Essential laboratory determinations for monitoring high-dose methotrexate treatment with citrovorum factor rescue

The use of high-dose methotrexate (HDMTX) with citrovorum factor rescue (CFR) has considerably improved the prognosis of some pediatric malignancies. Massive doses of methotrexate (mtx) may lead to severe or even lethal toxicity. Safe administration of this regimen requires a wide pattern of laboratory tests as well as clinical supervision. One hundred and eighteen courses of HDMTX (12 gm/m2 over 6 hours iv) with CFR administered to 12 patients were analysed for changes of routine laboratory tests 0, 6, 24, 48, and 72 hours following infusion. Hgb, WBC, and platelets on average showed no change during the 72 hours follow-up period. Serum SGOT and SGPT were elevated with a maximum 24 hours following infusion and slowly returned to normal. The increase of serum LDH values were less marked and reached a maximum at 48 hours; changes of serum y-GT values were not significant. Evaluation of the elimination of mtx from serum in each individual patient throughout 14 sequential mtx courses gave no evidence of a prolonged serum half life due to impaired renal mtx clearance. There was also no evidence of enzyme induction in the liver resulting in a shortened serum half-life. Changes of serum enzymes also were not increasing throughout treatment. Careful monitoring of serum mtx levels is mandatory when HDMTX with CFR treatment is administered. Elevation of blood urea nitrogen and creatinine levels within 24 hours following mtx treatment identify the patient at risk for slow mtx elimination and severe toxicity requiring salvage by adequate doses of citrovorum factor.