Challenges and considerations for antifungal prophylaxis in children with acute myeloid leukemia

ABSTRACT

Introduction

Children receiving treatment for acute myeloid leukemia (AML) are at high risk of invasive fungal disease (IFD). Evidence from pediatric studies support the efficacy of antifungal prophylaxis in reducing the burden of IFD in children receiving therapy for AML, yet existing antifungal agents have specific limitations and comparative data to inform the optimal prophylactic approach are lacking.

Areas covered

This review summarizes the epidemiology of invasive fungal disease (IFD) and current antifungal prophylaxis recommendations for children with acute myeloid leukemia (AML). Challenges with currently available antifungal agents and considerations related to the changing landscape of AML therapy are reviewed. A keyword search was conducted to identify pediatric studies regarding IFD and antifungal prophylaxis in children with AML up to December 2023.

Expert opinion

Children undergoing treatment for AML are recommended to receive antifungal prophylaxis to reduce risk of IFD, with tolerability, pharmacokinetics, feasibility of administration and drug interactions all factors that require consideration in this context. With increased use of novel targeted agents for AML therapy, together with the development of new antifungal agents, data from well-designed clinical studies to optimize prophylactic approaches will be essential to limit the burden of IFD in this vulnerable cohort.

KEYWORDS:

• Acute myeloid leukemia
• invasive fungal disease
• antifungal prophylaxis
• FLT3 inhibitors
• venetoclax
• hypomethylating agents
• menin inhibitors

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Article highlights

• More than 10% of children receiving treatment for acute myeloid leukemia (AML) will develop invasive fungal disease (IFD)

• Antifungal prophylaxis can reduce the risk of IFD in children with AML

• The mould-active triazoles (e.g. posaconazole) and echinocandins (e.g. caspofungin and micafungin) are the preferred agents for prophylaxis

• Newer antifungal formulations and agents have distinct advantages which may favor their use in children

• A consideration of IFD risk and drug interactions associated with targeted molecular agents for AML treatment is vital in prescribing prophylaxis for children receiving these agents.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Table 1. Pediatric cohort studies reporting invasive fungal disease (IFD) during treatment for acute myeloid leukemia.

Table 2. Risk of invasive fungal disease (IFD) and important drug interactions for key targeted therapies in pediatric acute myeloid leukemia.

Additional information

Funding

This paper was not funded.