Persistent donor-specific alloreactivity may portend delayed liver rejection during drug minimization in children

Immunoreactivity, immunosuppression requirement and liver graft function was assessed serially for its relationship to delayed/recurrent acute cellular rejection (ACR) after the first 60 days in 36 pediatric primary liver transplant (LTx) recipients. Subjects were classified as rejectors (n=20) or Non-Rejectors (n=16) based on the presence/absence of biopsy-proven ACR in the first 60 days. All children received anti-lymphocyte induction and steroid-free Tacrolimus or Sirolimus monotherapy, as reported previously. Median age was 4 years (0.45-18) and follow-up was 570 days (106-1144). Compared with non-rejectors, rejectors 1. took significantly longer to achieve reduced donor-specific alloreactivity by MLR (p=0.049), and "low" TAC/SRL whole blood requirements defined as TAC levels < or = 8 ng/ml (p=0.0048), 2. experienced significantly greater variation in time to achieve reduced donor-specific immunoreactivity (SEM 0.8 vs 3.85, p=0.0048), and 3. experienced greater ACR incidence during minimization of immunosuppression (35% versus 6%, p=0.032). Serial monitoring of immunoreactivity may increase the safety with which immunosuppression is minimized in pediatric LTx.