Noninfectious pulmonary complications are varied and include diffuse alveolar hemorrhage, idiopathic pneumonia syndrome, bronchiolitis obliterans, bronchiolitis obliterans with organizing pneumonia, diffuse alveolar damage, lymphocytic interstitial pneumonia and nonclassifiable interstitial pneumonia. The therapeutic mainstay for these syndromes is the administration of immunosuppressant therapy in the form of corticosteroids. However, there is variable response to therapy depending on the syndrome. Bronchiolitis obliterans with organizing pneumonia responds well to therapy with corticosteroids. On the other hand, idiopathic pneumonia syndrome is far less responsive. The clinical response to standard therapy with high dose corticosteroids is limited. Ultimately, the diagnosis of idiopathic pneumonia is associated with mortality rates of 50% to 70%.In a recent case series, etanercept, a dimeric tumor necrosis factor alpha binding protein, and corticosteroids were administered to 3 consecutive pediatric patients as an alternative therapeutic regimen for the treatment of idiopathic pneumonia syndrome. In each case etanercept was well tolerated and resulted in significant improvement in pulmonary dysfunction.
A 53 year old female underwent allogeneic bone marrow transplant for M1 acute myelogenous leukemia. Her hospital course was uneventful and she was discharged after 2 weeks in the hospital. Five months after discharge from the hospital, the patient developed dyspnea with exertion, fevers and a non productive cough. Pulmonary function testing revealed moderate restriction. Computed tomography of the chest which revealed diffuse patchy ground glass opacities throughout both lung fields. Bronchoscopy with bronchoalveolar lavage revealed no evidence of infection with bacterial, viral or fungal organisms. Examination of transbronchial lung biopsy samples revealed histopathological findings consistent with idiopathic pneumonia syndrome after bone marrow transplantation. Etanercept at a dose of 25 mg twice a week in combination with prednisone at 1 mg/kg was initiated. The patient experienced symptomatic improvement after 7 days of therapy. Therapy was continued for 4 weeks. At the completion of therapy, there was a regression in pulmonary infiltrates and improvement in lung function.DISCUSSION: Idiopathic pneumonia syndrome is very serious and life threatening complication of bone marrow transplatation. The National Institutes of Health defines idiopathic pneumonia syndrome as widespread alveolar injury in the absence of active lower respiratory tract infection following bone marrow transplantation. The time course to the development of symptoms is variable but the prognosis is ultimately poor with reported mortality rates up to 70%.Several hypotheses exist regarding the pathogenesis of idiopathic pulmonary syndrome. Radiation therapy induced injury, cytokine mediation and occult infection have all been implicated in the pathogenesis of idiopathic pneumonia syndrome. Increasing evidence is mounting that points to cytokine mediation, namely tumor necrosis factor alpha, as an integral contributor to lung injury following bone marrow transplantation. There are elevated levels of tumor necrosis factor alpha in the serum of patients that develop lung injury after bone marrow transplantation. Additionally, neutralization of tumor necrosis factor alpha after bone marrow transplantation reduced the severity of idiopathic pneumonia syndrome in an experimental model. These findings in combination with the marked clinical and radiographic improvement in our patient point to etanercept, and tumor necrosis factor inhibition, as a central part in the treatment of idiopathic pneumonia syndrome
The combination of etanercept and corticosterid is a viable therapy for adult patients with clinical presentation consistent idiopathic pneumonia syndrome. The therapy is well tolerated and was associated with significant clinical and radiographic improvement. The poor prognosis previously associated with idiopathic pneumonia syndrome and the prompt response to therapy in this case highlights the need for further clinical trials in pediatric and adults with noninfectious lung injury after allogeneic bone marrow transplantation
K.H. Wallace, None.