DNA-thioguanine concentration and relapse risk in children and young adults with ALL

Methotrexate/6-mercaptopurine maintenance therapy improves outcomes of ALL. Cytotoxicity is mediated by DNA incorporation of thioguanine nucleotides (DNA-TG). An individual patient data meta-analysis (1910 children and young adults with non-high risk ALL) found that the relapse-specific risk hazard ratio per 100 fmol/μg increase in weighted mean DNA-TG was 0.87 (p=0,013) in the 839 patients who were minimal residual disease-positive at the end of induction therapy, while this was not the case in EOI MRD-negative patients (p=0,76). The authors conclude that the importance of DNA-TG as biomarker for maintenance therapy intenstity calls for novel strategies to increase DNA-TG.