Epidemiology of invasive fungal infection in acute leukaemia to inform infection prevention and surveillance practice: A systematic review and meta-analyses

OBJECTIVES: Invasive fungal infections (IFIs) are a significant cause of morbidity and mortality in acute leukaemia. This systematic review and meta-analyses sought to evaluate IFI epidemiology to inform infection prevention and surveillance practice. METHODS: A systematic search was conducted in PubMed, Embase and Web of Science (2019-2024). Meta-analyses using random-effects models with a DerSimonian-Laird variance-estimator were performed to describe IFI event-rates, pathogen aetiology and antifungal prophylaxis (AFP) use in breakthrough cases. RESULTS: Meta-analyses of 17 publications (n=3291) yielded a pooled IFI event rate of 8.0% (95% CI 6.0%-11.0%), highest in acute myeloid leukaemia/myelodysplastic syndrome; 8.0% (95% CI 6.0%-10.0%). Across 16 studies (n=3071), Aspergillus spp. predominated (5.0% event rate, 95% CI 4.0%-7.0%). Data from 14 studies (n=2537) suggested a breakthrough-IFI rate of 7.0% (95% CI 5.0%-10.0%), mainly Aspergillus spp.; 62.0% (95% CI 50.0%-74.0%). Across 12 studies (n=2035), most breakthroughs occurred on mould-active-azole-prophylaxis; 39.0% (95% CI 18.0%-60.0%). Heterogeneity was moderate-high (I²=55.4%-91.3%). Reporting of infection prevention measures was limited. CONCLUSIONS: IFIs remain a major complication in acute leukaemia, with a substantial burden of Aspergillus. These findings support the optimisation of mould-active AFP for high-risk patients whilst highlighting the importance of prospective surveillance alongside standardised reporting and integration of adjunctive stewardship and control measures to strengthen IFI prevention.