Pulmonary fibrosis subsequent to high doses of CCNU for chronic myeloid leukemia

Two patients treated for chronic myeloid leukemia with high doses of CCNU (1100 mg/m2 and 1240 mg/m2, respectively) developed a fatal pulmonary fibrosis. This side effect has never been reported for this nitrosourea but only for BCNU and methyl-CCNU. The responsibility of CCNU in the pathogenesis of pulmonary fibrosis seems very likely. The possibility that the underlying disease or other chemotherapeutic agents may increase the risk of pulmonary toxicity can, however, be discussed. In addition, 13 other adults treated for chronic myeloid leukemia with various doses of CCNU were reviewed. No respiratory symptoms appeared in the ten patients who were given less than 950 mg/m2. Three patients who received more than 1100 mg/m2 developed pulmonary symptoms with the same clinical and radiologic pattern as in the two cases with pathologic documents, and two of them died from acute respiratory failure. Although lung specimens were lacking from these three patients, it is suggested that the pulmonary toxicity of CCNU may be dose-related.