Liposomal amphotericin B retrospective multicentre study on mycosis prophylaxis (L-AmB_RUSCO): tolerability and safety of extended-dosing primary antifungal prophylaxis in children with newly diagnosed acute myeloid leukaemia.
This retrospective multinational multicentre study of 86 prophylaxis courses in children with newly diagnosed AML reports the tolerability, toxicity, and exploratory breakthrough fungal infection rate associated with extended-dosing liposomal amphotericin B.
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This retrospective multinational multicentre study of 86 prophylaxis courses in children with newly diagnosed AML reports the tolerability, toxicity, and exploratory breakthrough fungal infection rate associated with extended-dosing liposomal amphotericin B.
Research significance
The study provides observational evidence that extended-dosing liposomal amphotericin B can deliver mould-active prophylaxis with a 3% observed breakthrough proven or probable invasive fungal disease rate, but it is only an inference—not established comparative evidence—that this regimen could be a useful alternative when triazoles are contraindicated or daily echinocandin administration is impractical.
Source abstract
OBJECTIVES: To evaluate the tolerability and safety of extended-dosing liposomal amphotericin B (LAmB) as primary antifungal prophylaxis against invasive fungal disease (IFD) in children receiving chemotherapy for newly diagnosed acute myeloid leukaemia (AML); breakthrough proven or probable IFD was assessed as an exploratory secondary endpoint. METHODS: This retrospective, multinational, multicentre observational study included children treated for newly diagnosed AML between January 2019 and December 2023. LAmB was administered according to local protocols at 1 mg/kg three times weekly, 2.5 mg/kg twice weekly or 5 mg/kg once weekly. Clinical and laboratory adverse events (AEs) were assessed to evaluate tolerability and safety. Breakthrough proven or probable IFD, defined according to EORTC/MSG criteria, was recorded as an exploratory secondary outcome. RESULTS: Eighty-six courses of extended-dosing LAmB were analysed. The median age at first LAmB administration was 91 months (IQR 26-156). The median treatment duration was 13 weeks (IQR 3-21) at a median dose of 2.7 mg/kg per infusion, with a median estimated cumulative dose of 77.6 mg/kg (IQR 21.3-110.1). Clinical AEs occurred in 21% of courses, predominantly skin rash and lumbosacral pain. Laboratory AEs were mainly hypokalaemia (48%) and hepatotoxicity (19%), both dose related. Treatment discontinuation due to toxicity occurred in 15% of courses. Breakthrough proven or probable IFD occurred in 3% of cases. CONCLUSIONS: Extended-dosing LAmB represents a reasonably well-tolerated mould-active option for primary antifungal prophylaxis in children with newly diagnosed AML, particularly when triazoles are contraindicated or daily intravenous echinocandin administration is impractical; the low observed rate of breakthrough IFD should be interpreted cautiously given the absence of a comparator group.