Pulmonary Toxicity

Idiopathic pneumonia syndrome occurs in 10% or less of patients who undergo transplantation using mye-loablative preparative regimens. It occurs in similar frequency among allogeneic and autologous transplant recipients and has a high case-fatality rate, about 75%.134,135 IPS occurs a median of 21 days posttrans-plant and appears to be more common in allogeneic transplant recipients with severe acute GVHD and in patients transplanted for diagnoses other than leukemia.134 Almost 70% of patients with IPS require mechanical ventilation a median of 2 days after the onset of radiographic changes. Ventilated patients rarely survive to be discharged from the hospital.136137 Patients with IPS who die usually do so as a result of respiratory failure. Steroids are usually ineffective.

The precise mechanism of IPS is unclear, although the data suggest that a number of proinflammatory events in the peritransplant period are responsible. BAL fluid of patients with lung injury contains increased amounts of TNF-a.138'139 Schots et al. reported that serum levels of TNF-a and the inflammatory cytokines IL-6 and IL-8 are increased in patients who develop major treatment-related complications, including IPS.140 In a small series of patients, neutralization of TNF-a with Etanercept, a soluble, dimeric TNF-a binding protein, resulted in significant improvement in pulmonary function in patients with IPS.141

Other investigators have studied potential markers for IPS, in the hope that they might identify patients at risk and intervene before development of clinical disease. DiNubile and colleagues measured plasma gel-solin levels in 24 patients undergoing allogeneic stem cell transplantation.142 Gelsolin is one of several proteins found in plasma that bind actin. There was a significant association between the last measured gelsolin

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