The 5-year overall survival of childhood acute lymphoblastic leukemia (ALL) has increased to ∼90% [1]. To further improve overall survival, reducing treatment-related mortality (TRM) remains an important focus of interest. One of the leading causes of TRM in paediatric patients with haematological malignancies is invasive fungal disease (IFD) [2], most importantly Aspergillus infections. Two recent guidelines for paediatric haematology patients recommend considering antifungal prophylaxis during at-risk treatment courses of ALL treatment [3,4]. The majority of IFD occur during the induction and first consolidation course, when paediatric patients with ALL are severely immunocompromised [5]. Aspergillus spp. are most frequently responsible for fungal infections in this phase, with an incidence of ∼6% [data on file, Dutch Childhood Oncology Group (DCOG)] for invasive Aspergillus infections. This high incidence has prompted the use of Aspergillus prophylaxis during the early treatment phase of childhood ALL.

Finding a suitable antifungal agent for Aspergillus prophylaxis remains challenging during the induction course (first 35 days of treatment) of ALL treatment. The required antifungal agent needs to be compatible with the chemotherapeutic agents given, and must fit a patient-friendly dosing schedule during this mostly outpatient treatment phase. Triazoles are the preferred agents for primary prophylaxis in patients with a high risk to develop IFD [4]. Considering the clinically relevant drug-drug interaction of triazoles with vincristine [6], these agents do not meet the specific profile for a prophylactic agent outlined above. In the past years, echinocandin prophylaxis in a daily regimen has been demonstrated to be of value in paediatric patients with acute myeloid leukemia (AML) in a large controlled trial but with varying outcomes in other smaller studies for Aspergillus prophylaxis in paediatric haematology populations [7]. The proven efficacy of echinocandins for prophylaxis of invasive Aspergillus infections in patients with AML [7], offers an alternative perspective for Aspergillus prophylaxis in the early setting of ALL treatment. Echinocandins are generally well tolerated due to their fungi-specific target and no clinically relevant drug-drug interactions are expected [8]. The difficulty is their invasive daily intravenous dosing regimen.

An intermittent twice-a-week echinocandin dosing regimen may be a more patient-friendly approach for this outpatient treatment phase. The pharmacokinetic background of such intermittent regimens has been reported in adult patients for both anidulafungin and micafungin [9,10]. We recently showed that a twice-a-week micafungin regimen in paediatric patients was pharmacokinetically equivalent to a daily micafungin regimen in adult patients [11]. This paper describes the efficacy of this twice-a-week micafungin regimen for prophylaxis of invasive Aspergillus infections in the early phase of childhood ALL treatment.