Antithymocyte globulin and methotrexate therapy of severe or persistent cardiac allograft rejection

The treatment of severe or persistent acute rejection remains difficult despite newer immunosuppressive agents available. To evaluate the effectiveness of rabbit antithymocyte globulin and methotrexate as therapy for severe or persistent acute cardiac allograft rejection, we conducted a retrospective analysis of clinical and laboratory data from 150 consecutive heart transplant recipients between 1983 and 1994. Thirteen episodes of severe or refractory acute rejection were treated with rabbit antithymocyte globulin in 10 patients. Rabbit antithymocyte globulin (125 mg/day for 3 consecutive days) was effective in 90% of patients. Therapy was well tolerated, and contributed to one infectious complication, no malignancy, and long-term survival in 8 of 10 patients. Recurrent rejection developed in 60% of patients. Methotrexate (7.5 to 15 mg/wk for 16 weeks) was administered to 8 patients with persistent rejection documented on three consecutive endomyocardial biopsies. Therapy was effective in 6 of the 8 patients, with one infectious complication and no malignancy on follow-up. White blood cell count decreased significantly during therapy ( p = 0.008). Seven of the 8 patients in the methotrexate group are long-term survivors. Rabbit antithymocyte globulin is a valuable alternative in patients with severe or refractory acute rejection. Methotrexate is an important adjunct in patients with persistent rejection unresponsive to conventional immunosuppressive regimens.