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Chronic graft versus host disease (GVHD) is the most common complication of allogenic bone marrow transplantation. Because of the protracted clinical course of chronic GVHD, transplant centers and hematology/oncology offices are inadequately equipped to manage these immuno-incompetent patients with a multi-system disorder. Practitioners need to be able to recognize and effectively manage chronic GVHD as a late effect of more than half of allogenic transplantations. The text is oriented for the clinician, with chapters covering staging, organ site and system-specific manifestations, treatment options, and supportive care. Drs Georgia B. Vogelsang and Steven Z. Pavletic have been pioneers in the recognition of the multi-organ complexity of this disease and have gathered the input of a variety of subspecialist physicians for this book. This book fills the gap in practical literature on chronic GVHD, providing a comprehensive, up-to-date, and clinically relevant resource for anyone who deals with cancer patients post-transplant.
Chronic graft versus host disease (cGVHD) is a clinical syndrome characterized by pleomorphic manifestation occurring over time with periods of exacerbation of acute manifestations or development of new clinical features in previously uninvolved or involved organs. cGVHD can affect multiple sites (Figure 6.1) and resembles manifestations of scleroderma, Sjogren syndrome, wasting syndrome, primary biliary cirrhosis, bronchiolitis obliterans, immune cytopenias, and chronic immunodeficiency disorders. The etiology of the variable phenotype of cGVHD is poorly understood and may depend on the type and intensity of the inflammatory and cellular process caused by immune dysregulation associated with cGVHD. Immune mechanisms leading to the diverse clinical manifestations of cGVHD have not been elucidated. Autoimmunity is thought to be involved because of the clinical similarities between cGVHD and autoimmune diseases. Dysfunctional T-cell selection in the thymus leading to a population of TH2 self (recipient)-reactive T cells and differences in TH1 and TH2 responses by donor cells to recipient alloantigens may also play a role in pathogenesis. Recent studies reported that regulatory T cells (Treg) are major determinants of a persistent immune imbalance that may result in cGVHD.
Bone marrow transplantation has changed remarkably from its earliest days. Patients were transplanted with bone marrow as a last resort for refractory leukemia or aplastic anemia. The transplant procedure required prolonged hospital stays – often months - with significant uncontrolled toxicities from the preparative regimen, limited antimicrobial success, and even more limited ability to prevent or treat acute graft versus host disease (GVHD). The lucky survivors now marvel at how different the experience is for patients receiving allografts as outpatients.
Unfortunately, the same level of improvement has not been seen in chronic GVHD. The reasons for this lack of success are varied – including the latency of chronic GVHD, lack of accepted readily reproducible animal models, and complex underlying immuno-pathology. It is no wonder that patients with this affliction felt like abandoned stepchildren.
Over the last 5 years, there has been both a resurgence of interest and progress in chronic GVHD. To a significant degree, the NIH-sponsored Consensus Conference on Chronic GVHD is responsible for this change. This conference suggested working definitions, standardized staging and response criteria, recommended supportive care measures, and suggested areas for future study. Although the indolent nature of the disease means that clinical progress is going to be time consuming, there has been remarkable progress since the initial NIH-sponsored meeting. One of the main lessons learned is that it is imperative to have transplant centers cooperate in studying this disorder.