Optimization of the immunosuppressive protocol after lung transplantation

Background. The successful use of tacrolimus (Tac)-based immunosuppressive therapy in organ transplantation and our own positive experience in heart t ransplantation led us to investigate regimens including this agent at our c enter for lung transplantation. Methods. From 1991 to 1998, 86 patients underwent lung transplants at our c enter and 78 of them were included in this analysis. The first 34 patients were treated with cyclosporin (CsA), azathioprine (Aza), and rabbit antilym phocyte globulin; the subsequent 30 patients received Tac with Aza, and the most recent 12 patients Tac with mycophenolate mofetil (MMF). In addition, all patients received prednisone, Results. The number of acute rejection episodes per 100 patient days was 1. 5, 0.6, and 0.3 for three treatment groups, respectively. Similarly, the in cidence of refractory acute rejection per 100 patient days was lower in bot h Tac groups (0.20, 0.03, and 0, respectively). Freedom from acute rejectio n was highest in the Tac-MMF group (P=0.0037 vs. Tac/Aza, P=0.0007 vs. CsA/ Aza). Freedom from recurrent acute rejection was significantly higher in bo th Tac groups (P=0.027 Tac/Aza vs. CsA/Aza and P=0.025 Tac/MMF vs. CsA/Aza) . The incidence of infections per 100 patient days was similar (0.8, 0.5, a nd 0.8) in all three treatment groups, with a similar distribution of funga l, bacterial, and viral infections, Freedom from infection also showed no d ifference. The survival rate was significantly higher for the Tac populatio n, with actuarial 1- and 3-year survival rates of 93% and 71%, compared wit h the CsA group (71% and 51%, respectively, P=0.04), Prevalence of renal dy sfunction (creatinine >2.0 mg/ dL) was 18%, 13%, and 0% in the 3 treatment groups, respectively. The development of glucose metabolism disorders was l ower in the CsA group than in the Tac-Aza group (15% vs. 27%, P < 0.05). Conclusions. Tac-based immunosuppressive therapy results in a lower rate of acute rejection after pulmonary transplantation, with similar infection ra tes and a slightly higher incidence of new onset diabetes mellitus compared with CsA-based therapy.