Incidence and Risk Factors for Invasive Mold Infections in Children During First-Line Chemotherapy for Primary Acute Leukemia: A National Retrospective Cohort Study

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ID: 332602
2026
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Abstract
BACKGROUND: Invasive mold infections (IMI) are life-threatening complications during treatment for pediatric acute leukemia. Population-based data on IMI incidence, timing, and outcomes during first-line therapy remain limited. We aimed to provide a nationwide epidemiological overview of IMI during first-line treatment of pediatric acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL) and explore potential treatment-related risk factors. METHODS: We conducted a retrospective nationwide cohort study of all children (<18 years) initiating first-line chemotherapy for AML or ALL in Denmark during 2008-2022. IMIs were classified as proven or probable according to 2020 EORTC/MSGERC criteria by review of microbiology, imaging, pathology, and chart data. Follow-up covered first-line chemotherapy. Competing risk-adjusted cumulative incidence of IMI was estimated, risk factors were evaluated using Cox regression, and survival after IMI was analyzed using the Kaplan-Meier method. RESULTS: Among 621 patients, 43 (6.9%) developed IMI: 14/90 (15.6%) with AML and 29/531 (5.5%) with ALL. In adjusted Cox regression, AML was associated with higher IMI hazard than ALL (HR 5.6, 95% CI 2.6 to 12.1), whereas no other prespecified risk factors were independently associated with IMI. Incidence rates were 38.6 per 100 patient-years in AML and 2.7 in ALL. Nearly half of IMIs occurred beyond 90 days after initiation of first-line chemotherapy. Four patients experienced a second distinct IMI episode; Aspergillus species accounted for 37/47 (79%) episodes and non-Aspergillus molds for 10/47 (21%). IMI-associated death occurred in 10 patients (1.6% of the cohort), yielding a case fatality rate of 23% among IMI cases; IMI was present in 43% of all deaths. CONCLUSIONS: In this nationwide cohort, IMI occurred more frequently than reported in many previous pediatric studies, particularly in AML. IMIs were observed throughout first-line therapy, despite antifungal prophylaxis, and were associated with substantial mortality, emphasizing the need for sustained clinical vigilance beyond induction.
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Authors Rasmus Møller Duus, Emma Soendergaard Joergensen, Emil Bach Offendal, Nadja Hawwa Vissing, Kristian Løvvik Juul-Dam, Flemming Schønning Rosenvinge, Dorthe Wiig Grosen, Nina Marie Birk, Katja Majlund Harder, Steffen Husby, Jesper Bonnet Moeller, Robin Christensen, Louise Aarup Duus, Mathias Rathe
Journal journal of the pediatric infectious diseases society
Year 2026
DOI
10.1093/jpids/piag112
URL
https://doi.org/10.1093/jpids/piag112
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