Updated systematic review and meta-analysis of the predictive value of serum biomarkers in the assessment and management of fever during neutropenia in children with cancer.

Tasnim Arif,Robert S Phillips

doi:10.1002/pbc.27887

Abstract

Routinely measurable biomarkers as predictors for adverse outcomes in febrile neutropenia could improve management through risk stratification. This systematic review assesses the predictive role of biomarkers in identifying events such as bacteraemia, clinically documented infections, microbiologically documented infection, severe sepsis requiring intensive care or high dependency care and death. This review collates 8319 episodes from 4843 patients. C-reactive protein (CRP), interleukin (IL)-6, IL-8 and procalcitonin (PCT) consistently predict bacteraemia and severe sepsis; other outcomes have highly heterogeneous results. Performance of the biomarkers at admission using different thresholds demonstrates that PCT>0.5ng/mL offers the best compromise between sensitivity and specificity: sensitivity 0.67 (confidence interval [CI] 0.53-0.79) specificity 0.73 (CI 0.66-0.77). Seventeen studies describe the use of serial biomarkers, with PCT having the greatest discriminatory role. Biomarkers, potentially with serial measurements, may predict adverse outcomes in paediatric febrile neutropenia and their role in risk stratification is promising.

Highlights

Neutropenic sepsis, or febrile neutropenia (FN), remains a serious complication of childhood cancer therapy with an incidence of bacteraemia in 11-24% cases, paediatric intensive care unit (PICU) admissions in 0.9-11% cases, and fatality in 0.2-3% cases.1–8 For this reason, children receiving anticancer treatment are frequently required to present to hospital if they have a fever
Two further studies were excluded before quantitative synthesis because there were insufficient studies looking at similar outcomes using interleukin (IL)-1024 or insufficient numbers examining adrenomedullin
Hematopoietic stem cell transplant (HSCT) patients were not represented in this population

Summary

Introduction

Neutropenic sepsis, or febrile neutropenia (FN), remains a serious complication of childhood cancer therapy with an incidence of bacteraemia in 11-24% cases, paediatric intensive care unit (PICU) admissions in 0.9-11% cases, and fatality in 0.2-3% cases. For this reason, children receiving anticancer treatment are frequently required to present to hospital if they have a fever. Neutropenic sepsis, or febrile neutropenia (FN), remains a serious complication of childhood cancer therapy with an incidence of bacteraemia in 11-24% cases, paediatric intensive care unit (PICU) admissions in 0.9-11% cases, and fatality in 0.2-3% cases.. Neutropenic sepsis, or febrile neutropenia (FN), remains a serious complication of childhood cancer therapy with an incidence of bacteraemia in 11-24% cases, paediatric intensive care unit (PICU) admissions in 0.9-11% cases, and fatality in 0.2-3% cases.1–8 For this reason, children receiving anticancer treatment are frequently required to present to hospital if they have a fever. There are at least 25 different paediatric clinical decision rules for the assessment of FN These require local calibration before implementation, and lack of discriminatory value in the adolescents and young adult (AYA) group suggests this group may need its own risk prediction model..

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