METHOTREXATE SYSTEMIC CLEARANCE INFLUENCES PROBABILITY OF RELAPSE IN CHILDREN WITH STANDARD-RISK ACUTE LYMPHOCYTIC LEUKAEMIA

William E. Evans, Clinton F. Stewart, Chen Hsin Chen, William R. Crom, W. Paul Bowman, Minnie Abromowitch, Joseph V. Simone

Research output: Contribution to journalArticle

99 Scopus citations

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.

Original languageEnglish
Pages (from-to)359-362
Number of pages4
JournalThe Lancet
Volume323
Issue number8373
DOIs
StatePublished - 18 Feb 1984

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