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Therapy response of glucocorticoid-refractory acute GVHD of the lower intestinal tract

Acute graft-versus-host disease (aGVHD) is a major life-threatening complication of allogeneic hematopoietic cell transplantation. While most studies report therapy-response of aGVHD including a cumulative grade of skin, liver and intestinal tract manifestations, there is a lack of information speci...

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Autores principales: Biavasco, Francesca, Ihorst, Gabriele, Wäsch, Ralph, Wehr, Claudia, Bertz, Hartmut, Finke, Jürgen, Zeiser, Robert
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9532244/
https://www.ncbi.nlm.nih.gov/pubmed/35768570
http://dx.doi.org/10.1038/s41409-022-01741-3
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author Biavasco, Francesca
Ihorst, Gabriele
Wäsch, Ralph
Wehr, Claudia
Bertz, Hartmut
Finke, Jürgen
Zeiser, Robert
author_facet Biavasco, Francesca
Ihorst, Gabriele
Wäsch, Ralph
Wehr, Claudia
Bertz, Hartmut
Finke, Jürgen
Zeiser, Robert
author_sort Biavasco, Francesca
collection PubMed
description Acute graft-versus-host disease (aGVHD) is a major life-threatening complication of allogeneic hematopoietic cell transplantation. While most studies report therapy-response of aGVHD including a cumulative grade of skin, liver and intestinal tract manifestations, there is a lack of information specifically on lower gastrointestinal tract aGVHD (GI-GVHD) therapy-response, which is highly relevant in light of novel therapies that target intestinal regeneration such as IL-22, R-spondin or GLP-2. Here we retrospectively analyzed patients who developed GI-GVHD over a 6-year period. A total of 144 patients developed GI-GVHD and 82 (57%) were resistant to glucocorticoid-therapy (SR). The most commonly used second-line therapy was ruxolitinib (74%). Overall and complete response (CR) to ruxolitinib on day 28 were 44.5% and 13%, respectively. SR-GVHD patients experienced a lower 5-year overall survival (OS) (34.8 vs 53.3%, p = 0.0014) and higher incidence of 12-months non-relapse-mortality (39.2 vs 14.3%, p = 0.016) compared to glucocorticoid-sensitive patients. SR-GI-GVHD patients, that achieved a CR on day 28 after ruxolitinib start, experienced a higher OS compared to non-CR patients (p = 0.04). These findings indicate that therapy response of SR-GI-GVHD to different immunosuppressive approaches is still low, and that novel therapies specifically aiming at enhanced intestinal regeneration should be tested in clinical trials.
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spelling pubmed-95322442022-10-06 Therapy response of glucocorticoid-refractory acute GVHD of the lower intestinal tract Biavasco, Francesca Ihorst, Gabriele Wäsch, Ralph Wehr, Claudia Bertz, Hartmut Finke, Jürgen Zeiser, Robert Bone Marrow Transplant Article Acute graft-versus-host disease (aGVHD) is a major life-threatening complication of allogeneic hematopoietic cell transplantation. While most studies report therapy-response of aGVHD including a cumulative grade of skin, liver and intestinal tract manifestations, there is a lack of information specifically on lower gastrointestinal tract aGVHD (GI-GVHD) therapy-response, which is highly relevant in light of novel therapies that target intestinal regeneration such as IL-22, R-spondin or GLP-2. Here we retrospectively analyzed patients who developed GI-GVHD over a 6-year period. A total of 144 patients developed GI-GVHD and 82 (57%) were resistant to glucocorticoid-therapy (SR). The most commonly used second-line therapy was ruxolitinib (74%). Overall and complete response (CR) to ruxolitinib on day 28 were 44.5% and 13%, respectively. SR-GVHD patients experienced a lower 5-year overall survival (OS) (34.8 vs 53.3%, p = 0.0014) and higher incidence of 12-months non-relapse-mortality (39.2 vs 14.3%, p = 0.016) compared to glucocorticoid-sensitive patients. SR-GI-GVHD patients, that achieved a CR on day 28 after ruxolitinib start, experienced a higher OS compared to non-CR patients (p = 0.04). These findings indicate that therapy response of SR-GI-GVHD to different immunosuppressive approaches is still low, and that novel therapies specifically aiming at enhanced intestinal regeneration should be tested in clinical trials. Nature Publishing Group UK 2022-06-29 2022 /pmc/articles/PMC9532244/ /pubmed/35768570 http://dx.doi.org/10.1038/s41409-022-01741-3 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits 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 license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license 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 license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Biavasco, Francesca
Ihorst, Gabriele
Wäsch, Ralph
Wehr, Claudia
Bertz, Hartmut
Finke, Jürgen
Zeiser, Robert
Therapy response of glucocorticoid-refractory acute GVHD of the lower intestinal tract
title Therapy response of glucocorticoid-refractory acute GVHD of the lower intestinal tract
title_full Therapy response of glucocorticoid-refractory acute GVHD of the lower intestinal tract
title_fullStr Therapy response of glucocorticoid-refractory acute GVHD of the lower intestinal tract
title_full_unstemmed Therapy response of glucocorticoid-refractory acute GVHD of the lower intestinal tract
title_short Therapy response of glucocorticoid-refractory acute GVHD of the lower intestinal tract
title_sort therapy response of glucocorticoid-refractory acute gvhd of the lower intestinal tract
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9532244/
https://www.ncbi.nlm.nih.gov/pubmed/35768570
http://dx.doi.org/10.1038/s41409-022-01741-3
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