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Biomarkers of immune activation to screen for severe, acute GVHD

Bone Marrow Transplantation volume 46, pages 601–604 (2011)Cite this article

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Severe acute GVHD (AGVHD) occurring after allogeneic hematopoietic SCT (AHSCT) is often unresponsive to glucocorticoids and, as a result, frequently fatal.1 A preemptive approach, similar to that used for CMV infection could be more effective.1, 2 We conducted a prospective study of plasma markers of immune activation to assess whether the incipient immunologic graft-vs-host response can be detected in a diverse group of transplant recipients before the clinical manifestations of severe AGVHD emerge. Five markers were selected: four markers of T-cell activation, soluble CD8 (sCD8), soluble IL-2 receptor (sIL-2R), soluble CD40 ligand (sCD40L) and soluble CD28 (sCD28) as well as soluble TNF receptor 1 (sTNFR1), an inflammatory marker. These markers are measurable in the blood and have been shown to be increased in clinical AGVHD or other immune-mediated processes.3, 4, 5, 6, 7, 8, 9, 10, 11 The primary hypothesis tested in this study was that by using these markers, preclinical AGVHD can be diagnosed by transplant day 15 with a sensitivity and specificity of at least 80%.

Eligible pediatric and adult patients scheduled to undergo AHSCT at Children's Healthcare of Atlanta or the Winship Cancer Institute of Emory University from 1 May 2006 to 30 May 2008 were consented and enrolled before beginning conditioning. Our intent was to develop a test that would be applicable across a wide range of patient ages, diseases, stem cell sources, donor types and conditioning approaches; eligibility, then, was broadly defined.

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Acknowledgements

This work was supported by a Friends Grant from the Children's Healthcare of Atlanta.

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Authors and Affiliations

  1. Aflac Cancer Center and Blood Disorders Service, Emory University and Children's Healthcare of Atlanta, Atlanta, GA, USA

    K J August, K-Y Chiang, D Worthington-White, P Rowland, K F Moore & J T Horan

  2. Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, GA, USA

    R M Bostick & W D Flanders

  3. Winship Cancer Institute, Emory University School of Medicine, Atlanta, GA, USA

    R M Bostick, E K Waller, A Langston & H J Khoury

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  1. K J August
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Correspondence to K J August.

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August, K., Chiang, KY., Bostick, R. et al. Biomarkers of immune activation to screen for severe, acute GVHD. Bone Marrow Transplant 46, 601–604 (2011). https://doi.org/10.1038/bmt.2010.165

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