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Pharmacogenetic aspect of busulfan based conditioning regimens prior to allogenic hematopoietic stem cell transplantation in children

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Defense Thèse de privat-docent : Univ. Genève, 2013
Abstract Allogenic hematopoietic stem cell transplantation (HSCT) is a well-established but complex treatment option for malignant and non-malignant disorders in pediatrics. Most commonly used myeloablative and non-myeloablative conditioning regimens in children comprise alkylating agents, such as busulfan (BU) and cyclophosphamide (CY). There exists inter-individual variability in the pharmacokinetics of these alkylating agents resulting in either poor conditioning of the patient and therefore relapse or rejection due to under exposures or occurrence of toxicities due to over exposures. With the introduction of the intravenous formulation of BU, this variability has been reduced but still could not be fully predicted. Interestingly, inter and intra-individual variability of BU kinetics is more common in children compared to adults and toxicity of BU based regimens is still a concern. It has been hypothesized that some of this variability in treatment outcomes, especially the toxicity might be predicted by genetic variants of enzymes involved in the metabolism of BU and co-administered agent CY. This review intends to summarize the studies performed to date on the pharmacokinetics and mainly on the pharmacogenetics of BU myeloablative therapy, specifically in relation to children.
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ANSARI DJABERI, Marc Georges. Pharmacogenetic aspect of busulfan based conditioning regimens prior to allogenic hematopoietic stem cell transplantation in children. Université de Genève. Thèse de privat-docent, 2013. https://archive-ouverte.unige.ch/unige:38558

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Deposited on : 2014-07-08

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