Variants in TPMT, ITPA, ABCC4 and ABCB1 Genes As Predictors of 6-mercaptopurine Induced Toxicity in Children with Acute Lymphoblastic Leukemia.

摘要: Background Acute lymphoblastic leukemia is the most common childhood malignancy. Optimal use of anti leukemic drugs has led to less toxicity and adverse reactions, a higher survival rate. Thiopurine drugs, including 6-mercaptopurine, are mostly used as antileukemic medications in maintenance phase treatment for children with acute leukemia. For those patients, TPMT genotype- tailored 6-mercaptopurine therapy already implemented protocols. We investigated role TPMT, ITPA, ABCC4 ABCB1 genetic variants predictors outcome induced during pediatric Methods Sixty-eight were enrolled this study. Patients have been treated according ALL IC-BFM 2002 or 2009 Toxicity events monitored via surrogate markers (off-therapy weeks, episodes leu - ko penia average dose) prob- abilistic model was employed predict overall related toxicity. Results confirmed that patients carry inactive allele(s) require 6- mercaptopurine dose reduction. ITPA failed show an association 6-mercapto purine phase. Carriers variant allele experienced greater hepatotoxicity. The probabilistic Neural net which considered all analysed assessed be best prediction model. It able discriminate good poor 6-mercaptopurin tolerance 71% cases (AUC=0.71). Conclusions This study contributes design panel pharmacogenetic predicting thiopurineinduced ALL.