METHOTREXATE THERAPY IN PEDIATRIC HEART-TRANSPLANTATION AS TREATMENT OF RECURRENT MILD-TO-MODERATE ACUTE CELLULAR REJECTION

We have used adjunctive therapy with methotrexate as treatment of recu rrent mild-to-moderate acute cellular rejection and in an attempt to r educe rejection frequency and corticosteroid dosage. The purpose of th is study was to review our experience with this treatment strategy. Ei ght patients, 13.1 +/- 1.1 years of age (mean +/- standard error of th e mean) at the time of transplantation, were given methotrexate in add ition to their standard triple therapy immunosuppression. Methotrexate was started at 6.2 +/- 2 months after transplantation after an averag e of 3.1 +/- 0.4 rejection episodes. Patients were given methotrexate weekly for 8 weeks at 2.5 or 5 mg orally every 12 hours for three dose s (0.23 +/- 0.02 mg/kg/week). The time to resolution of rejection was 17.9 +/- 4 days after initiating methotrexate therapy. The number of r ejections per month decreased significantly from the 2 months before m ethotrexate therapy (1.49 +/- 0.1) when compared with both the 2 month s during methotrexate therapy (0.50 +/- 0.1) and the 2 months after me thotrexate therapy was completed (0.44 +/- 0.3) (p < 0.005). Furthermo re, when comparing total rejection frequency since transplantation and before methotrexate therapy to a follow-up period of 21.8 +/- 5 month s after completion of methotrexate therapy, the rejection frequency wa s significantly less (0.81 +/- 0.2 versus 0.10 +/- 0.06 rejections/mon th) (p < 0.01). Prednisone dosage was also significantly less when com paring the time before methotrexate therapy to immediately after compl etion of methotrexate therapy (0.23 +/- 0.04 versus 0.15 +/- 0.03 mg/k g/day) (p < 0.05). The only adverse effect seen was mild leukopenia (a s low as 2.5 x 10(3)/mul) in five patients during methotrexate therapy . We conclude that methotrexate is safe and effective in treating recu rrent mild-to-moderate acute cellular rejection and may decrease rejec tion frequency and corticosteroid dosage in pediatric heart transplant recipients receiving triple-drug immunosuppression therapy.