Risk factors and prognostic analysis of delayed excretion of high-dose methotrexate in the treatment of pediatric medulloblastoma

ZHANG Jin; GONG Xiao-jun; SUN Yan-ling; DU Shu-xu; WU Wan-shui; WANG Tian-you

doi:10.19538/j.ek2025080615

Abstract：Objective High-dose methotrexate(HD-MTX)is a widely employed chemotherapy regimen for the treatment of medulloblastoma in pediatric patients.This study is aimed to investigate the risk factors associated with delayed methotrexate excretion and to evaluate the correlation between delayed excretion and the prognosis of the children.Methods A retrospective analysis was conducted on children with medulloblastoma who received high-dose methotrexate(HD-MTX)treatment in the Department of Pediatrics of Beijing Shijitan Hospital,Capital Medical University between January 2019 and December 2020.Clinical data were collected,including gender,age at onset,histological type,molecular subtype,and disease stage.Additionally,24-hour(C24)and 42-hour(C42)blood drug concentrations,as well as blood routine and liver and kidney function indices,were recorded.The Mann-Whitney U test and Kruskal-Wallis H test were used to analyze the differences in blood drug concentrations across various clinical characteristics.Logistic regression analysis was employed to identify risk factors associated with delayed drug excretion.Furthermore,univariate and multivariate survival analyses were conducted using the Cox proportional hazards model.Results A total of 41 children(24 boys,17 girls)with medulloblastoma were enrolled in this study,with a median age of 2.9 years(ranging from 0.6 to 13.6 years)at diagnosis.A total of 167 HD-MTX chemotherapy sessions were conducted,of which 31 sessions(18.6％)exhibited delayed excretion.Intrathecal MTX injection was performed in 133 sessions(80％).C24 levels were significantly elevated in children who did not receive intrathecal injection(P=0.017)and those with leukopenia(P=0.044),and C42 levels were significantly elevated in children aged 3 years or older(P=0.006)and those with cerebrospinal fluid metastasis(P＜0.001).No statistically significant difference in adverse reactions was observed between children with normal excretion and those with delayed excretion.Cerebrospinal fluid metastasis was identified as an independent risk factor for delayed excretion in children with medulloblastoma(P=0.002,OR=4.864,95％CI 1.797-13.167).Delayed MTX excretion was not a factor affecting the prognosis of children with medulloblastoma.Conclusion The HD-MTX treatment exhibits favorable safety in pediatric patients with medulloblastoma.Cerebrospinal fluid metastasis is identified as a risk factor for delayed MTX excretion;however,the delayed excretion does not have a significant impact on the prognosis of the children.