How long can folinic acid rescue be delayed after high-dose methotrexate without toxicity?

To determine the optimal time of folinic acid rescue after methotrexate (MTX) treatment in patients with ALL, we selected and evaluated relevant studies that included doses, rescue delay, and side effects. Rescue at 42-48 hours resulted in considerable toxicity, except when low doses of MTX were used (1 g/m(2)) or serum MTX levels remained consistently low at 24, 30, and 36 hours. Rescue started at 30-36 hours was safe. In the absence of evidence that later rescue improves prognosis, we suggest that folinic acid rescue (105 mg/m(2)) be started no later than 36 hours from the start of MTX (5-6 g/m(2)).