A Three Biomarker Panel at Days 7 and 14 Can Predict Development of Grade II-IV Acute Graft-Versus-Host Disease

Paczesny, Sophie; Braun, Thomas; Lugt, Mark Vander; Harris, Andrew C.; Fiema, Bryan; Hernandez, James R.; Choi, Sung Won; Kitko, Carrie L.; Magenau, John; Yanik, Gregory A.; Peres, Edward; Pawarode, Attaphol; Mineishi, Shin; Whitfield, Joel; Jones, David B.; Couriel, Daniel R.; Pavan, Renata Bigatti Bellizzotti; Hanash, Samir M.; Ferrara, James L.M.; Levine, John E.

doi:10.1016/j.bbmt.2010.12.048

Cited by 7 publications

(6 citation statements)

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“…This study did not compare plasma concentrations of patients at GVHD onset with those of patients who had similar symptoms (rash or diarrhoea) that were proven to be from other causes, however, so investigators sought organ‐specific biomarkers that could differentiate GVHD rash or diarrhoea from other causes of similar symptoms. Elafin, a protease found in the skin with antimicrobial properties (Verrier et al , ), was discovered and validated as a plasma biomarker of skin GVHD through a large‐scale, unbiased proteomic approach (Paczesny et al , ). Elevated plasma concentrations of elafin help discriminate GVHD rash from rashes of other causes (e.g.…”

Section: Plasma Proteinsmentioning

confidence: 99%

Advances in predicting acute GVHD

2012

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Summary Acute graft-versus-host disease (GVHD) is a leading cause of non-relapse mortality following allogeneic haematopoietic cell transplantation. Attempts to improve treatment response in clinically-established GVHD have not improved overall survival, often due to the increased risk of infectious complications. Alternative approaches to decrease GVHD-related morbidity and mortality have focused on the ability to predict GVHD prior to clinical manifestation in an effort to provide an opportunity to abort GVHD development, and to gain new insights into GVHD pathophysiology. This review outlines the research efforts to date that have identified clinical and laboratory-based factors that are predictive of acute GVHD and describes future directions in developing algorithms that will improve the ability to predict the development of clinically relevant GVHD.

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Section: Plasma Proteinsmentioning

confidence: 99%

Advances in predicting acute GVHD

2012

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“…Analysis showed reasonably good specificity (75%) and fair sensitivity (57%) for the development of acute GVHD. 39 Other investigators have used mass spectrometry-based approaches. The advantage of using mass spectrometry is that the identification of candidate proteins is not biased by the availability of antibodies, as is the case for microarray or ELISAbased techniques.…”

Section: Il-2mentioning

confidence: 99%

Biomarkers for acute GVHD: can we predict the unpredictable?

2012

Bone Marrow Transplant

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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-a, 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 reg3a, 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.

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“…Measurement of this biomarker panel before HSCT predicted grade 2-4 GVHD with a specificity of 75% and sensitivity of 57%. 84 Indicators of success must include not only a lower incidence of GVHD but also reductions in infectious complications and relapse. Ultimately, a randomized trial is needed to assess the effectiveness of GVHD preemption.…”

Section: Study Using Biomarkers That Predict Unresponsiveness To Gvhdmentioning

confidence: 99%

Discovery and validation of graft-versus-host disease biomarkers

Paczesny

2013

Blood

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Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is the most effective tumor immunotherapy available. Although allo-HSCT provides beneficial graft-versus-tumor effects, acute GVHD (aGVHD) is the primary source of morbidity and mortality after HSCT. Diagnosis of aGVHD is typically based on clinical symptoms in one or more of the main target organs (skin, liver, gastrointestinal tract) and confirmed by biopsy. However, currently available diagnostic and staging tools often fail to identify patients at higher risk of GVHD progression, unresponsiveness to therapy, or death. In addition, there are shortcomings in the prediction of GVHD before clinical signs develop, indicating the urgent need for noninvasive and reliable laboratory tests. Through the continuing evolution of proteomics technologies seen in recent years, plasma biomarkers have been identified and validated as promising diagnostic tools for GVHD and prognostic tools for nonrelapse mortality. These biomarkers may facilitate timely and selective therapeutic intervention but should be more widely validated and incorporated into a new grading system for risk stratification of patients and better-customized treatment. This review identifies biomarkers for detecting GVHD, summarizes current information on aGVHD biomarkers, proposes future prospects for the blinded evaluation of these biomarkers, and discusses the need for biomarkers of chronic GVHD. (Blood. 2013;121(4):585-594) IntroductionAllogeneic hematopoietic stem cell transplantation (allo-HSCT) is a widely used therapy for a variety of malignant and nonmalignant hematologic diseases. In malignant disease, the donor immune system recognizes residual tumor cells as foreign and eradicates them by immunologic means, known as the graft-versustumor (GVT) effect. Unfortunately, donor immune cells may also attack normal host tissue, particularly the skin, liver, and gastrointestinal (GI) tract, resulting in acute GVHD (aGVHD). GVHD remains one of the major barriers to a more widespread and successful application of allo-HSCT. Known risk factors that increase the incidence and severity of aGVHD include the use of HLA-mismatched unrelated donors rather than HLA-matched sibling donors. 1 A major barrier to GVHD research and treatment is that diagnosis and prognosis rely almost entirely on the presence of clinical symptoms and should be confirmed by biopsy of the involved target organs. No currently used laboratory tests can predict the risk of developing GVHD, responsiveness to treatment, or patient survival. The importance of biomarkers in HSCT settings is crucial because the ability to identify patients at high risk for GVHD early in their transplantation and treatment course has important therapeutic consequences, including more stringent monitoring and/or preventive care. The ability to identify patients who will not respond to traditional treatment and are at particularly high risk for subsequent morbidity and mortality could enable tailored treatment plans, such as additional immunosuppressive...

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A Three Biomarker Panel at Days 7 and 14 Can Predict Development of Grade II-IV Acute Graft-Versus-Host Disease

Cited by 7 publications

References 0 publications

Advances in predicting acute GVHD

Advances in predicting acute GVHD

Biomarkers for acute GVHD: can we predict the unpredictable?

Discovery and validation of graft-versus-host disease biomarkers

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