title: Increased regulatory T cell graft content is associated with improved outcome in haematopoietic stem cell transplantation: a systematic review.
abstract: Allogeneic haematopoietic stem cell transplant (HSCT) recipients are at increased risk of morbidity and mortality, often due to the development of acute or chronic graft-versus-host disease (GVHD). Low numbers or proportions of regulatory T cells (Tregs) have been reported in patients who develop GVHD. We undertook a systematic review of studies that reported the Treg composition of HSCT grafts in patients with haematological malignancies. Fourteen eligible studies were identified, eight of which stratified patients by Tregs (absolute dose or ratio to CD3+ or CD4+ cells). Meta-analyses showed that high levels of Tregs in the grafts were associated with improved overall survival [hazard ratio (HR) 0·42, 95% confidence interval (CI) 0·23-0·74, P = 0·003, 2 studies], with a significant reduction in non-relapse mortality (HR 0·30, 95% CI 0·14-0·64, P = 0·002, 2 studies) and a reduced risk of acute GVHD (relative risk (RR) 0·59, 95% CI 0·40-0·89, P = 0·01, 6 studies). The consistency of these findings strongly suggests that the Treg composition of HSCT grafts has a powerful effect on the success of allogeneic HSCT. The major challenge is to translate these findings into better selection of allografts and future donors to provide a substantial improvement in allogeneic HSCT outcomes and practice.
authors.affiliation: NHS Blood and Transplant, Oxford, UK.|Nuffield Division of Clinical Laboratory Sciences, Radcliffe Department of Medicine, University of Oxford, Oxford, UK.
authors.forename: Sheila A
authors.initials: SA
authors.lastname: Fisher
authors.affiliation: NHS Blood and Transplant, Oxford, UK.|Nuffield Division of Clinical Laboratory Sciences, Radcliffe Department of Medicine, University of Oxford, Oxford, UK.
authors.forename: Abigail
authors.initials: A
authors.lastname: Lamikanra
authors.affiliation: NHS Blood and Transplant, Oxford, UK.|Nuffield Division of Clinical Laboratory Sciences, Radcliffe Department of Medicine, University of Oxford, Oxford, UK.
authors.forename: Carolyn
authors.initials: C
authors.lastname: Dorée
authors.affiliation: Oxford University Medical School, University of Oxford, Oxford, UK.
authors.forename: Betty
authors.initials: B
authors.lastname: Gration
authors.affiliation: NHS Blood and Transplant, Oxford, UK.|Nuffield Division of Clinical Laboratory Sciences, Radcliffe Department of Medicine, University of Oxford, Oxford, UK.
authors.forename: Pat
authors.initials: P
authors.lastname: Tsang
authors.affiliation: Department of Haematology, Oxford University Hospitals NHS Trust, Churchill Hospital, Oxford, UK.|Anthony Nolan Research Institute, London, UK.
authors.forename: Robert D
authors.initials: RD
authors.lastname: Danby
authors.affiliation: NHS Blood and Transplant, Oxford, UK.|Nuffield Division of Clinical Laboratory Sciences, Radcliffe Department of Medicine, University of Oxford, Oxford, UK.|Department of Haematology, Oxford University Hospitals NHS Trust, Churchill Hospital, Oxford, UK.
authors.forename: David J
authors.initials: DJ
authors.lastname: Roberts
mesh_terms: D064591:Allografts; D006086:Graft vs Host Disease / Q000517:prevention & control; D019337:Hematologic Neoplasms / Q000150:complications / Q000401:mortality / Q000628:therapy*; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D006801:Humans; D050378:T-Lymphocytes, Regulatory / Q000166:cytology*; D019737:Transplants / Q000166:cytology* / Q000276:immunology; D016896:Treatment Outcome
keywords: T cells; graft-versus-host; regulatory; survival; transplant