Accuracy of Gene Expression Test for Heart Transplant Patients Confirmed by Independent Clinical Data
Simple Blood Test May Predict Absence of Transplant Rejection
Dec 21, 2006
For many Americans living with a heart transplant, invasive heart-muscle biopsies that check for organ rejection are a fact of life. Now, a simple blood test that analyzes a patient's genes has been evaluated by leading transplant centers and shows that it can accurately detect the absence of heart transplant rejection, according to new data reported in an invited editorial authored by a consensus team of international heart transplant experts, including a physician-scientist at NewYork-Presbyterian Hospital and Columbia University Medical Center, and available today in the online edition of the Journal of Heart and Lung Transplantation (JHLT).
In 2006, the CARGO (Cardiac Allograft Rejection Gene Expression Observational Study) study reported the utility of a gene expression profiling (GEP) test, called AlloMap® molecular expression test, which led to the test's commercial availability in January 2005. Currently 40 transplant centers in the U.S. offer the test.
"GEP testing is not only less invasive and less risky than biopsy, it also monitors the absence of organ rejection and raises suspicion of damage before any damage to the heart happens. Biopsy records damage that has already occurred," says Dr. Mario Deng, the article's senior author. He is director of cardiac transplantation research and associate professor of clinical medicine at Columbia University College of Physicians and Surgeons, and cardiologist at NewYork-Presbyterian/Columbia.
The editorial's first author is Dr. Randall C. Starling, vice chairman of cardiovascular medicine and section head of heart failure and cardiac transplant medicine at Cleveland Clinic.
Approximately 30 percent of all heart transplant patients reject their new heart at least once in the first year after transplantation. When testing reveals organ rejection, a patient's immunosuppressive regimen is adjusted.
Based on new data, in more than 99 percent of cases, the AlloMap test successfully predicted heart-muscle biopsies that showed absence of moderate or severe acute cellular organ-transplant rejection. These results confirmed the findings of the CARGO study.
The AlloMap test was developed to rule out rejection, meaning that a low test score very reliably identifies transplant patients who are not rejecting their transplanted heart. The primary advantage of the test is to identify low-risk patients who can be monitored and managed using noninvasive methods and who may benefit from being more aggressively weaned off intensive immunosuppressive regimens that are associated with serious side effects.
"Additional clinical roles for this new mode of transplantation rejection monitoring will be identified in ongoing studies by our international study group," adds Dr. Deng.
The AlloMap test was developed in partnership with eight major U.S. research universities and XDx, a molecular diagnostics company in South San Francisco, Calif., and presents a snapshot of the immune status of the transplanted heart recipient. The test uses genomics technology (DNA microarray and real-time polymerase chain reaction – PCR), applying a complex algorithm to analyze the patient's genes. The Allomap test is currently being developed for use in lung transplantation.
The heart-muscle biopsy has for decades been the most reliable method available for detecting rejection of the transplanted heart. Invasive heart biopsies are performed initially once a week for the first two months, then every four-to-eight weeks for the first year, and then finally tapered to once every three to six months, often for the patient's lifetime.
Currently, the AlloMap test is available to heart transplant patients, ages 15 and older, after two months post-transplantation.
NewYork-Presbyterian/Columbia has the largest heart transplant program in the country, with 118 transplants completed in 2005 and more than 1,700 since the inception of the program in 1977.
Other contributing authors represent more than 20 major U.S. and international heart transplant centers, including Drs. E. Rene Rodriguez, David O. Taylor and H. Mohamed Yamani (Cleveland Clinic, OH); Charles C. Marboe (Columbia University, NY); Hannah Valantine and Michael Pham (Stanford University, CA); Howard Eisen (Drexel University, PA); Jon Kobashigawa (UCLA, CA); Kenneth McCurry (University of Pittsburgh, PA); Mandeep Mehra (University of Maryland, MD); Leslie Miller (Fairview University, MN); and Andreas Zuckermann (Medical University of Vienna, Austria).
XDx funded the original CARGO study and XDx is the sole proprietor of this technique.
For more information, patients may call 866-NYP-NEWS.
NewYork-Presbyterian Hospital – based in New York City – is the nation's largest not-for-profit, non-sectarian hospital, with 2,224 beds. It provides state-of-the-art inpatient, ambulatory and preventive care in all areas of medicine at five major centers: NewYork-Presbyterian Hospital/Weill Cornell Medical Center, NewYork-Presbyterian Hospital/Columbia University Medical Center, Morgan Stanley Children's Hospital of NewYork-Presbyterian, NewYork-Presbyterian Hospital/Allen Pavilion and NewYork-Presbyterian Hospital/Westchester Division. One of the largest and most comprehensive health-care institutions in the world, the Hospital is committed to excellence in patient care, research, education, and community service. It ranks among the top 10 in U.S.News & World Report's guide to "America's Best Hospitals," has the greatest number of physicians listed in New York magazine's "Best Doctors" issue, and is included among Solucient's top 15 major teaching hospitals. The Hospital has academic affiliations with two of the nation's leading medical colleges: Joan and Sanford I. Weill Medical College of Cornell University and Columbia University College of Physicians and Surgeons.
Columbia University Medical Center
Columbia University Medical Center provides international leadership in pre-clinical and clinical research, in medical and health sciences education, and in patient care. The medical center trains future leaders and includes the dedicated work of many physicians, scientists, nurses, dentists, and public health professionals at the College of Physicians & Surgeons, the College of Dental Medicine, the School of Nursing, the Mailman School of Public Health, the biomedical departments of the Graduate School of Arts and Sciences, and allied research centers and institutions. For more information, visit www.cumc.columbia.edu.
T.J. Crawford [email protected]