Date: Sunday, June 12, 2016
Session Time: 4:30pm-6:00pm
Presentation Time: 4:42pm-4:54pm
Location: Room 312
Background: In preclinical evaluation, CD154+TcM predict acute cellular rejection after LTx or ITx with sensitivity/specificity of 80%. Purpose/Methods: To summarize test indications and performance during clinical use in the first 180 children with LTx or ITx. Rejection-risk is increased in this cell-culture-based assay leading to a positive test, if donor-specific CD154+TcM are increased 1.1-fold or more over non-specific alloreactive CD154+TcM. Results: Of 180 children sampled at least once, 10 were excluded because steroids were escalated for presumed rejection before sampling. For the remaining 170 children, median age was 12 years (0.6-21), gender M: F was 92: 78, transplant type LTx: ITx: combined LTx-ITx was 129: 14: 27. Testing occurred at median 2298 days (range 8-7568) after transplantation and coincided with allograft dysfunction or surveillance. Fifty children demonstrated rejection on biopsy (n=44) or clinically (n=6) and 130 children did not in the 60 day post-sampling period. Test sensitivity, specificity, positive and negative predictive values and respective 95% confidence intervals for predicting rejection were 78% (64-88), 85% (77-91), 68% (55-80) and 90% (83-95), respectively. False positive tests were associated with blood sampling significantly later after transplantation (3141+/-1923 vs 1534+/-1529 days, p=0.002) and lower Tacrolimus whole blood concentrations (4.1+/-3.2 vs 8.3+/-6.3, p=0.01) compared with true positive tests. In logistic regression analysis relating CD154+TcM to rejection, the timing of sample after transplantation emerged as a significant covariate. Test predictions concurred with rejection/non-rejection outcomes in a) children with and without EBV viremia (41/50 or 82% vs 37/53 or 70%, p=0.173, NS), b) all five LTx recipients with allograft cholangitis and all three ITx recipients with allograft enteritis, c) a child with CMV viremia 9800 copies/ml. Conclusions: Clinical rejection-risk assessment of pediatric LTx and ITx with allospecific CD154+TcM confirms clinically acceptable test performance observed during preclinical evaluation and is unaffected by common transplant viruses and allograft cholangitis or enteritis. Enhanced rejection risk in stable long-term allograft recipients on low immunosuppression merits follow-up to establish clinical relevance.
CITATION INFORMATION: Soltys K, Bond G, Mazariegos G, O'Toole L, Trautz C, Remaley L, Zeevi A, Ashokkumar C, Sindhi R. Clinical Rejection-Risk Assessment with Allospecific CD154+T-Cytotoxic Memory Cells (CD154+TcM) After Pediatric Liver or Intestine Transplantation (LTx, ITx). Am J Transplant. 2016;16 (suppl 3).
To cite this abstract in AMA style:Soltys K, Bond G, Mazariegos G, O'Toole L, Trautz C, Remaley L, Zeevi A, Ashokkumar C, Sindhi R. Clinical Rejection-Risk Assessment with Allospecific CD154+T-Cytotoxic Memory Cells (CD154+TcM) After Pediatric Liver or Intestine Transplantation (LTx, ITx). [abstract]. Am J Transplant. 2016; 16 (suppl 3). http://atcmeetingabstracts.com/abstract/clinical-rejection-risk-assessment-with-allospecific-cd154t-cytotoxic-memory-cells-cd154tcm-after-pediatric-liver-or-intestine-transplantation-ltx-itx/. Accessed August 22, 2017.
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