Judit C. Sági1, Anna Artner1, Nóra Kutszegi1, Andrea Kelemen1, Bálint Egyed1,2, Andrea Rzepiel2, Gábor T. Kovács2, Csaba Szalai1,3, Dániel J. Erdélyi2, Ágnes F. Semsei1, Andras Gezsi1
1Department of Genetics, Cell- and Immunobiology, Semmelweis
University, Budapest, Hungary
22nd Department of Paediatrics, Semmelweis University, Budapest,
3Heim Pal Children Hospital, Budapest, Hungary
The prognosis of pediatric acute lymphoblastic leukemia (ALL) has a favorable prognosis thanks to the combined chemotherapy used nowadays, however, relapsed disease and serious adverse effects caused by the treatment still needs to take in consideration. In this study, we focused on relapse recurring in the central nervous system (CNS) and on the adverse effect, acute toxic encephalopathy (ATE). The neurologic symptoms of ATE are diverse like depressed level of consciousness, seizures, palsies, aphasia. Interindividual differences regarding the diversity of symptoms could be explained by the genetic background.
We hypothesized genetic polymorphisms can influence these events modifying the function of enzymes and transporters in the metabolism of chemotherapeutic drugs resulting in relapse or toxicity.
Our study population consisted of pediatric patients with ALL, 672 patients for ATE and 842 for CNS relapse projects, respectively. Clinical data were collected retrospectively from the patients’ medical records. ATE symptoms were graded according to the Common Terminology Criteria for Adverse Events v3.0. DNA was isolated from blood collected in remission (QIAmp® Blood DNA Maxi Kit, Qiagen). Genotyping was performed using TaqMan® OpenArray™ Genotyping System (Thermo Fisher Scientific). We studied the association between 62 single nucleotide polymorphisms (SNPs) and relapse/ ATE. Logistic regression adjusted for potential confounders was performed using SPSS 25.
ATE occured in 6,5% of the patients. GSTP1 rs1695 G allele protected against the toxic event (p=0.002; OR=0.239; CI95%=0.096-0.597). Evaluating the association between these 62 SNPs and relapse disease is still running.
Neuroprotective function of GSTP1 expressed in cerebral capillary endothelium has been confirmed. In our analysis GSTP1 variant associated with reduced incidence of ATE. Our result might contribute to personalized medicine in pediatric ALL with a possible genetic marker for risk of ATE.
This study is supported by the Hungarian Paediatric Oncology Network (07/MGYH-MGYGYT/2018).
7/4.Molecular Medicine, Basis of Human Molecular Genetics and Gene Diagnostics
Agnes Felne dr. Semsei