# Detecting Methotrexate in Pediatric Patients Using Artificial Neural Networks
###### Abstract
The study [16] identified that the 677 TT genotype of the MTHFR gene is associated with decreased clearance of MTX and that genetic polymorphisms in the folate pathway and SLC19A1 were associated with MTX toxicity. Five variants in four genes (MTHFR, ABCB1, ABCC2, and TYMS) were shown to be associated with toxicity, and they also found a statistically significant association between MTHFR rs1801133 and anemia in the consolidation phase [17]. By investigating key genes involved in the MTX pathway, the authors of [18] detected genetic polymorphisms associated with MTX pharmacokinetics, toxicity, and outcomes. The strongest association was observed between the SLCO1B1 rs4149056 SNP and MTX pharmacokinetic parameters such as clearance \(C_{\text{24h}}\) and \(AUC_{\text{0-48h}}\). The aim of the study [19] was to analyze the influence of genetic polymorphisms in RFC1 (reduced folate carrier), MS (methionine synthase), and MTRR (methionine synthase reductase) on the occurrence of adverse effects from MTX therapy, such as hematological disorders, hepatotoxicity, and nephrotoxicity. Polymorphisms in genes coding drug-metabolizing enzymes may cause individual differences in the effectiveness and toxicity of many medications, including cytostatics. In ALL [20], too many stem cells become a type of white blood cell called lymphocytes. These lymphocytes are also called lymphoblasts or leukemic cells. There are three types of lymphocytes: (1) B lymphocytes produce antibodies to help fight infections, (2) T lymphocytes (3) natural aggressor cells attack cancer cells or viruses. The factors that increase the risk of contracting a disease are called risk factors. Having a risk factor does not mean that you are going to get cancer, and not having a risk factor does not mean that you are not going to get cancer. Possible risk factors for ALL include the following aspects: having a brother with leukemia, having been exposed to X-rays before birth, being exposed to radiation, having had previous treatment with chemotherapy or other medications that weaken the immune system, and having certain genetic disorders such as Down syndrome; possible signs of childhood ALL include fever and bruises [21]. MTX is an antimetabolic that has anti-proliferative and immunosuppressive activity by competitively inhibiting the enzyme di-hydrofolate reductase (DFR), a key enzyme in the metabolism of folic acid that regulates the amount of intracellular folate available for the synthesis of proteins and nucleic acids. It prevents the formation of tetrahydrofolate necessary for the synthesis of nucleic acids. It catalyzes the reduction of 5.10 methylene tetrahydrofolate to 5 methyl tetrahydrofolate, a form in which endogenous folate circulates, which is the donor of methyl groups necessary for the conversion of homocysteine to methionine during protein synthesis. This mainly affects cells that are in the phase of the cell cycle [1]. Mucositis is caused by the rapid proliferation of epithelial cells, causing the orophynx and gastrointestinal tract to be particularly vulnerable to treatment with MTX. The combination of intensive chemotherapy and radiotherapy increases the damage of this drug to the level of the mucous membranes. Many factors are involved in the pathophysiology of mucositis, beginning with damage to connective tissue and blood vessels in the submuc. This is followed by the release of proinflammatory cytokines and reactive oxygen species that exacerbate vascular damage and turn the process into a vicious circle that leads to tissue destruction. Bacterial colonization of ulcers increases tissue damage by the inflammation that is generated to control the infection. MTX poisoning can be avoided in the following way: it should not be administered in patients with renal or hepatic deficiency or both and also in those with a pleural effusion or ascites to avoid plasma concentrations of MTX, which are a predictive value for such toxicity. In addition, constant monitoring to reverse the undesirable effects of the medication should be undertaken.