Chlorambucil is an alkylating agent commonly used in treatment of chronic lymphocytic leukemia (CLL). We report a case of interstitial pneumonitis developing in an 83-year-old man 1.5 months after completing a six-month course of chlorambucil for CLL. The interstitial pneumonitis responded to therapy with prednisone. We performed a systematic review of literature and identified 13 other case reports of chlorambucil-induced pulmonary toxicity, particularly interstitial pneumonitis. No unifying risk factor could be discerned and the mechanism of injury remains unknown. In contrast, major randomized trials of chlorambucil therapy in CLL have not reported interstitial pneumonitis as an adverse effect, which may be due to the rarity of the phenomenon or due to underreporting of events occurring after completion of treatment. Clinicians should consider drug-induced interstitial pneumonitis in the differential diagnosis of a suggestive syndrome developing even after discontinuation of chlorambucil. 1. Introduction Chlorambucil is an alkylating agent used for treatment of indolent lymphoproliferative disorders, particularly chronic lymphocytic leukemia (CLL) [1]. It is a relatively well-tolerated drug with myelosuppression constituting its principal toxicity [2]. Other alkylating agents such as busulfan and cyclophosphamide have been implicated in toxic lung injury [3]. Data regarding chlorambucil-induced lung injury is however very limited and consists of scattered case reports. Pulmonary toxicity has been reported as a dose-independent adverse effect of chlorambucil occurring during or after discontinuation of the therapy. We report a case of chlorambucil-induced interstitial pneumonitis along with a systematic review of literature summarizing the evidence of lung toxicity as a rare adverse effect of the agent. 2. Case Report An 83-year-old man presented to our hospital with acute onset of dyspnea and hypoxia. The patient had been diagnosed with CLL 14 months prior to the event, with asymptomatic lymphocytosis of 15.5？×？109/L, evidence of CD5, CD23, and CD38-positive, CD10-negative B-cell leukemia on flow cytometry, hemoglobin of 133？g/L, and platelet count of 132？×？109/L. After 8 months of watchful waiting he experienced progressive adenopathy and thrombocytopenia, which constituted indications for therapy. The patient received single-agent oral chlorambucil at the dose of 0.6？mg/kg every 14 days for 6 months. There were no significant toxicities during therapy, which resulted in a partial remission of CLL and resolution of adenopathy and cytopenias. Six
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