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Study On The Influencing Factors Ot Methotrexate Plasma Concentration And The Relationship Between MTHFR C677T Gene Polymorphism And HD-MTX Toxic Side Effects In Children With Acute Lymphoblastic Leukemia

Posted on:2020-10-30Degree:MasterType:Thesis
Country:ChinaCandidate:T T WuFull Text:PDF
GTID:2404330578979747Subject:Pediatrics
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Objective1?By monitoring the 48-hour blood concentration of children with acute lymphoblastic leukemia(ALL)after treatment with high-dose methotrexate(HD-MTX)in CCCG-ALL 2015 regimen,the relationship between influencing factors such as gender,age,weight,risk and excretion delay was analyzed.In addition,in clinical applications,risk factors are avoided as much as possible,and the incidence of excretion delay is reduced.2?By detecting the single nucleotide polymorphism(SNP)of the MTHFR C677T locus in children with acute lymphoblastic leukemia,the relationship between the MTHFR C677T gene polymorphism and drug-related side effects after high-dose methotrexate chemotherapy was investigated.Improve the safety and rationality of HD-MTX clinical application,and avoid the occurrence of toxic side reactions as much as possible.Methods1?A total of 532 children with B-ALL were selected from the Department of Hematology,Children's Hospital Affiliated to Suzhou University from January 1,2015 to August 31,2018,and treated with CCCG-ALL 2015 HD-MTX regimen.The clinical data of sex,age,height,weight,risk,fusion gene and chromosome,and the blood MTX concentration at 48 hours after initial HD-MTX regimen were analyzed.IBM SPSS 20.0 statistical software was used to process the data,and the correlation between the influencing factors of appeal and the defecation delay was analyzed.2?A retrospective analysis was made of 144 children with ALL of Han nationality who were first diagnosed in the Department of Hematology,Children,s Hospital Affiliated to Suzhou University from May 2008 to August 2018.The genotype of C677T locus of MTHFR gene was analyzed by gene detection technology before HD-MTX treatment.The serum MTX concentration and drug-related side effects(such as gastrointestinal reaction,mucosal damage,bone marrow suppression,liver and kidney function damage)of children treated with HD-MTX were collected,and the relationship between MTHFR C677T gene polymorphism and toxic side effects of HD-MTX chemotherapy was analyzed.Results1?Among the 532 children with B-ALL included in the study,88 had delayed excretion,so the rate of delay in excretion was 16.5%.Univariate analysis showed that 48-hour MTX excretion delay was significantly correlated with age,weight,body mass index,risk and liver function before chemotherapy(P<0.05),but not with sex,body surface area,fusion gene type and chromosome number.Multivariate analysis showed that the risk of MTX in children was an independent factor leading to delayed excretion of MTX in 48 hours.2?The risk of platelet or neutrophil decrease in CT+TT genotype carriers at MTHFR C677T locus was significantly higher than that in CC genotype carriers(P<0.05).The risk of platelet or neutrophil decrease in CT+TT genotype carriers was 2.223 times(95%Cl:1.472-3.356)and 4.643 times(95%Cl:1.641-13.141),respectively.Conclusions1?Age,risk,body weight,body mass index and liver function of children with acute lymphoblastic leukemia have influence on the occurrence of delayed methotrexate excretion.The risk of ALL is an independent factor affecting delayed methotrexate excretion for 48 hours.2?The MTHFR C677T gene polymorphism is associated with bone marrow suppression in children with acute lymphoblastic leukemia after high-dose methotrexate treatment.The risk of thrombocytopenia and neutropenia in CC genotype carriers is lower than that in CT+TT genotype carriers.
Keywords/Search Tags:Acute lymphoblastic leukemia, Methotrexate, plasma Concentration, Excretion delay, Genetic polymorphism, Methylenetetrahydrofolate Reductase, Toxicity
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