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Mario C Deng - One of the best experts on this subject based on the ideXlab platform.
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Utility of Gene Expression Profiling Score Variability to Predict Clinical Events in Heart Transplant Recipients
Transplantation, 2014Co-Authors: Mario C Deng, M X Pham, Thomas P Cappola, Allen S. Anderson, Jeffrey J. Teuteberg, Abdallah G. Kfoury, Randall C. Starling, Andrew Kao, Barbara Elashoff, William G CottsAbstract:Background. Gene Expression Profiling test scores have primarily been used to identify heart transplant recipients who have a low probability of rejection at the time of surveillance testing. We hypothesized that the variability of Gene Expression Profiling test scores within a patient may predict risk of future events of allograft dysfunction or death. Method. Patients from the IMAGE study with rejection surveillance Gene Expression Profiling tests performed at 1- to 6-month intervals were selected for this cohort study. Gene Expression Profiling score variability was defined as the standard deviation of an individual’s cumulative test scores. Gene Expression Profiling ordinal score (range, 0Y39), threshold score (binary value=1 if ordinal score Q34), and score variability were studied in multivariate Cox regression models to predict future clinical events. Results. Race, age at time of transplantation, and time posttransplantation were significantly associated with future events in the univariate analysis. In the multivariate analyses, Gene Expression Profiling score variability, but not ordinal scores or scores over threshold, was independently associated with future clinical events. The regression coefficient P values were G0.001, 0.46, and 0.773, for Gene Expression Profiling variability, ordinal, and threshold scores, respectively. The hazard ratio for a 1 unit increase in variability was 1.76 (95% CI, 1.4Y2.3). Discussion. The variability of a heart recipient’s Gene Expression Profiling test scores over time may provide prognostic utility. This information is independent of the probability of acute cellular rejection at the time of testing that is rendered from a single ordinal Gene-Expression Profiling test score.
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Gene Expression Profiling for rejection surveillance after cardiac transplantation
The New England Journal of Medicine, 2010Co-Authors: M X Pham, William G Cotts, Thomas P Cappola, Allen S. Anderson, Mario C Deng, Gregory A Ewald, Jeffrey J. Teuteberg, Abdallah G. Kfoury, Randall C. Starling, D A BaranAbstract:Background Endomyocardial biopsy is the standard method of monitoring for rejection in recipients of a cardiac transplant. However, this procedure is uncomfortable, and there are risks associated with it. Gene-Expression Profiling of peripheral-blood specimens has been shown to correlate with the results of an endomyocardial biopsy. Methods We randomly assigned 602 patients who had undergone cardiac transplantation 6 months to 5 years previously to be monitored for rejection with the use of GeneExpression Profiling or with the use of routine endomyocardial biopsies, in addition to clinical and echocardiographic assessment of graft function. We performed a noninferiority comparison of the two approaches with respect to the composite primary outcome of rejection with hemodynamic compromise, graft dysfunction due to other causes, death, or retransplantation. Results During a median follow-up period of 19 months, patients who were monitored with Gene-Expression Profiling and those who underwent routine biopsies had similar 2-year cumulative rates of the composite primary outcome (14.5% and 15.3%, respectively; hazard ratio with Gene-Expression Profiling, 1.04; 95% confidence interval, 0.67 to 1.68). 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). 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). Conclusions Among selected patients who had received a cardiac transplant more than 6 months previously and who were at a low risk for rejection, a strategy of monitoring for rejection that involved Gene-Expression Profiling, as compared with routine biopsies, was not associated with an increased risk of serious adverse outcomes and resulted in the performance of significantly fewer biopsies. (ClinicalTrials.gov number, NCT00351559.)
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Gene-Expression Profiling for rejection surveillance after cardiac transplantation.
The New England journal of medicine, 2010Co-Authors: M X Pham, William G Cotts, Thomas P Cappola, Allen S. Anderson, Mario C Deng, Jeffrey J. Teuteberg, Abdallah G. Kfoury, Randall C. Starling, Andrew Kao, Gregory A EwaldAbstract:Background Endomyocardial biopsy is the standard method of monitoring for rejection in recipients of a cardiac transplant. However, this procedure is uncomfortable, and there are risks associated with it. Gene-Expression Profiling of peripheral-blood specimens has been shown to correlate with the results of an endomyocardial biopsy. Methods We randomly assigned 602 patients who had undergone cardiac transplantation 6 months to 5 years previously to be monitored for rejection with the use of GeneExpression Profiling or with the use of routine endomyocardial biopsies, in addition to clinical and echocardiographic assessment of graft function. We performed a noninferiority comparison of the two approaches with respect to the composite primary outcome of rejection with hemodynamic compromise, graft dysfunction due to other causes, death, or retransplantation. Results During a median follow-up period of 19 months, patients who were monitored with Gene-Expression Profiling and those who underwent routine biopsies had similar 2-year cumulative rates of the composite primary outcome (14.5% and 15.3%, respectively; hazard ratio with Gene-Expression Profiling, 1.04; 95% confidence interval, 0.67 to 1.68). 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). 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
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noninvasive discrimination of rejection in cardiac allograft recipients using Gene Expression Profiling
American Journal of Transplantation, 2006Co-Authors: Mario C Deng, Randall C. Starling, H J Eisen, Mandeep R Mehra, M Billingham, Charles C Marboe, Gerald J Berry, J A Kobashigawa, F L Johnson, S MuraliAbstract:Rejection diagnosis by endomyocardial biopsy (EMB) is invasive, expensive and variable. We investigated Gene Expression Profiling of peripheral blood mononuclear cells (PBMC) to discriminate ISHLT grade 0 rejection (quiescence) from moderate/severe rejection (ISHLT ≥3A). Patients were followed prospectively with blood sampling at post-transplant visits. Biopsies were graded by ISHLT criteria locally and by three independent pathologists blinded to clinical data. Known alloimmune pathways and leukocyte microarrays identified 252 candidate Genes for which real-time PCR assays were developed. An 11 Gene real-time PCR test was derived from a training set (n = 145 samples, 107 patients) using linear discriminant analysis (LDA), converted into a score (0–40), and validated prospectively in an independent set (n = 63 samples, 63 patients). The test distinguished biopsy-defined moderate/severe rejection from quiescence (p = 0.0018) in the validation set, and had agreement of 84% (95% CI 66% C94%) with grade ISHLT ≥3A rejection. Patients >1 year post-transplant with scores below 30 (approximately 68% of the study population) are very unlikely to have grade ≥3A rejection (NPV = 99.6%). Gene Expression testing can detect absence of moderate/severe rejection, thus avoiding biopsy in certain clinical settings. Additional clinical experience is needed to establish the role of molecular testing for clinical event prediction and immunosuppression management.
Randall C. Starling - One of the best experts on this subject based on the ideXlab platform.
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Utility of Gene Expression Profiling Score Variability to Predict Clinical Events in Heart Transplant Recipients
Transplantation, 2014Co-Authors: Mario C Deng, M X Pham, Thomas P Cappola, Allen S. Anderson, Jeffrey J. Teuteberg, Abdallah G. Kfoury, Randall C. Starling, Andrew Kao, Barbara Elashoff, William G CottsAbstract:Background. Gene Expression Profiling test scores have primarily been used to identify heart transplant recipients who have a low probability of rejection at the time of surveillance testing. We hypothesized that the variability of Gene Expression Profiling test scores within a patient may predict risk of future events of allograft dysfunction or death. Method. Patients from the IMAGE study with rejection surveillance Gene Expression Profiling tests performed at 1- to 6-month intervals were selected for this cohort study. Gene Expression Profiling score variability was defined as the standard deviation of an individual’s cumulative test scores. Gene Expression Profiling ordinal score (range, 0Y39), threshold score (binary value=1 if ordinal score Q34), and score variability were studied in multivariate Cox regression models to predict future clinical events. Results. Race, age at time of transplantation, and time posttransplantation were significantly associated with future events in the univariate analysis. In the multivariate analyses, Gene Expression Profiling score variability, but not ordinal scores or scores over threshold, was independently associated with future clinical events. The regression coefficient P values were G0.001, 0.46, and 0.773, for Gene Expression Profiling variability, ordinal, and threshold scores, respectively. The hazard ratio for a 1 unit increase in variability was 1.76 (95% CI, 1.4Y2.3). Discussion. The variability of a heart recipient’s Gene Expression Profiling test scores over time may provide prognostic utility. This information is independent of the probability of acute cellular rejection at the time of testing that is rendered from a single ordinal Gene-Expression Profiling test score.
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Gene Expression Profiling for rejection surveillance after cardiac transplantation
The New England Journal of Medicine, 2010Co-Authors: M X Pham, William G Cotts, Thomas P Cappola, Allen S. Anderson, Mario C Deng, Gregory A Ewald, Jeffrey J. Teuteberg, Abdallah G. Kfoury, Randall C. Starling, D A BaranAbstract:Background Endomyocardial biopsy is the standard method of monitoring for rejection in recipients of a cardiac transplant. However, this procedure is uncomfortable, and there are risks associated with it. Gene-Expression Profiling of peripheral-blood specimens has been shown to correlate with the results of an endomyocardial biopsy. Methods We randomly assigned 602 patients who had undergone cardiac transplantation 6 months to 5 years previously to be monitored for rejection with the use of GeneExpression Profiling or with the use of routine endomyocardial biopsies, in addition to clinical and echocardiographic assessment of graft function. We performed a noninferiority comparison of the two approaches with respect to the composite primary outcome of rejection with hemodynamic compromise, graft dysfunction due to other causes, death, or retransplantation. Results During a median follow-up period of 19 months, patients who were monitored with Gene-Expression Profiling and those who underwent routine biopsies had similar 2-year cumulative rates of the composite primary outcome (14.5% and 15.3%, respectively; hazard ratio with Gene-Expression Profiling, 1.04; 95% confidence interval, 0.67 to 1.68). 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). 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). Conclusions Among selected patients who had received a cardiac transplant more than 6 months previously and who were at a low risk for rejection, a strategy of monitoring for rejection that involved Gene-Expression Profiling, as compared with routine biopsies, was not associated with an increased risk of serious adverse outcomes and resulted in the performance of significantly fewer biopsies. (ClinicalTrials.gov number, NCT00351559.)
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Gene-Expression Profiling for rejection surveillance after cardiac transplantation.
The New England journal of medicine, 2010Co-Authors: M X Pham, William G Cotts, Thomas P Cappola, Allen S. Anderson, Mario C Deng, Jeffrey J. Teuteberg, Abdallah G. Kfoury, Randall C. Starling, Andrew Kao, Gregory A EwaldAbstract:Background Endomyocardial biopsy is the standard method of monitoring for rejection in recipients of a cardiac transplant. However, this procedure is uncomfortable, and there are risks associated with it. Gene-Expression Profiling of peripheral-blood specimens has been shown to correlate with the results of an endomyocardial biopsy. Methods We randomly assigned 602 patients who had undergone cardiac transplantation 6 months to 5 years previously to be monitored for rejection with the use of GeneExpression Profiling or with the use of routine endomyocardial biopsies, in addition to clinical and echocardiographic assessment of graft function. We performed a noninferiority comparison of the two approaches with respect to the composite primary outcome of rejection with hemodynamic compromise, graft dysfunction due to other causes, death, or retransplantation. Results During a median follow-up period of 19 months, patients who were monitored with Gene-Expression Profiling and those who underwent routine biopsies had similar 2-year cumulative rates of the composite primary outcome (14.5% and 15.3%, respectively; hazard ratio with Gene-Expression Profiling, 1.04; 95% confidence interval, 0.67 to 1.68). 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). 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
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noninvasive discrimination of rejection in cardiac allograft recipients using Gene Expression Profiling
American Journal of Transplantation, 2006Co-Authors: Mario C Deng, Randall C. Starling, H J Eisen, Mandeep R Mehra, M Billingham, Charles C Marboe, Gerald J Berry, J A Kobashigawa, F L Johnson, S MuraliAbstract:Rejection diagnosis by endomyocardial biopsy (EMB) is invasive, expensive and variable. We investigated Gene Expression Profiling of peripheral blood mononuclear cells (PBMC) to discriminate ISHLT grade 0 rejection (quiescence) from moderate/severe rejection (ISHLT ≥3A). Patients were followed prospectively with blood sampling at post-transplant visits. Biopsies were graded by ISHLT criteria locally and by three independent pathologists blinded to clinical data. Known alloimmune pathways and leukocyte microarrays identified 252 candidate Genes for which real-time PCR assays were developed. An 11 Gene real-time PCR test was derived from a training set (n = 145 samples, 107 patients) using linear discriminant analysis (LDA), converted into a score (0–40), and validated prospectively in an independent set (n = 63 samples, 63 patients). The test distinguished biopsy-defined moderate/severe rejection from quiescence (p = 0.0018) in the validation set, and had agreement of 84% (95% CI 66% C94%) with grade ISHLT ≥3A rejection. Patients >1 year post-transplant with scores below 30 (approximately 68% of the study population) are very unlikely to have grade ≥3A rejection (NPV = 99.6%). Gene Expression testing can detect absence of moderate/severe rejection, thus avoiding biopsy in certain clinical settings. Additional clinical experience is needed to establish the role of molecular testing for clinical event prediction and immunosuppression management.
M X Pham - One of the best experts on this subject based on the ideXlab platform.
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Utility of Gene Expression Profiling Score Variability to Predict Clinical Events in Heart Transplant Recipients
Transplantation, 2014Co-Authors: Mario C Deng, M X Pham, Thomas P Cappola, Allen S. Anderson, Jeffrey J. Teuteberg, Abdallah G. Kfoury, Randall C. Starling, Andrew Kao, Barbara Elashoff, William G CottsAbstract:Background. Gene Expression Profiling test scores have primarily been used to identify heart transplant recipients who have a low probability of rejection at the time of surveillance testing. We hypothesized that the variability of Gene Expression Profiling test scores within a patient may predict risk of future events of allograft dysfunction or death. Method. Patients from the IMAGE study with rejection surveillance Gene Expression Profiling tests performed at 1- to 6-month intervals were selected for this cohort study. Gene Expression Profiling score variability was defined as the standard deviation of an individual’s cumulative test scores. Gene Expression Profiling ordinal score (range, 0Y39), threshold score (binary value=1 if ordinal score Q34), and score variability were studied in multivariate Cox regression models to predict future clinical events. Results. Race, age at time of transplantation, and time posttransplantation were significantly associated with future events in the univariate analysis. In the multivariate analyses, Gene Expression Profiling score variability, but not ordinal scores or scores over threshold, was independently associated with future clinical events. The regression coefficient P values were G0.001, 0.46, and 0.773, for Gene Expression Profiling variability, ordinal, and threshold scores, respectively. The hazard ratio for a 1 unit increase in variability was 1.76 (95% CI, 1.4Y2.3). Discussion. The variability of a heart recipient’s Gene Expression Profiling test scores over time may provide prognostic utility. This information is independent of the probability of acute cellular rejection at the time of testing that is rendered from a single ordinal Gene-Expression Profiling test score.
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Gene Expression Profiling for rejection surveillance after cardiac transplantation
The New England Journal of Medicine, 2010Co-Authors: M X Pham, William G Cotts, Thomas P Cappola, Allen S. Anderson, Mario C Deng, Gregory A Ewald, Jeffrey J. Teuteberg, Abdallah G. Kfoury, Randall C. Starling, D A BaranAbstract:Background Endomyocardial biopsy is the standard method of monitoring for rejection in recipients of a cardiac transplant. However, this procedure is uncomfortable, and there are risks associated with it. Gene-Expression Profiling of peripheral-blood specimens has been shown to correlate with the results of an endomyocardial biopsy. Methods We randomly assigned 602 patients who had undergone cardiac transplantation 6 months to 5 years previously to be monitored for rejection with the use of GeneExpression Profiling or with the use of routine endomyocardial biopsies, in addition to clinical and echocardiographic assessment of graft function. We performed a noninferiority comparison of the two approaches with respect to the composite primary outcome of rejection with hemodynamic compromise, graft dysfunction due to other causes, death, or retransplantation. Results During a median follow-up period of 19 months, patients who were monitored with Gene-Expression Profiling and those who underwent routine biopsies had similar 2-year cumulative rates of the composite primary outcome (14.5% and 15.3%, respectively; hazard ratio with Gene-Expression Profiling, 1.04; 95% confidence interval, 0.67 to 1.68). 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). 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). Conclusions Among selected patients who had received a cardiac transplant more than 6 months previously and who were at a low risk for rejection, a strategy of monitoring for rejection that involved Gene-Expression Profiling, as compared with routine biopsies, was not associated with an increased risk of serious adverse outcomes and resulted in the performance of significantly fewer biopsies. (ClinicalTrials.gov number, NCT00351559.)
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Gene-Expression Profiling for rejection surveillance after cardiac transplantation.
The New England journal of medicine, 2010Co-Authors: M X Pham, William G Cotts, Thomas P Cappola, Allen S. Anderson, Mario C Deng, Jeffrey J. Teuteberg, Abdallah G. Kfoury, Randall C. Starling, Andrew Kao, Gregory A EwaldAbstract:Background Endomyocardial biopsy is the standard method of monitoring for rejection in recipients of a cardiac transplant. However, this procedure is uncomfortable, and there are risks associated with it. Gene-Expression Profiling of peripheral-blood specimens has been shown to correlate with the results of an endomyocardial biopsy. Methods We randomly assigned 602 patients who had undergone cardiac transplantation 6 months to 5 years previously to be monitored for rejection with the use of GeneExpression Profiling or with the use of routine endomyocardial biopsies, in addition to clinical and echocardiographic assessment of graft function. We performed a noninferiority comparison of the two approaches with respect to the composite primary outcome of rejection with hemodynamic compromise, graft dysfunction due to other causes, death, or retransplantation. Results During a median follow-up period of 19 months, patients who were monitored with Gene-Expression Profiling and those who underwent routine biopsies had similar 2-year cumulative rates of the composite primary outcome (14.5% and 15.3%, respectively; hazard ratio with Gene-Expression Profiling, 1.04; 95% confidence interval, 0.67 to 1.68). 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). 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
William G Cotts - One of the best experts on this subject based on the ideXlab platform.
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Utility of Gene Expression Profiling Score Variability to Predict Clinical Events in Heart Transplant Recipients
Transplantation, 2014Co-Authors: Mario C Deng, M X Pham, Thomas P Cappola, Allen S. Anderson, Jeffrey J. Teuteberg, Abdallah G. Kfoury, Randall C. Starling, Andrew Kao, Barbara Elashoff, William G CottsAbstract:Background. Gene Expression Profiling test scores have primarily been used to identify heart transplant recipients who have a low probability of rejection at the time of surveillance testing. We hypothesized that the variability of Gene Expression Profiling test scores within a patient may predict risk of future events of allograft dysfunction or death. Method. Patients from the IMAGE study with rejection surveillance Gene Expression Profiling tests performed at 1- to 6-month intervals were selected for this cohort study. Gene Expression Profiling score variability was defined as the standard deviation of an individual’s cumulative test scores. Gene Expression Profiling ordinal score (range, 0Y39), threshold score (binary value=1 if ordinal score Q34), and score variability were studied in multivariate Cox regression models to predict future clinical events. Results. Race, age at time of transplantation, and time posttransplantation were significantly associated with future events in the univariate analysis. In the multivariate analyses, Gene Expression Profiling score variability, but not ordinal scores or scores over threshold, was independently associated with future clinical events. The regression coefficient P values were G0.001, 0.46, and 0.773, for Gene Expression Profiling variability, ordinal, and threshold scores, respectively. The hazard ratio for a 1 unit increase in variability was 1.76 (95% CI, 1.4Y2.3). Discussion. The variability of a heart recipient’s Gene Expression Profiling test scores over time may provide prognostic utility. This information is independent of the probability of acute cellular rejection at the time of testing that is rendered from a single ordinal Gene-Expression Profiling test score.
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Gene Expression Profiling for rejection surveillance after cardiac transplantation
The New England Journal of Medicine, 2010Co-Authors: M X Pham, William G Cotts, Thomas P Cappola, Allen S. Anderson, Mario C Deng, Gregory A Ewald, Jeffrey J. Teuteberg, Abdallah G. Kfoury, Randall C. Starling, D A BaranAbstract:Background Endomyocardial biopsy is the standard method of monitoring for rejection in recipients of a cardiac transplant. However, this procedure is uncomfortable, and there are risks associated with it. Gene-Expression Profiling of peripheral-blood specimens has been shown to correlate with the results of an endomyocardial biopsy. Methods We randomly assigned 602 patients who had undergone cardiac transplantation 6 months to 5 years previously to be monitored for rejection with the use of GeneExpression Profiling or with the use of routine endomyocardial biopsies, in addition to clinical and echocardiographic assessment of graft function. We performed a noninferiority comparison of the two approaches with respect to the composite primary outcome of rejection with hemodynamic compromise, graft dysfunction due to other causes, death, or retransplantation. Results During a median follow-up period of 19 months, patients who were monitored with Gene-Expression Profiling and those who underwent routine biopsies had similar 2-year cumulative rates of the composite primary outcome (14.5% and 15.3%, respectively; hazard ratio with Gene-Expression Profiling, 1.04; 95% confidence interval, 0.67 to 1.68). 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). 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). Conclusions Among selected patients who had received a cardiac transplant more than 6 months previously and who were at a low risk for rejection, a strategy of monitoring for rejection that involved Gene-Expression Profiling, as compared with routine biopsies, was not associated with an increased risk of serious adverse outcomes and resulted in the performance of significantly fewer biopsies. (ClinicalTrials.gov number, NCT00351559.)
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Gene-Expression Profiling for rejection surveillance after cardiac transplantation.
The New England journal of medicine, 2010Co-Authors: M X Pham, William G Cotts, Thomas P Cappola, Allen S. Anderson, Mario C Deng, Jeffrey J. Teuteberg, Abdallah G. Kfoury, Randall C. Starling, Andrew Kao, Gregory A EwaldAbstract:Background Endomyocardial biopsy is the standard method of monitoring for rejection in recipients of a cardiac transplant. However, this procedure is uncomfortable, and there are risks associated with it. Gene-Expression Profiling of peripheral-blood specimens has been shown to correlate with the results of an endomyocardial biopsy. Methods We randomly assigned 602 patients who had undergone cardiac transplantation 6 months to 5 years previously to be monitored for rejection with the use of GeneExpression Profiling or with the use of routine endomyocardial biopsies, in addition to clinical and echocardiographic assessment of graft function. We performed a noninferiority comparison of the two approaches with respect to the composite primary outcome of rejection with hemodynamic compromise, graft dysfunction due to other causes, death, or retransplantation. Results During a median follow-up period of 19 months, patients who were monitored with Gene-Expression Profiling and those who underwent routine biopsies had similar 2-year cumulative rates of the composite primary outcome (14.5% and 15.3%, respectively; hazard ratio with Gene-Expression Profiling, 1.04; 95% confidence interval, 0.67 to 1.68). 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). 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
Thomas P Cappola - One of the best experts on this subject based on the ideXlab platform.
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Utility of Gene Expression Profiling Score Variability to Predict Clinical Events in Heart Transplant Recipients
Transplantation, 2014Co-Authors: Mario C Deng, M X Pham, Thomas P Cappola, Allen S. Anderson, Jeffrey J. Teuteberg, Abdallah G. Kfoury, Randall C. Starling, Andrew Kao, Barbara Elashoff, William G CottsAbstract:Background. Gene Expression Profiling test scores have primarily been used to identify heart transplant recipients who have a low probability of rejection at the time of surveillance testing. We hypothesized that the variability of Gene Expression Profiling test scores within a patient may predict risk of future events of allograft dysfunction or death. Method. Patients from the IMAGE study with rejection surveillance Gene Expression Profiling tests performed at 1- to 6-month intervals were selected for this cohort study. Gene Expression Profiling score variability was defined as the standard deviation of an individual’s cumulative test scores. Gene Expression Profiling ordinal score (range, 0Y39), threshold score (binary value=1 if ordinal score Q34), and score variability were studied in multivariate Cox regression models to predict future clinical events. Results. Race, age at time of transplantation, and time posttransplantation were significantly associated with future events in the univariate analysis. In the multivariate analyses, Gene Expression Profiling score variability, but not ordinal scores or scores over threshold, was independently associated with future clinical events. The regression coefficient P values were G0.001, 0.46, and 0.773, for Gene Expression Profiling variability, ordinal, and threshold scores, respectively. The hazard ratio for a 1 unit increase in variability was 1.76 (95% CI, 1.4Y2.3). Discussion. The variability of a heart recipient’s Gene Expression Profiling test scores over time may provide prognostic utility. This information is independent of the probability of acute cellular rejection at the time of testing that is rendered from a single ordinal Gene-Expression Profiling test score.
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Gene Expression Profiling for rejection surveillance after cardiac transplantation
The New England Journal of Medicine, 2010Co-Authors: M X Pham, William G Cotts, Thomas P Cappola, Allen S. Anderson, Mario C Deng, Gregory A Ewald, Jeffrey J. Teuteberg, Abdallah G. Kfoury, Randall C. Starling, D A BaranAbstract:Background Endomyocardial biopsy is the standard method of monitoring for rejection in recipients of a cardiac transplant. However, this procedure is uncomfortable, and there are risks associated with it. Gene-Expression Profiling of peripheral-blood specimens has been shown to correlate with the results of an endomyocardial biopsy. Methods We randomly assigned 602 patients who had undergone cardiac transplantation 6 months to 5 years previously to be monitored for rejection with the use of GeneExpression Profiling or with the use of routine endomyocardial biopsies, in addition to clinical and echocardiographic assessment of graft function. We performed a noninferiority comparison of the two approaches with respect to the composite primary outcome of rejection with hemodynamic compromise, graft dysfunction due to other causes, death, or retransplantation. Results During a median follow-up period of 19 months, patients who were monitored with Gene-Expression Profiling and those who underwent routine biopsies had similar 2-year cumulative rates of the composite primary outcome (14.5% and 15.3%, respectively; hazard ratio with Gene-Expression Profiling, 1.04; 95% confidence interval, 0.67 to 1.68). 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). 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). Conclusions Among selected patients who had received a cardiac transplant more than 6 months previously and who were at a low risk for rejection, a strategy of monitoring for rejection that involved Gene-Expression Profiling, as compared with routine biopsies, was not associated with an increased risk of serious adverse outcomes and resulted in the performance of significantly fewer biopsies. (ClinicalTrials.gov number, NCT00351559.)
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Gene-Expression Profiling for rejection surveillance after cardiac transplantation.
The New England journal of medicine, 2010Co-Authors: M X Pham, William G Cotts, Thomas P Cappola, Allen S. Anderson, Mario C Deng, Jeffrey J. Teuteberg, Abdallah G. Kfoury, Randall C. Starling, Andrew Kao, Gregory A EwaldAbstract:Background Endomyocardial biopsy is the standard method of monitoring for rejection in recipients of a cardiac transplant. However, this procedure is uncomfortable, and there are risks associated with it. Gene-Expression Profiling of peripheral-blood specimens has been shown to correlate with the results of an endomyocardial biopsy. Methods We randomly assigned 602 patients who had undergone cardiac transplantation 6 months to 5 years previously to be monitored for rejection with the use of GeneExpression Profiling or with the use of routine endomyocardial biopsies, in addition to clinical and echocardiographic assessment of graft function. We performed a noninferiority comparison of the two approaches with respect to the composite primary outcome of rejection with hemodynamic compromise, graft dysfunction due to other causes, death, or retransplantation. Results During a median follow-up period of 19 months, patients who were monitored with Gene-Expression Profiling and those who underwent routine biopsies had similar 2-year cumulative rates of the composite primary outcome (14.5% and 15.3%, respectively; hazard ratio with Gene-Expression Profiling, 1.04; 95% confidence interval, 0.67 to 1.68). 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). 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