METHOTREXATE FOR REJECTION PROPHYLAXIS AFTER HEART-TRANSPLANTATION

Background: The addition of vincristine to ''quadruple-drug'' inductio n immunotherapy (OKT3, cyclosporine, azathioprine, prednisone) after h eart transplantation decreases the incidence of rejection but is limit ed by neurotoxicity. We hypothesized that methotrexate, when added to quadruple therapy, may also decrease the incidence of rejection but wi th less toxicity. Methods: We randomized 36 heart transplant recipient s to receive either quadruple therapy (OKT3, cyclosporine, azathioprin e, corticosteroids) (n = 19) or quadruple therapy plus methotrexate (n = 17). Methotrexate was given weekly for 8 weeks beginning at the con clusion of OKT3 therapy (postoperative days 8 to 16), and dosed accord ing to white blood cell count. Results: Six methotrexate patients did not complete the protocol, leaving 11 patients on weekly methotrexate at a mean dose of 8.6 mg/week (range 0 to 15 mg/wk). Multiple indexes of rejection were similar between the two groups, including days to fi rst rejection, number of treated rejection episodes, mean biopsy score s, and number of patients requiring intravenous corticosteroids or ant ilymphocyte therapy. Toxicity and infection rates were not significant ly different between the two groups. Conclusions: Although toxicity wa s minimal, an 8-week course of methotrexate appears to add no signific ant benefit to quadruple-drug immunotherapy.