TY - JOUR
T1 - A Risk Scoring Model for High-Dose Methotrexate-Induced Liver Injury in Children With Acute Lymphoblastic Leukemia Based on Gene Polymorphism Study
AU - He, Xia
AU - Yao, Pingli
AU - Li, Mengting
AU - Liang, Hong
AU - Liu, Yilong
AU - Du, Shan
AU - Zhang, Min
AU - Sun, Wenzhuo
AU - Wang, Zeyuan
AU - Hao, Xin
AU - Yu, Ze
AU - Gao, Fei
AU - Liu, Xinxia
AU - Tong, Rongsheng
N1 - Funding Information:
This work was supported by National key R&D Program of China (2020YFC2005500) and Key Research and Development Program of Science and Technology Department of Sichuan Province (2019YFS0514) and Sichuan Medical Association (S16068) and Sichuan Provincial People’s Hospital (2020LY06) for RT. This work was also supported by Sichuan Provincial People’s Hospital (2015QN08) and Health and Family Planning Commission of Sichuan Province (16PJ480) for XH. This work was also supported by The Science and Technology Project of Health and Family Planning Commission of Sichuan Province (19PJ269) and Research Fund for the Doctoral Program of Sichuan Academy of Medical Sciences and Sichuan Provincial People’s Hospital (2015BS04) for XL.
Publisher Copyright:
© Copyright © 2021 He, Yao, Li, Liang, Liu, Du, Zhang, Sun, Wang, Hao, Yu, Gao, Liu and Tong.
PY - 2021/9/29
Y1 - 2021/9/29
N2 - A study on 70 acute lymphoblastic leukemia (ALL) children (age ≤16 years) treated with high-dose methotrexate (HD-MTX) in Sichuan Provincial People’s Hospital was conducted. The aim of the study was to establish a risk-scoring model to predict HD-MTX-induced liver injury, considering gene polymorphisms’ effects. Data screening was performed through t-test, chi-square test, and ridge regression, and six predictors were identified: age, MTRR_AA, MTRR_AG, SLCO1B1_11045879_CC, albumin_1 day before MTX administration, and IBIL_1 day before MTX administration (p < 0.1). Then, the risk-scoring model was established by ridge regression and evaluated the prediction performance. In a training cohort (n = 49), the area under the curve (AUC) was 0.76, and metrics including accuracy, precision, sensitivity, specificity, positive predictive value, and negative predictive value were promising (0.86, 0.81, 0.76, 0.91, 0.81, 0.88, respectively). In a test cohort (n = 21), the AUC was 0.62 and negative predictive value was 0.80; other evaluation metrics were not satisfactory, possibly due to the limited sample size. Ultimately, the risk scores were stratified into three groups based on their distributions: low- (≤48), medium- (49–89), and high-risk (>89) groups. This study could provide knowledge for the prediction of HD-MTX-induced liver injury and reference for the clinical medication.
AB - A study on 70 acute lymphoblastic leukemia (ALL) children (age ≤16 years) treated with high-dose methotrexate (HD-MTX) in Sichuan Provincial People’s Hospital was conducted. The aim of the study was to establish a risk-scoring model to predict HD-MTX-induced liver injury, considering gene polymorphisms’ effects. Data screening was performed through t-test, chi-square test, and ridge regression, and six predictors were identified: age, MTRR_AA, MTRR_AG, SLCO1B1_11045879_CC, albumin_1 day before MTX administration, and IBIL_1 day before MTX administration (p < 0.1). Then, the risk-scoring model was established by ridge regression and evaluated the prediction performance. In a training cohort (n = 49), the area under the curve (AUC) was 0.76, and metrics including accuracy, precision, sensitivity, specificity, positive predictive value, and negative predictive value were promising (0.86, 0.81, 0.76, 0.91, 0.81, 0.88, respectively). In a test cohort (n = 21), the AUC was 0.62 and negative predictive value was 0.80; other evaluation metrics were not satisfactory, possibly due to the limited sample size. Ultimately, the risk scores were stratified into three groups based on their distributions: low- (≤48), medium- (49–89), and high-risk (>89) groups. This study could provide knowledge for the prediction of HD-MTX-induced liver injury and reference for the clinical medication.
KW - acute lymphoblastic leukemia
KW - children
KW - gene polymorphism
KW - high-dose methotrexate
KW - liver injury
KW - ridge regression model
UR - http://www.scopus.com/inward/record.url?scp=85117097211&partnerID=8YFLogxK
U2 - 10.3389/fphar.2021.726229
DO - 10.3389/fphar.2021.726229
M3 - Article
AN - SCOPUS:85117097211
SN - 1663-9812
VL - 12
JO - Frontiers in Pharmacology
JF - Frontiers in Pharmacology
M1 - 726229
ER -