N-acetylcysteine in the treatment of steroid-resistant acute graft-versus-host-disease - Preliminary results

Background Acute graft-versus-host disease (GVHD) results from reactivity o f donor immunocompetent cells versus host tissues. Its pathogenesis involve s co-stimulatory molecules, cytokines, free radicals, and oxidative stress products, N-Acetylcysteine (NAC) is an antioxidant that inhibits the B7-1/C D28 expression in vitro, and it may contrabalance the effects of free radic als and oxidative stress; it has been tested in eight patients with steroid -resistant acute GVHD. Methods. NAC was given at the dose of 150 mg/kg bolus intravenously, follow ed 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. Results, We achieved prompt response in six patients: four had complete res ponse, two partial response. Two patients died of acute GVHD, and four of i ntercurrent disease. We noticed significant decrease in CD80, CD25, and CD8 + cells after NAC therapy. Conclusion, NAC therapy is feasible; it may give response in steroid-resist ant acute GVHD. More extensive studies are needed to confirm these data.