Biomarkers for risk stratification of febrile neutropenia among children with malignancy: a pilot study

Pediatr Blood Cancer. 2012 Aug;59(2):238-45. doi: 10.1002/pbc.24158. Epub 2012 Apr 25.


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.

Procedure: 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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Biomarkers / analysis*
  • Calcitonin / blood
  • Calcitonin Gene-Related Peptide
  • Child
  • Child, Preschool
  • Female
  • Hospitalization
  • Humans
  • Infant
  • Intensive Care Units
  • Interleukin-10 / blood
  • Interleukin-3 / blood
  • Interleukin-6 / blood
  • Interleukin-8 / blood
  • Male
  • Neoplasms / complications*
  • Neoplasms / drug therapy
  • Neutropenia / drug therapy
  • Neutropenia / etiology*
  • Pilot Projects
  • Prognosis
  • Prospective Studies
  • Protein Precursors / blood
  • ROC Curve
  • Risk Factors
  • Tumor Necrosis Factor-alpha / blood
  • Young Adult


  • Biomarkers
  • CALCA protein, human
  • Interleukin-3
  • Interleukin-6
  • Interleukin-8
  • Protein Precursors
  • Tumor Necrosis Factor-alpha
  • Interleukin-10
  • Calcitonin
  • Calcitonin Gene-Related Peptide