Abstract
During the 1950s, methotrexate replaced aminopterin as the cornerstone of antifolate therapy in the treatment of several malignancies, including childhood acute lymphoblastic leukemia (ALL). Today, the 5-yr event-free survival (EFS) rate for children with ALL exceeds 75%, and methotrexate is a component of essentially all childhood ALL chemotherapy regimens (1–18). However, de novo or acquired resistance of leukemic cells to chemotherapy remains an obstacle to cure in the remaining 20–25% of patients. Giving high doses of methotrexate followed by leucovorin rescue is a widely used strategy to overcome resistance to antifolate therapy. To this end, methotrexate doses ranging from 20 to 33,000 mg/m2 have been used in clinical trials, but the optimal dose for childhood ALL remains unknown. This chapter discusses the rationale for highdose methotrexate (HDMTX) therapy in childhood ALL and reviews laboratory and clinical studies that provide insighsc into the appropriate dosage of methotrexate.
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