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      Higher response rates in patients with severe chronic skin graft-versus-host disease treated with extracorporeal photopheresis

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          Abstract

          Introduction

          Different forms of graft-versus-host disease (GVHD) remain a major cause of morbidity and mortality after allogeneic hematopoietic stem cell transplantation (HSCT). The prognosis for steroid-refractory chronic GVHD (cGVHD) remains poor. Our aim was to evaluate extracorporeal photopheresis (ECP) treatment in cGVHD patients with different organ involvement to detect subgroups of patients with the best response.

          Material and methods

          Thirty-four patients who underwent HSCT and developed moderate (n = 7) or severe (n = 27) steroid-refractory or steroid-dependent cGVHD treated with ECP were included in the analysis. A matched cGVHD control patient group untreated with ECP was collected for comparison.

          Results

          Compared to the control group and the stable/progressive disease (SD/PD) patients, individuals with complete/partial remission have higher overall survival and lower transplant-related mortality. Furthermore, patients with complete and partial remission (CR/PR) had significantly higher levels of albumin and platelets after ECP treatment compared to patients with stable or progressive cGVHD (SD/PD). Corticosteroid treatment and other immunosuppressive agents could successfully be tapered in the CR/PR group compared to the SD/PD patients. In this study patients with skin cGVHD are those with the highest rate of CR/PR after ECP treatment.

          Conclusions

          Our results suggest that ECP treatment is safe and effective for patients with predominantly skin, oral and liver cGVHD.

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          Most cited references 25

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          Chronic graft-versus-host syndrome in man. A long-term clinicopathologic study of 20 Seattle patients.

            (1980)
          This study of chronic graft-versus-host disease (GVHD) describes the clinical, pathologic and laboratory features, and the causes of morbidity and mortality in 20 patients who received allogeneic marrow transplants from HLA identical sibling donors. Chronic GVHD is a pleiotrophic syndrome with variability in the time of onset, organ systems involved and rate of progression. The clinical-pathologic features resemble an overlap of several collagen vascular diseases with frequent involvement of the skin, liver, eyes, mouth, upper respiratory tract, esophagus and less frequent involvement of the serosal surfaces, lower gastrointestinal tract and skeletal muscles. Major causes of morbidity are scleroderma with contractures and ulceration, dry eyes and mouth, pulmonary insufficiency and wasting. Chronic GVHD has features of immune dysregulation with elevated levels of eosinophils, circulating autoantibodies, hypergammaglobulinemia and plasmacytosis of viscera and lymph nodes. In this study, three patients had limited chronic GVHD with relatively favorable prognosis characterized by localized skin involvement and/or hepatic disease without chronic aggressive histology. Most patients, however, had extensive disease with a progressive course. Survival was largely determined by the presence or absence of serious recurrent bacterial infections. The over-all severity of disease was best assessed by using the Karnofsky performance rating.
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            Bone-marrow transplantation (second of two parts).

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              Antithymocyte globulin for graft-versus-host disease prophylaxis in transplants from unrelated donors: 2 randomized studies from Gruppo Italiano Trapianti Midollo Osseo (GITMO).

              One hundred nine patients with hematologic malignancies, undergoing bone marrow transplants (BMT) from unrelated donors, were randomized in 2 consecutive trials to receive or not to receive antithymocyte globulin (ATG) in the conditioning regimen, as follows: (A) 54 patients (median age, 28 years; 39% with advanced disease) were randomized to no ATG (n = 25) versus 7.5 mg/kg rabbit ATG (Thymoglobulin; Sangstat, Lyon, France) (n = 29); (B) 55 patients (median age, 31 years, 71% with advanced disease) were randomized to no ATG (n = 28) versus 15 mg/kg rabbit ATG (n = 27). Grade III-IV graft-versus-host disease (GVHD) was diagnosed in 36% versus 41% (P =.8) in the first and in 50% versus 11% (P =.001) in the second trial. Transplant-related mortality (TRM), relapse, and actuarial 3-year survival rates were comparable in both trials. In fact, despite the reduction of GVHD in the second trial, a higher risk for lethal infections (30% vs 7%; P =.02) was seen in the arm given 15 mg/kg ATG. Extensive chronic GVHD developed overall more frequently in patients given no ATG (62% vs 39%; P =.04), as confirmed by multivariate analysis (P =.03). Time to 50 x 10(9)/L platelets was comparable in the first trial (21 vs 24 days; P =.3) and delayed in the ATG arm in the second trial (23 vs 38 days; P =.02). These trials suggest that (1) 15 mg/kg ATG before BMT significantly reduces the risk for grade III-IV acute GVHD, (2) this does not translate to a reduction in TRM because of the increased risk for infections, and (3) though survival is unchanged, extensive chronic GVHD is significantly reduced in patients receiving ATG.
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                Author and article information

                Journal
                Cent Eur J Immunol
                Cent Eur J Immunol
                CEJI
                Central-European Journal of Immunology
                Polish Society of Experimental and Clinical Immunology
                1426-3912
                1644-4124
                15 April 2019
                2019
                : 44
                : 1
                : 84-91
                Affiliations
                [1 ]Hematology Centre, Karolinska University Laboratory, Stockholm, Sweden
                [2 ]Division of Hematology, Department of Medicine, Karolinska Institutet, Stockholm, Sweden
                [3 ]Department of Clinical Immunology and Transfusion Medicine, Karolinska University Laboratory, Stockholm, Sweden
                [4 ]Department of Clinical Science, Intervention and Technology, Division of Transplantation Surgery, Karolinska Institutet, Karolinska Institutet, Stockholm, Sweden
                [5 ]Centre for Allogeneic Stem Cell Transplantation, Karolinska University Hospital, Stockholm, Sweden
                [6 ]Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden
                [7 ]Hematology/Immunology/SCT Section, Astrid Lindgren Children’s Hospital, Karolinska University Hospital, Stockholm, Sweden
                [8 ]Division of Pediatrics, Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Stockholm, Sweden
                [9 ]Department of Hematology, Uppsala University Hospital, Uppsala, Sweden
                Author notes
                Correspondence: Gabriel Afram, Hematologiskt Centrum M54, Karolinska University Hospital, Huddinge SE-141 86 Stockholm, Sweden. e-mail: gabriel.afram@ 123456karolinska.se
                [*]

                The authors contributed equally to this work.

                Article
                75831
                10.5114/ceji.2018.75831
                6526584
                Copyright: © 2019 Polish Society of Experimental and Clinical Immunology

                This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0) License, allowing third parties to copy and redistribute the material in any medium or format and to remix, transform, and build upon the material, provided the original work is properly cited and states its license.

                Categories
                Clinical Immunology

                ecp, cgvhd, treatment

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