Gene Expression Profiling Scores (Allomap) Can Successfully Predict the Absence of Serious Rejection in a Pediatric Heart Transplant Population; Single Center Experience

Abstract

Allomap has been used successfully in adult cardiac transplantation as a screening tool to predict the absence of serious rejection. In adult studies, an Allomap score less than 34 has been highly correlated (Negative Predictive Value [NPV] of 98%) with biopsy grade 0-1R rejection. However, there are minimal studies using Allomap in pediatric patients. We sought to determine if using an Allomap score in pediatric patients ages 10-21 years old could also predict absence of serious rejection in our population. Heart transplant recipients >more than 3 months after transplant, who were between 10-21 years of age at the time of testing, who were taking a prednisone dose less than 15 mg/day and who had cardiac catheterization with biopsy performed had blood drawn for Allomap testing the same day. The blood was handled by a certified lab according to CareDx protocol and then sent to CareDx for testing. Allomap scores were then compared to cellular biopsy grading (serious rejection = 2R or greater). The data points were assessed for sensitivity and specificity using the Youden index and distance to (0,1), as was done in the CARGO studies. Eighty-one patients (mean age 14 +/- 2.9 years, 44% female) had 265 total Allomap tests and biopsy pairs evaluated between 2013 and 2019. Sixty-three (63) patients had more than one Allomap sample and biopsy pair. Race mix was Caucasian 44%, Hispanic 38%, African American 12%, Asian 2.5%, others 3.5%. Biopsy grade 0-1R represented 94% of the sample population. The NPVs for Allomap scores were 100% at 32 and 98.8% at 34, similar to what was found for adults in the CARGO studies. ROC curve demonstrates a c-statistic of 0.7566. Allomap scores in children and adolescents can be used to successfully predict absence of rejection with NPVs between 98%-100%; scores less than or equal to 32 correlated 100% with biopsy grades of 0-1R in this population. Given these results, we speculate that Allomap use will lead to a reduced need for cardiac catheterization and biopsy in this population but further studies in a larger pediatric transplant population is warranted.