Prospective Evaluation of Galactomannan and (1→3) β-d-Glucan Assays as Diagnostic Tools for Invasive Fungal Disease in Children, Adolescents, and Young Adults With Acute Myeloid Leukemia Receiving Fungal Prophylaxis.
acute myeloid leukemia
fungal biomarkers
fungal disease
pediatrics
surveillance
Journal
Journal of the Pediatric Infectious Diseases Society
ISSN: 2048-7207
Titre abrégé: J Pediatric Infect Dis Soc
Pays: England
ID NLM: 101586049
Informations de publication
Date de publication:
23 Sep 2021
23 Sep 2021
Historique:
received:
18
09
2020
accepted:
30
04
2021
pubmed:
27
6
2021
medline:
25
9
2021
entrez:
26
6
2021
Statut:
ppublish
Résumé
Patients receiving chemotherapy for acute myeloid leukemia (AML) are at high risk for invasive fungal disease (IFD). Diagnosis of IFD is challenging, leading to interest in fungal biomarkers. The objective was to define the utility of surveillance testing with Platelia Aspergillus galactomannan (GM) enzyme immunoassay (EIA) and Fungitell β-d-glucan (BDG) assay in children with AML receiving antifungal prophylaxis. Twice-weekly surveillance blood testing with GM EIA and BDG assay was performed during periods of neutropenia in the context of a randomized trial of children, adolescents, and young adults with AML allocated to fluconazole or caspofungin prophylaxis. Proven or probable IFD was adjudicated using blinded central reviewers. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated for Platelia and Fungitell assays alone and in combination for the outcomes of proven and probable invasive aspergillosis (IA) or invasive candidiasis (IC). Among 471 patients enrolled, 425 participants (209 fluconazole and 216 caspofungin) contributed ≥1 blood specimen. In total, 6103 specimens were evaluated, with a median of 15 specimens per patient (range 1-43). The NPV was >99% for GM EIA and BDG assay alone and in combination. However, there were no true positive results, resulting in sensitivity and PPV for each assay of 0%. The GM EIA and the BDG assay alone or in combination were not successful at detecting IA or IC during periods of neutropenia in children, adolescents, and young adults with AML receiving antifungal prophylaxis. Utilization of these assays for surveillance in this clinical setting should be discouraged.
Sections du résumé
BACKGROUND
BACKGROUND
Patients receiving chemotherapy for acute myeloid leukemia (AML) are at high risk for invasive fungal disease (IFD). Diagnosis of IFD is challenging, leading to interest in fungal biomarkers. The objective was to define the utility of surveillance testing with Platelia Aspergillus galactomannan (GM) enzyme immunoassay (EIA) and Fungitell β-d-glucan (BDG) assay in children with AML receiving antifungal prophylaxis.
METHODS
METHODS
Twice-weekly surveillance blood testing with GM EIA and BDG assay was performed during periods of neutropenia in the context of a randomized trial of children, adolescents, and young adults with AML allocated to fluconazole or caspofungin prophylaxis. Proven or probable IFD was adjudicated using blinded central reviewers. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated for Platelia and Fungitell assays alone and in combination for the outcomes of proven and probable invasive aspergillosis (IA) or invasive candidiasis (IC).
RESULTS
RESULTS
Among 471 patients enrolled, 425 participants (209 fluconazole and 216 caspofungin) contributed ≥1 blood specimen. In total, 6103 specimens were evaluated, with a median of 15 specimens per patient (range 1-43). The NPV was >99% for GM EIA and BDG assay alone and in combination. However, there were no true positive results, resulting in sensitivity and PPV for each assay of 0%.
CONCLUSIONS
CONCLUSIONS
The GM EIA and the BDG assay alone or in combination were not successful at detecting IA or IC during periods of neutropenia in children, adolescents, and young adults with AML receiving antifungal prophylaxis. Utilization of these assays for surveillance in this clinical setting should be discouraged.
Identifiants
pubmed: 34173659
pii: 6309958
doi: 10.1093/jpids/piab036
pmc: PMC8527733
doi:
Substances chimiques
Glucans
0
Mannans
0
beta-Glucans
0
galactomannan
11078-30-1
Galactose
X2RN3Q8DNE
Types de publication
Journal Article
Randomized Controlled Trial
Langues
eng
Sous-ensembles de citation
IM
Pagination
864-871Subventions
Organisme : Children's Oncology Group
ID : U10CA 180886
Organisme : NCI NIH HHS
ID : U10 CA180899
Pays : United States
Organisme : CCR NIH HHS
ID : HHSN261200800001C
Pays : United States
Organisme : NCI NIH HHS
ID : U10 CA180886
Pays : United States
Organisme : NCI NIH HHS
ID : HHSN261200800001E
Pays : United States
Organisme : NCI NIH HHS
ID : UG1 CA189955
Pays : United States
Organisme : Children's Oncology Group
ID : U10CA 180886
Informations de copyright
© The Author(s) 2021. Published by Oxford University Press on behalf of The Journal of the Pediatric Infectious Diseases Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.
Références
Clin Infect Dis. 2005 Jun 15;40(12):1762-9
pubmed: 15909264
Clin Infect Dis. 2004 Jul 15;39(2):199-205
pubmed: 15307029
Clin Infect Dis. 2008 Aug 15;47(4):503-9
pubmed: 18611163
Pediatr Infect Dis J. 2013 Dec;32(12):e451-5
pubmed: 23907262
Mycoses. 1999;42(5-6):403-8
pubmed: 10536432
Blood. 2001 Mar 15;97(6):1604-10
pubmed: 11238098
JAMA. 2019 Nov 5;322(17):1673-1681
pubmed: 31688884
Clin Infect Dis. 2014 Dec 15;59(12):1696-702
pubmed: 25165088
J Clin Oncol. 2017 Jun 20;35(18):2082-2094
pubmed: 28459614
Clin Infect Dis. 2008 Jun 15;46(12):1813-21
pubmed: 18462102
Clin Infect Dis. 2016 Nov 15;63(10):1340-1348
pubmed: 27567122
J Clin Oncol. 2015 Feb 10;33(5):501-9
pubmed: 25559816
Eur J Clin Microbiol Infect Dis. 2008 Apr;27(4):245-51
pubmed: 18193305
J Clin Microbiol. 2014 Jun;52(6):2108-11
pubmed: 24719449
Clin Infect Dis. 2005 Nov 1;41(9):1232-9
pubmed: 16206095
Clin Vaccine Immunol. 2007 Jul;14(7):924-5
pubmed: 17538119
Med Mycol. 2009;47 Suppl 1:S233-40
pubmed: 18720216
Pediatr Blood Cancer. 2014 Mar;61(3):393-400
pubmed: 24424789
Cancer. 2009 Mar 1;115(5):1100-8
pubmed: 19156894
Blood. 2007 Nov 15;110(10):3532-9
pubmed: 17660380
Antimicrob Agents Chemother. 2006 Oct;50(10):3450-3
pubmed: 17005829
Pediatrics. 2006 Apr;117(4):e711-6
pubmed: 16533892