Antifungal use in children with acute leukaemia: state of current evidence and directions for future research

Abstract

Invasive fungal disease (IFD) remains a common and serious complication in children treated for leukaemia. Antifungal prescription in children with leukaemia presents unique challenges, particularly due to variation in IFD risk between and within leukaemia treatment protocols, drug toxicities and interactions between antifungals and chemotherapeutic agents. With recent advances in the understanding of IFD epidemiology and large clinical trials in adults assessing antifungals for IFD treatment and prophylaxis, together with paediatric clinical and pharmacokinetic studies, there is a growing body of data to inform optimal antifungal use in children. A panel of infectious diseases and haematology-oncology clinicians with expertise in IFD management compiled a list of 10 key clinical questions following development of the 2021 Australia and New Zealand Mycology Antifungal Consensus Guidelines. A focused literature review was conducted to explore available evidence and identify gaps in knowledge to direct future research. With the changing epidemiology of IFD globally, the ongoing evolution of paediatric leukaemia treatment and the increasing availability of novel antifungal agents, advocacy for paediatric clinical studies will remain vital to optimize IFD prevention and treatment in children with leukaemia.

Blinatumomab as bridging therapy in paediatric B‐cell acute lymphoblastic leukaemia complicated by invasive fungal disease

“…Concomitant use of these agents in patients with ALL may lead to severe neurotoxicity, further complicating treatment decisions. 12 The use of blinatumomab allowed for ongoing triazole antifungal therapy in seven of our patients, avoiding the need for triazole dose interruptions due to the potential for adverse drug reactions around vincristine dosing.…”

“…Voriconazole and posaconazole, recommended agents for treatment of invasive aspergillosis and mucormycosis respectively, 5,6 inhibit vincristine metabolism via cytochrome P450. Concomitant use of these agents in patients with ALL may lead to severe neurotoxicity, further complicating treatment decisions 12 . The use of blinatumomab allowed for ongoing triazole antifungal therapy in seven of our patients, avoiding the need for triazole dose interruptions due to the potential for adverse drug reactions around vincristine dosing.…”

Antimicrobial use in pediatric oncology and hematology in Germany and Austria, 2020/2021: a cross-sectional, multi-center point-prevalence study with a multi-step qualitative adjudication process

“… 21 This may be explained by the fact that invasive fungal diseases (IFD) strongly impact morbidity and mortality in immunocompromised patients. 22 , 23 …”

The Challenge of Diagnosing Invasive Pulmonary Aspergillosis in Children: A Review of Existing and Emerging Tools

“…Updated studies documenting CT findings in children with IPA in the setting of improvements in CT techniques, changes in immunosuppressive regimens and supportive care including use of anti-mould prophylaxis are required [14,22]. Furthermore, important differences in imaging findings between adult risk groups have been observed 4 yet there are limited data on the CT in IPA for paediatric solid organ transplant recipients and children with primary immunodeficiency specifically [6]. Similarly, adult studies have documented differences in imaging findings between IPA and pulmonary mucormycosis [33,34], equivalent paediatric data are lacking.…”