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

Background: Tacrolimus is an immunosuppressive agent that is gaining widesp read use in solid organ transplantation. This study was undertaken to evalu ate the efficacy of tacrolimus in treating steroid-resistant cellular myoca rdial rejection. Methods: We retrospectively analyzed the incidence of rejection and clinica l outcome of 21 heart transplant recipients who were electively converted f rom cyclosporine to tacrolimus for recurrent episodes of steroid-resistant cellular rejection. These were compared to a historic group of 6 hemodynami cally stable patients who were treated electively with Orthoclone OKT3 (Mur omonab/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 start ed 2.4 +/- 2.0 months posttransplant, and the mean follow-up duration on ta crolimus was 11.0 +/- 7.0 months; After conversion, a significant decline w as noted in both the number of episodes of acute rejection per patient (3.1 4 +/- 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 compari son, OKT3 was started 5.25 +/- 9.20 months post-transplant. Similarly, ther e was a significant decrease in the incidence of acute rejection per 100 pa tient-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. The re was no significant difference in the actuarial 1-year survival between t he tacrolimus and OKT3-treated groups (93% vs 80%, p = 0.5). Conclusions: Outpatient conversion to tacrolimus is safe, well tolerated, a nd an effective therapeutic strategy for the treatment of steroid-resistant cellular rejection in heart transplant recipients. It is more cost-effecti ve than OKT3 in the hemodynamically stable patient and outcomes are similar .