ETANERCEPT FOR TREATMENT OF SUB-ACUTE PULM DYSFUNCTION AFTER ALLOGENEIC BMT

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 异基因骨髓移植(BMT)是许多白血病或淋巴瘤患者的唯一治愈方法。不幸的是，异基因骨髓移植后肺损伤很常见，限制了这种治疗的成功。肺损伤发生在骨髓移植后的早期和晚期，既可以是传染性的，也可以是非传染性的。移植后数月至数年发生的非感染性肺损伤对我们的患者来说尤其麻烦。从历史上看，削弱免疫系统的药物一直是治疗的主流，但这种方法很少成功，而且有相当大的副作用。利用小鼠骨髓移植模型，我们已经确定在这种情况下，一种名为肿瘤坏死因子α的蛋白质与肺损伤有关。重要的是，我们使用FDA批准的药物(Etanercept)将这一令人兴奋的实验室发现带给我们的患者，该药物中和了TNFx的影响，并发现该药物对我们的慢性肺损伤患者安全且潜在有效。因此，这项建议将建立在以前的实验室临床见解的基础上，并将把一项新的研究试验与最先进的实验室技术结合起来：1)确定依那西普是否对我们的骨髓移植患者有效，2)加深我们对这种并发症的生物学基础的理解。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Allogeneic bone marrow transplantation (BMT) is the only curative treatment for many patients with leukemia or lymphoma. Unfortunately, injury to the lung is common after allogeneic BMT and limits the success of this therapy. Lung injury occurs early and late after BMT and can be either infectious or non-infectious in origin. Non-infectious lung injury occurring months to years after transplant is particularly troublesome for our patients. Historically, medications that weaken the immune system have been the mainstay of therapy, but this approach is rarely successful and has considerable side effects. Using mouse BMT models, we have determined that a protein called TNF alfa contributes to lung injury in this context. Importantly, we have brought this exciting laboratory discovery back to our patients using an FDA approved drug (etanercept) that neutralizes the effects of TNFx, and found that this drug is safe and potentially effective in our patients with chronic lung injury. This proposal will, therefore, build upon prior laboratory clinical insights and will combine a novel research trial with state of the art laboratory techniques to: 1) determine whether etanercept is an effective treatment for our BMT patients, and 2) further our understanding of the biologic basis of this complication.'