title: Biomarkers for risk stratification of febrile neutropenia among children with malignancy: a pilot study.
abstract: BACKGROUND
  Patients receiving myelosuppressive chemotherapy remain at increased risk for developing febrile neutropenia (FN). For this heterogeneous population, a biomarker based risk stratification of FN patients may be a useful clinical tool. We hypothesized that serum biomarkers during initial presentation of an FN event could be predictive of subsequent clinical outcome.
  
  
  METHODS
  Eighty-nine FN events from 36 non-consecutive subjects were analyzed. "High-risk" FN criteria included prolonged hospitalization (≥ 7 days), admission to pediatric intensive care unit (PICU) or a microbiology confirmed bacteremia. Patients with "low risk" FN had none of the above. Biomarkers measured during the first 2 days of FN hospitalization were analyzed and correlated with respective clinical outcome.
  
  
  RESULTS
  Of the 89 FN events, 44 (49%) fulfilled pre-defined high-risk criteria and 45 (51%) were low-risk. Procalcitonin level (>0.11 ng/ml) was found to be associated with the high-risk FN outcome with sensitivity of 97%. With an increase in log scale by 1, the odds of being high-risk FN increased twofold. Hs-CRP >100 mg/L had sensitivity of 88% in predicting high-risk FN. The odds of a high-risk FN event increased by approximately 1.8-fold with an increase in the log scale of hs-CRP by 1 (10-fold). In univariate analysis, IL-6, IL-8, and IL-10 were statistically significant and associated with high-risk FN. However, no statistically significant difference was found for IL-1α, sIL-2Ra, IL-3, or TNF-α.
  
  
  CONCLUSIONS
  Biomarkers with appropriate critical threshold values may be a useful clinical tool for appropriate risk stratification of children with FN.
authors.affiliation: Department of Pediatric Hematology-Oncology, College of Medicine, University of Arkansas Medical Sciences, Arkansas Children's Hospital, Little Rock, Arkansas 72205, USA. mianamir@uams.edu
authors.forename: Amir
authors.initials: A
authors.lastname: Mian
authors.forename: David
authors.initials: D
authors.lastname: Becton
authors.forename: Robert
authors.initials: R
authors.lastname: Saylors
authors.forename: Laura
authors.initials: L
authors.lastname: James
authors.forename: Xinyu
authors.initials: X
authors.lastname: Tang
authors.forename: Adnan
authors.initials: A
authors.lastname: Bhutta
authors.forename: Parthak
authors.initials: P
authors.lastname: Prodhan
mesh_terms: D000293:Adolescent; D000328:Adult; D015415:Biomarkers / Q000032:analysis*; D002116:Calcitonin / Q000097:blood; D015740:Calcitonin Gene-Related Peptide; D002648:Child; D002675:Child, Preschool; D005260:Female; D006760:Hospitalization; D006801:Humans; D007223:Infant; D007362:Intensive Care Units; D016753:Interleukin-10 / Q000097:blood; D007377:Interleukin-3 / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D016209:Interleukin-8 / Q000097:blood; D008297:Male; D009369:Neoplasms / Q000150:complications* / Q000188:drug therapy; D009503:Neutropenia / Q000188:drug therapy / Q000209:etiology*; D010865:Pilot Projects; D011379:Prognosis; D011446:Prospective Studies; D011498:Protein Precursors / Q000097:blood; D012372:ROC Curve; D012307:Risk Factors; D014409:Tumor Necrosis Factor-alpha / Q000097:blood; D055815:Young Adult
chemical_list: D015415:Biomarkers; C000606589:CALCA protein, human; D007377:Interleukin-3; D015850:Interleukin-6; D016209:Interleukin-8; D011498:Protein Precursors; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D002116:Calcitonin; D015740:Calcitonin Gene-Related Peptide