CD48 as a Novel Early Biomarker Complementing Procalcitonin and Lactate for Predicting Bacteremia in Pediatric Febrile Neutropenia: A Prospective Cohort Study.

Background: Febrile neutropenia (FN) remains a frequent and potentially life-threatening complication in pediatric oncology, where prompt recognition of bacteremia is critical for risk-adapted therapy and antimicrobial stewardship. Traditional biomarkers such as C-reactive protein (CRP) and procalcitonin (PCT) are widely used, yet their early predictive value is inconsistent across studies. Cellular activation markers measured by flow cytometry, particularly CD48, have been scarcely investigated in this setting. This study aimed to evaluate conventional, metabolic, and immune biomarkers for predicting bacteremia in children with FN and to assess the incremental diagnostic value of CD48. Methods: This prospective single-center cohort enrolled 38 pediatric oncology patients presenting with 46 FN episodes over 9 months. Clinical data, blood cultures, and serial measurements of CRP, PCT, lactate, interleukin-6, interleukin-8, MCP-1, sTREM-1, CD48, and CD64 were obtained at 0, 24, 48, and 72 hours. Bacteremia was defined by positive culture for a recognized pathogen. Receiver operating characteristic (ROC) analyses were performed to determine the area under the curve (AUC), sensitivity, and specificity. A multivariable logistic regression model evaluated the combined performance of biomarkers. Results: Bacteremia occurred in 12 (26.1%) FN episodes. Sepsis, tachycardia, and elevated lactate were more common among bacteremic patients. CRP showed limited early discrimination (AUC 0.62 on day 2) but improved by day 4 (AUC 0.74). PCT was consistently higher in bacteremia (AUC 0.89 at day 4), and lactate demonstrated strong early predictive value (AUC 0.81). CD48 was significantly elevated from 0-24 h (AUC 0.78), outperforming CD64 (AUC 0.60) and preceding the rise in CRP. In combined modeling, PCT + CD48 + lactate achieved the highest discrimination (AUC 0.92; sensitivity 92%, specificity 85%). Post-hoc power analysis showed 82% power to detect AUC differences ≥0.15. Conclusion: Integration of CD4 with PCT and Lactate markedly improved diagnostic accuracy in this cohort; however, given the limited number of bacteremic episodes, these findings should be considered exploratory and require external validation in larger, multicenter studies before clinical implementation.