[Radiational basis and practice of the citrovorum factor (Leucovorin) protection after high-dose methotrexate therapy. High-dose methotrexate/leucovorin]

Abstract

The effects of methotrexate on the DNA metabolism of human lymphoblast cultures and bone marrow cells were estimated. The ratio of the 3H-deoxyuridine and 3H-thymidine incorporation rates ia a good parameter for the methotrexate effect. Citrovorum factor (5-formyltetrahydrofolic acid) reverses methotrexate toxicity only when its concentration exceeds that of methotrexate at least ten times. Guidelines for the practice of high-dose methotrexate therapy and the following citrovorum factor rescue, especially for patients with retarded methotrexate elimination are presented. A new simple formula enables the exact calculation of the citrovorum factor dose for individual patients according to their methotrexate serum levels. This formula, derived from the experimental data of the bone marrow and lymphoblast culture cells, gives a rational basis for the high-dose rescue with citrovorum factor in cases with expected or manifest toxicity, and means, moreover, a safety factor for the practice of high-dose methotrexate therapy.