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
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.