Chronic Graft-Versus-Host Disease
- 1 January 2006
- journal article
- review article
- Published by Springer Science and Business Media LLC in Drugs
- Vol. 66 (8), 1041-1057
- https://doi.org/10.2165/00003495-200666080-00002
Abstract
Chronic graft-versus-host disease (cGVHD) is the most common and severe complication among patients surviving >100 days after allogeneic transplantation. It starts with the expansion of donor T cells in response to alloantigens or autoantigens that are unchecked by normal thymic or peripheral mechanisms of deletion. The T cells induce damage to target organs either directly through cytolytic attack, inflammatory cytokines and fibrosis, or by promoting B cell activation and production of autoantibodies. HLA disparity, donor and patient age and sex, source of progenitor cells, graft composition and previous acute GVHD are the main factors that predict the risk of developing cGVHD. Once the diagnosis has been established, patients needing treatment (extensive cGVHD) must be identified. Poor prognostic factors such as extensive skin involvement, thrombocytopenia and progressive-type onset of cGVHD must be considered in order to define the immunosuppressive treatment requirements. Prednisone, together with a calcineurin inhibitor such as ciclosporin or tacrolimus, can be considered the standard regimen as primary treatment for cGVHD. Using that approach, among high-risk patients (identified as those with extensive cGVHD plus thrombocytopenia) 3-year survival reached 52%. Concerning salvage regimens, to date there is no clear standard regimen for cGVHD treatment, the best choice being to enter the patient into a clinical trial. Immunosuppressive drugs that inhibit T cell activation, proliferation or survival, such as mycophenolate mofetil, the anti-interleukin-2α receptor antagonist daclizumab, sirolimus (rapamycin), extracorporeal photopheresis and pentostatin (deoxycoformycin), among other agents, have been used with a very wide range of complete responses ranging from 5% to 50%. In addition, anti-cytokine or B cell inhibitors such as etanercept or rituximab have also been evaluated. The severe immunosuppression induced by those drugs increases the risk of infectious complications and may have a deleterious effect on the graft versus tumour effect after transplant so that newer strategies based on the selective depletion of alloreactive T cells and induction of more specific immunotolerance against host tissues are required.Keywords
This publication has 133 references indexed in Scilit:
- Long-Term Use of Oral Beclomethasone Dipropionate for the Treatment of Gastrointestinal Graft-versus-Host DiseaseTransplantation and Cellular Therapy, 2005
- Immune regulation by regulatory T cells: implications for transplantationTransplant Immunology, 2003
- Can tolerogenic dendritic cells help to modulate allo-immune responses in the setting of hematopoietic cell transplantation?Transplant Immunology, 2003
- Generation and function of antigen-specific suppressor and regulatory T cellsTransplant Immunology, 2003
- Influence of immunosuppressive drugs on dendritic cellsTransplant Immunology, 2003
- Decreased interleukin 10 and increased interferon-γ production in patients with chronic graft-versus-host disease after allogeneic bone marrow transplantationBone Marrow Transplantation, 1997
- Impairment of leukaemia-free survival by addition of interleukin-2-receptor antibody to standard graft-versus-host prophylaxisThe Lancet, 1995
- L3T4+ T cells induce hepatic lesions resembling primary biliary cirrhosis in mice with graft-versus-host reactions due to major histocompatibility complex class II disparityClinical Immunology and Immunopathology, 1991
- Antileukemic Effect of Chronic Graft-versus-Host DiseaseThe New England Journal of Medicine, 1981
- Antileukemic Effect of Graft-versus-Host Disease in Human Recipients of Allogeneic-Marrow GraftsThe New England Journal of Medicine, 1979