Abstract
Acute Lymphoblastic leukemia (ALL) is the most common children hematologic malignancy diagnosed in children and represents 25% of all malignancies in children. In general, treatment typically comprises 3 phases: induction of remission, intensification (or consolidation), and continuation or antimetabolite-based maintenance therapy with 6-mercaptopurine (6-MP), which is continued until 2-3 years from the time of being diagnosed. However, treatment with 6-MP-related toxicity can lead to life-threatening because of the narrow therapeutic index and is the primary cause of interruption or discontinuation of chemotherapy. The purpose of this study was to investigate the association between genetic polymorphisms of drug-metabolizing enzymes: Thiopurine S-methyltransferase (TPMT), Nucleoside diphosphate-linked moiety X-type motif 15 (NUDT15), and 6-MP related myelosuppression, active metabolites 6-TGN and TPMT enzyme activity in Thai children with ALL. This research study collected a sample of 101 volunteers participating in the research project, with complete data for six visits, one-month intervals, 84 subjects, and 17 subjects undergoing follow-up. Therefore, the data was analyzed from 84 subjects found that patients with NUDT15 genetic polymorphisms only tend to be associated with side effects of Absolute Neutrophil Count grade 3-4 (p-value = 0.08). In addition, following treatment over the past six times, we found that the activity level of TPMT enzyme in the patients with genetic polymorphisms of TPMT and NUDT15 and patients with TPMT polymorphisms only showed a statistically significantly lower TPMT activity when compared with normal genotype patients (p-value = 0.0004, 0.0001, respectively). Patients with TPMT combined with NUDT15 genetic polymorphisms were associated with significantly higher levels of the active metabolite 6-TGN (p-value = 0.0027) compared to patients without genetic polymorphisms. When the average dose of 6-mercaptopurine was analyzed over six months of treatment, it was found that patients with the poor metabolizer NUDT15 genetic polymorphisms had the lowest dose. This was statistically significantly different from patients without genetic polymorphisms in both TPMT and NUDT15 (p-value = 0.05). From the preliminary analysis results, patients with genetic polymorphisms in both or one of the genes are at greater risk of side effects from 6-mercaptopurine treatment. However, the results of this study are preliminary. Suppose the number of patients participating in the project is complete according to the treatment follow-up period. We will analyze the data again in order to make the research results reliable and as close to reality in the population as possible.
