Active Lung Fibrosis up to 17 Years after Chemotherapy with Carmustine (BCNU) in Childhood

Abstract

Carmustine (BCNU) is an anticancer drug known to produce pulmonary fibrosis as a side effect within three years of treatment. It is not known whether pulmonary fibrosis can appear later. To investigate the clinical range of this side effect, we studied the survivors among 31 children treated with carmustine for brain tumors between 1972 and 1976. Fourteen had died of their tumor; of the remaining 17, 6 had died of lung fibrosis--2 within 3 years of treatment and 4 from 8 to 13 years after treatment. This report focuses primarily on the 11 survivors, 8 of whom were available for detailed study 13 to 17 years (mean, 14) after treatment. Of the eight survivors studied, six had abnormal chest radiographs showing predominantly upper-zone fibrotic changes. These patients also had abnormal CT scans, showing a previously undescribed pattern of upper-zone fibrosis. All the survivors studied had restrictive spirometric defects (mean [+/- SD] vital capacity, 54 +/- 19 percent of the predicted value). Bronchoalveolar-lavage fluid contained abnormal proportions of specific macrophage subgroups. Light and electron microscopy in six patients revealed interstitial fibrosis and elastosis with damage to epithelial and endothelial cells. Four patients had symptoms (shortness of breath, cough, or both). Carmustine chemotherapy in childhood causes lung fibrosis that may remain asymptomatic for many years or become symptomatic at any time.