Biomarkers for acute GVHD: can we predict the unpredictable?

• Published in: Bone marrow transplantation (Basingstoke) Vol. 48; no. 6; pp. 755 - 760
• Main Authors: Chen, Y-B, Cutler, C S
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.06.2013; Nature Publishing Group
• Subjects: 631/250/1904; 631/532/1542; 692/53; 692/699/249/1529; Acute Disease; Allografts; Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy; Antigens, Neoplasm - blood; Biological and medical sciences; Biological markers; Biomarkers; Biomarkers - blood; Biomarkers, Tumor - blood; Biopsy; Bone marrow; Bone marrow, stem cells transplantation. Graft versus host reaction; Cell activation; Cell Biology; Cell surface; Complications; Cytokines; Diagnosis; Drug therapy; Elafin - blood; Graft versus host reaction; Graft vs Host Disease - blood; Graft vs Host Disease - diagnosis; Graft vs Host Disease - therapy; Health aspects; Hematology; Hematopoietic Stem Cell Transplantation; Hematopoietic stem cells; Humans; Immunology; Inflammation; Interleukin 2; Interleukin-2 - blood; Internal Medicine; Lectins, C-Type - blood; Leukocyte migration; Leukocytes; Medical sciences; Medicine; Medicine & Public Health; Pancreatitis-Associated Proteins; Pathogenesis; Patients; Peripheral blood; Proteomics; Proteomics - methods; Public Health; review; Risk factors; Stem cell transplantation; Stem Cells; Transfusions. Complications. Transfusion reactions. Cell and gene therapy; Transplantation; Tumor Necrosis Factor-alpha - blood; Tumor necrosis factor-α; United States; transplant; biomarkers; GVHD; Immunopathology; Graft versus host disease; Hematology; Acute; Stem cell; Hematopoietic cell; Biological marker; Predictive factor
• ISSN: 0268-3369; 1476-5365
• DOI: 10.1038/bmt.2012.143

Acute GVHD remains an important complication after allogeneic hematopoietic cell transplantation (HCT). Many efforts have been devoted to identifying potential noninvasive peripheral blood biomarkers to help improve the diagnosis or management of acute GVHD while avoiding invasive tissue biopsies. Early attempts to identify biomarkers focused on inflammatory cytokines, especially IL-2 or TNF-α, however, both of these and others were not specific for GVHD, often being elevated in the setting of generalized inflammation, accompanying other major complications of HCT as well. More recent efforts have focused on additional cytokines and other cell-surface molecules, which function in leukocyte trafficking and activation with the hope that these can also serve as targets for novel therapeutic approaches. Modern proteomic methods have allowed the screening of large numbers of patient samples and yielded several novel candidate biomarkers, including elafin and reg3α, which may not be directly involved in the immunological pathogenesis of GVHD, but may be unique biomarkers for end-organ injury. Combining these new molecules with traditionally identified cytokines to form an acute GVHD biomarker panel has recently shown the ability to predict outcomes in patients who develop acute GVHD. The ultimate goals of identifying a specific biomarker are to refine diagnosis, guide therapy and develop risk-adapted approaches in order to better treat patients and improve outcomes after allogeneic HCT. These approaches include differential treatment for patients who develop acute GVHD with a high-risk biomarker profile as well as pre-emptive therapy in patients after HCT prior to the development of symptoms. With the recent progress summarized below, these goals may soon be realized.