Editors' ChoiceCardiac Transplant

Blood-Based Diagnostics—A Biopsy Surrogate

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Science Translational Medicine  09 Jun 2010:
Vol. 2, Issue 35, pp. 35ec91
DOI: 10.1126/scitranslmed.3001331

Endomyocardial biopsy is standard for monitoring acute allograft rejection after cardiac transplantation. Unfortunately, this procedure is associated with significant patient discomfort, substantial financial cost, and, at times, potentially lethal complications. Now, Pham and colleagues have demonstrated a possible alternative. By using an expression profile of 11 common blood-based genes previously shown to predict rejection, they were able to reduce the need for subsequent biopsies by over fivefold in 300 posttransplant patients when compared with an equally matched control group that were followed by standard of care. Quality-of-life measures were also found to be significantly better in the noninvasively monitored group, and, most importantly, they found no difference at 2 years between the groups with respect to the primary endpoint of allograft dysfunction, death, and retransplantation. However, several limitations of this study require mentioning. First, only 20% of eligible patients were actually enrolled. Second, the study was a statistical noninferiority study with wide confidential intervals, which means that a small intergroup difference in the primary outcome could have been missed. Third, only 6 of the 34 allograft rejection events in the gene expression cohort were detected through RNA profiling. The rest were detected by clinical and echocardiographic monitoring. Thus, going forward, DNA- and RNA-based assays require further testing in larger well-designed trials before any definitive conclusion of their utility in transplant medicine can be made. Nevertheless, rest assured that, while they may not replace traditional biopsies, blood-based diagnostics are here to stay.

M. X. Pham et al., Gene-expression profiling for rejection surveillance after cardiac transplantation. N. Engl. J. Med. 362, 1890–1900 (2010). [Abstract]

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