Influence of Methylenetetrahydrofolate Reductase C677T Polymorphism on High-Dose Methotrexate Toxicity in Pediatric Mature B-cell lymphoma Patients
10.19746/j.cnki.issn1009-2137.2024.06.015
- VernacularTitle:MTHFR C677T基因多态性对儿童成熟B细胞淋巴瘤患者大剂量甲氨蝶呤治疗相关毒性的影响
- Author:
Jia-Qian XU
1
,
2
;
Juan WANG
;
Su-Ying LU
;
Yan-Peng WU
;
Lan-Ying GUO
;
Bo-Yun SHI
;
Fei-Fei SUN
;
Jun-Ting HUANG
;
Jia ZHU
;
Zi-Jun ZHEN
;
Xiao-Fei SUN
;
Yi-Zhuo ZHANG
Author Information
1. 广州医科大学附属第五医院儿童肿瘤科,广东广州 510700
2. 中山大学肿瘤防治中心儿童肿瘤科,华南肿瘤学国家重点实验室,肿瘤医学协同创新中心,广东广州 510060
- Keywords:
mature B-cell lymphoma;
children;
methotrexate;
toxicity;
polymorphism
- From:
Journal of Experimental Hematology
2024;32(6):1733-1737
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To investigate the effect of genetic polymorphism of MTHFR C677T (rs1801133) on methotrexate (MTX) related toxicity in pediatric mature B-cell lymphoma patients. Methods:Fifty-eight intermediate and high risk patients under 18 years of age with mature B-cell lymphoma who received 5 g/m2 MTX (24 h intravenous infusion) in Sun Yat-sen University Cancer Center from August 2014 to December 2021 were included,and their toxicity of high-dose MTX (HD-MTX) were monitored and analyzed. Results:Among the 58 pediatric patients,the number of CC,CT,and TT genotypes for MTHFR C677T was 33,19 and 6,respectively. A total of 101 courses of HD-MTX therapy were counted,of which plasma MTX level>0.2 μmol/L at 48 h post-MTX infusion were observed in 35 courses,≤0.2 μmol/L in 66 courses. Inter-group comparison showed that plasma MTX level>0.2 μmol/L at 48 h post-MTX infusion increased the risk of developing oral mucositis (P<0.05). Compared with wild-type (CC genotype),patients in the mutant group (CT+TT genotype) were more likely to develop myelosuppression,manifested as anemia,leucopenia,neutropenia and thrombocytopenia. However,plasma MTX level at 48 h was not associated with MTHFR C677T gene polymorphism. Conclusion:The risk of developing oral mucositis in children with mature B-cell lymphoma is associated with plasma MTX concentration. Polymorphism of MTHFR C677T gene is not related to plasma MTX concentration in children with mature B-cell lymphoma,but is related to grade Ⅲ to Ⅳ hematological toxicity.