Graft-vs-host disease (GVHD) remains the major complication of allogeneic bone marrow transplantation (BMT). Research in several laboratories, including that of the principal investigator, have demonstrated that the inflammatory cytokine Interleukin-1 (IL-1) is an important effector molecule of GVHD providing a new opportunity for additional prophylaxis against this complication. This study will test the hypothesis that the interruption of the inflammatory cytokine cascade can lead to a reduced incidence and severity of clinical GVHD after allogeneic BMT.
Specific Aims : 1) Perform a randomized trial of IL-1 receptor antagonist (IL-1ra) vs. placebo plus standard GVHD prophylaxis (methotrexate and cyclosporine) in order to reduce the incidence and severity of significant acute GVHD (Grades B-D) after allogeneic bone marrow transplantation 2) Evaluate levels of inflammatory cytokines (IL-1, TNF-a), their antagonists (IL-1ra, sTNFR) and cofactors endotoxin or lipopolysaccharide (LPS) as surrogate markers for acute GVHD and other transplant related toxicities during the course of the study.
Showing the most recent 10 out of 463 publications