The Effect of Iron Overload on the Mobilization of Peripheral Blood Hematopoietic Stem Cells in Pediatric Patients with Thalassemia Major.

INTRODUCTION: The purpose of this study was to examine the effect of iron overload on the mobilization of peripheral blood stem cells (PBSCs) in pediatric patients with ß-thalassemia major (TM). METHODS: We retrospectively reviewed the records of 226 patients with TM from whom PBSCs were collected. Iron overload was based on serum ferritin level, and liver and cardiac iron overload was measured by magnetic resonance imaging (MRI) T2*. RESULTS: The mean age of the TM patients was 7.35 ± 3.41 years. Of the patients, only 171 received MRI. Of the 171 patients, 35 had normal liver iron levels, 39 mild liver iron overload, 90 intermediate liver iron overload, and 7 severe liver iron overload. The intermediate + severe group was associated with significantly higher age and BMI and lower leukapheresis product white blood cell count and CD34+ cell levels (all, p < 0.05). CONCLUSION: Leukapheresis indices were similar between patients with different degrees of iron overload according to the ferritin level and cardiac iron overload, in which the later might be due to the small number of patients with cardiac overload. In patients with TM, the intermediate and severe liver iron overload was associated with poorer mobilization of PBSCs.

Therapeutic drug monitoring and CYP2C19 genotyping guide the application of voriconazole in children.

Background: This study used therapeutic drug monitoring (TDM) and CYP2C19 gene polymorphism analysis to explore the efficacy and safety of different doses of voriconazole (VCZ) for the clinical treatment of pediatric patients, with the aim of providing guidelines for individualized antifungal therapy in children. Methods: Our study enrolled 94 children with 253 VCZ concentrations. The genotyping of CYP2C19 was performed by polymerase chain reaction (PCR)-pyrosequencing. VCZ trough concentration (Ctrough) was detected by high-performance liquid chromatography-tandem mass spectrometry. SPSS 23.0 was used to analyze the correlations between VCZ concentration, CYP2C19 phenotype, adverse effects (AEs), and drug-drug interactions. Results: A total of 94 children aged between 1 and 18 years (median age 6 years) were enrolled in the study. In total, 42.6% of patients reached the therapeutic range at initial dosing, while the remaining patients reached the therapeutic range after the adjustment of the dose or dosing interval. CYP2C19 gene polymorphism was performed in 59 patients. Among these patients, 24 (40.7%) had the normal metabolizer (NM) phenotype, 26 (44.1%) had the intermediate metabolizer (IM) phenotype, and 9 (15.3%) had the poor metabolizer (PM) phenotype. No cases of the rapid metabolizer (RM) or ultrarapid metabolizer (UM) phenotypes were found. The initial VCZ Ctrough was significantly higher in patients with the PM and IM phenotypes than in those with the NM phenotype. The combination of immunosuppressive drugs (ISDs) did not affect VCZ Ctrough. The incidence of AEs was 25.5%, and liver function damage (46.2%) and gastrointestinal reactions (19.2%) were the most common. Conclusions: Our study showed significant individual differences of VCZ metabolism in children. Combining TDM with CYP2C19 gene polymorphism has important guiding significance for individualized antifungal therapy in pediatric patients.