallogeneic transplant in a phase 2 study. Fifty patients were infused with a single dose of 2 × 10(7)cells/m(2) after day 28 post-transplant. Twenty-six patients reactivated CMV posttransplant (only 5 post-CTL infusion) and 9 required therapy with ganciclovir or foscarnet (only 1 post-CTL infusion). There was 1 case of fatal CMV disease, attributable to high levels of antithymocyte globulin at the time of T cell infusion. We compared the patients in the phase 2 study with a group of contemporaneous controls also treated at the trial centers. There was no increase in acute or chronic graft-versus-host disease attributable to CTL infusion; overall and progression-free survival were similar in both groups. There was a reduction in the percentage of patients who required CMV directed antiviral therapy (17% vs 36%, P = .01) and in the total number of treatment days in the cohort receiving CTL (3.4 days vs 8.9 days, P = .03) without a reduction in CMV reactivation rates. We postulate that adoptively transferred cells are able to expand in response to viral antigen, limit viral replication, and prevent progression to tissue infection. This study was registered on the Australian Clinical Trial Registry as #ACTRN12605000213640 and #ACTRN12607000224426.
authors: Westmead Millennium Institute, University of Sydney, Sydney, Australia. emily.blyth@sydney.edu.au
authors: Emily
authors: E
authors: Blyth
authors: Leighton
authors: L
authors: Clancy
authors: Renee
authors: R
authors: Simms
authors: Chun K K
authors: CK
authors: Ma
authors: Jane
authors: J
authors: Burgess
authors: Shivashni
authors: S
authors: Deo
authors: Karen
authors: K
authors: Byth
authors: Ming-Celine
authors: MC
authors: Dubosq
authors: Peter J
authors: PJ
authors: Shaw
authors: Kenneth P
authors: KP
authors: Micklethwaite
authors: David J
authors: DJ
authors: Gottlieb
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000627:therapeutic use*; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D017322:Clinical Trials, Phase II as Topic / Q000706:statistics & numerical data; D015331:Cohort Studies; D003587:Cytomegalovirus / Q000276:immunology*; D003586:Cytomegalovirus Infections / Q000097:blood / Q000188:drug therapy / Q000276:immunology* / Q000517:prevention & control*; D005260:Female; D005500:Follow-Up Studies; D019337:Hematologic Neoplasms / Q000097:blood / Q000150:complications / Q000401:mortality / Q000628:therapy*; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects; D006801:Humans; D016219:Immunotherapy, Adoptive; D008297:Male; D008875:Middle Aged; D013601:T-Lymphocytes / Q000276:immunology / Q000637:transplantation*; D014019:Tissue Donors; D014184:Transplantation, Homologous; D014775:Virus Activation / Q000276:immunology; D055815:Young Adult
chemical_list: D000998:Antiviral Agents