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      EBMT—NIH—CIBMTR Task Force position statement on standardized terminology & guidance for graft-versus-host disease assessment

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      1 , , 2 , 3 , 4 , 3 , 5 , 6 , 2 , 7 , 8 , 4 , 9 , 10 , 11 , EBMT (European Society for Blood and Marrow Transplantation) Transplant Complications Working Party and the “EBMT−NIH (National Institutes of Health)−CIBMTR (Center for International Blood and Marrow Transplant Research) GvHD Task Force”
      Bone marrow transplantation

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          Abstract

          Several international recommendations address the assessment of graft-versus-host disease (GvHD) after hematopoietic cell transplantation (HCT). This position statement by GvHD experts from the European Society for Blood and Marrow Transplantation (EBMT), the National Institutes of Health (NIH) and the Center for International Blood and Marrow Transplant Research (CIBMTR) reviews the existing guidelines for both acute and chronic GvHD, addresses potential confusions that arise in daily practice and proposes consensus definitions for many key terms. We provide a historical perspective on the currently available guidelines and recommend the Mount Sinai Acute GvHD International Consortium (MAGIC) criteria for acute GvHD and the NIH 2014 criteria for chronic GvHD as the most comprehensive and detailed criteria available. This statement also offers practical guidance for the implementation of these recommendations and a set of consensus definitions for commonly used GvHD terms in order to facilitate future clinical and translational research. To assist the dissemination of these recommendations, a web-application based on this position statement is available ( https://www.uzleuven.be/egvhd). We believe that adherence to a common set of GvHD assessment criteria is vitally important to improve the quality of data, compare results of retrospective studies and prospective clinical trials, and make therapeutic recommendations based on quality evidence.

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          National Institutes of Health Consensus Development Project on Criteria for Clinical Trials in Chronic Graft-versus-Host Disease: I. The 2014 Diagnosis and Staging Working Group report.

          The 2005 National Institutes of Health (NIH) Consensus Conference proposed new criteria for diagnosing and scoring the severity of chronic graft-versus-host disease (GVHD). The 2014 NIH consensus maintains the framework of the prior consensus with further refinement based on new evidence. Revisions have been made to address areas of controversy or confusion, such as the overlap chronic GVHD subcategory and the distinction between active disease and past tissue damage. Diagnostic criteria for involvement of mouth, eyes, genitalia, and lungs have been revised. Categories of chronic GVHD should be defined in ways that indicate prognosis, guide treatment, and define eligibility for clinical trials. Revisions have been made to focus attention on the causes of organ-specific abnormalities. Attribution of organ-specific abnormalities to chronic GVHD has been addressed. This paradigm shift provides greater specificity and more accurately measures the global burden of disease attributed to GVHD, and it will facilitate biomarker association studies.
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            Chronic graft-versus-host syndrome in man

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              International, Multicenter Standardization of Acute Graft-versus-Host Disease Clinical Data Collection: A Report from the Mount Sinai Acute GVHD International Consortium.

              Acute graft-versus-host disease (GVHD) remains a leading cause of morbidity and nonrelapse mortality after allogeneic hematopoietic cell transplantation. The clinical staging of GVHD varies greatly between transplant centers and is frequently not agreed on by independent reviewers. The lack of standardized approaches to handle common sources of discrepancy in GVHD grading likely contributes to why promising GVHD treatments reported from single centers have failed to show benefit in randomized multicenter clinical trials. We developed guidelines through international expert consensus opinion to standardize the diagnosis and clinical staging of GVHD for use in a large international GVHD research consortium. During the first year of use, the guidance followed discussion of complex clinical phenotypes by experienced transplant physicians and data managers. These guidelines increase the uniformity of GVHD symptom capture, which may improve the reproducibility of GVHD clinical trials after further prospective validation.
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                Author and article information

                Contributors
                Journal
                8702459
                2334
                Bone Marrow Transplant
                Bone Marrow Transplant.
                Bone marrow transplantation
                0268-3369
                1476-5365
                9 January 2019
                05 June 2018
                November 2018
                01 November 2019
                : 53
                : 11
                : 1401-1415
                Affiliations
                [1 ]Department of Hematology, University Hospital Leuven and KU Leuven, Leuven, Belgium
                [2 ]Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA
                [3 ]Division of Hematology and Medical Oncology, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA
                [4 ]Department of Internal Medicine III, University Hospital Regensburg, Regensburg, Germany
                [5 ]Michael Cuccione Childhood Cancer Research Program, BC Children’s Hospital, UBC, Vancouver, Canada
                [6 ]Center for International Blood and Bone Marrow Transplant Research (CIBMTR), Medical College of Wisconsin, Milwaukee, WI, USA
                [7 ]Clinical Research Institute, Helsinki University Hospital, Helsinki, Finland
                [8 ]Division of Hematology, Medical University of Graz, Graz, Austria
                [9 ]Department of Hematology, Oncology and Internal Medicine, Medical University of Warsaw, Warszawa, Poland
                [10 ]Hospital Universitario Puerta de Hierro Majadahonda, Madrid, Spain
                [11 ]Center for Cancer Research National Cancer Institute, National Institutes of Health, Bethesda, MD, USA
                Author notes

                Author contributions

                HMS coordinated the project, performed the research and wrote the manuscript. All authors (HMS, SJL, JLF, DW, JEL, KRS, BES, MEF, TR, HG, EH, GB, RFD and SZP) participated in expert discussions. SJL, JLF, DW, JEL, and BES iteratively reviewed the manuscript. RFD and SZP designed the research, performed the research and wrote the manuscript. All authors reviewed the final version and approved submission.

                Author information
                http://orcid.org/0000-0002-7568-8239
                http://orcid.org/0000-0002-0001-6438
                http://orcid.org/0000-0003-3858-8180
                Article
                NIHMS1003987
                10.1038/s41409-018-0204-7
                6786777
                29872128
                10740134-48e2-4b7e-bf35-d8de8b8877d3

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                Transplantation
                Transplantation

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