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EClinicalMedicine. 2020 Jan 7;18:100220. doi: 10.1016/j.eclinm.2019.11.013. eCollection 2020 Jan.

Risk stratification in children with cancer and febrile neutropenia: A national, prospective, multicentre validation of nine clinical decision rules.

Author information

1
Department of Infectious Diseases, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia.
2
NHMRC National Centre for Infections in Cancer, Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, Victoria, Australia.
3
Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, Victoria, Australia.
4
The Victorian Paediatric Integrated Cancer Service, Victoria State Government, Melbourne, Australia.
5
Infection Diseases Unit, Department of General Medicine, Royal Children's Hospital, Melbourne, Victoria, Australia.
6
Department of Medicine, University of Melbourne, Melbourne, Victoria, Australia.
7
NHMRC National Centre for Antimicrobial Stewardship, The Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, Australia.
8
Victorian Infectious Diseases Service, The Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, Australia.
9
Department of Emergency Medicine, Royal Children's Hospital, Melbourne, Victoria, Australia.
10
Paediatric Research in Emergency Departments International Collaborative (PREDICT).
11
Murdoch Children's Research Institute, Melbourne, Victoria, Australia.
12
Department of Paediatrics, Faculty of Medicine, Dentistry and Health Sciences, University of Melbourne, Melbourne, Victoria, Australia.
13
Centre for Health Economics Research and Evaluation, University of Technology Sydney, Sydney, New South Wales, Australia.
14
Children's Cancer Centre, The Royal Children's Hospital, Melbourne, Victoria, Australia.
15
Unité d'hématologie immunologie pédiatrique, Hopital Robert Debré, APHP Nord Université de Paris, France.
16
Centre for Reviews and Dissemination, University of York, York, United Kingdom.
17
Leeds Children's Hospital, Leeds General Infirmary, Leeds, United Kingdom.

Abstract

Background:

Reduced intensity treatment of low-risk febrile neutropenia (FN) in children with cancer is safe and improves quality of life. Identifying children with low-risk FN using a validated risk stratification strategy is recommended. This study prospectively validated nine FN clinical decision rules (CDRs) designed to predict infection or adverse outcome.

Methods:

Data were collected on consecutive FN episodes in this multicentre, prospective validation study. The reproducibility and discriminatory ability of each CDR in the validation cohort was compared to the derivation dataset and details of missed outcomes were reported.

Findings:

There were 858 FN episodes in 462 patients from eight hospitals included. Bacteraemia occurred in 111 (12·9%) and a non-bacteraemia microbiological documented infection in 185 (21·6%). Eight CDRs exhibited reproducibility and sensitivity ranged from 64% to 96%. Rules that had >85% sensitivity in predicting outcomes classified few patients (<20%) as low risk. For three CDRs predicting a composite outcome of any bacterial or viral infection, the sensitivity and discriminatory ability improved for prediction of bacterial infection alone. Across all CDRs designed to be implemented at FN presentation, the sensitivity improved at day 2 assessment.

Interpretation:

While reproducibility was observed in eight out of the nine CDRs, no rule perfectly differentiated between children with FN at high or low risk of infection. This is in keeping with other validation studies and highlights the need for additional safeguards against missed infections or adverse outcomes before implementation can be considered.

KEYWORDS:

Cancer; Children; Febrile neutropenia; Risk prediction

Conflict of interest statement

GMH reports grants from the Victorian Cancer Agency during the conduct of the study. FEB reports grants from The Royal Children's Hospital Foundation during the conduct of the study. RDAL reports grants from the NHMRC during the conduct of this study. KAT, MS, ZA and FM and RP have nothing to disclose.

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