CD48 AS A NOVEL EARLY BIOMARKER COMPLEMENTING PROCALCITONIN AND LACTATE FOR PREDICTING BACTEREMIA IN PEDIATRIC FEBRILE NEUTROPENIA: A PROSPECTIVE COHORT STUDY

CD48 A NOVEL EARLY BIOMARKER PREDICTING BACTERIEMIA

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 nine 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 area under the curve (AUC), sensitivity, and specificity. A multivariable logistic regression model evaluated combined biomarker performance.

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 at 0–24 h (AUC 0.78), outperforming CD64 (AUC 0.60) and preceding CRP rise. 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: PCT and CD48 serve as reliable early biomarkers of bacteremia in pediatric FN, with lactate adding metabolic context. Integration of CD48 with PCT and lactate markedly improves diagnostic accuracy, supporting inclusion in future FN risk algorithms to enhance early diagnosis and promote safer antibiotic stewardship.