AlloMap molecular expression testing: Difference between revisions

Revision as of 01:28, 15 September 2010

Revision as of 22:42, 24 September 2010

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{{Orphan|date=September 2010}}

'''AlloMap molecular expression testing''', developed and commercialized by XDx, is a gene expression profiling test to identify [[heart transplantation|heart transplant]] recipients with a low probability of one type of [[organ transplant|transplant]] rejection. The test is performed on a [[blood]] sample, providing a non-invasive test to help manage the care of patients post transplant. Prior to the availability of this test, the primary method for managing heart [[transplant rejection]] was the invasion technique of endomyocardial biopsy. <ref>{{cite web | last=Thomlison | first=B | title=Success With AlloMap Molecular Expression Testing | publisher=Medical News Today | date=2007-05-12 | url=http://www.medicalnewstoday.com/articles/70268.php }}</ref>

Test results are reported as a single score indicating thr probability of moderate/severe [[acute rejection|acute cellular rejection]] (ACR) . The performance characteristics of the test make it best suited to help indicate that an acute cellar rejection is not present. The score is based on the amount of [[RNA]] from each gene in a 20-gene panel comprising of 11 rejection-related genes and 9 genes used for normalization and quality control. Many of the rejection-related genes are associated with biological pathways involved in the [[immune]] response and rejection processes.<ref>Dedrick{{cite R.journal Understanding [[Gene Expression]] Patterns in Immune-Mediated Disorders. ''Journal of Immunotoxicology'' 2007 Jul;4(3):201-7. [http://www.ncbi.nlm.nih.gov/pubmed/18958729 PMID:|pmid=18958729]}}</ref>

'''AlloMap molecular expression testing''', developed and commercialized by XDx, is a gene expression profiling test to identify [[heart transplantation|heart transplant]] recipients with a low probability of one type of [[organ transplant|transplant]] rejection. The test is performed on a [[blood]] sample, providing a non-invasive test to help manage the care of patients post transplant. Prior to the availability of this test, the primary method for managing heart [[transplant rejection]] was the invasion technique of endomyocardial biopsy. <ref>{{cite web | last=Thomlison | first=B | title=Success With AlloMap Molecular Expression Testing | publisher=Medical News Today | date=2007-05-12 | url=http://www.medicalnewstoday.com/articles/70268.php }}</ref>

Test results are reported as a single score indicating thr probability of moderate/severe [[acute rejection|acute cellular rejection]] (ACR) . The performance characteristics of the test make it best suited to help indicate that an acute cellar rejection is not present. The score is based on the amount of [[RNA]] from each gene in a 20-gene panel comprising of 11 rejection-related genes and 9 genes used for normalization and quality control. Many of the rejection-related genes are associated with biological pathways involved in the [[immune]] response and rejection processes.<ref>Dedrick R. Understanding [[Gene Expression]] Patterns in Immune-Mediated Disorders. ''Journal of Immunotoxicology'' 2007 Jul;4(3):201-7. [http://www.ncbi.nlm.nih.gov/pubmed/18958729 PMID:18958729]</ref>

The test score is used, along with other standard clinical assessments, to evaluate the patient’s probability of acute cellular rejection and the need for additional evaluations. This test is not designed to be informative about other forms of heart rejections such as antibody-mediated rejection (AMR) or [[cardiac]] [[allograft]] vasculopathy (CAV).

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AlloMap has been commercially available since 2005 as a CLIA approved Laboratory Developed Test (LDT) and was cleared by the [[FDA]] in 2008 as a Class II Medical Device.<ref>http://www.accessdata.fda.gov/cdrh_docs/reviews/K073482.pdf</ref> It is available only from the XDx Reference Laboratory in Brisbane, CA.

The use of the test is described in the recommendations for the non-invasive monitoring of acute heart transplant rejection in the first evidence-based clinical practice guidelines for the care of heart transplant recipients issued by the International Society of Heart and Lung Transplantation.<ref>Costanzo{{cite MRjournal et al. The International Society of Heart and Lung Transplantation Guidelines for the care of heart transplant recipients. ''Journal of Heart and Lung Transplantation'' 2010 Aug;29(8):914-56. [http://www.ncbi.nlm.nih.gov/pubmed/|pmid=20643330 PMID: 20643330] http://www.ishlt.org/publications/guidelines.asp}}</ref>

== Development ==

The test was developed using genomics and bioinformatics technologies. [[DNA microarrays]] were used to discover 252 candidate genes for which the amount of RNA in blood samples was related to rejection. Quantitative [[real-time polymerase chain reaction]] technology (qRT-PCR) confirmed 68 of the candidate genes from which the 20-gene gene expression panel was selected. The diagnostic performance was verified using independent patient samples from a multicenter clinical study.<ref name="Deng">Deng{{cite MC,journal Eisen|pmid=16433769}}</ref> HJ,Initial Mehraclinical MR,experience etat al.three Noninvasivemedical discriminationcenters ofwas rejectionpublished in cardiac2006, allograftconfirming recipients usingthe geneefficacy expressionand profiling. ''American Journalperformance of Transplantation''the 2006;6:150-160.AlloMap [http://wwwtest.ncbi.nlm.nih.gov/pubmed/16433769<ref PMID:name="Starling">{{cite 16433769]journal |pmid=17178330}}</ref>

Initial clinical experience at three medical centers was published in 2006, confirming the efficacy and performance of the AlloMap test.<ref name="Starling">Starling RC, Pham M, Valantine H, et al. Molecular testing in the management of cardiac transplant recipients: initial clinical experience. ''Journal of Heart and Lung Transplantation'' 2006 Dec;25(12):1389-95. [http://www.ncbi.nlm.nih.gov/pubmed/17178330 PMID: 17178330]</ref>

== Clinical studies==

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=== IMAGE Study ===

A comparative effectiveness study, the Invasive Monitoring Attenuation through Gene Expression (IMAGE) Study, compared clinical outcomes of patients managed with AlloMap to outcomes of patients managed with endomyocardial biopsy. The study, which ran from 2005–09, included 602 patients from thirteen U.S. centers who were at least six months post-transplant. The results showed that AlloMap was not inferior to endomyocardial biopsy with respect to clinical outcomes when used to monitor stable, asymptomatic heart transplant patients.<ref>Pham,{{cite Michael X., Teuteberg, Jeffrey J., Kfoury, Abdallah G., Starling, Randall C., Deng, Mario C., Cappola, Thomas P., Kao, Andrew, Anderson, Allen S., Cotts, William G., Ewald, Gregory A., Baran, David A., Bogaev, Roberta C., Elashoff, Barbara, Baron, Helen, Yee, James, Valantine, Hannah A., the IMAGE Study Group. Gene-Expression profiling for rejection surveillance after cardiac transplantation ''[[New England Journal of Medicine]]'' 2010 0: NEJMoa0912965. [http://www.ncbi.nlm.nih.gov/pubmed/20413602 PMID:journal |pmid=20413602]}}</ref>

== Indications for Use ==