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dc.contributor.authorLocke, FL
dc.contributor.authorPidala, J
dc.contributor.authorStorer, B
dc.contributor.authorMartin, PJ
dc.contributor.authorPulsipher, MA
dc.contributor.authorChauncey, TR
dc.contributor.authorJacobsen, N
dc.contributor.authorKröger, N
dc.contributor.authorWalker, I
dc.contributor.authorLight, S
dc.contributor.authorShaw, BE
dc.contributor.authorBeato, F
dc.contributor.authorLaport, GG
dc.contributor.authorNademanee, A
dc.contributor.authorKeating, A
dc.contributor.authorSocie, G
dc.contributor.authorAnasetti, C
dc.date.accessioned2018-02-20T11:16:31Z
dc.date.issued2017-03
dc.identifier.citationBiology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation, 2017, 23 (3), pp. 405 - 411
dc.identifier.issn1083-8791
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/1369
dc.identifier.eissn1523-6536
dc.identifier.doi10.1016/j.bbmt.2016.12.624
dc.description.abstractDaclizumab, a humanized monoclonal antibody, binds CD25 and blocks formation of the IL-2 receptor on T cells. A study of daclizumab as acute graft-versus-host disease (GVHD) prophylaxis after unrelated bone marrow transplantation was conducted before the importance of CD25 + FOXP3 + regulatory T cells (Tregs) was recognized. Tregs can abrogate the onset of GVHD. The relation between Tregs and a graft-versus-malignancy effect is not fully understood. An international, multicenter, double-blind clinical trial randomized 210 adult or pediatric patients to receive 5 weekly doses of daclizumab at 0.3 mg/kg (n = 69) or 1.2 mg/kg (n = 76) or placebo (n = 65) after unrelated marrow transplantation for treatment of hematologic malignancies or severe aplastic anemia. The risk of acute GVHD did not differ among the groups (P = .68). Long-term follow-up of clinical outcomes and correlative analysis of peripheral blood T cell phenotype suggested that the patients treated with daclizumab had an increased risk of chronic GVHD (hazard ratio [HR], 1.49; 95% confidence interval [CI], 1.0 to 2.3; P = .08) and a decreased risk of relapse (HR, 0.57; 95% CI, 0.3 to 1.0; P = .05), but similar survival (HR, 0.89; 95% CI, 0.6 to 1.3; P = .53). T cells from a subset of patients (n = 107) were analyzed by flow cytometry. Compared with placebo, treatment with daclizumab decreased the proportion of Tregs among CD4 T cells at days 11-35 and increased the proportion of central memory cells among CD4 T cells at 1 year. Prophylactic administration of daclizumab does not prevent acute GVHD, but may increase the risk of chronic GVHD and decrease the risk of relapse. By delaying Treg reconstitution and promoting immunologic memory, anti-CD25 therapy may augment alloreactivity and antitumor immunity.
dc.formatPrint-Electronic
dc.format.extent405 - 411
dc.languageeng
dc.language.isoeng
dc.subjectHumans
dc.subjectGraft vs Host Disease
dc.subjectImmunoglobulin G
dc.subjectCD4 Lymphocyte Count
dc.subjectHematopoietic Stem Cell Transplantation
dc.subjectTransplantation, Homologous
dc.subjectDouble-Blind Method
dc.subjectAdolescent
dc.subjectAdult
dc.subjectMiddle Aged
dc.subjectChild
dc.subjectChild, Preschool
dc.subjectInfant
dc.subjectFemale
dc.subjectMale
dc.subjectT-Lymphocytes, Regulatory
dc.subjectInterleukin-2 Receptor alpha Subunit
dc.subjectYoung Adult
dc.subjectAntibodies, Monoclonal, Humanized
dc.subjectDaclizumab
dc.titleCD25 Blockade Delays Regulatory T Cell Reconstitution and Does Not Prevent Graft-versus-Host Disease After Allogeneic Hematopoietic Cell Transplantation.
dc.typeJournal Article
dcterms.dateAccepted2016-12-14
rioxxterms.versionofrecord10.1016/j.bbmt.2016.12.624
rioxxterms.licenseref.startdate2017-03
rioxxterms.typeJournal Article/Review
dc.relation.isPartOfBiology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation
pubs.issue3
pubs.notesNot known
pubs.organisational-group/ICR
pubs.organisational-group/ICR/Primary Group
pubs.organisational-group/ICR/Primary Group/Royal Marsden Clinical Units
pubs.organisational-group/ICR
pubs.organisational-group/ICR/Primary Group
pubs.organisational-group/ICR/Primary Group/Royal Marsden Clinical Units
pubs.publication-statusPublished
pubs.volume23
pubs.embargo.termsNot known
dc.contributor.icrauthorMarsden,en


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