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

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Abstract

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.

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Acknowledgments

We would like to acknowledge Kate Lewis-Light for her work on the searching for this review.

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Corresponding author

Correspondence to Jessica E. Morgan.

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Funding

JM is funded by Candlelighters Children’s Charity (Registered Charity No: 1045077) for the PhD of which this systematic review is a part.

Conflict of interest

The authors declare that they have no competing interests.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Online Resource 1

Database search strategies (PDF 194 kb)

Online Resource 2

Reasons for study exclusions (PDF 317 kb)

Online Resource 3

Demographics of included studies (PDF 500 kb)

Online Resource 4

Study interventions and definitions (PDF 451 kb)

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Morgan, J.E., Cleminson, J., Atkin, K. et al. Systematic review of reduced therapy regimens for children with low risk febrile neutropenia. Support Care Cancer 24, 2651–2660 (2016). https://doi.org/10.1007/s00520-016-3074-9

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  • DOI: https://doi.org/10.1007/s00520-016-3074-9

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