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Blood, 15 October 2008, Vol. 112, No. 8, pp. 3073-3081.
Prepublished online as a Blood First Edition Paper on July 29, 2008; DOI 10.1182/blood-2008-03-143412.
 Previous Article | Next Article 
Submitted March 7, 2008
Accepted July 7, 2008
The impact of soluble tumor necrosis factor receptor: etanercept on the treatment of idiopathic pneumonia syndrome following allogeneic hematopoietic stem cell transplantation
Gregory A Yanik*, Vincent T Ho, John E Levine, Eric S White, Thomas Braun, Joseph H Antin, Joel Whitfield, Joseph Custer, Dawn Jones, James LM Ferrara, and Kenneth R Cooke
Department of Pediatrics, Blood and Marrow Transplantation Program, University of Michigan, Ann Arbor, MI, United States
Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, United States
Department of Internal Medicine, Blood and Marrow Transplantation Program, University of Michigan, Ann Arbor, MI, United States
Department of Internal Medicine, Division of Pulmonary and Critical Care Medicine, University of Michigan, Ann Arbor, MI, United States
Department of Biostatistics, University of Michigan, Ann Arbor, MI, United States
Department of Pediatrics, Critical Care Medicine, University of Michigan, Ann Arbor, MI, United States
* Corresponding author; email: gyanik{at}umich.edu.
Idiopathic Pneumonia Syndrome (IPS) refers to a diffuse, non-infectious, acute lung injury following hematopoietic stem cell transplantation (HCT). Historically, IPS is associated with respiratory failure and mortality rates exceeding 50%. Pre-clinical studies have implicated TNF as an important effector molecule in the development of disease. We studied the TNF inhibitor, etanercept, combined with corticosteroids in treating 15 patients (median 18 yrs, range 1 - 60 yrs) with IPS. Eight of 15 patients required mechanical ventilation at therapy onset. Etanercept was administered subcutaneously at a dose of 0.4 mg/kg (maximum 25 mg) twice weekly, for a maximum of eight doses. Therapy was well tolerated with no infectious pulmonary complications noted. Ten of 15 patients had a complete response, defined as the ability to discontinue supplemental oxygen support during study therapy. The median time to complete response was 7 days (range 3-18 days), with a day 28 survival of 73%. IPS onset was associated with elevations of several inflammatory proteins in the bronchoalveolar lavage (BAL) fluid and plasma, and response to therapy correlated with reductions in pulmonary and systemic inflammation. The combination of etanercept and corticosteroids is safe, and is associated with high response rates and improved survival in patients with IPS.
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