BACKGROUND: Allospecific CD154+T-cytotoxic memory cells (CD154+TcM) are used clinically to predict acute cellular rejection (ACR) after intestine transplantation (ITx) in children <21 years old within the 60-day post-sampling period.

PURPOSE: To determine whether increased pre-transplant rejection-risk measured by CD154+TcM predicts increased immunosuppression with tacrolimus and steroids in 60-month follow-up in children with ITx who were enrolled in in pivotal studies of this test system (National Clinical Trial 1163578). METHODS: The clinical course of 22 children, in whom rejection-risk was measured with the immunoreactivity index (IR) of CD154+TcM before ITx was evaluated for 60 months after ITx. An immunoreactivity index of 1.23 or greater implies increased rejection-risk, as described previously. Tacrolimus whole blood concentrations and prednisone doses were recorded at 12-monthly intervals until month 60, and compared between children at increased and decreased rejection-risk. Immunosuppression management was based on clinical protocols.

RESULTS: Median age was 2 years (range 0.7-15). The distribution of male: female gender was 13: 9, and Caucasian: non-caucasian race was 11: 11. Ten children demonstrated increased rejection-risk and 12 children demonstrated decreased rejection-risk before ITx. In between-group comparisons over a 60-month follow-up period, children with increased rejection-risk demonstrated 1) significantly shorter median time to the first biopsy-proven acute cellular rejection event (22 vs 281 days, p=0.033, K-M test), 2) significantly lower 5-year rejection-free survival (8% vs 40%, p=0.033, K-M test) and 3) higher mean (+/-SEM) tacrolimus whole blood, which achieved significance at 12 (9.3+/-0.9 vs 4.5+/-0.7 ng/ml, p-value=0.001) 48 (6.5+/-0.9 vs 3.3+/-0.4 ng/ml, p-value=0.01) and 60 months (6.0+/-0.8 vs 3.2+/-0.3 ng/ml, p-value=0.02) after ITx. No differences were seen in steroid use or steroid doses between the two groups.

CONCLUSIONS: Increased rejection-risk measured with allospecific CD154+T-cytotoxic memory cells before intestine transplantation predicts delayed minimization of tacrolimus in children. Therefore, pre-transplant rejection-risk assessment may be a useful adjunct to immunosuppression management after pediatric ITx.

CITATION INFORMATION: Soltys K., Ashokkumar C., Mazariegos G., Bond G., Ningappa M., Khanna A., Ganoza A., Sun Q., Sindhi R. Increased Pre-Transplant Rejection-Risk Measured with Allospecific T-Cells Predicts Delayed Immunosuppression Minimization in Children with Intestine Transplantation. Am J Transplant. 2017;17 (suppl 3).

« Back to 2018 American Transplant Congress