A clinical research consortium sponsored by NIAID and JDRF
Feng S, Ekong U, Lobritto S, Demetris A, Rosenthal P, Alonso E, Tchao N
Surgery, UCSF, San Francisco, CA; Pediatrics, Northwestern U, Chicago, IL; Pediatrics, Columbia U, New York, NY; Pathology, U Pittsburgh, Pittsburgh, PA; UCSF/ITN, San Francisco, CA
Background: Lifelong immunosuppression (IS) confers morbidity and mortality for pediatric liver transplant (tx) recipients. ITN029ST is a prospective, multicenter, single arm pilot trial of complete IS withdrawal for pediatric recipients of parental liver grafts.
Methods: From 5/06 to 7/08, 20 recipients were enrolled at 3 centers. Inclusion criteria included 1) tx with a parental graft as a child >4 yrs prior to enrollment for diseases other than viral or autoimmune hepatitis, 2) stable graft function on calcineurin inhibitor monotherapy, and 3) screening liver biopsy showing no rejection and fibrosis stage <2 (Ishak). IS was withdrawn according to protocol over >8 months. Tapering was terminated for any delay in dose reduction >4 wks or any episode of rejection requiring treatment. Planned follow-up after successful IS withdrawal is for 4 yrs and includes protocol biopsies; safety follow-up after failed IS withdrawal is for 1 yr.
Results: For the 20 enrollees, median (range) age at tx was .58 (.3-7.5) yrs and at enrollment was 8.5 (5-15) yrs. Eleven participants successfully weaned IS over 8.2 (8-12) mos. They have been off IS for 14.9 (3-20) mos with normal graft function and without rejection since IS discontinuation. Tapering was terminated in 4 patients: 1 for inclusion criteria violation, 1 for moderate acute rejection treated with corticosteroids, and 2 for abnormal liver tests with biopsies non-diagnostic of rejection. 5 patients are still tapering. Autoantibody and alloantibody titers have not increased with IS weaning.
Conclusion: Preliminary results suggest that IS withdrawal is safe in selected pediatric liver tx recipients. Substantial efforts are underway to identify molecular signatures predictive of operational tolerance. Our findings justify larger studies to better define the safety, efficacy, benefit, and generalizability of IS withdrawal for the pediatric liver tx population.
