title: High proportions of regulatory T cells in PBSC grafts predict improved survival after allogeneic haematopoietic SCT.
abstract: Regulatory T cells (Tregs) modulate immune responses and improve survival in murine transplant models. However, whether the Treg content of allogeneic cell grafts influences the outcome in human haematopoietic stem cell (HSC) transplantation is not well established. In a prospective study of 94 adult allogeneic PBSC transplants (60% unrelated; 85% reduced intensity conditioning), the median Treg (CD3(+)CD4(+)CD25(+)FOXP3(+)CD127(dim/-)) dose transplanted was 4.7 × 10(6)/kg, with Tregs accounting for a median of 2.96% of CD4(+) T cells. Patients transplanted with grafts containing a Treg/CD4(+) T-cell ratio above the median had a 3-year overall survival of 75%, compared with 49% in those receiving grafts with a Treg/CD4(+) T-cell ratio below the median (P=0.02), with a 3-year non-relapse mortality of 13% and 35%, respectively (P=0.02). In multivariate analysis, a high graft Treg/CD4(+) T-cell ratio was an independent predictor of lower non-relapse mortality (hazard ratio (HR), 0.30; P=0.02), improved overall survival (HR, 0.45; P=0.03) and improved sustained neutrophil (HR, 0.52; P=0.002), platelet (HR, 0.51; P<0.001) and lymphocyte (HR, 0.54; P=0.009) recovery. These data support the hypothesis that the proportion of Tregs in allogeneic HSC grafts influences clinical outcome and suggest that Treg therapies could improve allogeneic HSC transplantation.
authors.affiliation: Department of Haematology Cancer and Haematology Centre, Oxford University Hospitals NHS Trust, Churchill Hospital, Oxford, UK.|NHS Blood and Transplant, John Radcliffe Hospital, Oxford, UK.
authors.forename: R D
authors.initials: RD
authors.lastname: Danby
authors.affiliation: NHS Blood and Transplant, John Radcliffe Hospital, Oxford, UK.|Radcliffe Department of Medicine, University of Oxford, Oxford, UK.
authors.forename: W
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Department of Haematology, Derriford Hospital, Plymouth, UK.
authors.forename: P
authors.initials: P
authors.lastname: Medd
authors.affiliation: Department of Haematology Cancer and Haematology Centre, Oxford University Hospitals NHS Trust, Churchill Hospital, Oxford, UK.
authors.forename: T J
authors.initials: TJ
authors.lastname: Littlewood
authors.affiliation: Department of Haematology Cancer and Haematology Centre, Oxford University Hospitals NHS Trust, Churchill Hospital, Oxford, UK.
authors.forename: A
authors.initials: A
authors.lastname: Peniket
authors.affiliation: Department of Haematology Cancer and Haematology Centre, Oxford University Hospitals NHS Trust, Churchill Hospital, Oxford, UK.|NHS Blood and Transplant, John Radcliffe Hospital, Oxford, UK.
authors.forename: V
authors.initials: V
authors.lastname: Rocha
authors.affiliation: Department of Haematology Cancer and Haematology Centre, Oxford University Hospitals NHS Trust, Churchill Hospital, Oxford, UK.|Radcliffe Department of Medicine, University of Oxford, Oxford, UK.
authors.forename: D J
authors.initials: DJ
authors.lastname: Roberts
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D064591:Allografts; D000818:Animals; D018572:Disease-Free Survival; D005260:Female; D006085:Graft Survival; D019337:Hematologic Neoplasms / Q000097:blood / Q000401:mortality / Q000628:therapy; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D018655:Lymphocyte Count; D008297:Male; D051379:Mice; D008875:Middle Aged; D015996:Survival Rate; D050378:T-Lymphocytes, Regulatory