Combined immunosuppressive therapy with tacrolimus and mycophenolate mofetil for small bowel transplantation in pigs

Mario Alessiani, Marco Spada, Paolo Dionigi, Eloisa Arbustini, Mario Regazzi, Gian Silvio Fossati, Aris Zonta

Research output: Contribution to journalArticlepeer-review

Abstract

In a swine model of orthotopic small bowel transplantation, we assessed 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 immunosuppression; group 2 (n=10), tacrolimus, 0.3 mg/kg daily i.m. for 7 days, followed by b.i.d. oral doses to maintain blood levels of 15-25 ng/ml; and 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, plus oral mycophenolate mofetil (10 mg/kg twice daily). Follow-up time was limited to 60 days. Median survival time was 11, 27, and >60 days in 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%) and two animals each in groups 2 and 3 (20%) died of technical complications. Rejection was the cause of death of 80% of animals of group 1 and of no animals in either group 2 or 3. None of the immunosuppressed animals developed clinical or histopathological evidence of graft-versus- host disease. Sixty percent of animals in group 2 (n=6) and 10% in group 3 (n=l) 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 within 1 month. In conclusion, double-drug therapy with tacrolimus and mycophenolate mofetil consistently allowed extended survival after small bowel transplantation in swine, preventing or controlling acute cellular rejection without a high incidence of lethal complications related to overimmunosuppression.

Original languageEnglish
Pages (from-to)563-567
Number of pages5
JournalTransplantation
Volume62
Issue number5
Publication statusPublished - Sep 15 1996

ASJC Scopus subject areas

  • Transplantation
  • Immunology

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