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Adult heart transplantation under tacrolimus (FK506) immunosuppression: Histopathologic observations and comparison to a cyclosporine-based regimen with lympholytic (ATG) induction

Tsamandas, AC and Pham, SM and Seaberg, EC and Pappo, O and Kormos, RL and Kawai, A and Griffith, BP and Zeevi, A and Duquesnoy, R and Fung, JJ and Starzl, TE and Demetris, AJ (1997) Adult heart transplantation under tacrolimus (FK506) immunosuppression: Histopathologic observations and comparison to a cyclosporine-based regimen with lympholytic (ATG) induction. Journal of Heart and Lung Transplantation, 16 (7). 723 - 734. ISSN 1053-2498

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Abstract

Background: Tacrolimus (FK506) is an effective immunosuppressant for human heart transplantation, but information about its effects on cardiac allograft and nonallograft kidney and liver histopathologic study is limited. Methods: We therefore reviewed 1145 endomyocardial biopsy specimens and eight autopsy results from 80 heart transplant recipients who received tacrolimus as baseline immunosuppression. These were compared with 619 endomyocardial biopsy specimens and four autopsy results from 51 patients treated with cyclosporine-based immunosuppression with lympholytic induction (CLI) by use of rabbit anti-thymocyte globulin. Twenty-one histologic features including the International Society for Heart and Lung Transplantation histopathologic grade were retrospectively assessed without knowledge of the treatment regimen. The lymphocyte growth index on biopsy specimens obtained from these patients was also compared. Results: In general, there were no qualitative differences in the histopathologic appearance of various allograft syndromes between tacrolimus- and CLI-treated patients. Thus histopathologic criteria 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 tacrolimus 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 contrast, 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 frequency of Quilty lesions (p = 0.05). Although overall freedom from any grade 3A or higher rejection was greater in the CLI-treated arm, tacrolimus was successfully used to treat refractory rejection in three patients 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 evidence to support either of these contentions was detected in this patient population. In contrast, tacrolimus is clearly nephrotoxic, although similar to cyclosporine in this regard. Conclusions: Tacrolimus is an effective immunosuppressive drug for heart transplantation. The cardiac allograft histopathologic study of patients treated with tacrolimus immunosuppression does not significantly differ from those given conventional, cyclosporine-based triple therapy with lympholytic induction.


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Details

Item Type: Article
Status: Published
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Tsamandas, AC
Pham, SM
Seaberg, EC
Pappo, O
Kormos, RLkormos@pitt.eduKORMOS
Kawai, A
Griffith, BP
Zeevi, A
Duquesnoy, R
Fung, JJ
Starzl, TEtes11@pitt.eduTES11
Demetris, AJ
Centers: Other Centers, Institutes, or Units > Thomas E. Starzl Transplantation Institute
Date: 12 August 1997
Date Type: Publication
Journal or Publication Title: Journal of Heart and Lung Transplantation
Volume: 16
Number: 7
Page Range: 723 - 734
Institution: University of Pittsburgh
Refereed: Yes
ISSN: 1053-2498
Other ID: uls-drl:31735062127828, Starzl CV No. 2061
Date Deposited: 08 Apr 2010 17:35
Last Modified: 13 Oct 2017 21:57
URI: http://d-scholarship.pitt.edu/id/eprint/5447

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