الفهرس | Only 14 pages are availabe for public view |
Abstract Acute lymphoblastic leukemia (ALL) is the most common malignant disease in childhood. It is characterized by neoplastic proliferation and accumulation of B or T lymphoblast in bone marrow or/ and peripheral blood.The current study was conducted to identify the relationship between methotrexate induced hepatic toxicity and ATP Binding Cassette Subfamily B Member 1 (ABCB1 gene) ABCB1 3435 C->T in Children with ALL during maintenance phase. The study included 50 ALL patients during maintenance phase of chemotherapy , they were 36 males and 14 females . their ages ranged from 2.5 to 17.5 years & 50 age and sex matched healthy peers from Pediatric General Outpatient Clinics of Mansoura University Children Hospital (MUCH). All patients and control were subjected to History and physical examination , Thorough detailed history and physical examination. , Abdominal ultrasound finding , liver function test (ALT, AST, total serum bilirubin, direct serum bilirubin, serum albumin) , INR , serum ferritin APRI score , FIB-4 score and AST to ALT ratio index and ATP Binding Cassette Subfamily B Member 1 gene (ABCB1 3435 C->T gene). Results of this study showed that There was a statistically significantly higher proportion of ‘T/T’ genotype in case vs. control (risk genotype). Therefore, there was a significant association between ALL and ‘T/T’ genotype of medium strength. Participants with ‘T/T’ genotype have 5.6 times higher odds to exhibit ALL compared to those with ‘C/C’ genotype. The incidence of methotrexate associated hepatotoxicity was 34% , There was no statistically significant difference in genotype distribution in hepatic toxicity vs. no hepatic toxicity. However, there was a low strength of association (Cramer’s V lies between 0.1 – 0.3). Participants with ‘C/T’ or ‘T/T’ genotype have 2.2- and 1.5-times higher odds to exhibit hepatic toxicity compared to those with ‘C/C’ genotype though it is not statistically significant. There was a statistically significantly lower age and AST/ALT ratio, and a statistically significantly higher APRI score, AST, and ALT in the group with hepatic toxicity vs. the other group without hepatotoxicity. Conclusion: So far, the information on the relationship between the ABCB1 3435 C>T and methotrexate hepatotoxicity in pediatric ALL patients has been limited. The study observed that there was a significant association between ALL and ‘T/T’ genotype. Also there was no statistically significant difference in genotype distribution in hepatic toxicity vs. no hepatic toxicity. |