Continuous infusion of methotrexate in children with acute leukemia

Two methods of prolonged infusion of methotrexate are described. Amounts of drug many times larger than commonly used are given. Remissions were induced in patients who were resistant to this drug when it was given orally (2.5 mg) or twice a week intramuscularly (30 mg per m2). Infusions of methotrexate lasting 18 hours, or multiples of this duration, were used for the induction of remission. Massive multiple platelet transfusions were required to protect such patients from bleeding. These studies indicate that a lack of response to customary doses of methotrexate may be due to increased tolerance of leukemic cells to the drug rather than to absolute resistance to it. The induction of remission with the above treatments is of considerable theoretical interest but of little practical value. The toxic manifestations associated with extended periods of infusion of methotrexate (longer than 18 hours) and the need of massive supportive transfusions discourage the routine use of such methods. The lesser toxicity of large doses of methotrexate given in short infusions (4 hours) and at intervals of longer than 3 weeks suggests that improved ways of using methotrexate for the maintenance of remissions may become available.