- Optimization of pediatric haematopoietic stem cell transplant outcomes through the application of pharmacokinetics and supportive care
- Award date
- 4 December 2013
- Number of pages
- Document type
- PhD thesis
- Faculty of Medicine (AMC-UvA)
The research described in this thesis aims to optimize drug-related outcomes in children undergoing haematopoietic stem cell transplant (HSCT). The use of pharmacokinetics to individualize exposure to busulfan and cyclosporine; the assessment of the symptom burden of children receiving chemotherapy including HSCT conditioning and the application of evidence to improve chemotherapy-induced nausea and vomiting (CINV) control during conditioning are emphasized.
Busulfan pharmacokinetics in children and the association between area-under-the-curve (AUC) and HSCT outcomes as well as the relationship between cyclosporine pharmacokinetics and acute graft-vs-host disease (aGVHD) are described. Limited sampling strategies for busulfan and cyclosporine AUC determination were developed and validated which will enable future research on the clinical impact of busulfan and cyclosporine AUC monitoring.
A survey of parents of children receiving cancer treatment helped us understand the symptom burden these children experience. As a first step to adopting, adapting or developing a pediatric self-report symptom assessment tool, we evaluated the published pediatric symptom assessment scales. Since none had been used to screen for symptoms, we established the need to develop such a tool.
We used established guideline adaptation methodology to develop guidelines for the classification of chemotherapy emetogenicity and to prevent acute chemotherapy-induced nausea and vomiting in children. To facilitate future investigation of the efficacy and safety of aprepitant in young children, an extemporaneous oral liquid aprepitant formulation with acceptable stability was developed.
In summary, this thesis focuses on optimization of drug-related outcomes in children undergoing HSCT with a focus on busulfan and cyclosporine pharmacokinetics and supportive care.
- Research conducted at: Universiteit van Amsterdam
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