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      Extracorporeal photopheresis in acute and chronic steroid‑refractory graft-versus-host disease: an evolving treatment landscape

      review-article
      1 , , 2 , 3
      Leukemia
      Nature Publishing Group UK
      Drug development, Translational research

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          Abstract

          Patients with steroid-refractory graft-versus-host disease (GvHD) are known to have a poor prognosis and for decades no approved drug has been available to treat this serious condition. Although ruxolitinib, a selective Janus kinase (JAK)1/2 inhibitor demonstrated significantly higher response rates in randomized trials compared to the best available therapy, and thus, is of benefit in both acute as well as chronic GvHD, there is an urgent medical need to improve results, such as durability of responses, response in eye, liver and lung manifestations and reduction of infectious complications. In this “Review” article we would like to offer strategies for improving treatment results in patients with steroid-refractory GvHD by combining ruxolitinib with extracorporeal photopheresis (ECP), a leukapheresis-based immunomodulatory treatment frequently applied in T-cell mediated immune disease including GvHD. Our article explores key published evidence supporting the clinical efficacy of both ruxolitinib and ECP in the treatment of GvHD and highlights their potentially complementary mechanisms of action.

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          Most cited references81

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          Graft-versus-host disease.

          Haemopoietic-cell transplantation (HCT) is an intensive therapy used to treat high-risk haematological malignant disorders and other life-threatening haematological and genetic diseases. The main complication of HCT is graft-versus-host disease (GVHD), an immunological disorder that affects many organ systems, including the gastrointestinal tract, liver, skin, and lungs. The number of patients with this complication continues to grow, and many return home from transplant centres after HCT requiring continued treatment with immunosuppressive drugs that increases their risks for serious infections and other complications. In this Seminar, we review our understanding of the risk factors and causes of GHVD, the cellular and cytokine networks implicated in its pathophysiology, and current strategies to prevent and treat the disease. We also summarise supportive-care measures that are essential for management of this medically fragile population.
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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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              Acute Graft-versus-Host Disease — Biologic Process, Prevention, and Therapy

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                Author and article information

                Contributors
                Hildegard.Greinix@medunigraz.at
                Journal
                Leukemia
                Leukemia
                Leukemia
                Nature Publishing Group UK (London )
                0887-6924
                1476-5551
                24 September 2022
                24 September 2022
                2022
                : 36
                : 11
                : 2558-2566
                Affiliations
                [1 ]GRID grid.11598.34, ISNI 0000 0000 8988 2476, Division of Haematology, , Medical University Graz, ; Auenbruggerplatz 38, 8036 Graz, Austria
                [2 ]GRID grid.13648.38, ISNI 0000 0001 2180 3484, Department of Stem Cell Transplantation, , University Medical Center Hamburg-Eppendorf, ; Hamburg, Germany
                [3 ]GRID grid.5963.9, Department of Medicine I - Medical Centre, Faculty of Medicine, , University of Freiburg, ; Freiburg, Germany
                Author information
                http://orcid.org/0000-0002-2780-3300
                http://orcid.org/0000-0001-6565-3393
                Article
                1701
                10.1038/s41375-022-01701-2
                9613461
                36153436
                3cc71c06-796a-4e74-b185-a5eac7d9b398
                © The Author(s) 2022

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 6 May 2022
                : 26 August 2022
                : 6 September 2022
                Categories
                Review Article
                Custom metadata
                © Springer Nature Limited 2022

                Oncology & Radiotherapy
                drug development,translational research
                Oncology & Radiotherapy
                drug development, translational research

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