Predictive value of cytokines and procalcitonin on infection in children with hematological malignancies

Abstract

Objective: To explore the value of cytokines and procalcitonin (PCT) in predicting the potential pathogen and the severity of infection in children with hematological malignancies. Methods: This was a prospective cohort study. A total of 1 543 children (3 912 episodes) with hematological malignancies admitted to the Department of Hematology/Oncology in Children's Hospital of Zhejiang University School of Medicine from November 2010 to June 2018 were prospectively enrolled in this study. According to the pathogen, the patients were divided into sepsis group with positive blood culture (380 patients/608 episodes), sepsis group with negative blood culture (539/1 484), non-septic infection group (549/1 709), viral infection group (18/21) and fungal infection group (57/90). The patients were also divided into two groups in either shock group (171/187) or non-shock group (1 372/3 725). Meanwhile, 89 children (112 episodes) with matched hematological malignancies without fever were enrolled as the control group. The levels of PCT and cytokines were measured for detecting the potential relationship between these markers and infection severity. Mann-Whitney U test or Kruskal-Wallis H test was used to compare the differences between groups. The Receiver Operator Characteristic curve analysis was used to explore the predictive value. Results: (1) There were significantly higher levels of interleukin (IL) 6 (H=210.002, P<0.01), IL-10 (H=223.045, P<0.01), and PCT (H=76.799, P<0.01) in the infection group, with area under curre (AUC) of 0.67 (95%CI 0.64-0.69), 0.69 (95%CI 0.66-0.71) and 0.59 (95%CI 0.56-0.61), respectively. (2) Among the patients in the shock group, IL-6 (Z=11.460, P<0.01), IL-10 (Z=14.242, P<0.01) and PCT (Z=10.813, P<0.01) were significantly higher than those in the non-shock group, with the AUC of 0.75 (95%CI 0.70-0.79), 0.81 (95%CI 0.77-0.84) and 0.73 (95%CI 0.69-0.77), respectively. (3) In patients with septic shock, the incidence of Gram negative bacteria (GNB) infection (60 episodes) was significantly higher than Gram positive bacteria (GPB) infection (22 episodes) (χ(2)=29.665, P<0.01). The AUC of IL-6, IL-10 and PCT for predicting GNB infection were 0.75 (95%CI 0.72-0.78), 0.82 (95%CI 0.79-0.85) and 0.67 (95%CI 0.63-0.70), respectively. (4) The predictive power of IL-6, IL-10 and PCT combination (AUC=0.994) was superior to IL-10 alone (AUC=0.810) in predicting septic shock (Z=10.211, P<0.01). Conclusions: IL-6 and IL-10 are better predictors of GNB infection than PCT in hematology-oncology children. Furthermore, the combination of these two cytokines and PCT is more valuable in predicting the severity of infection.