Increased rejection-risk measured with allospecific T-cells is associated with delayed immunosuppression minimization in children with liver transplantation.
AASLD LiverLearning®. Sindhi R. Oct 22, 2017; 195226
Rakesh Sindhi
Rakesh Sindhi
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TITLE: Increased rejection-risk measured with allospecific T-cells is associated with delayed immunosuppression minimization in children with liver transplantation.

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BACKGROUND: Allospecific CD154+T-cytotoxic memory cells (CD154+TcM) are used clinically to predict clinical acute cellular rejection (ACR) after liver transplantation (LTx) in children. Rejection is predicted within the 60 day period after sampling.
PURPOSE: To determine whether increased rejection-risk measured by CD154+TcM in pivotal studies (National Clinical Trial 1163578) predicts increased immunosuppression with tacrolimus and steroids in 60-month follow-up.
METHODS: The clinical course of 57 children less than 21 years old, in whom rejection-risk was measured with CD154+TcM during the first 60 days after LTx was evaluated over the course of 60 months or 5 years after LTx. Rejection risk was measured with the immunoreactivity index (IR) of CD154+TcM. An IR greater than 1.1 implies increased rejection-risk, as described previously. Tacrolimus whole blood concentrations and prednisone use was recorded at 12-monthly intervals, and compared between children with increased and decreased rejection-risk. Immunosuppression management was based on established clinical protocols.
RESULTS: Mean age was 6.6 years (range (0.1-20.3). The distribution of male: female gender was 36: 21, and Caucasian: non-Caucasian race was 40: 17. During the 60-day follow-up period, 21 of 26 children with increased rejection-risk experienced ACR (positive predictive value 81%) while 27 of 31 children with decreased rejection-risk did not (negative predictive value 87%). During 60-month follow-up, higher mean (+/-SEM) tacrolimus whole blood concentrations were observed in children with increased rejection-risk, compared with those with decreased risk, and achieved significance at 36 (4.8+/-0.7 vs 3.3+/-0.23 ng/ml, p-value=0.028) and 60 months (5.8+/-1.1 vs 3.4+/-0.39 ng/ml, p-value=0.026) (one-tailed t-test). Similarly, prednisone use was more frequent in children with increased rejection risk achieving significance at 36 (9/26 or 35%, vs 2/31 or 6%, p=0.01) and 48 months (8/26 or 31%, vs 3/31 or 10%, p=0.047) (one tailed Fisher’s exact test).
CONCLUSIONS: Increased rejection-risk measured with allospecific CD154+T-cytotoxic memory cells, which is seen during the early post-LTx period portends delayed minimization of tacrolimus and steroids in children in extended follow-up.

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