Micafungin twice-a-week for prophylaxis of invasive Aspergillus infections in children with acute lymphoblastic leukaemia: a controlled cohort study

• Published in: International journal of antimicrobial agents 2024-01, Vol.63 (1), p.107058-107058, Article 107058
• Main Authors: Bury, D, Wolfs, T F W, Muilwijk, E W, Fiocco, M, Pieters, R, Brüggemann, R J M, Tissing, W J E
• Format: Article
• Language: English
• ISSN: 0924-8579; 1872-7913
• DOI: 10.1016/j.ijantimicag.2023.107058

Invasive Aspergillus infections during the early phase of childhood acute lymphoblastic leukemia (ALL) treatment come with morbidity and mortality. The interaction with vincristine hampers first-line azole prophylaxis. We describe the efficacy of an alternative twice-a-week micafungin regimen for Aspergillus prophylaxis. Newly diagnosed paediatric patients with ALL treated according to the ALL-11 protocol received micafungin twice-a-week (9 mg/kg/dose [max. 300 mg]) during the induction course (first 35 days of treatment) as part of routine care. A historical control cohort without Aspergillus prophylaxis was used. During the first consolidation course (day 36-79), standard itraconazole prophylaxis was used in both groups. The percentage of proven/probable Aspergillus infections during the induction/first consolidation course was compared between the cohorts. The cumulative incidence of proven/probable Aspergillus infections was estimated using a competing risk model. For safety evaluation, liver laboratory chemistry values were analysed. A total of 169 and 643 paediatric patients with ALL were treated in the micafungin cohort (median age: 4 years [range 1-17]) and historical cohort (median age: 5 years [range 1-17]). The percentage of proven/probable Aspergillus infections was 1∙2% (2/169) in the micafungin cohort versus 5∙8% (37/643) in the historical cohort (p=0.013; Fisher's exact test). The differences in estimated cumulative incidence were assessed (p=0∙014; Gray's test). Although significantly higher ALT/AST values were reported in the micafungin cohort, no clinically relevant side effects were observed. Twice-a-week micafungin prophylaxis during the induction course significantly reduced the occurrence of proven/probable Aspergillus infections in the early phase of childhood ALL treatment.