METHOTREXATE THERAPY FOR COMPLEX GRAFT-REJECTION IN PEDIATRIC HEART-TRANSPLANT RECIPIENTS

Background: We retrospectively reviewed all pediatric heart transplant recipients at Loma Linda University Medical Center between January 1990 and September 1993 to evaluate the efficacy and safety of methotrexate when it is used for the treatment of graft rejection. Methods: Twenty-eight of 156 patients (18%) received methotrexate therapy. The dose used for recurrent rejection was 10 mg/m(2)/week given every 12 hours for three doses. Rejection history, complete blood counts, liver function tests, and infectious complications were reviewed. Results: Eighteen patients were treated for recurrent rejection. Methotrexate was begun at a median of 115 days (13 to 1093 days). Older patients were more likely to receive methotrexate (p < 0.01). Efficacy was assessed as rejection episodes (mean +/- standard deviation) occurring in the 2 months before methotrexate administration compared with the 2 months after methiotrexate administration and fell from 2.0 +/- 0.2 to 0.6 +/- 0.2 episodes (p < 0.001). The rejection rate (rejections per patient-month) fell in treated patients to a rate similar to patients who did not receive methotrexate. Two patients (11%) died while receiving methotrexate. An additional nine patients were treated for acute rejection with hemodynamic compromise, and one was treated for graft-versus-host disease. The incidence of significant infections was 50% (but no deaths were due to infection) during methotrexate therapy in all patients treated (n = 28). The minimum white blood cell count in the first month of methotrexate therapy occurred at 2 weeks (median of 2700 to 3500 x 10(6) cells/L). Only one patient had elevated transaminase levels. Conclusion: Methotrexate is an effective and safe adjunct in the management of chronic pediatric cardiac graft rejection.