Why is leucovorin rescue used with high-dose methotrexate?

• A. To replenish folinic acid and protect normal cells from MTX toxicity while maintaining antitumor effect
• B. To increase MTX toxicity
• C. To reduce hydration requirements
• D. To block MTX uptake

Answer: (A)

Leucovorin rescue works by supplying a form of reduced folate that bypasses the block MTX creates. High-dose methotrexate blocks the enzyme that converts dihydrofolate to tetrahydrofolate, which stops thymidylate and purine synthesis and leads to toxicity in normal cells. Leucovorin (folinic acid) can be converted into the needed folate cofactors without going through that blocked step, allowing normal cells to resume DNA synthesis and survive, while keeping MTX’s antitumor effects. The rescue is timed after MTX dosing to maximize tumor kill before normal cells are protected, and to minimize normal-cell damage. It doesn’t increase MTX toxicity, it doesn’t reduce hydration needs, and it doesn’t block MTX uptake.