Fungal Infections in Pediatric Patients With Hematologic Malignancies and Stem Cell Transplantation: Impact on the Upper and Lower Respiratory Systems

Invasive fungal infections (IFIs) are a leading cause of morbidity and mortality in children with hematological malignancies as well as those undergoing hematopoietic stem cell transplantation (HSCT). Extreme immunological dysregulation secondary to severe neutropenia, T-cell lymphopenia, graft-versus-host disease (GVHD), intensive chemotherapy regimens, and conditioning therapy for HSCT, as well as primary immunodeficiencies (PIDs), render these patients highly susceptible to both opportunistic and pathogenic fungal infections. Despite advances in antifungal drugs and diagnostic tools, it is very difficult in these children to provide timely diagnosis and optimal management of IFIs because of the nonspecific clinical manifestations, the invasiveness of present diagnostic modalities in pediatric patients, and biomarker kinetics differences in various pediatric age groups, along with a lack of incorporation of immunological-pharmacological maturity-associated variability in the existing scoring systems borrowed from adults. This narrative review provides a comprehensive and contemporary assessment of the epidemiology, host-related risk factors, clinical presentations, diagnostic criteria, and management practices for IFIs in children with hematological malignancies and following HSCT. It also highlights the role of EORTC/MSGERC criteria in defining IFIs as probable, proven, and possible infections and explores the sensitivity and specificity of noninvasive methods such as the galactomannan index, polymerase chain reaction (PCR), ß-D-glucan assay, high-resolution CT scans (HRCTs), and the latest approaches including next-generation sequencing (NGS) and metagenomics. This review points out significant gaps in pediatric research studies and supports efforts to optimize healthcare use with risk-prediction models rather than just relying on current algorithms.