Background: The addition of vincristine to "quadruple-drug" induction immunotherapy (OKT3, cyclosporine, azathioprine, prednisone) after heart transplantation decreases the incidence of rejection but is limited by neurotoxicity. We hypothesized that methotrexate, when added to quadruple therapy, may also decrease the incidence of rejection but with less toxicity.
Methods: We randomized 36 heart transplant recipients to receive either quadruple therapy (OKT3, cyclosporine, azathioprine, corticosteroids) (n = 19) or quadruple therapy plus methotrexate (n = 17). Methotrexate was given weekly for 8 weeks beginning at the conclusion of OKT3 therapy (postoperative days 8 to 16), and dosed according 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 first rejection, number of treated rejection episodes, mean biopsy scores, and number of patients requiring intravenous corticosteroids or antilymphocyte therapy. Toxicity and infection rates were not significantly different between the two groups.
Conclusions: Although toxicity was minimal, an 8-week course of methotrexate appears to add no significant benefit to quadruple-drug immunotherapy.