Infection, frequently presenting as fever and neutropenia (FN), is the most common complication of the treatment of childhood cancer and the leading cause of unplanned hospital admissions. In contrast to adult patients with cancer, there is no validated clinical decision rule (CDR) that reliably identifies children at low and high risk of a severe infection. The current standard of treatment is admission of all children with FN, irrespective of underlying risk, for intravenous antibiotics until resolution of fever and recovery of neutrophil count. While this approach produces low mortality rates, it does over-treat up to 75% of children who do not have a documented infection.

Identifying these low-risk individuals and adopting a personalised approach to FN with reduced intensity treatment and early discharge will minimise the burden of FN on the child, their family and the healthcare system. The aim of this project is to identify a clinical decision rule (CDR) that reliably stratifies children with cancer and fever and neutropenia (FN) into low and high risk for severe infection so as to optimise their management and quality of life and improve resource allocation.

Study design

Multi-centre, prospective observational study

Time frame

2016 – 2018

Funding

National Health and Medical Research Council (project)

Sample

845 children < 18years with febrile neutropaenia

Clinical trial registrations

Click here

Contact

Gabrielle Haeusler, Gabrielle.Haeusler@petermac.org

Publications to date

Zhao Z, Patel PA, Slatnick L, Sitthi-Amorn A, Bielamowicz KJ, Nunez FA, Walsh AM, Hess J, Rossoff J, Elgarten C, Myers R, Saab R, Basbous M, Mccormick M, Aftandilian C, Richards R, Nessle CN, Tribble AC, Sheth Bhutada JK, Coven SL, Runco D, Wilkes J, Gurunathan A, Guinipero T, Belsky JA, Lee K, Wong V, Malhotra M, Armstrong A, Jerkins LP, Cross SJ, Fisher L, Stein MT, Wu NL, Yi T, Orgel E, Haeusler GM, Wolf J, Demedis JM, Miller TP, Esbenshade AJ. Prospective External Validation of the Esbenshade Vanderbilt Models Accurately Predicts Bloodstream Infection Risk in Febrile Non-Neutropenic Children With Cancer. J Clin Oncol. 2024 Mar 1;42(7):832-841. doi: 10.1200/JCO.23.01814. Epub 2023 Dec 7.PMID: 38060973. [Link]

Vargas C, Haeusler GM, Slavin MA, Babl FE, Mechinaud F, Phillips R, Thursky K, Lourenco RA; Australian PICNICC Study Group. An analysis of the resource use and costs of febrile neutropenia events in pediatric cancer patients in Australia. Pediatr Blood Cancer. 2023 Nov;70(11):e30633. doi: 10.1002/pbc.30633. Epub 2023 Aug 17. [Link]

Corrente C, Satkumaran S, Segal A, Butters C, Fernandez C, Babl FE, Orme LM, Thursky K, Haeusler GM. Evaluating the accuracy and efficacy of an electronic medical record alert to identify paediatric patients with low-risk febrile neutropenia. Int J Med Inform. 2023 Oct;178:105205. doi: 10.1016/j.ijmedinf.2023.105205. Epub 2023 Aug 30.PMID: 37703799. [Link]

Jackson TJ, Napper R, Haeusler GM, Pizer B, Bate J, Grundy RG, Samarasinghe S, Angelini P, Ball-Gamble A, Phillips B, Morgan JE. Can I go home now? The safety and efficacy of a new UK paediatric febrile neutropenia protocol for risk-stratified early discharge on oral antibiotics. Arch Dis Child. 2023 Mar;108(3):192-197. doi: 10.1136/archdischild-2021-323254. Epub 2022 Dec 12.PMID: 36600323. [Link]

Tew M, De Abreu Lourenco R, Gordon JR, Thursky KA, Slavin MA, Babl FA, Orme L, Bryant PA, Teh BW, Dalziel K, Haeusler GM. Cost-effectiveness of home-based care of febrile neutropenia in children with cancer. Pediatr Blood Cancer. 2022 Jul;69(7):e29469. doi: 10.1002/pbc.29469. Epub 2021 Dec 2. PMID: 34854550. [Link]

Haeusler GM, Garnham AL, Li-Wai-Suen CS, Clark JE, Babl FE, Allaway Z, Slavin MA, Mechinaud F, Smyth GK, Phillips B, Thursky KA, Pellegrini M, Doerflinger M. Blood transcriptomics identifies immune signatures indicative of infectious complications in childhood cancer patients with febrile neutropenia. Clin Transl Immunology. 2022 May 17;11(5):e1383. doi: 10.1002/cti2.1383. eCollection 2022.PMID: 35602885. [Link]

Crothers A, Haeusler GM, Slavin MA, Babl FE, Mechinaud F, Phillips R, Tapp H, Padhye B, Zeigler D, Clark J, Walwyn T, Super L, Alvaro F, Thursky K, De Abreu Lourenco R.  Examining health-related quality of life in pediatric cancer patients with febrile neutropenia: Factors predicting poor recovery in children and their parents.  EClinicalMedicine. 2021 Aug 20;40:101095. doi: 10.1016/j.eclinm.2021.101095. eCollection 2021 Oct.PMID: 34746716. [Link]

Haeusler GM, Thursky KA, Slavin MA, Babl FE, De Abreu Lourenco R, Allaway Z, Mechinaud F, Phillips R; Australian PICNICC study group and the PREDICT network. Risk stratification in children with cancer and febrile neutropenia: A national, prospective, multicentre validation of nine clinical decision rules. EClinicalMedicine. 2020 Jan 7;18:100220. doi: 10.1016/j.eclinm.2019.11.013. eCollection 2020 Jan. [link].

Haeusler G, Phillips R, Slavin M, Babl FE, De Abreu Lourenco R, Mechinaud F, Thursky K on behalf of the Australian PICNICC study group and the PREDICT network. Re-evaluating and recalibrating predictors of bacterial infection in children with cancer and febrile neutropenia. EClinicalMedicine. June 2020, 15;23. doi: 10.1016/j.eclinm.2020.100394. eCollection 2020 Jun. PMID: 32637894. [link].

Haeusler GM, Gaynor L, Teh B, Babl FE, Orme LM, Segal A, Mechinaud F, Bryant PA, Phillips B, Lourenco RA, Slavin MA, Thursky KA. Home-based care of low-risk febrile neutropenia in children-an implementation study in a tertiary paediatric hospital.  Support Care Cancer. 2020 Aug 1. doi: 10.1007/s00520-020-05654-z. Online ahead of print. PMID: 32740894. [link].

McMullan BJ, Haeusler GM, Hall L, Cooley L, Stewardson AJ, Blyth CC, Jones CA, Konecny P, Babl FE, Mechinaud F, Thursky K; Australian PICNICC study group and the PREDICT network. Aminoglycoside use in paediatric febrile neutropenia – Outcomes from a nationwide prospective cohort study. PLoS One. 2020 Sep 16;15(9):e0238787. doi: 10.1371/journal.pone.0238787. PMID: 32936822; PMCID: PMC7494114. [Link]

Haeusler GM, De Abreu Lourenco R, Bakos C, O’Brien T, Slavin MA, Clark JE, McMullan B, Borland ML, Babl FE, Krishnasamy M, Vanevski M, Thursky KA, Hall L. Managing low-risk febrile neutropenia in children in the time of COVID-19: What matters to parents and clinicians. J Paediatr Child Health. 2021 Jun;57(6):826-834. doi: 10.1111/jpc.15330. Epub 2021 Feb 3. PMID: 33533525; PMCID: PMC8013774. [Link]

Doerflinger M, Haeusler GM, Li-Wai-Suen CSN, Clark JE, Slavin M, Babl FE, Allaway Z, Mechinaud F, Smyth GK, De Abreu Lourenco R, Phillips B, Pellegrini M, Thursky KA. Procalcitonin and Interleukin-10 May Assist in Early Prediction of Bacteraemia in Children With Cancer and Febrile Neutropenia. Front Immunol. 2021 May 20;12:641879. doi: 10.3389/fimmu.2021.641879. PMID: 34093531; PMCID: PMC8173204. [Link]