Comparative study of prophylaxis with high and low doses of voriconazole in children with malignancy

Background and Purpose:Children with acute myeloid leukemia and relapses of leukemia are at high risk of developing fungal infections and need antifungal prophylaxis. This study aimed to compare the efficacy and toxicity of two different dosage regimens of voriconazole (VRCZ) during prophylactic administration in children with malignancyand neutropenia. Materials and Methods:This prospective study was conducted at the Belarusian Research Center for Pediatric Oncology, Hematology, and Immunology fromMay ۲۰۱۷ to December ۲۰۱۹. The present study included ۲۱ Caucasian patients with malignant hematological diseases (۲۰ patients with acute myeloid leukemia and relapses of leukemia and ۱ patient with Non-Hodgkin's lymphoma) aged ۲-۱۸ years. All patients were randomly divided into two groups that received different dosage regimens of VRCZ prophylaxis. Patients in the “high-dose” group received VRCZat a dose of ۹ mg/kg twice a day PO, or ۸ mg/kg twice a day IV without a loading dose (children of ۲-۱۱ and adolescents and of ۱۲-۱۴ years old with Results:In the high-dosegroup (n=۲۰ episodes of prophylaxis), invasive fungal infections (IFI) signs were recorded in one (۵%) case. In the low-dose group (n=۲۰ episodes), IFI signs were observed in six (۳۰%) cases (P=۰.۰۳۷۵). The residual serum concentration was significantly higher in patients who received high doses of VRCZ (p <۰.۰۰۰۱). Most patients with IFI (n=۶, ۸۶%) had a mean value (i.e., Conclusion:The likelihood of IFI was significantly lower in children who prophylactically received VRCZ in high doses (P=۰.۰۳۷۵) and had ≥ ۰.۷۴ μg/ml residual serum concentration of the medication (P=۰.۰۲۵۸). Residual serum concentration of VRCZ reached a plateau by day sixth of the treatment. In children, the dosage was the only highly significant factor affecting the metabolism of VRCZ.

Keywords:

Fungal infections , children , Prophylaxis , voriconazole