Yoshihiro Inamoto1, Mary E D Flowers. 1. Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington 98109-1024, USA.
Abstract
PURPOSE OF REVIEW: This article summarizes recent reports on the risks, pathogenesis and treatment of chronic graft-versus-host disease (GVHD). RECENT FINDINGS: Chronic GVHD remains an elusive disorder to characterize and to treat. Recent evidence on tolerance induction by regulatory T-cells and on B-cell involvement shed some insights into the pathogenesis of chronic GVHD. In a recent large comparative study, the overall risk profiles for acute and for chronic GVHD were similar, but risk factors were not changed after adjustment for prior acute GVHD, supporting the concept that chronic GVHD is not an end stage of acute GVHD. Glucocorticoids remain the standard initial treatment of chronic GVHD, but the outcomes are not satisfactory, particularly for patients with high-risk features. Many treatments for chronic GVHD including extracorporeal photopheresis, rituximab, sirolimus, mycofenolate mofetil, imatinib, pentostatin and infusion of mesenchymal stem cells have been reported in several retrospective and relatively small phase I/II studies with a wide range of overall responses. SUMMARY: No current therapies used for chronic GVHD have been approved by the US Food and Drug Administration. Large well designed prospective studies are warranted to establish better treatments. Targeted therapies based on the pathogenesis of chronic GVHD may lead to better outcomes.
PURPOSE OF REVIEW: This article summarizes recent reports on the risks, pathogenesis and treatment of chronic graft-versus-host disease (GVHD). RECENT FINDINGS: Chronic GVHD remains an elusive disorder to characterize and to treat. Recent evidence on tolerance induction by regulatory T-cells and on B-cell involvement shed some insights into the pathogenesis of chronic GVHD. In a recent large comparative study, the overall risk profiles for acute and for chronic GVHD were similar, but risk factors were not changed after adjustment for prior acute GVHD, supporting the concept that chronic GVHD is not an end stage of acute GVHD. Glucocorticoids remain the standard initial treatment of chronic GVHD, but the outcomes are not satisfactory, particularly for patients with high-risk features. Many treatments for chronic GVHD including extracorporeal photopheresis, rituximab, sirolimus, mycofenolate mofetil, imatinib, pentostatin and infusion of mesenchymal stem cells have been reported in several retrospective and relatively small phase I/II studies with a wide range of overall responses. SUMMARY: No current therapies used for chronic GVHD have been approved by the US Food and Drug Administration. Large well designed prospective studies are warranted to establish better treatments. Targeted therapies based on the pathogenesis of chronic GVHD may lead to better outcomes.
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