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https://hdl.handle.net/2440/124443
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dc.contributor.author | Withers, B. | - |
dc.contributor.author | Blyth, E. | - |
dc.contributor.author | Clancy, L.E. | - |
dc.contributor.author | Yong, A. | - |
dc.contributor.author | Fraser, C. | - |
dc.contributor.author | Burgess, J. | - |
dc.contributor.author | Simms, R. | - |
dc.contributor.author | Brown, R. | - |
dc.contributor.author | Kliman, D. | - |
dc.contributor.author | Dubosq, M.-C. | - |
dc.contributor.author | Bishop, D. | - |
dc.contributor.author | Sutrave, G. | - |
dc.contributor.author | Ma, C.K.K. | - |
dc.contributor.author | Shaw, P.J. | - |
dc.contributor.author | Micklethwaite, K.P. | - |
dc.contributor.author | Gottlieb, D.J. | - |
dc.date.issued | 2017 | - |
dc.identifier.citation | Blood Advances, 2017; 1(24):2193-2205 | - |
dc.identifier.issn | 2473-9529 | - |
dc.identifier.issn | 2473-9537 | - |
dc.identifier.uri | http://hdl.handle.net/2440/124443 | - |
dc.description.abstract | Donor-derived adoptive T-cell therapy is a safe and effective treatment of viral infection posttransplant, but it is limited by donor serostatus and availability and by its personalized nature. Off-the-shelf, third-party virus-specific T cells (VSTs) appear promising, but the long-term safety and durability of responses have yet to be established. We conducted a prospective study of 30 allogeneic hemopoietic stem cell transplant (HSCT) patients with persistent or recurrent cytomegalovirus (CMV) (n = 28), Epstein-Barr virus (n = 1), or adenovirus (n = 1) after standard therapy. Patients were treated with infusions of partially HLA-matched, third-party, ex vivo-expanded VSTs (total = 50 infusions) at a median of 75 days post-HSCT (range, 37 to 349 days). Safety, viral dynamics, and immune recovery were monitored for 12 months. Infusions were safe and well tolerated. Acute graft versus host disease occurred in 2 patients, despite a median HLA match between VSTs and the recipient of 2 of 6 antigens. At 12 months, the cumulative incidence of overall response was 93%. Virological control was durable in the majority of patients; the reintroduction of antiviral therapy after the final infusion occurred in 5 patients. CMV-specific T-cell immunity rose significantly and coincided with a rise in CD8+ terminal effector cells. PD-1 expression was elevated on CD8+ lymphocytes before the administration of third-party T cells and remained elevated at the time of viral control. Third-party VSTs show prolonged benefit, with virological control achieved in association with the recovery of CD8+ effector T cells possibly facilitated by VST infusion. This trial was registered at www.clinicaltrials.gov as #NCT02779439 and www.anzctr.org.au as #ACTRN12613000603718. | - |
dc.description.statementofresponsibility | Barbara Withers, Emily Blyth, Leighton E. Clancy, Agnes Yong, Chris Fraser, Jane Burgess ... et al. | - |
dc.language.iso | en | - |
dc.publisher | American Society of Hematology | - |
dc.rights | © 2017 by The American Society of Hematology | - |
dc.source.uri | http://dx.doi.org/10.1182/bloodadvances.2017010223 | - |
dc.title | Long-term control of recurrent or refractory viral infections after allogeneic HSCT with third-party virus-specific T cells | - |
dc.type | Journal article | - |
dc.identifier.doi | 10.1182/bloodadvances.2017010223 | - |
dc.relation.grant | http://purl.org/au-research/grants/nhmrc/1032431 | - |
pubs.publication-status | Published | - |
dc.identifier.orcid | Yong, A. [0000-0001-9452-1533] | - |
Appears in Collections: | Aurora harvest 8 Medicine publications |
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