Invasive fungal diseases in children with hematological malignancies and stem cell transplant recipients

Abstract

Invasive Fungal Disease (IFD) remains a major cause of morbidity and mortality in patients with hematological malignancies or undergoing stem cell transplantation. New surrogate markers of IFD -galactomannan antigen, β-D-glucan, fungal polymerase chain reaction…- and the availability of modern antifungal drugs have changed the management of this serious complication, but both have limitations in children. There are still some unclear issues, particularly in pediatric patients, regardless of the medical and economic possibilities of hospitals: IFD remains difficult to diagnose in a timely way, stem cell transplant recipients have different risk of IFD, antifungal drugs are not free from adverse effects and prospective studies in children are scarce. In this sense, diagnosis criteria have to be assessed, risk stratification should be redefined and the different types of prophylaxis/treatment -prophylaxis, preemptive, empiric and targeted treatment- must be used correctly. We consider low risk for IFD children undergoing autologous stem cell transplantation and children with acute lymphoblastic leukemia, both should receive fluconazole as primary prophylaxis and empiric therapy with an agent with activity against mold. In those undergoing allogeneic stem cell transplantation or chemotherapy for acute myeloid leukemia, prophylaxis should be performed with a mold active agent -triazoles priority-. We rarely use preemptive therapy because of a high false positive rate of galactomannan. In proven and probable IFD we use targeted therapy, selecting a drug based on the type of infection, sensitivity to the drug in our hospital and prior antifungal prophylaxis/treatment. In selected patients, antifungal combination therapy should be a valid option. Despite great advances, there are still thought provoking questions on the diagnosis and management of IFD in children with hematological diseases.