High-dose pulse infusions of methotrexate followed by leucovorin calcium (citrovorum factor) rescue has been used in the treatment of many neoplastic diseases, including osteogenic sarcoma1,2 and actue lymphoblastic leukemia.3 Methotrexate inhibits the enzyme, dihydrofolate reductase, and thus causes a fall in reduced folate pools, which are essential cofactors for DNA, purine, and protein synthesis. Leucovorin calcium supplies the product of the inhibited enzyme and thus can prevent, and rescue normal cells from, the adverse biologic effects of methotrexate. Leucovorin calcium rescue, therefore, allows for the use of very large doses of methotrexate and results in a greater response rate at a lower cost in toxicity than methotrexate alone in equivalent dosage. The toxic effects of high-dose pulse infusion of methotrexate followed by leucovorin calcium rescue have included bone marrow depression, renal toxicity, stomatitis, anorexia, vomiting, diarrhea, alterations in liver function tests, and skin reactions of various kinds. These
LANZKOWSKY P, JAYABOSE S, SHENDE A, LEVY R. Vasculitis as a Complication of High-Dose Methotrexate in the Treatment of Acute Leukemia. Am J Dis Child. 1976;130(6):675. doi:10.1001/archpedi.1976.02120070101020
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