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Diagnostic Performance of (1→3)-β-D-Glucan Alone and in Combination with Aspergillus PCR and Galactomannan in Serum of Pediatric Patients after Allogeneic Hematopoietic Stem Cell Transplantation

Data on biomarker-assisted diagnosis of invasive aspergillosis (IA) in pediatric patients is scarce. Therefore, we conducted a cohort study over two years including 404 serum specimens of 26 pediatric patients after allogeneic hematopoietic stem cell transplantation (alloSCT). Sera were tested prosp...

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Autores principales: Springer, Jan, Held, Jürgen, Mengoli, Carlo, Schlegel, Paul Gerhardt, Gamon, Florian, Träger, Johannes, Kurzai, Oliver, Einsele, Hermann, Loeffler, Juergen, Eyrich, Matthias
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8004996/
https://www.ncbi.nlm.nih.gov/pubmed/33810069
http://dx.doi.org/10.3390/jof7030238
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author Springer, Jan
Held, Jürgen
Mengoli, Carlo
Schlegel, Paul Gerhardt
Gamon, Florian
Träger, Johannes
Kurzai, Oliver
Einsele, Hermann
Loeffler, Juergen
Eyrich, Matthias
author_facet Springer, Jan
Held, Jürgen
Mengoli, Carlo
Schlegel, Paul Gerhardt
Gamon, Florian
Träger, Johannes
Kurzai, Oliver
Einsele, Hermann
Loeffler, Juergen
Eyrich, Matthias
author_sort Springer, Jan
collection PubMed
description Data on biomarker-assisted diagnosis of invasive aspergillosis (IA) in pediatric patients is scarce. Therefore, we conducted a cohort study over two years including 404 serum specimens of 26 pediatric patients after allogeneic hematopoietic stem cell transplantation (alloSCT). Sera were tested prospectively twice weekly for Aspergillus-specific DNA, galactomannan (GM), and retrospectively for (1→3)-β-D-glucan (BDG). Three probable IA and two possible invasive fungal disease (IFD) cases were identified using the European Organization for Research and Treatment of Cancer and the Mycoses Study Group (EORTC/MSGERC) 2019 consensus definitions. Sensitivity and specificity for diagnosis of probable IA and possible IFD was 80% (95% confidential interval (CI): 28–99%) and 55% (95% CI: 32–77%) for BDG, 40% (95% CI: 5–85%) and 100% (95% CI: 83–100%) for GM, and 60% (95% CI: 15–95%) and 95% (95% CI: 75–100%) for Aspergillus-specific real-time PCR. However, sensitivities have to be interpreted with great caution due to the limited number of IA cases. Interestingly, the low specificity of BDG was largely caused by false-positive BDG results that clustered around the date of alloSCT. The following strategies were able to increase BDG specificity: two consecutive positive BDG tests for diagnosis (specificity 80% (95% CI: 56–94%)); using an optimized cutoff value of 306 pg/mL (specificity 90% (95% CI: 68–99%)) and testing BDG only after the acute posttransplant phase. In summary, BDG can help to diagnose IA in pediatric alloSCT recipients. However, due to the poor specificity either an increased cutoff value should be utilized or BDG results should be confirmed by an alternative Aspergillus assay.
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spelling pubmed-80049962021-03-29 Diagnostic Performance of (1→3)-β-D-Glucan Alone and in Combination with Aspergillus PCR and Galactomannan in Serum of Pediatric Patients after Allogeneic Hematopoietic Stem Cell Transplantation Springer, Jan Held, Jürgen Mengoli, Carlo Schlegel, Paul Gerhardt Gamon, Florian Träger, Johannes Kurzai, Oliver Einsele, Hermann Loeffler, Juergen Eyrich, Matthias J Fungi (Basel) Article Data on biomarker-assisted diagnosis of invasive aspergillosis (IA) in pediatric patients is scarce. Therefore, we conducted a cohort study over two years including 404 serum specimens of 26 pediatric patients after allogeneic hematopoietic stem cell transplantation (alloSCT). Sera were tested prospectively twice weekly for Aspergillus-specific DNA, galactomannan (GM), and retrospectively for (1→3)-β-D-glucan (BDG). Three probable IA and two possible invasive fungal disease (IFD) cases were identified using the European Organization for Research and Treatment of Cancer and the Mycoses Study Group (EORTC/MSGERC) 2019 consensus definitions. Sensitivity and specificity for diagnosis of probable IA and possible IFD was 80% (95% confidential interval (CI): 28–99%) and 55% (95% CI: 32–77%) for BDG, 40% (95% CI: 5–85%) and 100% (95% CI: 83–100%) for GM, and 60% (95% CI: 15–95%) and 95% (95% CI: 75–100%) for Aspergillus-specific real-time PCR. However, sensitivities have to be interpreted with great caution due to the limited number of IA cases. Interestingly, the low specificity of BDG was largely caused by false-positive BDG results that clustered around the date of alloSCT. The following strategies were able to increase BDG specificity: two consecutive positive BDG tests for diagnosis (specificity 80% (95% CI: 56–94%)); using an optimized cutoff value of 306 pg/mL (specificity 90% (95% CI: 68–99%)) and testing BDG only after the acute posttransplant phase. In summary, BDG can help to diagnose IA in pediatric alloSCT recipients. However, due to the poor specificity either an increased cutoff value should be utilized or BDG results should be confirmed by an alternative Aspergillus assay. MDPI 2021-03-22 /pmc/articles/PMC8004996/ /pubmed/33810069 http://dx.doi.org/10.3390/jof7030238 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) ).
spellingShingle Article
Springer, Jan
Held, Jürgen
Mengoli, Carlo
Schlegel, Paul Gerhardt
Gamon, Florian
Träger, Johannes
Kurzai, Oliver
Einsele, Hermann
Loeffler, Juergen
Eyrich, Matthias
Diagnostic Performance of (1→3)-β-D-Glucan Alone and in Combination with Aspergillus PCR and Galactomannan in Serum of Pediatric Patients after Allogeneic Hematopoietic Stem Cell Transplantation
title Diagnostic Performance of (1→3)-β-D-Glucan Alone and in Combination with Aspergillus PCR and Galactomannan in Serum of Pediatric Patients after Allogeneic Hematopoietic Stem Cell Transplantation
title_full Diagnostic Performance of (1→3)-β-D-Glucan Alone and in Combination with Aspergillus PCR and Galactomannan in Serum of Pediatric Patients after Allogeneic Hematopoietic Stem Cell Transplantation
title_fullStr Diagnostic Performance of (1→3)-β-D-Glucan Alone and in Combination with Aspergillus PCR and Galactomannan in Serum of Pediatric Patients after Allogeneic Hematopoietic Stem Cell Transplantation
title_full_unstemmed Diagnostic Performance of (1→3)-β-D-Glucan Alone and in Combination with Aspergillus PCR and Galactomannan in Serum of Pediatric Patients after Allogeneic Hematopoietic Stem Cell Transplantation
title_short Diagnostic Performance of (1→3)-β-D-Glucan Alone and in Combination with Aspergillus PCR and Galactomannan in Serum of Pediatric Patients after Allogeneic Hematopoietic Stem Cell Transplantation
title_sort diagnostic performance of (1→3)-β-d-glucan alone and in combination with aspergillus pcr and galactomannan in serum of pediatric patients after allogeneic hematopoietic stem cell transplantation
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8004996/
https://www.ncbi.nlm.nih.gov/pubmed/33810069
http://dx.doi.org/10.3390/jof7030238
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