Antifungal use in children with acute leukaemia: state of current evidence and directions for future research

Author:

Yeoh Daniel K.1234ORCID,Haeusler Gabrielle M.234567,McMullan Brendan J.2389,Butters Coen410,Bryant Penelope A.4711,Clark Julia E.1213,Cooper Celia M.14,Gwee Amanda4715,Kotecha Rishi S.161718ORCID,Lai Tony1920ORCID,Slavin Monica A.235ORCID,Thursky Karin A.23521,Blyth Christopher C.1222324ORCID

Affiliation:

1. Department of Infectious Diseases, Perth Children’s Hospital , Perth, WA, Australia

2. Sir Peter MacCallum Department of Oncology, University of Melbourne , Parkville, Victoria, Australia

3. National Centre for Infections in Cancer, Peter MacCallum Cancer Centre , Melbourne, Victoria, Australia

4. Murdoch Children’s Research Institute , Parkville, Victoria, Australia

5. Department of Infectious Diseases, Peter MacCallum Cancer Centre , Melbourne, Victoria, Australia

6. The Paediatric Integrated Cancer Service , Melbourne, Victoria, Australia

7. Department of Infectious Diseases, Royal Children’s Hospital , Parkville, Victoria, Australia

8. Department of Immunology and Infectious Diseases, Sydney Children’s Hospital , Randwick, NSW, Australia

9. School of Women’s and Children’s Health, UNSW , Sydney, NSW, Australia

10. Department of General Paediatrics and Adolescent Medicine, John Hunter Children’s Hospital , Newcastle, NSW, Australia

11. Hospital in the Home, Royal Children’s Hospital , Melbourne, Victoria, Australia

12. Infection Management Service, Queensland Children’s Hospital , Brisbane, Queensland, Australia

13. School of Clinical Medicine, Children’s Health Queensland Clinical Unit, The University of Queensland , Brisbane, QLD, Australia

14. Department of Microbiology and Infectious Diseases, South Australia Pathology, Women’s and Children’s Hospital , North Adelaide, South Australia, Australia

15. Department of Paediatrics, The University of Melbourne , Victoria, Australia

16. Department of Clinical Haematology, Oncology, Blood and Marrow Transplantation, Perth Children’s Hospital , Perth, Western Australia, Australia

17. Curtin Medical School, Curtin University , Perth, Western Australia, Australia

18. Leukaemia Translational Research Laboratory, Telethon Kids Cancer Centre, Telethon Kids Institute, University of Western , Perth, Western Australia, Australia

19. Department of Pharmacy, Westmead Children’s Hospital , Sydney, NSW, Australia

20. Sydney Institute for Infectious Diseases, University of Sydney , NSW, Australia

21. National Centre for Antimicrobial Stewardship, Department of Infectious Diseases, University of Melbourne , VIC, Australia

22. Department of Microbiology, PathWest Laboratory Medicine WA , Nedlands, WA, Australia

23. Wesfarmers Centre of Vaccines and Infectious Diseases, Telethon Kids Institute, University of Western Australia , Perth, WA, Australia

24. School of Medicine, University of Western Australia , Perth, WA, Australia

Abstract

Abstract Invasive fungal disease (IFD) remains a common and serious complication in children treated for leukaemia. Antifungal prescription in children with leukaemia presents unique challenges, particularly due to variation in IFD risk between and within leukaemia treatment protocols, drug toxicities and interactions between antifungals and chemotherapeutic agents. With recent advances in the understanding of IFD epidemiology and large clinical trials in adults assessing antifungals for IFD treatment and prophylaxis, together with paediatric clinical and pharmacokinetic studies, there is a growing body of data to inform optimal antifungal use in children. A panel of infectious diseases and haematology-oncology clinicians with expertise in IFD management compiled a list of 10 key clinical questions following development of the 2021 Australia and New Zealand Mycology Antifungal Consensus Guidelines. A focused literature review was conducted to explore available evidence and identify gaps in knowledge to direct future research. With the changing epidemiology of IFD globally, the ongoing evolution of paediatric leukaemia treatment and the increasing availability of novel antifungal agents, advocacy for paediatric clinical studies will remain vital to optimize IFD prevention and treatment in children with leukaemia.

Funder

Australian Government Research Training Program Postgraduate Scholarship

Publisher

Oxford University Press (OUP)

Subject

Infectious Diseases,Pharmacology (medical),Pharmacology,Microbiology (medical)

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