The clinical management of invasive mold infection in children with cancer or undergoing hematopoietic stem cell transplantation

ABSTRACT

Introduction: Invasive fungal disease (IFD) is a significant cause for morbidity and mortality in children receiving chemotherapy or undergoing hematopoietic stem cell transplantation (HSCT). As compared to adults, children may differ from adults in specific aspects regarding epidemiology, diagnosis and management of IFD.

Areas covered: The review provides an overview over the epidemiology of IFD in children with cancer or undergoing HSCT, diagnostic tools, preventive and therapeutic strategies.

Expert opinion: Whereas the risk for IFD is highest in children with acute myeloid leukemia, relapse of acute leukemia, and allogeneic HSCT, the individual risk for IFD needs to be better defined in the large and heterogenous group of children with acute lymphoblastic leukemia. In contrast to galactomannan, pediatric data on beta-D-glucan and PCR testing are scarce. Findings of imaging studies in children are often not typical, but may prompt invasive diagnostic procedures. No substantial differences exist between children and adult regarding antifungal chemoprophylaxis, empirical, pre-emptive and specific therapy. However, antifungal strategies in children are limited as a number of antifungal compounds are not licensed for children or their pediatric dosage is unknown.

KEYWORDS:

• Antifungal prophylaxis
• Aspergillus
• cancer
• child
• empirical antifungal therapy
• hematopoietic stem cell transplantation
• invasive mold infection
• pre-emptive antifungal therapy

Article highlights

• The risk for invasive fungal disease (IFD) is highest in children with acute myeloid leukemia, relapse of acute leukemia and allogeneic hematopoietic stem cell transplant recipients

• The performance of biomarkers such as galactomannan and beta-D-glucan may differ between children and adults

• Findings of imaging studies in children are often non-specific but may prompt invasive diagnostic procedures

• Antifungal chemoprophylaxis is indicated in patients at high risk for IFD, and in subpopulations of patients with acute lymphoblastic leukemia. These subpopulations, however, have to be better defined

• Empirical antifungal therapy is the standard of care in most institutions

• Little data exist on pre-emptive antifungal therapy in children, which requires the rapid availability of galactomannan testing results and computerized tomography

• There are no fundamental differences between children and adults in the treatment of established mold infections, but a number of antifungal compounds is not approved for children or the pediatric dosage is unknown

• Immunotherapeutic strategies using granulocytes, anti-fungal T cells or NK cells are promising, but clinical data are missing or inconclusive

Declaration of interest

T Lehrnbecher received grants from Gilead Sciences, is a consultant to Astellas, Basilea, Gilead Sciences, and Merck/MSD, and served at the speaker’s bureau of Astellas, Gilead Sciences, Merck/MSD, and Pfizer. The author has no other 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 apart from those disclosed.

Reviewer disclosure

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

Additional information

Funding

This paper was not funded.