Infection Biomarkers in Children with Chemotherapy-Induced Severe Neutropenia

Febrile neutropenia is a frequent and potentially life-threatening complication in pediatric oncology patients receiving chemotherapy. Due to profound immunosuppression, early diagnosis of infections remains a major clinical challenge. This review evaluates the diagnostic and prognostic utility of infection biomarkers in children with chemotherapy-induced severe neutropenia.

We reviewed clinical studies that assessed the diagnostic performance of inflammatory biomarkers-including C-reactive protein (CRP), procalcitonin (PCT), interleukins (IL-6, IL-8, IL-10), and others-in pediatric febrile neutropenia. The review includes data on sensitivity, specificity, predictive value, and clinical applications.

CRP remains a common but nonspecific marker, often insufficient for early stratification. PCT showed consistently high negative predictive value and early responsiveness to bacterial infections. IL-6 and IL-10 demonstrated strong early diagnostic accuracy in the early phase (AUC > 0.80 in multiple studies) and were particularly useful in predicting septic shock when combined. IL-8, while less specific, may help rule out infection when levels are low. Emerging biomarkers such as presepsin, MR-proADM, and PSP showed promising diagnostic performance. Presepsin achieved near-perfect accuracy in some cohorts (AUC up to 0.996), outperforming CRP and PCT, though its ability to discriminate bacteremia at fever onset varied. MR-proADM demonstrated consistent AUCs above 0.75 and may support early sepsis identification. PSP was associated with significantly elevated levels in sepsis. Additional novel markers-including sTNFR-II, sIL-2R, IP-10, Flt-3L, MCP-1-a, and MBL-showed encouraging diagnostic profiles in individual studies, particularly due to high specificity, but require external validation. G-CSF also emerged as a promising candidate in multimarker models. In contrast, TNF-α and IL-1β displayed limited utility as standalone indicators.

Biomarkers such as PCT, IL-6, Il-8, and IL-10 offer valuable tools for early infection detection and risk stratification in pediatric febrile neutropenia. Emerging markers-including presepsin, MR-proADM, and PSP-further enhance diagnostic precision and may support early identification of sepsis. Multimarker strategies, particularly those incorporating presepsin, IL-10, or MR-proADM, show potential to improve diagnostic performance beyond conventional markers. Further prospective validation is needed to optimize clinical implementation and guide personalized treatment decisions.