Pharmacogenetic Aspects of Drug Metabolizing Enzymes in Busulfan Based Conditioning Prior to Allogenic Hematopoietic Stem Cell Transplantation in Children
Patricia Huezo-Diaz, Chakradhara Rao S. Uppugunduri, Anuj Kumar Tyagi, Maja Krajinovic and Marc AnsariAffiliation:
Department of Pediatrics, Onco-Hematology unit; University Hospitals of Geneva, Rue Willy Donzé 6, 1211 Geneva 14, Switzerland.
AbstractAllogenic hematopoietic stem cell transplantation (HSCT) is a well established but complex treatment option for malignant and non-malignant disorders in pediatric patients. Most commonly used myeloablative and non-myeloablative conditioning regimens in children comprise alkylating agents, such as busulfan (BU) and cyclophosphamide. Inter-individual variability in the pharmacokinetics of BU can result in altered conditioning of the patient and therefore lead to 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 cannot be fully predicted. 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 BU pharmacokinetics and treatment outcomes, especially the toxicity, might be predicted by genetic variants of enzymes involved in the metabolism of BU. This review intends to summarize the studies performed to date on the pharmacokinetics and pharmacogenetics of BU based conditioning, specifically in relation to children.
Busulfan, CYP, dose adjustment, GSTA, pharmacogenetics, pharmacokinetics, SNP, sulfolane, TDM.
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