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Chlorambucil-induced pulmonary injury

Section Editors
Kevin R Flaherty, MD, MS
James R Jett, MD
Deputy Editors
Helen Hollingsworth, MD
Diane MF Savarese, MD


Chlorambucil is an alkylating chemotherapy agent. It can be given orally and is mainly used in the treatment of chronic lymphocytic leukemia (CLL). Very rarely, it has been used as an immunosuppressive agent in refractory autoimmune and inflammatory conditions like rheumatoid arthritis and sarcoidosis. (See "Selection of initial therapy for symptomatic or advanced chronic lymphocytic leukemia", section on 'Chlorambucil-based therapy'.)

Other than myelosuppression, less common side effects of chlorambucil involve the gastrointestinal tract, liver, skin, and the central nervous system; lung toxicity is rare but well documented. Chlorambucil-induced pulmonary injury will be discussed here. A more general discussion of the clinical presentation, diagnosis, and treatment of pulmonary toxicity in patients receiving systemic antineoplastic therapy is presented elsewhere. (See "Pulmonary toxicity associated with systemic antineoplastic therapy: Clinical presentation, diagnosis, and treatment".)  


While the pulmonary toxicity of other alkylating agents like busulfan and cyclophosphamide is well recognized, chlorambucil-induced pulmonary injury is rare [1]. The literature is confined to isolated case reports [2-19]. The absolute magnitude of risk is undefined. Contemporary clinical trials of chlorambucil in over 600 patients with a hematologic malignancy did not identify any cases of chlorambucil-induced pneumonitis [20-22]. This could be due to the rarity of the phenomenon or to underreporting of events occurring after completion of treatment.

There are no unifying risk factors. Pulmonary toxicity may develop while the patient is taking chlorambucil, or after stopping the drug. There appears to be no direct correlation between the dose or duration of therapy and the incidence of lung toxicity [8]; pulmonary injury has been described in patients receiving cumulative chlorambucil doses ranging from 540 to 8340 mg [5,9].


The most common pattern of lung injury reported in chlorambucil treated patients is chronic interstitial pneumonitis (nonspecific interstitial pneumonia, although this nomenclature postdates most reports of chlorambucil lung toxicity), but acute interstitial pneumonia, pulmonary fibrosis, and organizing pneumonia (formerly known as bronchiolitis obliterans organizing pneumonia or BOOP) have also been reported [5-8,11,12,18-20]. Interstitial lung disease may develop while the patient is taking chlorambucil or after stopping it.

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Literature review current through: Nov 2017. | This topic last updated: Aug 07, 2017.
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