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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...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
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.
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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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