Utility and Pitfalls of β-D-Glucan for Diagnosis and Response Monitoring of Chronic Disseminated Candidiasis in Paediatric Cancer Patients.

Abstract

Background: β-D-Glucan (BDG) is a useful but nonspecific biomarker in patients with suspected invasive fungal diseases including Pneumocystis pneumonia. Little is known, however, about its utility for response monitoring in chronic disseminated candidiasis (CDC).

Patients and methods: We describe the utility and pitfalls of serum BDG in paediatric cancer patients with suspected CDC. BDG in serum was measured serially (i.e., 5 to 10 times of a time period of 200 to 400 days) by a commercially available assay (Fungitell; Associates of Cape Cod, MA, USA) and values were correlated to patient- and disease-related variables.

Results: Five paediatric patients (4f/1 m; 4-18 years) with acute lymphoblastic leukaemia (n = 4) and Ewing sarcoma (n = 1) followed between 2013 and 2024 were included. CDC was located in the spleen (n = 5), liver (n = 4), lungs (n = 3), CNS (n = 2), kidney (n = 1), and skin (n = 1); and diagnosed based on imaging, a positive blood culture (n = 1), a positive BDG assay in serum (n = 5), and absence of other etiologies. Patients received IV liposomal amphotericin B and/or caspofungin, followed by fluconazole orally for 184 to > 365 days, respectively. BDG concentrations in serum (35 time points) stayed elevated for prolonged periods of time, were independent of clinical symptoms, and returned to normal with resolution of imaging findings in the four leukaemia patients. In the patient with Ewing sarcoma, liver biopsy performed 5 months after diagnosis due to lack of improvement revealed disseminated aspergillosis.

Conclusions: BDG in serum is useful for microbiological diagnosis and monitoring of probable CDC; however, it remains a non-specific fungal biomarker whose results need to be scrutinised in patients who do not respond to treatment as expected.