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High proportions of regulatory T cells in PBSC grafts predict improved survival after allogeneic haematopoietic SCT
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 adul...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Nature Publishing Group
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4705424/ https://www.ncbi.nlm.nih.gov/pubmed/26389831 http://dx.doi.org/10.1038/bmt.2015.215 |
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author | Danby, R D Zhang, W Medd, P Littlewood, T J Peniket, A Rocha, V Roberts, D J |
author_facet | Danby, R D Zhang, W Medd, P Littlewood, T J Peniket, A Rocha, V Roberts, D J |
author_sort | Danby, R D |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-4705424 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-47054242016-01-25 High proportions of regulatory T cells in PBSC grafts predict improved survival after allogeneic haematopoietic SCT Danby, R D Zhang, W Medd, P Littlewood, T J Peniket, A Rocha, V Roberts, D J Bone Marrow Transplant Original Article 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. Nature Publishing Group 2016-01 2015-09-21 /pmc/articles/PMC4705424/ /pubmed/26389831 http://dx.doi.org/10.1038/bmt.2015.215 Text en Copyright © 2016 Macmillan Publishers Limited http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ |
spellingShingle | Original Article Danby, R D Zhang, W Medd, P Littlewood, T J Peniket, A Rocha, V Roberts, D J High proportions of regulatory T cells in PBSC grafts predict improved survival after allogeneic haematopoietic SCT |
title | High proportions of regulatory T cells in PBSC grafts predict improved survival after allogeneic haematopoietic SCT |
title_full | High proportions of regulatory T cells in PBSC grafts predict improved survival after allogeneic haematopoietic SCT |
title_fullStr | High proportions of regulatory T cells in PBSC grafts predict improved survival after allogeneic haematopoietic SCT |
title_full_unstemmed | High proportions of regulatory T cells in PBSC grafts predict improved survival after allogeneic haematopoietic SCT |
title_short | High proportions of regulatory T cells in PBSC grafts predict improved survival after allogeneic haematopoietic SCT |
title_sort | high proportions of regulatory t cells in pbsc grafts predict improved survival after allogeneic haematopoietic sct |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4705424/ https://www.ncbi.nlm.nih.gov/pubmed/26389831 http://dx.doi.org/10.1038/bmt.2015.215 |
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