title: Methotrexate systemic clearance influences probability of relapse in children with standard-risk acute lymphocytic leukaemia.
abstract: 108 children with standard-risk acute lymphocytic leukaemia (ALL) were randomised to a post-induction treatment protocol including 15 doses of intermediate-dose methotrexate (1000 mg/m2) in addition to conventional oral therapy of mercaptopurine and low-dose methotrexate. After median follow-up of 26 months, 22 patients have had relapses. Among the 108 patients, rates of methotrexate systemic clearance ranged from 44.7 to 132 ml/min/m2. When the group was divided into three subgroups according to the patients' rates of methotrexate clearance, statistical analysis of the Kaplan-Meier curves estimating the probability of complete remission showed significant differences (p = 0.016) among the subgroups, patients with faster clearance having higher probability of relapse. Multivariate Cox's regression analysis incorporating other potential prognostic variables identified three significant variables influencing the risk of relapse--methotrexate clearance and white-blood-cell count and haemoglobin level at diagnosis (p = 0.0015). This study has demonstrated the potential clinical importance of the rate of drug clearance in children with ALL.
mesh_terms: D001856:Bone Marrow Examination; D002493:Central Nervous System Diseases / Q000188:drug therapy; D002648:Child; D002986:Clinical Trials as Topic; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D007700:Kinetics; D007945:Leukemia, Lymphoid / Q000188:drug therapy*; D008297:Male; D015122:Mercaptopurine / Q000008:administration & dosage; D008727:Methotrexate / Q000008:administration & dosage / Q000378:metabolism*; D011336:Probability; D011897:Random Allocation; D012008:Recurrence; D013736:Testicular Neoplasms / Q000188:drug therapy
chemical_list: D015122:Mercaptopurine; D008727:Methotrexate