Efficacy of tacrolimus in patients with steroid-resistant cardiac allograft cellular rejection.

BACKGROUND: Tacrolimus is an immunosuppressive agent that is gaining widespread use in solid organ transplantation. This study was undertaken to evaluate the efficacy of tacrolimus in treating steroid-resistant cellular myocardial rejection.

METHODS: We retrospectively analyzed the incidence of rejection and clinical outcome of 21 heart transplant recipients who were electively converted from cyclosporine to tacrolimus for recurrent episodes of steroid-resistant cellular rejection. These were compared to a historic group of 6 hemodynamically stable patients who were treated electively with Orthoclone OKT3 (Muromonab/CD3) for recurrent rejection.

RESULTS: Eighty five percent (56/66) of the episodes of rejection occurred within the first 3 months after heart transplantation. Tacrolimus was started 2. 4 +/- 2.0 months post-transplant, and the mean follow-up duration on tacrolimus was 11.0 +/- 7.0 months. After conversion, a significant decline was noted in both the number of episodes of acute rejection per patient (3.14 +/- 0.85-0.57 +/- 0.87, p < 0.0001), and the incidence of acute rejection per 100 patient-days (6.39 +/- 3.96-0. 25 +/- 0.47, p < 0.0001). In comparison, OKT3 was started 5.25 +/- 9. 20 months post-transplant. Similarly, there was a significant decrease in the incidence of acute rejection per 100 patient-days (8. 69 +/- 5.65-0.20 +/- 0.23, p < 0.0001). The average hospital charges per patient for the OKT3-treated group was $33,339 +/- $10,511. There was no significant difference in the actuarial 1-year survival between the tacrolimus and OKT3-treated groups (93% vs 80%, p = 0.5).

CONCLUSIONS: Outpatient conversion to tacrolimus is safe, well tolerated, and an effective therapeutic strategy for the treatment of steroid-resistant cellular rejection in heart transplant recipients. It is more cost-effective than OKT3 in the hemodynamically stable patient and outcomes are similar.