J Pediatr Gastroenterol Nutr 1995 Apr;20(3):291-9

The treatment of intractable rejection with tacrolimus (FK506) in pediatri
liver transplant recipients

McDiarmid SV, Wallace P, Vargas J, Ament ME, Busuttil RW
UCLA-Dumont Transplant Center, UCLA Medical Center 90024-1752

Abstract
We report our experience in 17 pediatric orthotopic liver transplant (OLT)
patients converted from cyclosporine (CsA) to FK506 for intractable acute and
chronic rejection. FK506 was initiated orally at a dose of 0.3 mg/kg/day in most
patients; the dose was then adjusted to achieve serum levels of 0.5-1.5 ng/ml.
Azathioprine was discontinued and low-dose prednisone maintained. The median
time between liver transplantation and FK506 conversion was 41 months. Patients
have been treated for an average of 14.8 +/- 9.6 months. Six patients were
converted for acute rejection and 11 for chronic rejection, i.e., vanishing bile
duct syndrome (VBDS). After FK506 conversion, the actual patient and graft
survival was 88% and 82%, respectively, in the group as a whole. Two patients
died, one of chronic active hepatitis C and the other of lymphoma. Three
patients, all with VBDS, did not respond to FK506 and therefore required
retransplantation. The serum bilirubin is currently normal in 14 patients and
the serum transaminases < 100 IU/ml in 12. The mean bilirubin pre-FK506 of
patients successfully converted to FK506 was 4.2 mg/dl compared to 11.8 mg/dl in
patients who failed conversion. Major complications included nephrotoxicity,
neurotoxicity, and lymphoma. The mean glomerular filtration rate (GFR) of 97 +/-
29 mls/min/1.73m2 prior to FK506 conversion dropped to 51 +/- 20 mls/min/1.73m2
(p = 0.0001) after a mean of 13.6 months of FK506 therapy. Three patients have
developed B-cell lymphomas; two of them responded to decreased immunosuppression
and one died. We conclude that intractable liver graft rejection in children is
most successfully reversed if FK506 is instituted before cholestasis becomes
pronounced.(ABSTRACT TRUNCATED AT 250 WORDS