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Prevention of acute graft-versus-host disease

Author
Nelson J Chao, MD
Section Editor
Robert S Negrin, MD
Deputy Editor
Alan G Rosmarin, MD

INTRODUCTION

Acute graft-verus-host disease (GVHD) is a common complication of allogeneic hematopoietic cell transplant (HCT) that classically presents in the early post-transplantation period. It is thought to be primarily a T cell mediated disease that occurs when immune cells transplanted from a non-identical donor (the graft) recognize the transplant recipient (the host) as foreign, thereby initiating an immune reaction that causes disease in the transplant recipient. The skin, gastrointestinal tract, and liver are the principal target organs in patients with acute GVHD.

Clinically significant acute GVHD occurs in 20 to 60 percent of patients who receive an allogeneic HCT, despite intensive prophylaxis with immunosuppressive agents. The development of moderate (grade II) or severe (grade III or IV) acute GVHD is associated with a significant decrease in survival. As such, all patients receiving an allogeneic HCT receive prophylaxis for acute GVHD.

This prevention of acute GVHD will be discussed here. The diagnosis and management of acute GVHD and the pathogenesis of GVHD are presented separately. (See "Clinical manifestations, diagnosis, and grading of acute graft-versus-host disease" and "Overview of immunosuppressive agents used for prevention and treatment of graft-versus-host disease" and "Treatment of acute graft-versus-host disease" and "Pathogenesis of graft-versus-host disease".)

OVERVIEW

Disease burden — Acute graft-verus-host disease (GVHD) is a significant cause of morbidity and mortality following allogeneic hematopoietic cell transplant (HCT), and intensive study continues to be directed towards prophylaxis. The reason for the focus on prophylaxis is twofold. First, the development of moderate (grade II) or severe (grade III or IV) acute GVHD is associated with significant morbidity, and severe GVHD is associated with a significant decrease in survival. Second, once GVHD occurs, it may not respond to treatment. Without prophylaxis, the incidence of clinically significant GVHD varies depending upon the degree of HLA mismatch and the type of transplantation, but may be as high as 70 to 100 percent [1,2]. With prophylaxis, the incidence of acute GVHD is decreased, but not eliminated. Risk factors for acute GVHD and grading of acute GVHD are discussed in more detail separately. (See "Clinical manifestations, diagnosis, and grading of acute graft-versus-host disease", section on 'Grading' and "Clinical manifestations, diagnosis, and grading of acute graft-versus-host disease", section on 'Risk factors'.)

Balancing GVHD and GVT effect — With nonidentical transplants, donor cytotoxic T cells (CTLs) may recognize neoplastic cells as foreign due to the expression of epitopes unique to the host (and the underlying malignancy). CTLs may subsequently become activated, lysing such cells. This graft-versus-tumor (GVT) effect is very similar to that which underlies GVHD. Although GVHD prophylaxis is clearly effective, an important concern had been that such therapy would also diminish the GVT effect, increasing the likelihood of recurrent disease.

                              

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Literature review current through: Nov 2016. | This topic last updated: Mon Jul 18 00:00:00 GMT+00:00 2016.
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