title: Association of ITPA genotype with event-free survival and relapse rates in children with acute lymphoblastic leukemia undergoing maintenance therapy.
abstract: Although the treatment of acute lymphoblastic leukemia (ALL) has improved significantly over recent decades, failure due to treatment-related toxicities and relapse of the disease still occur in about 20% of patients. This retrospective study included 308 pediatric ALL patients undergoing maintenance therapy and investigated the effects of genetic variants of enzymes involved in the 6-mercaptopurine (6-MP) metabolism and folate pathway on survival and relapse rates. The presence of at least one of the non-functional ITPA alleles (94C>A and/or IVS2+21A>C variant) was associated with longer event-free survival compared to patients with the wild-type ITPA genotype (p = 0.033). Furthermore, patients carrying at least one non-functional ITPA allele were shown to be at a lower risk of suffering early (p = 0.003) and/or bone marrow relapse (p = 0.017). In conclusion, the ITPA genotype may serve as a genetic marker for the improvement of risk stratification and therapy individualization for patients with ALL.
authors.affiliation: Faculty of Pharmacy, University of Ljubljana, Ljubljana, Slovenia.
authors.forename: Alenka
authors.initials: A
authors.lastname: Smid
authors.affiliation: Faculty of Pharmacy, University of Ljubljana, Ljubljana, Slovenia.
authors.forename: Natasa
authors.initials: N
authors.lastname: Karas-Kuzelicki
authors.affiliation: Faculty of Pharmacy, University of Ljubljana, Ljubljana, Slovenia.
authors.forename: Miha
authors.initials: M
authors.lastname: Milek
authors.affiliation: University Children's Hospital, University Medical Centre Ljubljana, Ljubljana, Slovenia.
authors.forename: Janez
authors.initials: J
authors.lastname: Jazbec
authors.affiliation: Faculty of Pharmacy, University of Ljubljana, Ljubljana, Slovenia.
authors.forename: Irena
authors.initials: I
authors.lastname: Mlinaric-Rascan
mesh_terms: D000293:Adolescent; D000483:Alleles; D000970:Antineoplastic Agents / Q000627:therapeutic use; D002648:Child; D002675:Child, Preschool; D018572:Disease-Free Survival; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D007223:Infant; D008297:Male; D009364:Neoplasm Recurrence, Local / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy / Q000235:genetics*; D011379:Prognosis; D011755:Pyrophosphatases / Q000235:genetics*; D012189:Retrospective Studies; D000097630:Inosine Triphosphatase
chemical_list: D000970:Antineoplastic Agents; D011755:Pyrophosphatases; C511829:ITPA protein, human; D000097630:Inosine Triphosphatase