INTERLEUKIN RECEPTOR ANTAGONIST--PREVENTION OF GVHD AFTER ALLOGENEIC BMT

移植物抗宿主病（GVHD）仍然是同种异体骨髓移植（BMT）的主要并发症。包括首席研究员在内的几个实验室的研究表明，炎症细胞因子白介素-1 （IL-1）是GVHD的重要效应分子，为进一步预防这种并发症提供了新的机会。本研究将验证炎症细胞因子级联的中断可能导致异基因BMT后临床GVHD的发病率和严重程度降低的假设。具体目标:1)进行IL-1受体拮抗剂（IL-1ra）与安慰剂加标准GVHD预防（甲氨蝶呤和环孢素）的随机试验，以降低同种异体骨髓移植后显著急性GVHD （B-D级）的发生率和严重程度2)评估炎症细胞因子（IL-1, TNF-a）及其拮抗剂（IL-1ra, IL-1ra, IL-1ra）的水平sTNFR)和辅助因子内毒素或脂多糖（LPS）作为研究过程中急性GVHD和其他移植相关毒性的替代标志物

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