Systematic review of reduced therapy regimens for children with low risk febrile neutropenia

Jessica E. Morgan*, Jemma Cleminson, Karl Atkin, Lesley A. Stewart, Robert S. Phillips

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review


PURPOSE: Reduced intensity therapy for children with low-risk febrile neutropenia may provide benefits to both patients and the health service. We have explored the safety of these regimens and the effect of timing of discharge.

METHODS: Multiple electronic databases, conference abstracts and reference lists were searched. Randomised controlled trials (RCT) and prospective observational cohorts examining the location of therapy and/or the route of administration of antibiotics in people younger than 18 years who developed low-risk febrile neutropenia following treatment for cancer were included. Meta-analysis using a random effects model was conducted. I (2) assessed statistical heterogeneity not due to chance. Registration: PROSPERO (CRD42014005817).

RESULTS: Thirty-seven studies involving 3205 episodes of febrile neutropenia were included; 13 RCTs and 24 prospective observational cohorts. Four safety events (two deaths, two intensive care admissions) occurred. In the RCTs, the odds ratio for treatment failure (persistence, worsening or recurrence of fever/infecting organisms, antibiotic modification, new infections, re-admission, admission to critical care or death) with outpatient treatment was 0.98 (95% confidence interval (95%CI) 0.44-2.19, I (2) = 0 %) and with oral treatment was 1.05 (95%CI 0.74-1.48, I (2) = 0 %). The estimated risk of failure using outpatient therapy from all prospective data pooled was 11.2 % (95%CI 9.7-12.8 %, I (2) = 77.2 %) and using oral antibiotics was 10.5 % (95%CI 8.9-12.3 %, I (2) = 78.3 %). The risk of failure was higher when reduced intensity therapies were used immediately after assessment, with lower rates when these were introduced after 48 hours.

CONCLUSIONS: Reduced intensity therapy for specified groups is safe with low rates of treatment failure. Services should consider how these can be acceptably implemented.

Original languageEnglish
Pages (from-to)2651–2660
Number of pages10
JournalSupportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer
Issue number6
Early online date13 Jan 2016
Publication statusPublished - 13 Jan 2016

Bibliographical note

© Springer Verlag 2016. This is an author produced version of a paper published in Supportive Care in Cancer. Uploaded in accordance with the publisher's self-archiving policy.


  • Febrile neutropenia
  • Oral antibiotics
  • Outpatient
  • Paediatric
  • Systematic review

Cite this