Outcome prediction in pediatric fever in neutropenia: Development of clinical decision rules and external validation of published rules based on data from the prospective multicenter SPOG 2015 FN definition study

PLoS One. 2023 Aug 2;18(8):e0287233. doi: 10.1371/journal.pone.0287233. eCollection 2023.


Background: Fever in neutropenia (FN) remains a serious complication of childhood cancer therapy. Clinical decision rules (CDRs) are recommended to help distinguish between children at high and low risk of severe infection. The aim of this analysis was to develop new CDRs for three different outcomes and to externally validate published CDRs.

Procedure: Children undergoing chemotherapy for cancer were observed in a prospective multicenter study. CDRs predicting low from high risk infection regarding three outcomes (bacteremia, serious medical complications (SMC), safety relevant events (SRE)) were developed from multivariable regression models. Their predictive performance was assessed by internal cross-validation. Published CDRs suitable for validation were identified by literature search. Parameters of predictive performance were compared to assess reproducibility.

Results: In 158 patients recruited between April 2016 and August 2018, 360 FN episodes were recorded, including 56 (16%) with bacteremia, 30 (8%) with SMC and 72 (20%) with SRE. The CDRs for bacteremia and SRE used four characteristics (type of malignancy, severely reduced general condition, leucocyte count <0.3 G/L, bone marrow involvement), the CDR for SMC two characteristics (severely reduced general condition and platelet count <50 G/L). Eleven published CDRs were analyzed. Six CDRs showed reproducibility, but only one in both sensitivity and specificity.

Conclusions: This analysis developed CDRs predicting bacteremia, SMC or SRE at presentation with FN. In addition, it identified six published CDRs that show some reproducibility. Validation of CDRs is fundamental to find the best balance between sensitivity and specificity, and will help to further improve management of FN.

Publication types

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

MeSH terms

  • Bacteremia* / complications
  • Child
  • Clinical Decision Rules
  • Fever / etiology
  • Humans
  • Neoplasms* / complications
  • Neoplasms* / drug therapy
  • Neutropenia* / complications
  • Neutropenia* / diagnosis
  • Prospective Studies
  • Reproducibility of Results

Associated data

  • figshare/10.6084/m9.figshare.22337248.v1

Grants and funding

This trial was supported by an unrestricted research grant from the Swiss Cancer League (KLS-3645-02-2015) and the Berner Stiftung für krebskranke Kinder (RAA). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.