title: Systematic review and meta-analysis of the value of initial biomarkers in predicting adverse outcome in febrile neutropenic episodes in children and young people with cancer.
abstract: BACKGROUND
  Febrile neutropenia is a frequently occurring and occasionally life-threatening complication of treatment for childhood cancer. Many biomarkers have been proposed as predictors of adverse events. We aimed to undertake a systematic review and meta-analysis to summarize evidence on the discriminatory ability of initial serum biomarkers of febrile neutropenic episodes in children and young people.
  
  
  METHODS
  This review was conducted in accordance with the Center for Reviews and Dissemination Methods, using three random effects models to undertake meta-analysis. It was registered with the HTA Registry of systematic reviews, CRD32009100485.
  
  
  RESULTS
  We found that 25 studies exploring 14 different biomarkers were assessed in 3,585 episodes of febrile neutropenia. C-reactive protein (CRP), pro-calcitonin (PCT), and interleukin-6 (IL6) were subject to quantitative meta-analysis, and revealed huge inconsistencies and heterogeneity in the studies included in this review. Only CRP has been evaluated in assessing its value over the predictive value of simple clinical decision rules.
  
  
  CONCLUSIONS
  The limited data available describing the predictive value of biomarkers in the setting of pediatric febrile neutropenia mean firm conclusions cannot yet be reached, although the use of IL6, IL8 and procalcitonin warrant further study.
authors.affiliation: Center for Reviews and Dissemination, University of York, York, UK. bob.phillips@york.ac.uk
authors.forename: Robert S
authors.initials: RS
authors.lastname: Phillips
authors.forename: Ros
authors.initials: R
authors.lastname: Wade
authors.forename: Thomas
authors.initials: T
authors.lastname: Lehrnbecher
authors.forename: Lesley A
authors.initials: LA
authors.lastname: Stewart
authors.forename: Alex J
authors.initials: AJ
authors.lastname: Sutton
mesh_terms: D000293:Adolescent; D014408:Biomarkers, Tumor / Q000097:blood*; D002097:C-Reactive Protein / Q000378:metabolism; D002648:Child; D005334:Fever / Q000097:blood* / Q000150:complications*; D006801:Humans; D009369:Neoplasms / Q000097:blood* / Q000150:complications* / Q000175:diagnosis; D009503:Neutropenia / Q000097:blood* / Q000150:complications*; D012372:ROC Curve; D016896:Treatment Outcome
chemical_list: D014408:Biomarkers, Tumor; D002097:C-Reactive Protein