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

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. 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. 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). 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.