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      Acute Graft-Versus-Host Disease: A Brief Review Translated title: Akut Graft Versus Host Hastalığı: Kısa Bir Derleme

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          Abstract

          Graft‐versus‐host disease (GvHD) is an important complication that can be observed after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Acute GvHD (aGvHD) is seen after allo-HSCT and the incidence of aGvHD is around 30%-50%. aGvHD prophylaxis is essential in patients undergoing allo-HSCT. Initial therapy for aGvHD is steroids. Prognosis is poor in aGvHD patients not responding to steroids. In this article, the pathobiology, clinical findings, prophylaxis, and treatment of aGvHD will be summarized.

          Translated abstract

          Akut graft‐versus‐host hastalığı (GvHD), allojeneik hematopoetik kök hücre nakli (alloHKHN) sonrasında görülebilen önemli bir komplikasyondur. Akut GvHD (aGvHD) insidansı yaklaşık %30-50 oranında görülmektedir. AlloHKHN yapılan hastalarda GvHD proflaksisi önemlidir. aGvHD gelişen hastalarda başlangıç tedavisi steroiddir. Steroide yanıtsız aGvHD’de prognoz kötüdür. Bu yazıda aGvHD patobiyolojisi, klinik bulguları, profilaksisi ve tedavisi özetlenecektir.

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          Risk factors for acute GVHD and survival after hematopoietic cell transplantation.

          Christopher Bredeson, Mukta Arora, Mary Flowers … (2012)
          Risk factors for acute GVHD (AGVHD), overall survival, and transplant-related mortality were evaluated in adults receiving allogeneic hematopoietic cell transplants (1999-2005) from HLA-identical sibling donors (SDs; n = 3191) or unrelated donors (URDs; n = 2370) and reported to the Center for International Blood and Marrow Transplant Research, Minneapolis, MN. To understand the impact of transplant regimen on AGVHD risk, 6 treatment categories were evaluated: (1) myeloablative conditioning (MA) with total body irradiation (TBI) + PBSCs, (2) MA + TBI + BM, (3) MA + nonTBI + PBSCs, (4) MA + nonTBI + BM, (5) reduced intensity conditioning (RIC) + PBSCs, and (6) RIC + BM. The cumulative incidences of grades B-D AGVHD were 39% (95% confidence interval [CI], 37%-41%) in the SD cohort and 59% (95% CI, 57%-61%) in the URD cohort. Patients receiving SD transplants with MA + nonTBI + BM and RIC + PBSCs had significantly lower risks of grades B-D AGVHD than patients in other treatment categories. Those receiving URD transplants with MA + TBI + BM, MA + nonTBI + BM, RIC + BM, or RIC + PBSCs had lower risks of grades B-D AGVHD than those in other treatment categories. The 5-year probabilities of survival were 46% (95% CI, 44%-49%) with SD transplants and 33% (95% CI, 31%-35%) with URD transplants. Conditioning intensity, TBI and graft source have a combined effect on risk of AGVHD that must be considered in deciding on a treatment strategy for individual patients.
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            Ruxolitinib in corticosteroid-refractory graft-versus-host disease after allogeneic stem cell transplantation: a multicenter survey.

            R Zeiser, A Burchert, C Lengerke … (2015)
            Despite major improvements in allogeneic hematopoietic cell transplantation over the past decades, corticosteroid-refractory (SR) acute (a) and chronic (c) graft-versus-host disease (GVHD) cause high mortality. Preclinical evidence indicates the potent anti-inflammatory properties of the JAK1/2 inhibitor ruxolitinib. In this retrospective survey, 19 stem cell transplant centers in Europe and the United States reported outcome data from 95 patients who had received ruxolitinib as salvage therapy for SR-GVHD. Patients were classified as having SR-aGVHD (n=54, all grades III or IV) or SR-cGVHD (n=41, all moderate or severe). The median number of previous GVHD-therapies was 3 for both SR-aGVHD (1-7) and SR-cGVHD (1-10). The overall response rate was 81.5% (44/54) in SR-aGVHD including 25 complete responses (46.3%), while for SR-cGVHD the ORR was 85.4% (35/41). Of those patients responding to ruxolitinib, the rate of GVHD-relapse was 6.8% (3/44) and 5.7% (2/35) for SR-aGVHD and SR-cGVHD, respectively. The 6-month-survival was 79% (67.3-90.7%, 95% confidence interval (CI)) and 97.4% (92.3-100%, 95% CI) for SR-aGVHD and SR-cGVHD, respectively. Cytopenia and cytomegalovirus-reactivation were observed during ruxolitinib treatment in both SR-aGVHD (30/54, 55.6% and 18/54, 33.3%) and SR-cGVHD (7/41, 17.1% and 6/41, 14.6%) patients. Ruxolitinib may constitute a promising new treatment option for SR-aGVHD and SR-cGVHD that should be validated in a prospective trial.
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              High-dose cyclophosphamide as single-agent, short-course prophylaxis of graft-versus-host disease.

              Leo Luznik, Javier Bolaños-Meade, Marianna Zahurak … (2010)
              Because of its potent immunosuppressive yet stem cell-sparing activity, high-dose cyclophosphamide was tested as sole prophylaxis of graft-versus-host disease (GVHD) after myeloablative allogeneic bone marrow transplantation (alloBMT). We treated 117 patients (median age, 50 years; range, 21-66 years) with advanced hematologic malignancies; 78 had human leukocyte antigen (HLA)-matched related donors and 39 had HLA-matched unrelated donors. All patients received conventional myeloablation with busulfan/cyclophosphamide (BuCy) and T cell-replete bone marrow followed by 50 mg/kg/d of cyclophosphamide on days 3 and 4 after transplantation. The incidences of acute grades II through IV and grades III through IV GVHD for all patients were 43% and 10%, respectively. The nonrelapse mortality at day 100 and 2 years after transplantation were 9% and 17%, respectively. The actuarial overall survival and event-free survivals at 2 years after transplantation were 55% and 39%, respectively, for all patients and 63% and 54%, respectively, for patients who underwent transplantation while in remission. With a median follow-up of 26.3 months among surviving patients, the cumulative incidence of chronic GVHD is 10%. These results suggest that high-dose posttransplantation cyclophosphamide is an effective single-agent prophylaxis of acute and chronic GVHD after BuCy conditioning and HLA-matched BMT (clinicaltrials.gov no. NCT00134017).
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                Author and article information

                Journal
                Journal ID (nlm-ta): Turk J Haematol
                Journal ID (iso-abbrev): Turk J Haematol
                Journal ID (publisher-id): TJH
                Title: Turkish Journal of Hematology
                Publisher: Galenos Publishing
                ISSN (Print): 1300-7777
                ISSN (Electronic): 1308-5263
                Publication date (Print): March 2020
                Publication date (Electronic): 20 February 2020
                Volume: 37
                Issue: 1
                Pages: 1-4
                Affiliations
                [1 ]Hacettepe University Faculty of Medicine, Department of Hematology, Ankara, Turkey
                [2 ]Ondokuz Mayıs University Faculty of Medicine, Department of Hematology, Samsun, Turkey
                Author notes
                * Address for Correspondence: Hacettepe University Faculty of Medicine, Department of Hematology, Ankara, Turkey Phone: +90 505 822 99 16 E-mail: hgoker1@ 123456yahoo.com
                Author information
                https://orcid.org/0000-0002-1206-9908
                https://orcid.org/0000-0001-7342-1760
                https://orcid.org/0000-0002-1039-7756
                Article
                Publisher ID: 36019
                DOI: 10.4274/tjh.galenos.2019.2019.0157
                PMC ID: 7057746
                PubMed ID: 31475512
                SO-VID: 887105e0-3c98-4e53-9a11-0d41cc2af104
                Copyright © © Copyright 2020 by Turkish Society of Hematology / Turkish Journal of Hematology, Published by Galenos Publishing House.
                License:

                This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                Date received : 14 April 2019
                Date accepted : 2 September 2019
                Categories
                Subject: Review

                Keywords: graft-versus-host disease,acute,chronic
                Data availability:
                Keywords: graft-versus-host disease, acute, chronic

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