Detection and Management of Invasive Mold Disease in Pediatric Hematological Cancer Patients

Infectious complications still remain a major challenge in the treatment of children with hematological malignancies. Invasive mold infections such as invasive aspergillosis or mucormycosis have a significant and negative impact on overall outcome in pediatric cancer patients. Although severe prolonged neutropenia is the major risk factor for invasive mold infection, other factors such as steroid exposure and acute or chronic graft-versus-host disease have to be considered in increasing the risk for infection. As clinical signs and symptoms are unspecific, diagnosis of invasive mold infection is mainly based on imaging and microbiological evaluation. Non-culture based tests using biomarkers such as galactomannan are more sensitive than culture-based tests, and there is major development of molecular techniques including next generation sequencing and analysis of cell-free DNA in order to improve both specificity and sensitivity. Antifungal strategies can be divided in prophylaxis (indicated for patients with a natural incidence of fungal infection ≥10%), empirical (eg, prolonged neutopenic fever despite broad-spectrum antibiotics) and pre-emptive therapy and treatment of established infection. Although there are exciting potent novel-class antifungal agents in the pipeline, pediatric approval of antifungal compounds significantly lags that for adult patients. To this end, despite major improvements over the last three decades, invasive mold infection is still a major challenge for pediatric patients with hematological malignancies.