In high‑dose methotrexate therapy, when should leucovorin rescue begin and for how long should it continue?

• A. Begin about 24 hours after MTX start and continue until MTX levels are below the institutional threshold (often 42–48 hours or longer).
• B. Begin immediately at the start of MTX infusion and continue for 24 hours.
• C. Begin 48 hours after MTX start and continue for 24 hours.
• D. Leucovorin rescue is not used with methotrexate.

Answer: (A)

Leucovorin rescue is timed to protect normal tissues after methotrexate has had time to work, while still allowing the drug to exert its anti-cancer effect. Starting it about 24 hours after the MTX infusion begins lets MTX act on cancer cells first, then rescue of healthy cells begins to prevent severe toxicity. The rescue is continued until MTX levels drop below the institution’s safe threshold, which is often defined by a time window of about 42–48 hours or longer, depending on how quickly MTX is cleared in that patient. If MTX clearance is delayed (due to kidney function, hydration, urine pH, etc.), the rescue interval can extend to ensure MTX is sufficiently cleared.