ALL-198: Pharmacogenetic Study on Central Nervous System Relapse Among Patients with Pediatric Acute Lymphoblastic Leukemia in Hungary

Abstract

<h3>Context</h3> Pediatric acute lymphoblastic leukemia (ALL) is the most common pediatric malignancy. In order to further improve results, gaining a better understanding of its complications is needed. Central nervous system (CNS) is an important site of relapse in ALL. In this study, the incidence of CNS relapse (REL) was investigated. <h3>Objective</h3> CNS-REL might associate with interindividual genomic differences. Single nucleotide polymorphisms (SNPs) are able to affect the function of metabolizing enzymes and transporters located in blood-brain-barrier (BBB). This may change the concentration of chemotherapeutic agents in CNS. <h3>Design</h3> Clinical data were collected retrospectively. DNA was isolated from peripheral blood collected in remission (QIAmp® Blood DNA Maxi Kit, Qiagen), genotyping was performed using TaqMan® OpenArray™ Genotyping System (Thermo Fisher Scientific). Association between 57 SNPs and the incidence of CNS-REL was studied. Logistic regression adjusted for potential confounders and Cox-regression to study survival were performed using SPSS v25 and RStatistics. <h3>Patients</h3> Study population consisted of 676 pediatric patients (0-18 years) diagnosed with ALL between 1990-2017. Cases (n=16) were isolated CNS-RELs or combined CNS and bone marrow RELs. <h3>Main outcome measures</h3> Candidate gene association study was performed to analyze SNPs' associations with the incidence of CNS- REL. <h3>Results</h3> GSTT1*0 genotype associated with the presence of CNS-REL (OR=3.95; P=0.002) in our cohort. <h3>Conclusions</h3> GSTT1 deletion correlated with the incidence of CNS-REL. This result may contribute to personalized medicine in ALL. <h3>Acknowledgements</h3> The study was supported by the UNKP-19-3-IV New National Excellence Program of the Ministry for Innovation and Technology; the National Research, Development and Innovation Office (NKFIH) Grants No. PD109200 (ÁF Semsei) and K115861 (DJ Erdélyi) and by the Hungarian Paediatric Oncology Group (07/MGYH-MGYGYT/2018).