The timing of leucovorin rescue is vital. It is typically administered 24 to 48 hours after methotrexate infusion. This delay allows methotrexate to exert its antitumor activity before leucovorin counteracts its toxic effects on normal cells. The determination of the appropriate leucovorin dose and timing is based on methotrexate serum levels and the patient's renal function, as delayed methotrexate clearance increases the risk of toxicity.