The Significance Of Thiopurine Genetic Diversity In The Treatment Of Pediatric Acute Lymphoblastic Leukemia.

Background: Acute lymphoblastic leukemia (ALL) is the most common childhood malignancy and 6-mercaptopurine (6-MP) is one of the significant drugs to cure ALL. However, 6-MP toxicity is individualized and influenced by genetic and environmental factors. Further study of genetic variants in Thiopurine Methyltransferase (TPMT) combined with environmental influence constitutes needed research about treatmentrelated toxicity. Purpose: The study examines how genetic variants of TPMT affect 6-MP doses required for ALL patients. Methodology: In this study, the control group consisted of 100 healthy children, while the patient group comprised 100 children with newly diagnosed ALL in the maintenance phase of their treatment. Thiopurine Methyltransferase (TPMT) gene to identify genetic variants. The level of drug toxicity was determined by Complete Blood Count (CBC), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), and serum creatinine before and 6 months after switching to 6-MP therapy. Results: The results show a significant decrease in hemoglobin (HB) and platelet count in patients before treatment and significant improvement after treatment. After treatment, AST and ALT levels were significantly increased, and the White Blood Cells (WBC) count decreased significantly. There were 13% heterozygous patients determined by TPMT genotyping. Conclusion: TPMT genotype before the treatment will help to determine high-risk patients, and accordingly, the dose of 6-MP could be diminished to reduce the risk of toxicity caused by 6-MP.