INTERLEUKIN RECEPTOR ANTAGONIST--PREVENTION OF GVHD AFTER ALLOGENEIC BMT

移植物抗宿主病(GVHD)仍然是 异基因骨髓移植。在几个方面的研究 实验室，包括首席调查员的实验室，已经 已证实炎性细胞因子白介素1(IL-1)是一种 GVHD的重要效应分子为GVHD提供新的机遇 针对这种并发症的额外预防措施。这项研究将测试 假设炎性细胞因子的中断 级联可降低临床移植物抗宿主病的发生率和严重程度 异基因骨髓移植后。 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A) 为了减少严重急性移植物抗宿主病的发生率和严重程度 (B-D级)异基因骨髓移植 2)评估炎症细胞因子(IL-1、肿瘤坏死因子-α)的水平，其 拮抗剂(IL-1ra、sTNFR)和辅因子内毒素或 脂多糖作为急性移植物抗宿主病等疾病的替代标志物 在研究过程中与移植相关的毒性。

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.