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

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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.'