Invasive fungal disease (IFD) still represents a major cause of morbidity and mortality in pediatric cancer patients as well as in patients with primary immunodeficiencies. Aspergillus spp and Candida spp are the most common pathogens causing IFD in these patient populations, whereas infections caused by mucormycetes occur less often, but are associated with an extremely poor prognosis. Patients at high risk for IFD are children undergoing treatment for acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), relapse of acute leukemia and patients undergoing hematopoietic stem cell transplantation (HSCT). Notably, children with ALL are a heterogenous group, and the risk for IFD depends on additional factors such as age and treatment protocol used. In addition, children suffering from granulocyte defects such as chronic granulomatous disease (CGD) are at high risk for IFD. As early and reliable diagnosis of IFD is difficult in these patient populations and early treatment of IFD is associated with better outcome, current guidelines recommend antifungal prophylaxis in patients with high risk for IFD. Non-pharmacological prophylactic measures include hand washing (against Candida spp), HEPA-filtered rooms and the avoidance of construction areas (against Aspergillus spp). Several classes of antifungals such as polyenes, triazoles and echinocandins are suitable for pharmacological antifungal prophylaxis. Unfortunately, not all compounds which have been proven to be effective in the adult population are approved for the use in the pediatric population, as it is the case for posaconazole. However, in particular in children undergoing therapy for ALL, where vincristine is the cornerstone of treatment, the prophylactic use of azoles may be problematic due to significant drug-drug interactions. In contrast to the triazoles, polyenes and echinocandines are available as intravenous formulation only. As daily administration of these compounds may significantly decrease quality of life, preliminary studies are reporting on intermittent dosing. The session will discuss 1) indication of antifungal prophylaxis 2) potential antifungal drugs for prophylaxis and 3) current data on efficacy and adverse events of studies on antifungal prophylaxis in children.
Full conference title:
- TIMM 8th (2017)