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Review Haematology Prevention of Chronic Graft-versus-host Disease and the Unique Role of Anti-human T-lymphocyte Immune Globulin Nicolaus Kröger Department of Stem Cell Transplantation, University Medical Center, University Hospital Hamburg-Eppendorf, Hamburg, Germany C hronic graft-versus-host disease (GVHD) is a major cause of late morbidity and mortality post-allogeneic haematopoietic stem- cell transplantation. Compared with acute GVHD, for which progress in preventative measures have been made, chronic GVHD describes a more diverse syndrome, and may adversely affect almost all organs in the body. A new prospective, multicentre, open-label, randomised phase III study (n=168) showed that the use of anti-human T-lymphocyte immune globulin (ATLG) in a myeloablative conditioning regimen for patients with acute leukaemia led to a significantly lower rate of chronic GVHD post-allogeneic transplantation compared with those receiving the same regimen without ATLG. Importantly, no increased rate of relapses in the patients who received ATLG was seen compared with those who did not. Thus, there was no apparent impairment in the graft-versus-leukaemia effect in ATLG-treated patients. The study was terminated at 2 years and more evidence about the long-term effect of ATLG on survival and GVHD relapses beyond this time-point are needed. Nonetheless, the findings represent a significant advance in the prevention of chronic GVHD. Keywords Chronic graft-versus-host disease (GVHD), allogeneic haematopoietic stem cell transplantation (HSCT), anti-human T-lymphocyte immune globulin, survival rate, relapse-free survival Disclosure: Nicolaus Kröger received research grant from Neovii Pharmaceuticals AG. Acknowledgements: Medical writing assistance was provided by Catherine Amey for Touch Medical Media funded by Neovii Pharmaceuticals AG. This study involves a review of the literature and did not involve any studies with human or animal subjects performed by any of the authors. Open Access: This article is published under the Creative Commons Attribution Noncommercial License, which permits any non-commercial use, distribution, adaptation and reproduction provided the original author(s) and source are given appropriate credit. Received: 23 June 2016 Accepted: 28 July 2016 Citation: European Oncology & Haematology, 2016;12(2):93–5 Corresponding Author: Nicolaus Kröger, University Hospital Hamburg-Eppendorf, Martinistrasse 52, 20246 Hamburg, Germany. E: Support: The publication of this article was supported by Neovii Pharmaceuticals AG, who were given the opportunity to review the article for scientific accuracy before submission. Any resulting changes were made at the author’s discretion. Chronic graft-versus-host disease (GVHD) is one of the major complications of allogeneic haematopoietic stem cell transplantation (HSCT) resulting from a complex interaction between the donor-derived immune system and recipient organ. 1 While acute GVHD is a distinctive syndrome consisting of the development of mainly dermatitis, hepatitis and enteritis, chronic GVHD describes a more diverse syndrome, potentially affecting almost all organs and tissues in the body. The National Institutes of Health (NIH) Consensus Development Project has proposed two subcategories for chronic GVHD: classic and overlap syndrome (Figure 1). These syndromes, which have been shown to have clinical validity, 2 are based on clinical features rather than time of onset. This is due to recognition that both classical features of chronic GVHD can occur within 100 days post-HSCT and that features of acute and chronic GVHD could occur together. 3 Therapies such as steroids that are effective in treating acute GVHD might be much less effective for chronic GVHD and this together with the differences in clinical presentation, suggest that unique physiologic mechanisms may be involved in chronic GVHD. 4 Unlike acute GVHD, which is mediated almost entirely by donor T cells, chronic GVHD immune pathology is more complicated and donor B cells have also been found to play an important role. 5 In the literature the incidence of chronic GVHD following allo-HSCT ranges from 6–80%, according to presence of risk factors and diagnostic criteria used. 3,6–8 Several potential risk factors have been described, including transplant from donors other than a matched sibling, 9,10 older recipients 11,12 and the use of peripheral blood graft. 13–15 Chronic GVHD can lead to later illness, including immune dysfunction and infection risk, a reduction in quality of life and a decline in life expectancy. 16,17 In a records review of 10,632 patients who were alive and disease free 2 years after receiving myeloablative allogeneic HCT before 2004, 3,788 patients were studied for 10 or more years. 16 The probability of being alive 10 years post-HCT was 85%. Older age and chronic GVHD were the main risk factors for late death. In a cohort of 2,574 patients who survived without recurrence for 5 years or more post- HCT, the estimated survival of the cohort was 80.4% (95% confidence interval [CI] 78.1–82.6%). The leading causes of additional deaths, in descending order, were second malignancies and recurrent disease, GVHD, respiratory diseases and cardiovascular diseases. A US report in 2011 from the Chronic GVHD Consortium revealed that patients with moderate and severe chronic GVHD had physical component scores comparable with scores reported for systemic sclerosis, systemic lupus erythematosus, and multiple sclerosis. They also had greater impairment compared with common chronic conditions including diabetes, hypertension, and chronic lung disease. 18 A comparison of the mean Short Form-36 scores between chronic GVHD patients and the normal US population showed significant impairment TOU CH MED ICA L MEDIA 93