TREATMENT OF RECALCITRANT CARDIAC ALLOGRAFT-REJECTION WITH METHOTREXATE

Acute rejection continues to be a major cause of mortality and morbidi ty 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. Methotrexat e was initiated in these patients for rejection refractory to conventi onal therapy or for multiple, recurrent rejection episodes. Before met hotrexate 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 ep isodes were reversed with methotrexate. Rejection resolution was typic ally delayed and was observed at 19+/-15 days after methotrexate initi ation. Compared to the 6 months before methotrexate thereapy, there wa s significant reduction in the linearized rejection rate (0.44+/-0.14 vs 0.06+/-0.09 episodes/patient/month), and the time spent in rejectio n (29.8+/-14.0 vs 5.8+/-8.7 days) in the 6 months after methotrexate i nitiation. Nadir white blood cell counts were observed at 4.0+/-1.8 we eks after methotrexate initiation, but were above 2000/mm(3) in all pa tients. Multiple infections occurred in 2 patients who received repeat courses of methotrexate and the highest cumulative doses of methotrex ate. These findings suggest that methotrexate may be effective in the management of recalcitrant cardiac allograft rejection. Methotrexate t herapy appears to be well tolerated by most patients. However, multipl e treatment courses of methotrexate and high cumulative dose may predi spose patients to an increased risk of infections.