Fungal infections in children with haematologic malignancies and stem cell transplant recipients

Abstract

Children with haematologic malignancies and haematopoietic stem cell transplant recipients are at high risk for invasive fungal diseases (IFD). There has been an increased number of at-risk children over the past two decades due to improvements in cancer therapies resulting in improved survival of children with high-risk and refractory malignancies. The predominant organisms that cause IFD include Candida spp., Aspergillus spp. and the Mucorales molds. Clinical presentations of IFD vary based on host immune status and the causative organism. Though serum biomarkers such as the galactomannan assay and beta-D-glucan assay have been validated in adults, there are limited data regarding their diagnostic value in children. Thus, the gold standard for IFD diagnosis remains tissue biopsy with histopathological and microbiological evaluation. Treatment of IFD is multimodal and involves antifungal drugs, correction of immune dysfunction and surgical resection when feasible. Paediatric practice regarding IFD is largely extrapolated from data generated in adult patients; in this review, we evaluate both primary paediatric studies and guidelines intended for adult patients that are applied to paediatric patients. There remain significant knowledge gaps with respect to the prevention, diagnosis and treatment of IFD in immunocompromised children, and further research is needed to help guide management decisions.

Keywords: antifungal prophylaxis; hematologic malignancies; immunocompromised; invasive fungal disease; pediatric.

Figure 1.

Common modes of entry for common pathogens seen in invasive fungal disease.

Figure 2.

The fungal cell wall and membrane and the sites of action of common antifungals. Triazole antifungals inhibit the synthesis of ergosterol, a key cell membrane component. Polyene antifungals (such as amphotericin B) act directly on ergosterol and disrupts membrane integrity. Echinocandins prevent the synthesis of (1,3)-β-D-glucan, a key component of the fungal cell wall.