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.

Abstract

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:

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:

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:

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.

• Authors: Brian T Fisher, Ted Westling, Craig L K Boge, Theoklis E Zaoutis, Christopher C Dvorak, Michael Nieder, Danielle M Zerr, John R Wingard, Doojduen Villaluna, Adam J Esbenshade, Sarah Alexander, Suphansa Gunn, Lawrence J Wheat, Lillian Sung
• Journal: Journal of the Pediatric Infectious Diseases Society (J Pediatric Infect Dis Soc) Vol. 10 Issue 8 Pg. 864-871 (Sep 23 2021) ISSN: 2048-7207 [Electronic] England
• PMID: 34173659 (Publication Type: Journal Article, Randomized Controlled Trial)
• 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: [email protected].

Chemical References

• Glucans
• Mannans
• beta-Glucans
• galactomannan
• Galactose

Topics

• Adolescent
• Child
• Galactose (analogs & derivatives)
• Glucans
• Humans
• Invasive Fungal Infections (diagnosis, drug therapy, prevention & control)
• Leukemia, Myeloid, Acute (complications, drug therapy)
• Mannans
• Sensitivity and Specificity
• Young Adult
• beta-Glucans