Genetic Screen Can Predict Transplant Rejection
Melissa Schorr
April 23, 2004 (San Francisco) - A blood test using a 10-gene molecular screening assay was able to significantly predict acute rejection in heart transplant patients, researchers reported here at the annual meeting of the International Society for Heart and Lung Transplantation (ISHLT).
"Molecular gene testing can predict the predilection for cellular rejection," said lead author Mandeep Rajinder Mehra, MD, vice chairman of the department of cardiology and director of the Cardiomyopathy and Heart Transplant Center at the Oschner Clinic Foundation in New Orleans, Louisiana. "These findings usher in an era of decreased need to use invasive biopsies."
The researchers conducted a prospective multicenter trial, called the Cardiac Allograft Rejection Gene Expression Observation (CARGO) study, evaluating the use of a 10-gene polymerase chain reaction (PCR) molecular test to assess the quiescent state of the transplanted heart.
More than 650 patients from eight medical centers were enrolled at the time of heart transplantation and they were followed for at least a year. About three quarters of the patients were white men, with an average age of 55 years.
Blood was collected at the time of endomyocardial biopsies at six and 16 weeks. The biopsies were graded for ISHLT criteria of acceptance by a panel of three expert cardiopathologists blinded to the clinical data.
Molecular testing based on the PCR test was rated negative or positive, suggesting acute rejection or graft dysfunction. The researchers correlated the test results with future development of clinical events including acute rejection and graft dysfunction, controlling for patient demographics, immunosuppression and the time posttransplant.
The algorithm assigned each patient a risk score from 0 to 6, with 0 to 3 being low risk and 4 to 6 being a high risk of rejection. The majority of the patients (92%) were given a low-risk score, and 94% had biopsies that were given an ISHLT grade of 0 or 1.
The researchers reported data from the first 200 patients, which revealed that the patients who received a positive result were significantly more likely to have an acute cellular rejection.
The greatest predictive power was found with measurements taken at six weeks and predicted out to 100 days, with a risk ratio of 4.6.
"The molecular testing is most useful for its negative predictive value for prediction of quiescence," Dr. Mehra said.
However, the 10-gene sequence was not found to be as predictive of graft dysfunction, possibly because there are multiple pathways involved not measured by this set of genes, he said. The researchers are exploring another set of 120 genes.
"The molecular significance of graft dysfunction is distinct and requires further development," Dr. Mehra noted.
The study was funded by Expression Diagnostics. The lead author disclosed consulting work for XDX, Fujisawa, Novartis, Roche, Pfizer, and Biosite Diagnostics.
ISHLT 24th Annual Meeting: Abstract 192. Presented April 23, 2004.
Reviewed by Gary D. Vogin, MD
Melissa Schorr is a freelance writer for Medscape.
Melissa Schorr
April 23, 2004 (San Francisco) - A blood test using a 10-gene molecular screening assay was able to significantly predict acute rejection in heart transplant patients, researchers reported here at the annual meeting of the International Society for Heart and Lung Transplantation (ISHLT).
"Molecular gene testing can predict the predilection for cellular rejection," said lead author Mandeep Rajinder Mehra, MD, vice chairman of the department of cardiology and director of the Cardiomyopathy and Heart Transplant Center at the Oschner Clinic Foundation in New Orleans, Louisiana. "These findings usher in an era of decreased need to use invasive biopsies."
The researchers conducted a prospective multicenter trial, called the Cardiac Allograft Rejection Gene Expression Observation (CARGO) study, evaluating the use of a 10-gene polymerase chain reaction (PCR) molecular test to assess the quiescent state of the transplanted heart.
More than 650 patients from eight medical centers were enrolled at the time of heart transplantation and they were followed for at least a year. About three quarters of the patients were white men, with an average age of 55 years.
Blood was collected at the time of endomyocardial biopsies at six and 16 weeks. The biopsies were graded for ISHLT criteria of acceptance by a panel of three expert cardiopathologists blinded to the clinical data.
Molecular testing based on the PCR test was rated negative or positive, suggesting acute rejection or graft dysfunction. The researchers correlated the test results with future development of clinical events including acute rejection and graft dysfunction, controlling for patient demographics, immunosuppression and the time posttransplant.
The algorithm assigned each patient a risk score from 0 to 6, with 0 to 3 being low risk and 4 to 6 being a high risk of rejection. The majority of the patients (92%) were given a low-risk score, and 94% had biopsies that were given an ISHLT grade of 0 or 1.
The researchers reported data from the first 200 patients, which revealed that the patients who received a positive result were significantly more likely to have an acute cellular rejection.
The greatest predictive power was found with measurements taken at six weeks and predicted out to 100 days, with a risk ratio of 4.6.
"The molecular testing is most useful for its negative predictive value for prediction of quiescence," Dr. Mehra said.
However, the 10-gene sequence was not found to be as predictive of graft dysfunction, possibly because there are multiple pathways involved not measured by this set of genes, he said. The researchers are exploring another set of 120 genes.
"The molecular significance of graft dysfunction is distinct and requires further development," Dr. Mehra noted.
The study was funded by Expression Diagnostics. The lead author disclosed consulting work for XDX, Fujisawa, Novartis, Roche, Pfizer, and Biosite Diagnostics.
ISHLT 24th Annual Meeting: Abstract 192. Presented April 23, 2004.
Reviewed by Gary D. Vogin, MD
Melissa Schorr is a freelance writer for Medscape.