COMBINED IMMUNOSUPPRESSIVE THERAPY WITH TACROLIMUS AND MYCOPHENOLATE MOFETIL FOR SMALL-BOWEL TRANSPLANTATION IN PIGS

Citation
M. Alessiani et al., COMBINED IMMUNOSUPPRESSIVE THERAPY WITH TACROLIMUS AND MYCOPHENOLATE MOFETIL FOR SMALL-BOWEL TRANSPLANTATION IN PIGS, Transplantation, 62(5), 1996, pp. 563-567
Citations number
23
Categorie Soggetti
Immunology,Surgery,Transplantation
Journal title
ISSN journal
00411337
Volume
62
Issue
5
Year of publication
1996
Pages
563 - 567
Database
ISI
SICI code
0041-1337(1996)62:5<563:CITWTA>2.0.ZU;2-D
Abstract
In a swine model of orthotopic small bowel transplantation, we assesse d the efficacy of combined therapy with a low dose of tacrolimus plus mycophenolate mofetil, compared with high-dose tacrolimus monotherapy. The bowel was replaced in 25 piglets: group 1 (n=5), no immunosuppres sion; group 2 (n=10), tacrolimus, 0.3 mg/kg daily i.m. for 7 days, fol lowed by b.i.d. oral doses to maintain blood levels of 15-25 ng/ml; an d group 3 (n=10), tacrolimus, 0.1 mg/kg i.m., in a single dose on day 0 and thereafter oral doses to maintain blood levels of 5-15 ng/ml, pl us oral mycophenolate mofetil (10 mg/kg twice daily). Follow-up time w as limited to 60 days, Median survival time was 11, 27, and >60 days i n groups 1, 2, and 3, respectively (P=0.001). Survival rates were 0%, 40%, and 80% at 30 days and 0%, 0%, and 70% at 60 days in groups 1, 2, and 3, respectively (P=0.03, group 1 vs. group 2; P=0.003, group 1 vs . group 3; P=0.02, group 2 vs, group 3). One animal in group 1 (20%) a nd two animals each in groups 2 and 3 (20%) died of technical complica tions. Rejection was the cause of death of 80% of animals of group 1 a nd of no animals in either group 2 or 3. None of the immunosuppressed animals developed clinical or histopathological evidence of graft-vers us-host disease. Sixty percent of animals in group 2 (n=6) and 10% in group 3 (n=1) died from infections; two other animals in group 2 died of emaciation. The seven animals of group 3 that were alive at 60 days had immunosuppression stopped at that time. All died of rejection wit hin 1 month. In conclusion, double-drug therapy with tacrolimus and my cophenolate mofetil consistently allowed extended survival after small bowel transplantation in swine, preventing or controlling acute cellu lar rejection without a high incidence of lethal complications related to overimmunosuppression.