Variability in gene expression profiling test scores in post-transplant heart patients over time may provide prognostic utility for risk for organ rejection, according to a study published March 27 in Transplantation. The importance of variability in predicting clinical stability is independent of a single ordinal test score. The noninvasive, blood-based gene expression profiling test (AlloMap; XDx [Brisbane, Calif.]) incorporates expression levels of the 11 genes and was developed to minimize serial endomyocardial biopsies needed to identify heart transplant recipients at risk of rejection. The U.S. Food and Drug Administration-approved test to date has been used to rule out acute cellular rejection. The researchers analyzed data from patients participating in the Monitoring Attenuation by Gene Expression Profiling (IMAGE) study, with rejection surveillance gene expression profiling tests performed at one- to six-month intervals. For most patients (86 percent) surveillance began 12 months post-transplantation. The standard deviation of an individual’s cumulative test scores was used to define variability in gene expression profiling scores. Over a median follow-up of 19 months, 297 patients were monitored with gene expression profiling (mean, 4.4 tests) and 305 patients were monitored with biopsies. Rates of adverse events were similar between the groups. Being nonwhite, younger at time of […]
Variability in gene expression profiling test scores in post-transplant heart patients over time may provide prognostic utility for risk for organ rejection, according to a study published March 27 in Transplantation. The importance of variability in predicting clinical stability is independent of a single ordinal test score.
The noninvasive, blood-based gene expression profiling test (AlloMap; XDx [Brisbane, Calif.]) incorporates expression levels of the 11 genes and was developed to minimize serial endomyocardial biopsies needed to identify heart transplant recipients at risk of rejection. The U.S. Food and Drug Administration-approved test to date has been used to rule out acute cellular rejection.
The researchers analyzed data from patients participating in the Monitoring Attenuation by Gene Expression Profiling (IMAGE) study, with rejection surveillance gene expression profiling tests performed at one- to six-month intervals. For most patients (86 percent) surveillance began 12 months post-transplantation. The standard deviation of an individual’s cumulative test scores was used to define variability in gene expression profiling scores. Over a median follow-up of 19 months, 297 patients were monitored with gene expression profiling (mean, 4.4 tests) and 305 patients were monitored with biopsies. Rates of adverse events were similar between the groups.
Being nonwhite, younger at time of transplantation, and having an earlier time of study entry post-transplantation were significantly associated with future events. Twenty percent of patients had variability less than 0.5, 43 percent had variability over 1.0, 18 percent had variability greater than 1.5, and 7 percent had variability over 2.0. Gene expression score variability was significantly associated with future clinical events, even when controlling for gene expression ordinal score.
“This new prognostic information complements and validates our clinical intuition during routine patient encounters and demonstrates the value of longitudinal genomic testing. This longitudinal genomic testing is part of a very exciting transition toward the paradigm of personalized medicine,” said lead author Mario Deng, M.D., from University of California, Los Angeles, in a statement.
Such information, the authors say, can lead to reducing immunosuppressive maintenance regimens in low-risk patients or evaluating higher-risk patients for overlooked infections or medication noncompliance. Ongoing studies are evaluating whether longer follow-up and the time interval for repeat testing confirm the current findings of the significance of variability.
Several authors report financial ties to XDx, which funded the study.
Takeaway: Changes in gene expression over time may predict the risk of negative transplantation outcomes better than a single measurement.
