Advances in the Pathogenesis and Treatment of Acute Graft-Versus
Advances in the Pathogenesis and Treatment of Acute Graft-Versus
Acute graft-versus-host disease (GVHD) remains a major obstacle shadowing the curative potential of allogeneic stem cell transplantation in many hematologic malignancies and disorders. During the past decade, a great deal of interest has been generated in preventing severe GVHD while maintaining the graft-versus-leukemia effect in transplant recipients. Recent data on T-cell subsets and cytokines may open new avenues for controlling GVHD. The role of CD4CD25 regulatory T cells in ameliorating acute GVHD in mice remains to be confirmed in clinical studies. Studies on cytokine gene polymorphism have introduced a molecular genetic method into the field for the prediction of GVHD. New agents such as sirolimus, keratinocyte growth factor, suberoylanilide hydroxamic acid, and various monoclonal antibodies against T cells and their receptors have started to be tested in clinical trials with early promising results. This article summarizes recent developments in etiology and management of acute GVHD.
Acute graft-versus-host disease (GVHD) mediated by donor T-cell alloreactivity against host tissue antigens occurs in approximately 50% of patients who receive unmanipulated HLA-matched sibling transplantations and up to 80% of patients who receive unrelated donor transplantations. In its mildest form, it is characterized by a rash.
As the disease worsens, however, the confluent rash may progress to skin blistering similar to that seen with severe burns, accompanied by profound diarrhea and abdominal pain and hepatic dysfunction with marked hyperbilirubinemia. Analysis of a biopsy specimen of the affected organ is essential to diagnosis. High-dose corticosteroids are the mainstay of therapy. However, outcomes for corticosteroid-resistant disease are disappointing: the overall fatality rate is about 20%, but in the severe form, the fatality rate exceeds 80%. Most patients with grade 4 disease do not survive. Recent data on the pathogenesis and treatment of GVHD are summarized in the following sections.
Acute graft-versus-host disease (GVHD) remains a major obstacle shadowing the curative potential of allogeneic stem cell transplantation in many hematologic malignancies and disorders. During the past decade, a great deal of interest has been generated in preventing severe GVHD while maintaining the graft-versus-leukemia effect in transplant recipients. Recent data on T-cell subsets and cytokines may open new avenues for controlling GVHD. The role of CD4CD25 regulatory T cells in ameliorating acute GVHD in mice remains to be confirmed in clinical studies. Studies on cytokine gene polymorphism have introduced a molecular genetic method into the field for the prediction of GVHD. New agents such as sirolimus, keratinocyte growth factor, suberoylanilide hydroxamic acid, and various monoclonal antibodies against T cells and their receptors have started to be tested in clinical trials with early promising results. This article summarizes recent developments in etiology and management of acute GVHD.
Acute graft-versus-host disease (GVHD) mediated by donor T-cell alloreactivity against host tissue antigens occurs in approximately 50% of patients who receive unmanipulated HLA-matched sibling transplantations and up to 80% of patients who receive unrelated donor transplantations. In its mildest form, it is characterized by a rash.
As the disease worsens, however, the confluent rash may progress to skin blistering similar to that seen with severe burns, accompanied by profound diarrhea and abdominal pain and hepatic dysfunction with marked hyperbilirubinemia. Analysis of a biopsy specimen of the affected organ is essential to diagnosis. High-dose corticosteroids are the mainstay of therapy. However, outcomes for corticosteroid-resistant disease are disappointing: the overall fatality rate is about 20%, but in the severe form, the fatality rate exceeds 80%. Most patients with grade 4 disease do not survive. Recent data on the pathogenesis and treatment of GVHD are summarized in the following sections.
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