Benefits of risk-adapted and mould-specific antifungal prophylaxis in childhood leukaemia

Abstract

Fluconazole is one of the most commonly used drugs for antifungal prophylaxis in childhood leukaemia. However, its interaction with vincristine may induce neuropathy and the emergence of antifungal drug resistance contributes to substantial mortality caused by invasive fungal infections (IFIs). In a retrospective single-centre study, we compared tolerability and outcome of different antifungal prophylaxis strategies in 198 children with acute leukaemia (median age 5·3 years). Until 2010, antifungal prophylaxis with fluconazole was offered to most of the patients and thereafter was replaced by liposomal amphotericin-B (L-AMB) and restricted to high-risk patients only. Vincristine-induced neurotoxicity was significantly reduced under L-AMB, as the percentage of patients with severe constipation decreased (15·4% vs. 3·7%, before vs. after 31 December·2010, P = 0·01) and stool frequency increased by up to 38% in polyene-treated patients (P = 0·005). Before 2011, 10 patients developed confirmed IFIs, most of them were infected with Aspergillus species. After risk adaption in 2011, IFIs were completely prevented (P = 0·007). L-AMB prophylaxis is beneficial in childhood leukaemia patients, as it offers effective antifungal activity with improved tolerability as compared to fluconazole. The potential impact of our risk-adapted antifungal treatment should be included in current prophylaxis guidelines for childhood leukaemia.

Keywords: cancer; childhood leukaemia; invasive fungal infection; liposomal amphotericin-B; prophylaxis.

Fig 1

Estimated probability of invasive fungal infections (IFIs, hazard function). Before 2011, the majority of patients were treated with fluconazole and confirmed IFIs were diagnosed in 10 patients (8·6% of the cohort before 2011, n = 116). In the year 2011 the antifungal strategy was adapted to the use of liposomal amphotericin‐B (L‐AMB) and restricted to patients with a high risk of IFIs. IFIs were completely prevented in all patients after 2010 (n = 82). The log‐rank test was used to compare the risk for IFI before and after 31 December 2010 (P = 0·007). [Colour figure can be viewed at wileyonlinelibrary.com]