Abstracts

USE OF MOLECULAR TESTING FOR CARDIAC ALLOGRAFT REJECTION EVALUATION IN CHILDREN: A MULTICENTER STUDY

Darren Y. Tayama, Seema Mital, Linda Addonizio, Daniel Bernstein, Tod M. Klingler, Jay G. Wohlgemuth, Steve Webber XDx Inc., South San Francisco, CA, USA; Columbia University, New York, NY, USA; Stanford University, Palo Alto, CA, USA; University of Pittsburgh, Pittsburgh, PA, USA

Purpose: A noninvasive tool to evaluate cardiac allograft status would be a major advance for pediatric recipients, minimizing the need for cardiac biopsy. Molecular testing of peripheral blood mononuclear cells has been validated in adults as a noninvasive means to monitor for rejection (CARGO study). We investigated whether adult gene expression signatures and pathways for molecular testing can be applied to the pediatric heart population.

Methods: Sixty-seven patients, ages 2 to 17 years (mean 12.0), were enrolled at 3 centers and 90 peripheral blood samples taken ≥6 weeks post-transplant were collected prospectively along with clinical data. Of the 90 samples, 7 were associated with an ISHLT Grade ≥3A endomyocardial biopsy, 20 Grade 1B, 15 Grade 1A and 47 Grade 0. Real-time PCR assays were performed and a multi-gene algorithm validated to distinguish rejection from quiescence in adult patients (AlloMap^TM) was applied.

Results: We found similar algorithm scores in children compared to adult samples for all biopsy grades, though with slightly elevated scores in children for each grade (Range of increase: 0.9-3.2, NS). Scores for Grade 0, 1A and 2 were not significantly different. Grade ≥3A samples had an average score of 30.2 vs. 23.4 for Grade 0 (p = 0.09). Furthermore, algorithm scores from Grade 1B samples were similar to those from Grade ≥3A (28.0 vs. 30.2, NS) and significantly elevated from Grades 0-1A/2 (28.0 vs. 23.4, p = 0.01).

Conclusions: Elevated scores in the pediatric population suggest heightened immune activity in children. Grade 1B samples demonstrate algorithm scores closer to acute rejection than to quiescence. The reclassification of rejection on a molecular basis reveals heterogeneity among the single class of ISHLT mild rejection (1A, 1B and 2). Molecular testing offers great promise for the noninvasive management of pediatric cardiac transplant recipients.