title: An analysis of the therapeutic benefits of genotyping in pediatric hematopoietic stem cell transplantation.
abstract: Hematopoietic stem cell transplantation is a high-risk procedure that is offered, with curative intent, to patients with malignant and nonmalignant disease. The clinical benefits of personalization of therapy by genotyping have been demonstrated by the reduction in transplant related mortality from donor-recipient HLA matching. However, defining the relationship between genotype and transplant conditioning agents is yet to be translated into clinical practice. A number of the therapeutic agents used in stem cell transplant preparative regimens have pharmacokinetic parameters that predict benefit of incorporating pharmacogenomic data into dosing strategies. Busulfan, cyclophosphamide, thio-TEPA and etoposide have well-described drug metabolism pathways, however candidate gene studies have identified there is a gap in the identification of pharmacogenomic data that can be used to improve transplant outcomes. Incorporating pharmacogenomics into pharmacokinetic modeling may demonstrate the therapeutic benefits of genotyping in transplant preparative regimen agents.
authors.affiliation: Kids Cancer Centre, Sydney Children's Hospital, Randwick, NSW, Australia.
authors.forename: Felicity A
authors.initials: FA
authors.lastname: Wright
authors.forename: Mary
authors.initials: M
authors.lastname: Bebawy
authors.forename: Tracey A
authors.initials: TA
authors.lastname: O'Brien
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D005838:Genotype; D005982:Glutathione Transferase / Q000235:genetics / Q000378:metabolism; D006086:Graft vs Host Disease / Q000209:etiology / Q000628:therapy; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects; D006801:Humans; D007527:Isoenzymes; D008020:Life Support Care; D008212:Lymphocyte Depletion; D010597:Pharmacogenetics; D011110:Polymorphism, Genetic; D057285:Precision Medicine; D011379:Prognosis; D019172:Transplantation Conditioning / Q000379:methods; D014184:Transplantation, Homologous; D016896:Treatment Outcome
chemical_list: D007527:Isoenzymes; D005982:Glutathione Transferase
keywords: pediatrics; pharmacogenetics; polymorphism; stem cell transplantation; transplantation conditioning