Prospective cohort study of the predictive value of inflammatory biomarkers over clinical variables in children and young people with cancer presenting with fever and neutropenia

Abstract

Introduction Fever during chemotherapy induced neutropenia is a common and potentially life-threatening complication of the treatment of childhood cancer. Predictions of poor outcome could be enhanced by incorporating serum biomarkers of inflammation at presentation and reassessment. Methods A prospective cohort study was conducted of children under 18 years old, being treated for cancer or a cancer-like condition, who presented with fever (≥ 38.0°C) and neutropenia (neutrophil count < 0.5*109/L). Clinical features were recorded, along with three experimental inflammatory biomarkers: procalcitonin (PCT), interleukin-6 (IL-6) and interleukin-8 (IL-8). Outcomes included serious medical complications (SMC): any infection related mortality, critical care and organ support, severe sepsis, septic shock, significant microbiologically defined infection, or radiologically confirmed pneumonia. Results Biomarker assessments were undertaken in 43 episodes of fever and neutropenia, from 31 patients aged between four months and 17 years old (median six years): 20 were female and 22 had acute leukaemia. Five episodes of SMC were noted. PCT, IL-6 and IL-8 had poor individual discriminatory ability (C-statistic 0.48 to 0.60) and did not add to the value of clinical risk stratification tools. Insufficient data were collected to formally assess the value of repeated assessments. Conclusions Incorporating serum biomarkers of inflammation at presentation of episodes of fever with neutropenia in childhood does not clearly improve risk stratification. The value of serial assessments requires further investigation.