Abstract

Acute graft-versus-host disease (GVHD) results from reactivity of donor immunocompetent cells versus host tissues. Its pathogenesis involves co-stimulatory molecules, cytokines, free radicals, and oxidative stress products. N-Acetylcysteine (NAC) is an antioxidant that inhibits the B7-1/CD28 expression in vitro, and it may contrabalance the effects of free radicals and oxidative stress; it has been tested in eight patients with steroid-resistant acute GVHD. NAC was given at the dose of 150 mg/kg bolus intravenously, followed by 50 mg/kg intravenous continuous infusion over 3 weeks or less up, to clinical GVHD resolution. In four patients, flow cytometric analysis of co-stimulatory molecules was performed on peripheral mononuclear cells before and after NAC therapy. We achieved prompt response in six patients: four had complete response, two partial response. Two patients died of acute GVHD, and four of intercurrent disease. We noticed significant decrease in CD80, CD25, and CD8+ cells after NAC therapy. NAC therapy is feasible; it may give response in steroid-resistant acute GVHD. More extensive studies are needed to confirm these data.

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