Diagnostic performance of serum galactomannan for detecting breakthrough invasive fungal infections in pediatric hematologic malignancies receiving mold-active prophylaxis.

BACKGROUND

This study aimed to evaluate the diagnostic performance of serum galactomannan for invasive fungal infections in children with hematologic malignancies and to assess the impact of mold-active antifungal prophylaxis on test sensitivity and specificity.

METHODS

We retrospectively evaluated 280 pediatric patients with acute leukemia or mixed-phenotypic leukemia treated between February 2019 and December 2023 at a tertiary referral center. Demographic characteristics, antifungal prophylaxis, serum and BAL GM levels, clinical and radiologic findings, and outcomes were recorded. IFIs were classified according to the 2020 EORTC/MSGERC criteria. Diagnostic performance metrics (sensitivity, specificity, PPV, NPV, LR⁺, LR⁻) were calculated, and multivariate logistic regression was used to identify independent predictors of IFI.

RESULTS

Among 280 pediatric patients with hematologic malignancies, 89 (31.8%) met IFI criteria, including 73 possible, 10 probable, and 6 proven cases. In the primary analysis restricted to proven/probable IFI, 16 patients (5.7%) were classified as having IFI and 264 (94.3%) as not having IFI. Baseline demographic and clinical characteristics were comparable between groups. Serum GM positivity was significantly associated with proven/probable IFI (62.5% vs. 2.3%, p < 0.001) and remained the only independent predictor in multivariable analysis (OR 73.040, 95% CI 11.979-445.344; p < 0.001). Serum GM showed moderate sensitivity (66.7%) and high specificity (97.3%), with PPV and NPV of 62.5% and 97.7%, respectively. GM positivity remained significant irrespective of antifungal prophylaxis, while mold-active prophylaxis did not significantly affect GM positivity or IFI rates.

CONCLUSIONS

Serum galactomannan was a highly specific but moderately sensitive marker for proven/probable IFI in pediatric patients with hematologic malignancies. While a positive result supported the diagnosis, a negative result was insufficient to exclude IFI. GM should therefore be interpreted together with clinical, radiologic, and other mycological findings rather than used alone.