TREATMENT OF RECALCITRANT CARDIAC ALLOGRAFT-REJECTION WITH METHOTREXATE

Acute rejection continues to be a major cause of mortality and morbidity among cardiac allograft recipients. In this retrospective analysis, we evaluated the efficacy and safety of methorexate in the treatment of recalcitrant rejection in 16 heart transplant patients. Methotrexate was initiated in these patients for rejection refractory to conventional therapy or for multiple, recurrent rejection episodes. Before methotrexate therapy, these patients had experienced 3.2+/-1.1 (mean+/-SD) episodes of allograft rejection. Methotrexate was administered at 5.9+/-5.3 months postransplant, at a starting oral dose of 7.8+/-2.7 mg/week. The methotrexate dose was increased as tolerated by white blood cell counts to 10-25 mg/week. These patients had been followed for 26+/-12 months after initiation of methotrexate. All ongoing rejection episodes were reversed with methotrexate. Rejection resolution was typically delayed and was observed at 19+/-15 days after methotrexate initiation. Compared to the 6 months before methotrexate thereapy, there was significant reduction in the linearized rejection rate (0.44+/-0.14 vs 0.06+/-0.09 episodes/patient/month), and the time spent in rejection (29.8+/-14.0 vs 5.8+/-8.7 days) in the 6 months after methotrexate initiation. Nadir white blood cell counts were observed at 4.0+/-1.8 weeks after methotrexate initiation, but were above 2000/mm(3) in all patients. Multiple infections occurred in 2 patients who received repeat courses of methotrexate and the highest cumulative doses of methotrexate. These findings suggest that methotrexate may be effective in the management of recalcitrant cardiac allograft rejection. Methotrexate therapy appears to be well tolerated by most patients. However, multiple treatment courses of methotrexate and high cumulative dose may predispose patients to an increased risk of infections.