Gene profiling to detect transplant rejection

While 1-year survival rates after cardiac transplantation are now of the order of 90%, approximately 30-40% of recipients suffer an episode of acute cellular rejection during their first year, and then at a reduced rate thereafter.  Endomyocardial biopsy remains the standard method of monitoring for rejection in recipients of a cardiac transplant but is uncomfortable for the patient and carries the risk of rare but potentially serious complications.  Gene-expression profiling from peripheral-blood has been explored as an alternative method for detecting transplant rejection and in earlier studies has been shown to correlate with the results of an endomyocardial biopsy.  This has led to the development of a commercially available test which monitors a combination of 11 genes and assigns a rejection score based on expression patterns.  However, evidence to support the clinical utility of this test was lacking and so the authours undertook the multi-centre Invasive Monitoring Attenuation through Gene Expression (IMAGE) trial, in which 602 patients who had undergone cardiac transplantation 6 months to 5 years previously were randomly assigned in a 1:1 ratio to either monitoring by gene expression profiling or routine endomyocardial biopsies, in addition to clinical and echocardiographic assessment of graft function.  If gene profiling scores or clinical or echo parameters suggested graft dysfunction then a biopsy was performed.  The study was powered for a noninferiority outcome with a primary composite end-point of rejection with hemodynamic compromise, graft dysfunction due to other causes, death, or retransplantation.  Patients were followed up for a median of 19 months and the results are impressive with similar 2-year cumulative rates of the primary outcome (14.5% and 15.3%, respectively; HR, 1.04; 95% CI, 0.67 to 1.68, P=0.86).  The 2-year rates of death from any cause were also similar in the two groups (6.3% and 5.5%, respectively; P=0.82).  Added to this, patients who were monitored with the use of gene-expression profiling underwent fewer biopsies per person-year of follow-up than did patients who were monitored with the use of endomyocardial biopsies (0.5 vs. 3.0, P<0.001), translating into a significant increase in patient satisfaction scores in the gene profiling group.  Although the study was not blinded, immunosuppressive intensity between the two groups was similar suggesting a lack of bias.

Conclusion:

The adoption of gene profiling technology in selected transplant patients may represent an important step forward in minimising discomfort while maintaining careful standards of care.
• Gene-Expression Profiling for Rejection Surveillance after Cardiac Transplantation. Pham MX, Teuteberg JJ, Kfoury AG, Starling RC, Deng MC, Cappola TP, Kao A, Anderson AS, Cotts WG, Ewald GA, Baran DA, Bogaev RC, Elashoff B, Baron H, Yee J and Valantine HA N Engl J Med. 2010 Apr 22. [Epub ahead of print]

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