TY - JOUR
T1 - Invasive fungal disease and antifungal prophylaxis in children with acute leukaemia
T2 - a multicentre retrospective Australian cohort study
AU - Yeoh, Daniel K.
AU - Blyth, Christopher C.
AU - Clark, Julia E.
AU - Abbotsford, Joanne
AU - Corrente, Claudia
AU - Cook, Sara
AU - Kotecha, Rishi S.
AU - Wang, Stacie S.
AU - Spelman, Tim
AU - Slavin, Monica A.
AU - Thursky, Karin A.
AU - Haeusler, Gabrielle M.
N1 - Publisher Copyright:
© 2024
PY - 2024/11
Y1 - 2024/11
N2 - Background: Invasive fungal disease (IFD) is a significant complication for children receiving treatment for leukaemia, contributing to morbidity and mortality. Recent regional paediatric epidemiological IFD data are lacking. Additionally uncertainty remains regarding the optimal prophylactic approach in this context. Methods: In a multi-centre Australian cohort study of children diagnosed with de novo acute leukaemia between 1st January 2017 and 30th June 2020, we characterised antifungal prophylaxis prescribing and IFD prevalence. Impact of antifungal prophylaxis was assessed using Kaplan Meier curves and Cox-proportional hazards regression adjusting for known IFD risk factors. Findings: A total of 434 children were included (47.2% female; median age 5.0 years, median follow-up 240 days). This cohort included 351 children with ALL (214 high-risk [HR-ALL]; 137 standard-risk [SR-ALL]), and 73 with AML. The prevalence of proven/probable IFD was 6.8% for AML, 14.0% for HR-ALL and 4.4% for SR-ALL. A mould was implicated as the causative pathogen in almost two thirds of cases. Antifungal prophylaxis was prescribed in 98.7% of chemotherapy cycles for AML, 56.7% for HR-ALL and 14.9% for SR-ALL. A mould-active agent was used in 77.4% of AML cycles and 21.2% of HR-ALL cycles. Mould-active prophylaxis was associated with a lower risk of IFD overall and increased IFD-free survival in AML. Interpretation: These data demonstrate the persistent high regional burden of IFD in children with HR-ALL, and the potential for mould-active prophylaxis to ameliorate this. Strategies to increase uptake of appropriate prophylaxis are required in this cohort. Funding: This study was supported by a Perth Children's Hospital Foundation grant (PCHF9973).
AB - Background: Invasive fungal disease (IFD) is a significant complication for children receiving treatment for leukaemia, contributing to morbidity and mortality. Recent regional paediatric epidemiological IFD data are lacking. Additionally uncertainty remains regarding the optimal prophylactic approach in this context. Methods: In a multi-centre Australian cohort study of children diagnosed with de novo acute leukaemia between 1st January 2017 and 30th June 2020, we characterised antifungal prophylaxis prescribing and IFD prevalence. Impact of antifungal prophylaxis was assessed using Kaplan Meier curves and Cox-proportional hazards regression adjusting for known IFD risk factors. Findings: A total of 434 children were included (47.2% female; median age 5.0 years, median follow-up 240 days). This cohort included 351 children with ALL (214 high-risk [HR-ALL]; 137 standard-risk [SR-ALL]), and 73 with AML. The prevalence of proven/probable IFD was 6.8% for AML, 14.0% for HR-ALL and 4.4% for SR-ALL. A mould was implicated as the causative pathogen in almost two thirds of cases. Antifungal prophylaxis was prescribed in 98.7% of chemotherapy cycles for AML, 56.7% for HR-ALL and 14.9% for SR-ALL. A mould-active agent was used in 77.4% of AML cycles and 21.2% of HR-ALL cycles. Mould-active prophylaxis was associated with a lower risk of IFD overall and increased IFD-free survival in AML. Interpretation: These data demonstrate the persistent high regional burden of IFD in children with HR-ALL, and the potential for mould-active prophylaxis to ameliorate this. Strategies to increase uptake of appropriate prophylaxis are required in this cohort. Funding: This study was supported by a Perth Children's Hospital Foundation grant (PCHF9973).
KW - Acute lymphoblastic leukaemia
KW - Acute myeloid leukaemia
KW - Antifungal prophylaxis
KW - Children
KW - Invasive fungal disease
KW - Invasive fungal infections
UR - http://www.scopus.com/inward/record.url?scp=85203534004&partnerID=8YFLogxK
U2 - 10.1016/j.lanwpc.2024.101201
DO - 10.1016/j.lanwpc.2024.101201
M3 - Article
C2 - 39318715
AN - SCOPUS:85203534004
SN - 2666-6065
VL - 52
JO - The Lancet Regional Health - Western Pacific
JF - The Lancet Regional Health - Western Pacific
M1 - 101201
ER -