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Performance of gene-expression profiling test score variability to predict future clinical events in heart transplant recipients
BACKGROUND: A single non-invasive gene expression profiling (GEP) test (AlloMap®) is often used to discriminate if a heart transplant recipient is at a low risk of acute cellular rejection at time of testing. In a randomized trial, use of the test (a GEP score from 0–40) has been shown to be non-inf...
Autores principales: | , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4600291/ https://www.ncbi.nlm.nih.gov/pubmed/26452346 http://dx.doi.org/10.1186/s12872-015-0106-1 |
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author | Crespo-Leiro, Maria G. Stypmann, Jörg Schulz, Uwe Zuckermann, Andreas Mohacsi, Paul Bara, Christoph Ross, Heather Parameshwar, Jayan Zakliczyński, Michal Fiocchi, Roberto Hoefer, Daniel Deng, Mario Leprince, Pascal Hiller, David Eubank, Lane Deljkich, Emir Yee, James P. Vanhaecke, Johan |
author_facet | Crespo-Leiro, Maria G. Stypmann, Jörg Schulz, Uwe Zuckermann, Andreas Mohacsi, Paul Bara, Christoph Ross, Heather Parameshwar, Jayan Zakliczyński, Michal Fiocchi, Roberto Hoefer, Daniel Deng, Mario Leprince, Pascal Hiller, David Eubank, Lane Deljkich, Emir Yee, James P. Vanhaecke, Johan |
author_sort | Crespo-Leiro, Maria G. |
collection | PubMed |
description | BACKGROUND: A single non-invasive gene expression profiling (GEP) test (AlloMap®) is often used to discriminate if a heart transplant recipient is at a low risk of acute cellular rejection at time of testing. In a randomized trial, use of the test (a GEP score from 0–40) has been shown to be non-inferior to a routine endomyocardial biopsy for surveillance after heart transplantation in selected low-risk patients with respect to clinical outcomes. Recently, it was suggested that the within-patient variability of consecutive GEP scores may be used to independently predict future clinical events; however, future studies were recommended. Here we performed an analysis of an independent patient population to determine the prognostic utility of within-patient variability of GEP scores in predicting future clinical events. METHODS: We defined the GEP score variability as the standard deviation of four GEP scores collected ≥315 days post-transplantation. Of the 737 patients from the Cardiac Allograft Rejection Gene Expression Observational (CARGO) II trial, 36 were assigned to the composite event group (death, re-transplantation or graft failure ≥315 days post-transplantation and within 3 years of the final GEP test) and 55 were assigned to the control group (non-event patients). In this case-controlled study, the performance of GEP score variability to predict future events was evaluated by the area under the receiver operator characteristics curve (AUC ROC). The negative predictive values (NPV) and positive predictive values (PPV) including 95 % confidence intervals (CI) of GEP score variability were calculated. RESULTS: The estimated prevalence of events was 17 %. Events occurred at a median of 391 (inter-quartile range 376) days after the final GEP test. The GEP variability AUC ROC for the prediction of a composite event was 0.72 (95 % CI 0.6-0.8). The NPV for GEP score variability of 0.6 was 97 % (95 % CI 91.4-100.0); the PPV for GEP score variability of 1.5 was 35.4 % (95 % CI 13.5-75.8). CONCLUSION: In heart transplant recipients, a GEP score variability may be used to predict the probability that a composite event will occur within 3 years after the last GEP score. TRIAL REGISTRATION: Clinicaltrials.gov identifier NCT00761787 ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12872-015-0106-1) contains supplementary material, which is available to authorized users. |
format | Online Article Text |
id | pubmed-4600291 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-46002912015-10-11 Performance of gene-expression profiling test score variability to predict future clinical events in heart transplant recipients Crespo-Leiro, Maria G. Stypmann, Jörg Schulz, Uwe Zuckermann, Andreas Mohacsi, Paul Bara, Christoph Ross, Heather Parameshwar, Jayan Zakliczyński, Michal Fiocchi, Roberto Hoefer, Daniel Deng, Mario Leprince, Pascal Hiller, David Eubank, Lane Deljkich, Emir Yee, James P. Vanhaecke, Johan BMC Cardiovasc Disord Research Article BACKGROUND: A single non-invasive gene expression profiling (GEP) test (AlloMap®) is often used to discriminate if a heart transplant recipient is at a low risk of acute cellular rejection at time of testing. In a randomized trial, use of the test (a GEP score from 0–40) has been shown to be non-inferior to a routine endomyocardial biopsy for surveillance after heart transplantation in selected low-risk patients with respect to clinical outcomes. Recently, it was suggested that the within-patient variability of consecutive GEP scores may be used to independently predict future clinical events; however, future studies were recommended. Here we performed an analysis of an independent patient population to determine the prognostic utility of within-patient variability of GEP scores in predicting future clinical events. METHODS: We defined the GEP score variability as the standard deviation of four GEP scores collected ≥315 days post-transplantation. Of the 737 patients from the Cardiac Allograft Rejection Gene Expression Observational (CARGO) II trial, 36 were assigned to the composite event group (death, re-transplantation or graft failure ≥315 days post-transplantation and within 3 years of the final GEP test) and 55 were assigned to the control group (non-event patients). In this case-controlled study, the performance of GEP score variability to predict future events was evaluated by the area under the receiver operator characteristics curve (AUC ROC). The negative predictive values (NPV) and positive predictive values (PPV) including 95 % confidence intervals (CI) of GEP score variability were calculated. RESULTS: The estimated prevalence of events was 17 %. Events occurred at a median of 391 (inter-quartile range 376) days after the final GEP test. The GEP variability AUC ROC for the prediction of a composite event was 0.72 (95 % CI 0.6-0.8). The NPV for GEP score variability of 0.6 was 97 % (95 % CI 91.4-100.0); the PPV for GEP score variability of 1.5 was 35.4 % (95 % CI 13.5-75.8). CONCLUSION: In heart transplant recipients, a GEP score variability may be used to predict the probability that a composite event will occur within 3 years after the last GEP score. TRIAL REGISTRATION: Clinicaltrials.gov identifier NCT00761787 ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12872-015-0106-1) contains supplementary material, which is available to authorized users. BioMed Central 2015-10-09 /pmc/articles/PMC4600291/ /pubmed/26452346 http://dx.doi.org/10.1186/s12872-015-0106-1 Text en © Crespo-Leiro et al. 2015 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
spellingShingle | Research Article Crespo-Leiro, Maria G. Stypmann, Jörg Schulz, Uwe Zuckermann, Andreas Mohacsi, Paul Bara, Christoph Ross, Heather Parameshwar, Jayan Zakliczyński, Michal Fiocchi, Roberto Hoefer, Daniel Deng, Mario Leprince, Pascal Hiller, David Eubank, Lane Deljkich, Emir Yee, James P. Vanhaecke, Johan Performance of gene-expression profiling test score variability to predict future clinical events in heart transplant recipients |
title | Performance of gene-expression profiling test score variability to predict future clinical events in heart transplant recipients |
title_full | Performance of gene-expression profiling test score variability to predict future clinical events in heart transplant recipients |
title_fullStr | Performance of gene-expression profiling test score variability to predict future clinical events in heart transplant recipients |
title_full_unstemmed | Performance of gene-expression profiling test score variability to predict future clinical events in heart transplant recipients |
title_short | Performance of gene-expression profiling test score variability to predict future clinical events in heart transplant recipients |
title_sort | performance of gene-expression profiling test score variability to predict future clinical events in heart transplant recipients |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4600291/ https://www.ncbi.nlm.nih.gov/pubmed/26452346 http://dx.doi.org/10.1186/s12872-015-0106-1 |
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