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Elafin as a Predictive Biomarker of Acute Skin Graft-Versus-Host Disease After Haploidentical Stem Cell Transplantation Using Post-Transplant High-Dose Cyclophosphamide
Haploidentical hematopoietic stem cell transplantation (haplo-HSCT) has shown favorable results in the treatment of hematological malignancies. Despite the use of post-transplant cyclophosphamide (PTCy), graft versus host disease (GVHD) remains as one of the main complications in this setting. Since...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7933467/ https://www.ncbi.nlm.nih.gov/pubmed/33679728 http://dx.doi.org/10.3389/fimmu.2021.516078 |
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author | Solán, Laura Carbonell, Diego Muñiz, Paula Dorado, Nieves Landete, Elena Chicano-Lavilla, María Anguita, Javier Gayoso, Jorge Kwon, Mi Díez-Martín, José Luis Martínez-Laperche, Carolina Buño, Ismael |
author_facet | Solán, Laura Carbonell, Diego Muñiz, Paula Dorado, Nieves Landete, Elena Chicano-Lavilla, María Anguita, Javier Gayoso, Jorge Kwon, Mi Díez-Martín, José Luis Martínez-Laperche, Carolina Buño, Ismael |
author_sort | Solán, Laura |
collection | PubMed |
description | Haploidentical hematopoietic stem cell transplantation (haplo-HSCT) has shown favorable results in the treatment of hematological malignancies. Despite the use of post-transplant cyclophosphamide (PTCy), graft versus host disease (GVHD) remains as one of the main complications in this setting. Since the skin appears affected in up to 80% of cases of acute GVHD (aGVHD), its prognosis and diagnosis are essential for the correct management of these patients. Plasma concentration of elafin, an elastase inhibitor produced by keratinocytes, has been described elevated at the diagnosis of skin GVHD, correlated with the grade of GVHD, and associated with an increased risk of death. In this study we explored elafin plasma levels in the largest series reported of T cell–replete haplo-HSCT with PTCy. Plasma samples drawn from 87 patients at days +15 and +30 were analyzed (“discovery cohort”). Elafin levels at days +15 were no associated with chronic GVHD, non-relapse mortality, relapse, therapy-resistant GVHD, or overall survival. In our series, elafin levels at day +30 were not associated with post-transplant complications. On the other hand, elafin plasma levels at day +15 were higher in patients with severe skin aGVHD (21,313 vs.14,974 pg/ml; p = 0.01). Of note, patients with higher elafin plasma levels at day +15 presented a higher incidence of stage III-IV skin aGVHD (HR = 18.9; p < 0.001). These results were confirmed (HR = 20.6; p < 0.001) in an independent group of patients (n = 62), i.e. the “validation cohort.” These data suggest that measurement of elafin in patients undergoing haplo-HSCT with PTCy might be useful for an early identification of those patients who are at higher risk of suffering severe skin aGVHD and thus, improve their treatment and prognosis. |
format | Online Article Text |
id | pubmed-7933467 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-79334672021-03-06 Elafin as a Predictive Biomarker of Acute Skin Graft-Versus-Host Disease After Haploidentical Stem Cell Transplantation Using Post-Transplant High-Dose Cyclophosphamide Solán, Laura Carbonell, Diego Muñiz, Paula Dorado, Nieves Landete, Elena Chicano-Lavilla, María Anguita, Javier Gayoso, Jorge Kwon, Mi Díez-Martín, José Luis Martínez-Laperche, Carolina Buño, Ismael Front Immunol Immunology Haploidentical hematopoietic stem cell transplantation (haplo-HSCT) has shown favorable results in the treatment of hematological malignancies. Despite the use of post-transplant cyclophosphamide (PTCy), graft versus host disease (GVHD) remains as one of the main complications in this setting. Since the skin appears affected in up to 80% of cases of acute GVHD (aGVHD), its prognosis and diagnosis are essential for the correct management of these patients. Plasma concentration of elafin, an elastase inhibitor produced by keratinocytes, has been described elevated at the diagnosis of skin GVHD, correlated with the grade of GVHD, and associated with an increased risk of death. In this study we explored elafin plasma levels in the largest series reported of T cell–replete haplo-HSCT with PTCy. Plasma samples drawn from 87 patients at days +15 and +30 were analyzed (“discovery cohort”). Elafin levels at days +15 were no associated with chronic GVHD, non-relapse mortality, relapse, therapy-resistant GVHD, or overall survival. In our series, elafin levels at day +30 were not associated with post-transplant complications. On the other hand, elafin plasma levels at day +15 were higher in patients with severe skin aGVHD (21,313 vs.14,974 pg/ml; p = 0.01). Of note, patients with higher elafin plasma levels at day +15 presented a higher incidence of stage III-IV skin aGVHD (HR = 18.9; p < 0.001). These results were confirmed (HR = 20.6; p < 0.001) in an independent group of patients (n = 62), i.e. the “validation cohort.” These data suggest that measurement of elafin in patients undergoing haplo-HSCT with PTCy might be useful for an early identification of those patients who are at higher risk of suffering severe skin aGVHD and thus, improve their treatment and prognosis. Frontiers Media S.A. 2021-02-19 /pmc/articles/PMC7933467/ /pubmed/33679728 http://dx.doi.org/10.3389/fimmu.2021.516078 Text en Copyright © 2021 Solán, Carbonell, Muñiz, Dorado, Landete, Chicano-Lavilla, Anguita, Gayoso, Kwon, Díez-Martín, Martínez-Laperche and Buño http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Immunology Solán, Laura Carbonell, Diego Muñiz, Paula Dorado, Nieves Landete, Elena Chicano-Lavilla, María Anguita, Javier Gayoso, Jorge Kwon, Mi Díez-Martín, José Luis Martínez-Laperche, Carolina Buño, Ismael Elafin as a Predictive Biomarker of Acute Skin Graft-Versus-Host Disease After Haploidentical Stem Cell Transplantation Using Post-Transplant High-Dose Cyclophosphamide |
title | Elafin as a Predictive Biomarker of Acute Skin Graft-Versus-Host Disease After Haploidentical Stem Cell Transplantation Using Post-Transplant High-Dose Cyclophosphamide |
title_full | Elafin as a Predictive Biomarker of Acute Skin Graft-Versus-Host Disease After Haploidentical Stem Cell Transplantation Using Post-Transplant High-Dose Cyclophosphamide |
title_fullStr | Elafin as a Predictive Biomarker of Acute Skin Graft-Versus-Host Disease After Haploidentical Stem Cell Transplantation Using Post-Transplant High-Dose Cyclophosphamide |
title_full_unstemmed | Elafin as a Predictive Biomarker of Acute Skin Graft-Versus-Host Disease After Haploidentical Stem Cell Transplantation Using Post-Transplant High-Dose Cyclophosphamide |
title_short | Elafin as a Predictive Biomarker of Acute Skin Graft-Versus-Host Disease After Haploidentical Stem Cell Transplantation Using Post-Transplant High-Dose Cyclophosphamide |
title_sort | elafin as a predictive biomarker of acute skin graft-versus-host disease after haploidentical stem cell transplantation using post-transplant high-dose cyclophosphamide |
topic | Immunology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7933467/ https://www.ncbi.nlm.nih.gov/pubmed/33679728 http://dx.doi.org/10.3389/fimmu.2021.516078 |
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