INTERLEUKIN RECEPTOR ANTAGONIST--PREVENTION OF GVHD AFTER ALLOGENEIC BMT

移植物抗宿主病（GVHD）仍然是抗宿主病的主要并发症

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.