[Reappraisal of high-dose methotrexate therapy]

High-dose methotrexate (MTX) therapy was developed nearly 50 years ago with the introduction of leucovorin (LV) rescue. Since then, its dosing and administration have been optimized for different diseases, subtypes, and risk groups. Important supportive modalities that are still in use today, such as high-volume hydration, alkalinization, and LV rescue, were established as high-dose MTX protocols were being developed. Glucarpidase (GCP), which directly hydrolyzes extracellular MTX, is now available in Japan as well. GCP can prevent or reduce complications, especially in patients with severely delayed MTX elimination or renal injury. The primary function of GCP is to avert or mitigate complications arising from excessive extracellular MTX. Due to the importance of conventional supportive care, it is crucial to be well-versed in its history and evidence.