ADULT HEART-TRANSPLANTATION UNDER TACROLIMUS (FK506) IMMUNOSUPPRESSION - HISTOPATHOLOGIC OBSERVATIONS AND COMPARISON TO A CYCLOSPORINE-BASED REGIMEN WITH LYMPHOLYTIC (ATG) INDUCTION

Background: Tacrolimus (FK506) is an effective immunosuppressant for h uman heart transplantation, but information about its effects on cardi ac allograft and nonallograft kidney and liver histopathologic study i s limited. Methods: We therefore reviewed 1145 endomyocardial biopsy s pecimens and eight autopsy results from 80 heart transplant recipients who received tacrolimus as baseline immunosuppression. These were com pared with 619 endomyocardial biopsy specimens and four autopsy result s from 51 patients treated with cyclosporine-based immunosuppression w ith lympholytic induction (CLI) by use of rabbit anti-thymocyte globul in. Twenty-one histologic features including the International Society for Heart and Lung Transplantation histopathologic grade were retrosp ectively assessed without knowledge of the treatment regimen. The lymp hocyte growth index on biopsy specimens obtained from these patients w as also compared. Results: In general, there were no qualitative diffe rences in the histopathologic appearance of various allograft syndrome s between tacrolimus- and CLI-treated patients. Thus histopathologic c riteria used to diagnose various graft syndromes are applicable under tacrolimus immunosuppression. However, early (between 10 and 30 days) after transplantation, biopsy specimens from patients treated with tac rolimus showed a significantly higher percentage of inflamed fragments (p = 0.02), the inflammation tended to be more severe (p = 0.09), and the rejection grade tended to be slightly higher (p = 0.08). In contr ast, during the late transplantation period (275 to 548 days), biopsy specimens from patients treated with CLI showed a significantly higher percentage of inflamed fragments (p = 0.03), more severe inflammation (p = 0.03), higher rejection grades (p = 0.01), and a higher frequenc y of Quilty lesions (p = 0.05). Although overall freedom from any grad e 3A or higher rejection was greater in the CLI-treated arm, tacrolimu s was successfully used to treat refractory rejection in three patient s from the CLI-treated arm. Concern has been raised in the literature about the possibility of tacrolimus being a direct hepatotoxin and an accelerant of allograft obliterative arteriopathy. However, no evidenc e to support either of these contentions was detected in this patient population. In contrast, tacrolimus is clearly nephrotoxic, although s imilar to cyclosporine in this regard. Conclusions: Tacrolimus is an e ffective immunosuppressive drug for heart transplantation. The cardiac allograft histopathologic study of patients treated with tacrolimus i mmunosuppression does not significantly differ from those given conven tional, cyclosporine-based triple therapy with lympholytic induction.