Long-term Follow-up of a Randomized Trial of Tacrolimus or Cyclosporine A Microemulsion in Children Post Liver Transplantation

Abstract

Background. The aim of this study was to determine the long-term efficacy and safety of tacrolimus (Tac) and cyclosporine immunosuppression in pediatric liver transplantation (LTx). Methods. One hundred fifty-six patients who had taken part in a multicenter, randomized, open, parallel study of Tac and corticosteroids versus cyclosporine A microemulsion (CyA-ME), corticosteroids, and azathioprine. Patients were assessed at regular intervals up to 14 y after LTx. Analysis was conducted descriptively. Results. In a long-term follow-up, there was a similar incidence of acute rejection (Tac versus CyA-ME, 5 versus 8) and graft loss (5 versus 10). There were 11 deaths in the cohort, which were from infectious complications/malignancy in the Tac group (n = 2/5) and from chronic rejection/liver failure in the CyA-ME group (n = 3/6). A similar incidence of Epstein-Barr virus and posttransplant lymphoproliferative disease was observed (8 versus 8, 3 versus 3). However, there was a greater incidence of cosmetic adverse events in the CyA-ME cohort, with higher incidences of hypertrichosis (8 versus 27) and gum hyperplasia (20 versus 6). Growth improved equally in both groups. Overall, 81% of patients randomized to Tac remained on Tac therapy at study end, compared with 31% of patients randomized to CyA-ME. Common reasons for switching from CyA-ME included steroid-resistant/acute rejection (n = 12/8) and cosmetic changes (n = 8). Conclusions. This study is the first prospective, observational follow-up study of pediatric patients randomized to Tac and CyA-ME to evaluate long-term outcomes. Our analysis was limited by the degree of switchover between the cohorts; however, there were fewer deaths from chronic rejection/liver failure and reduced adverse events with Tac. Long-term use of Tac and Tac combination therapy appears to be safe and effective immunosuppression for pediatric LTx recipients.

Early steroids after pediatric liver transplantation protect against T-cell–mediated rejection: Results from the ChilSFree study

“…However, since in these trials basiliximab had only been used in the Tac Mono group, this effect was widely attributed to the use of basiliximab for induction and not to the omission of steroids. This notion is supported by the fact that in another big multicenter European trial comparing the use of Tac plus steroids versus CSA plus steroids plus azathioprine (all without basiliximab), rejection rates in the Tac plus steroids group were 55.5% in the Tac plus steroids group [16,17] and thus much higher than in our study.…”

Chapter 6.6. The Role of ESPGHAN in Developing Effective Immunosuppression Following Paediatric Liver Transplantation

“…This clinical trial established the standard immunosupression regimen not just in Europe but internationally with Tacrolimus gradually replacing Cyclosporin as first line therapy. In view of the long term side effects of immunosuppression which include: renal toxicity, infection, diabetes mellitus, hypertension and hypercholesterolemia (5), the focus has changed to the use of induction therapy, addition of combination therapy to reduce the dosage of the more toxic CNI inhibitors and the evaluation of steroid free regimens.…”