Abstract
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.
Highlights
Acute lymphoblastic leukemia (ALL) is a malignancy with high incidence in children aged between 1 and 5 years, which needs a long course of treatment (Preethi, 2014)
The inclusion criteria were 1) Han children aged 1–16 years who were hospitalized and used the Chinese Children’s Leukemia Group (CCLG)-2008 chemotherapy regimen; 2) all patients were completely relieved after induction therapy and were in the consolidation phase of High-dose methotrexate (HD-MTX) treatment; 3) their liver and kidney function indexes were normal before HD-MTX treatment; 4) parents or guardians agreed to sign the informed consent
A total of 70 children with ALL were enrolled in our study, including 45 males (64.3%) and 25 females (35.7%), and the median age was 7.5 in a range between 1 and 16 years
Summary
Acute lymphoblastic leukemia (ALL) is a malignancy with high incidence in children aged between 1 and 5 years, which needs a long course of treatment (Preethi, 2014). Liver Injury in Leukemia Children improved significantly over the past years; the 5-years survival rate is expected to increase up to 90% (Imanishi et al, 2007; Yang et al, 2012). Being a result of longterm MTX treatment, the polyglutamates accumulate to higher levels, leading to a longer intracellular presence of the drug (Elbarbary et al, 2016). MTX-induced liver injury has been studied in patients aged >18 years with rheumatoid arthritis (RA); for instance, Japanese researchers investigated the risk factors for abnormal hepatic enzyme elevation by MTX in adult RA patients (Hakamata et al, 2018). The influencing factors of HDMTX and its risk prediction model for ALL children have not been sufficiently explored
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