title: CDA deficiency as a possible culprit for life-threatening toxicities after cytarabine plus 6-mercaptopurine therapy: pharmacogenetic investigations.
abstract: We describe here the case of a 7-year old girl with lymphoma who developed life-threatening toxicities upon cytarabine plus mercaptopurine. Surprisingly, initial investigations on canonical thiopurine methyltransferase genetic polymorphism proved to be negative. We focused next on deregulations affecting the CDA gene implicated in the liver disposition of cytarabine. This patient was homozygous for both the 79A>C and the -31delC polymorphisms on the CDA gene and promoter, two genotypes with reported opposite effects on CDA phenotype. To determine the CDA status of this patient, additional functional testing was performed and eventually demonstrated that this patient was a poor metabolizer. This case demonstrates that besides affecting thiopurine methyltransferase, dysregulations with CDA should be screened to anticipate toxicities with the cytarabine plus mercaptopurine combination.
authors.affiliation: Laboratoire de Pharmacocinétique, La Timone University Hospital of Marseille, UMR 911, Aix-Marseille University, Marseille, France.
authors.forename: Joseph
authors.initials: J
authors.lastname: Ciccolini
authors.forename: Alexandre
authors.initials: A
authors.lastname: Evrard
authors.forename: Lithaty
authors.initials: L
authors.lastname: M'Batchi
authors.forename: Bertrand
authors.initials: B
authors.lastname: Pourroy
authors.forename: Cédric
authors.initials: C
authors.lastname: Mercier
authors.forename: Athanassios
authors.initials: A
authors.lastname: Iliadis
authors.forename: Bruno
authors.initials: B
authors.lastname: Lacarelle
authors.forename: Arnaud
authors.initials: A
authors.lastname: Verschuur
authors.forename: L'Houcine
authors.initials: L
authors.lastname: Ouafik
authors.forename: Nicolas
authors.initials: N
authors.lastname: André
mesh_terms: D002648:Child; D003561:Cytarabine / Q000627:therapeutic use / Q000633:toxicity*; D003564:Cytidine Deaminase / Q000235:genetics*; D004338:Drug Combinations; D005091:Exons; D005260:Female; D006720:Homozygote; D006801:Humans; D008223:Lymphoma / Q000188:drug therapy*; D015122:Mercaptopurine / Q000627:therapeutic use / Q000633:toxicity*; D008780:Methyltransferases / Q000235:genetics; D017354:Point Mutation; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic; D017384:Sequence Deletion
chemical_list: D004338:Drug Combinations; D003561:Cytarabine; D015122:Mercaptopurine; D008780:Methyltransferases; C022745:thiopurine methyltransferase; D003564:Cytidine Deaminase