Donor-derived CMV-specific T cells reduce the requirement for CMV-directed pharmacotherapy after allogeneic stem cell transplantation

• Published in: Blood 2013-05, Vol.121 (18), p.3745-3758
• Main Authors: Blyth, Emily, Clancy, Leighton, Simms, Renee, Ma, Chun K.K., Burgess, Jane, Deo, Shivashni, Byth, Karen, Dubosq, Ming-Celine, Shaw, Peter J., Micklethwaite, Kenneth P., Gottlieb, David J.
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Aged; Antiviral Agents - therapeutic use; Case-Control Studies; Child; Child, Preschool; Clinical Trials, Phase II as Topic - statistics & numerical data; Cohort Studies; Cytomegalovirus - immunology; Cytomegalovirus Infections - blood; Cytomegalovirus Infections - drug therapy; Cytomegalovirus Infections - immunology; Cytomegalovirus Infections - prevention & control; Female; Follow-Up Studies; Hematologic Neoplasms - blood; Hematologic Neoplasms - complications; Hematologic Neoplasms - mortality; Hematologic Neoplasms - therapy; Hematopoietic Stem Cell Transplantation - adverse effects; Humans; Immunotherapy, Adoptive; Male; Middle Aged; T-Lymphocytes - immunology; T-Lymphocytes - transplantation; Tissue Donors; Transplantation, Homologous; Virus Activation - immunology; Young Adult
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2012-08-448977

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 × 107cells/m2 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. •Infusion of CMV-specific T cells early posttransplant does not increase acute or chronic graft-versus-host disease.•CMV-specific T cells early posttransplant reduce the need for pharmacotherapy without increased rates of CMV-related organ damage.