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Improved Therapeutic Approaches are Needed to Manage Graft-versus-Host Disease
Allogeneic haematopoietic stem cell transplantation (alloHSCT) offers a potentially curative therapy for patients suffering from diseases of the haematopoietic system but requires a high level of expertise and is both resource intensive and expensive. A frequent and life-threatening complication is...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Springer International Publishing
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8556206/ https://www.ncbi.nlm.nih.gov/pubmed/34657244 http://dx.doi.org/10.1007/s40261-021-01087-6 |
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author | Hooker, Deborah S. Grabe-Heyne, Kristin Henne, Christof Bader, Peter Toumi, Mondher Furniss, Stephen J. |
author_facet | Hooker, Deborah S. Grabe-Heyne, Kristin Henne, Christof Bader, Peter Toumi, Mondher Furniss, Stephen J. |
author_sort | Hooker, Deborah S. |
collection | PubMed |
description | Allogeneic haematopoietic stem cell transplantation (alloHSCT) offers a potentially curative therapy for patients suffering from diseases of the haematopoietic system but requires a high level of expertise and is both resource intensive and expensive. A frequent and life-threatening complication is graft-versus-host disease (GvHD). Acute GvHD (aGvHD) generally causes skin, gastrointestinal and liver symptoms, but chronic GvHD (cGvHD) has a different pathophysiology and may affect nearly every organ or tissue of the body. In Europe, GvHD prophylaxis is generally a calcineurin inhibitor in combination with methotrexate, with high-dose systemic steroids used for advanced GvHD treatment. Between 39% and 59% of alloHSCT patients will develop aGvHD and around 36–37% will develop cGvHD. Steroid response decreases with increasing disease severity, which in turn leads to an increase in non-relapse mortality. GvHD imposes a financial burden on healthcare systems, significantly increasing post-alloHSCT costs. Increased GvHD disease severity magnifies this. Balancing immunosuppression to control the GvHD whilst maintaining a degree of immunocompetence against infection is critical. European GvHD guidelines acknowledge the lack of evidence to support a standard second-line therapy, and improved long-term outcomes and quality-of-life (QoL) remain an unmet need. Evidence generation for potential treatments is challenging. Issues to overcome include choice of comparator (extensive off-label usage); blinding; selection of relevant patient-reported outcome measures (PROMs); and rarity of the condition, which may infeasibly increase timescales to achieve clinical and statistical relevance. |
format | Online Article Text |
id | pubmed-8556206 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Springer International Publishing |
record_format | MEDLINE/PubMed |
spelling | pubmed-85562062021-11-04 Improved Therapeutic Approaches are Needed to Manage Graft-versus-Host Disease Hooker, Deborah S. Grabe-Heyne, Kristin Henne, Christof Bader, Peter Toumi, Mondher Furniss, Stephen J. Clin Drug Investig Current Opinion Allogeneic haematopoietic stem cell transplantation (alloHSCT) offers a potentially curative therapy for patients suffering from diseases of the haematopoietic system but requires a high level of expertise and is both resource intensive and expensive. A frequent and life-threatening complication is graft-versus-host disease (GvHD). Acute GvHD (aGvHD) generally causes skin, gastrointestinal and liver symptoms, but chronic GvHD (cGvHD) has a different pathophysiology and may affect nearly every organ or tissue of the body. In Europe, GvHD prophylaxis is generally a calcineurin inhibitor in combination with methotrexate, with high-dose systemic steroids used for advanced GvHD treatment. Between 39% and 59% of alloHSCT patients will develop aGvHD and around 36–37% will develop cGvHD. Steroid response decreases with increasing disease severity, which in turn leads to an increase in non-relapse mortality. GvHD imposes a financial burden on healthcare systems, significantly increasing post-alloHSCT costs. Increased GvHD disease severity magnifies this. Balancing immunosuppression to control the GvHD whilst maintaining a degree of immunocompetence against infection is critical. European GvHD guidelines acknowledge the lack of evidence to support a standard second-line therapy, and improved long-term outcomes and quality-of-life (QoL) remain an unmet need. Evidence generation for potential treatments is challenging. Issues to overcome include choice of comparator (extensive off-label usage); blinding; selection of relevant patient-reported outcome measures (PROMs); and rarity of the condition, which may infeasibly increase timescales to achieve clinical and statistical relevance. Springer International Publishing 2021-10-16 2021 /pmc/articles/PMC8556206/ /pubmed/34657244 http://dx.doi.org/10.1007/s40261-021-01087-6 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by-nc/4.0/Open AccessThis article is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License, which permits any non-commercial use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc/4.0/ (https://creativecommons.org/licenses/by-nc/4.0/) . |
spellingShingle | Current Opinion Hooker, Deborah S. Grabe-Heyne, Kristin Henne, Christof Bader, Peter Toumi, Mondher Furniss, Stephen J. Improved Therapeutic Approaches are Needed to Manage Graft-versus-Host Disease |
title | Improved Therapeutic Approaches are Needed to Manage Graft-versus-Host Disease |
title_full | Improved Therapeutic Approaches are Needed to Manage Graft-versus-Host Disease |
title_fullStr | Improved Therapeutic Approaches are Needed to Manage Graft-versus-Host Disease |
title_full_unstemmed | Improved Therapeutic Approaches are Needed to Manage Graft-versus-Host Disease |
title_short | Improved Therapeutic Approaches are Needed to Manage Graft-versus-Host Disease |
title_sort | improved therapeutic approaches are needed to manage graft-versus-host disease |
topic | Current Opinion |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8556206/ https://www.ncbi.nlm.nih.gov/pubmed/34657244 http://dx.doi.org/10.1007/s40261-021-01087-6 |
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