Diagnostic performance of serum galactomannan and bronchoalveolar lavage Aspergillus PCR in febrile neutropenic haemato-oncology patients: a single-centre evaluation

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Abstract

Introduction Invasive fungal infections (IFI) are an important cause of morbidity and mortality in haemato-oncology (haem-onc) patients with neutropenia, requiring rapid and accurate diagnosis. Gap Statement With widespread use of mould-active prophylaxis, the diagnostic value of serum Aspergillus galactomannan (AGM) is uncertain; real-world data to guide cost-effective diagnostic strategies are limited. Aim To assess the diagnostic performance, clinical utility and cost-effectiveness of serum AGM compared with bronchoalveolar lavage fluid (BALF) Aspergillus PCR in neutropenic haem-onc patients. Methodology A single-centre evaluation at a large teaching hospital in the United Kingdom, including: (1) analysis of AGM testing performed in 2024; (2) clinical audit of neutropenic fever management in adult haem-onc patients; (3) laboratory verification of a commercial Aspergillus PCR assay; and (4) cost-benefit analysis of IFI diagnostic pathways. Results Among 1,187 AGM tests (860 serum; 327 BALF) performed in 2024, overall positivity was 3.1%. Serum AGM positivity was 1.0% overall and <0.5% in haem-onc patients, despite over 400 tests from haematology patients. Negative serum AGM rarely influenced management, and positive results did not alter treatment decisions, which were driven mainly by imaging and clinical assessment. BALF AGM showed higher positivity (around 8%). Aspergillus PCR demonstrated high sensitivity and specificity in cultured isolates and clinical BALF samples. A 20% reduction in total serum AGM testing, which is negative in >99% cases, would offset the cost of introducing Aspergillus PCR for all BALF samples. Conclusion Serum AGM has limited clinical value in prophylaxed neutropenic haem-onc patients, while CT imaging is essential. Incorporating BALF Aspergillus PCR while reducing serum AGM testing in neutropenic haem-onc patients could improve diagnostic pathways and deliver cost savings.

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