Comparison of the Diagnostic Power Between Cytokine Pattern and Procalcitonin for Predicting Infection in Pediatric Hematology/Oncology Patients

Objectives:Neutropenic fever is very common in chilidren with chemotherapy. Due to the fact that an infection is usually suggested, broad antibiotic therapy is usually administered. However, early diagnosis of the infection is usually difficult and the antibiotic therapy may not be alway appropriate. Furthermore, blood culture is usually negative for those heavily treated patients by antibiotics. So a sensitive biomarker for early recognition of inction is desired. Previous studies have shown that procalcitonin (PCT) is a good marker for predicting infection. However, in our experience, the sensitivity of infection recognition by PCT is low. Our previous studies have shown that cytokine profiles presented very high sensitivity and sepecificity for predicting infection in hematology-oncology children at the time of neutropenic fever. However, the diagnositic power between cytokine profiles and PCT in those patients has not been systemically compared. The aim of this study was to evaluate the diagnostic power of the cytokine pattern and serum PCT level for predicting infection in pediatric hematology/oncology patients.

Methods:In this retrospective study, a total of 3023 samples (2819 febrile episodes and 204 control samples) derived from 992 (including 164 afebrile patients as control) hospitalized hematology-oncology children. Th1/Th2 cytokines including Interleukin (IL)-2, Il-4, IL-6, IL-10, Tumor necrosis factor (TNF) α and interferon (IFN) γ were measured by a FACScalibur flow cytometer using cytometric bead array (CBA) techniques. According to the etiology, imaging and clinical symptoms, 2819 febrile episodes were divided into 5 groups including blood culture positive sepsis, clinical diagnosed sepsis, non-sepsis infection, viral infection and systemic fungal infection.

Results:IL-6 and IL-10 levels as well as positive rates in bacterial infection group were significantly higher than those in viral infection group and control group. In positive blood culture sepsis group, 92.8% (297/320) and 82.2% (263/320) patients had increased IL-6 and IL-10 levels that exceeded the upper limit of the normal range. However, the positive rates of PCT and C-reactive protein (CRP) in bacterial infection group were only 33.8% (108/320) and 73.1%(234/320), respectively, which were significantly lower than those of IL-6 and IL-10 (P<0.01). Based on the receiver operating characteristic (ROC) curves, PCT presented a poorer sensitivity in the diagnosis of severe infection, as compared with IL-6 and IL-10 (p<0.01). As for specificity, IL-6 and IL-10 was also significantly higher than PCT in the diagnosis of Gram-negative bacterial infection.

Conclusion:The specific cytokine pattern of highly elevated IL-6 and IL-10 shows higher diagnostic accuracy than PCT for bacterial and severe infection among febrile hematology-oncology children.