Parenteral Nutrition in the Pediatric Oncologic Population: Are There Any Sex Differences?

Gender-based medicine is attracting increasing interest every day, but studies on pediatric populations are still limited. In this setting, sex differences among patients undergoing total parenteral nutrition (TPN) have not been previously reported. This study investigated the presence of sex differences in parenteral nutrition composition and outcomes among a cohort of pediatric patients admitted at the Oncohematology and Bone Marrow Transplant Unit of the Institute for Maternal and Child Health "Burlo Garofolo" of Trieste, Italy. For all 145 recruited patients (87 males, 58 females), the following data were collected: age, sex, volume and duration of TPN, macro- and micronutrient composition of TPN bags, electrolytic or blood gases imbalance, glycolipid alterations, liver damage during TPN, and the incidence of sepsis and thrombosis. The analysis showed that females required higher daily phosphate intake (p = 0.054) and essential amino acid supplementation (p = 0.07), while males had a higher incidence of hypertriglyceridemia (p < 0.05) and cholestasis. A higher incidence of sepsis was found in the non-transplanted male population (p < 0.05). No significant differences were appreciable in other analyzed variables. This study aims to create a basis for future gender-based nutritional recommendations in the pediatric field.

Association of genetic polymorphism in the folate metabolic pathway with methotrexate pharmacokinetics and toxicity in childhood acute lymphoblastic leukaemia and malignant lymphoma.

PURPOSE: The objectives of this study were (1) to develop a population pharmacokinetic model of high-dose methotrexate (HD-MTX) in children with acute lymphoblastic leukaemia (ALL) and malignant lymphoma (ML) in order to investigate the influence of common polymorphisms in SLC19A1, MTHFR and ABCB1 on plasma levels of MTX and (2) to estimate MTX exposure in individual patients to study the association of genetic variability in the folate metabolic pathway with MTX toxicity. METHODS: The study population comprised 64 children with ALL/ML (age 1.6-16.8 years) who had received a total of 252 MTX courses (2-4 per patient). Common putative functional polymorphisms in the SLC19A1, MTHFR, MS, MTRR, TS and ABCB1 genes were analysed by PCR-based genotyping. Nonlinear mixed effects modelling was used for the pharmacokinetic analysis. RESULTS: The population typical value of clearance was 7.43 L/h (inter-individual variability 43.9%), central compartment volume was 16.7 L (46.6%), peripheral compartment volume was 2.6 L (63.3%) and distribution clearance was 0.0952 L/h (66.6%). MTX clearance decreased to 73.8% in patients with the MTHFR 677TT genotype. Patients homozygous for the variant MTHFR 1298A > C [odds ratio (OR) 0.14, 95% confidence interval (CI) 0.037-0.54] and SLC19A1 80A > G (OR 0.15, 95% CI 0.039-0.60) were at decreased risk for leucopenia. The TS 2R > 3R polymorphism was associated with a lower incidence of thrombocytopenia (OR 0.15, 95% CI 0.039-0.61) and mucositis (OR 0.016, 95% CI 0.0012-0.20). In contrast, the MTHFR 677TT polymorphism was associated with an increased incidence of mucositis (OR 23, 95% CI 2.1-240). CONCLUSIONS: A population pharmacokinetic model developed in this study implies only a limited influence of genetic factors on the systemic disposition of MTX. Clearance is moderately reduced in patients with the MTHFR 677TT genotype. Genetic polymorphisms in the folate metabolic pathway and SLC19A1 were associated with HD-MTX toxicity.