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Busulfan-induced pulmonary injury

Authors
Erich W Russi, MD
Robert S Negrin, MD
Section Editors
Kevin R Flaherty, MD, MS
James R Jett, MD
Deputy Editors
Helen Hollingsworth, MD
Diane MF Savarese, MD

INTRODUCTION

Busulfan is an alkylating agent that was previously used for treatment of chronic myelogenous leukemia, but is now used exclusively as a component of a preparative regimen prior to hematopoietic stem cell transplantation (HCT). Busulfan was the first cytotoxic drug reportedly associated with pulmonary toxicity [1]. The reported patterns of pulmonary toxicity include acute lung injury, chronic interstitial fibrosis, and alveolar hemorrhage. Busulfan is often used in combination with other drugs, many of which cause pulmonary toxicity, which can make it difficult to ascertain which drug is the culprit. (See "Preparative regimens for hematopoietic cell transplantation", section on 'Chemotherapy without radiation'.)

The clinical characteristics of busulfan-induced pulmonary injury will be reviewed here. Pulmonary toxicity caused by other chemotherapeutic agents is discussed separately. (See "Pulmonary toxicity associated with systemic antineoplastic therapy: Clinical presentation, diagnosis, and treatment" and "Pulmonary toxicity associated with antineoplastic therapy: Cytotoxic agents" and "Pulmonary toxicity associated with antineoplastic therapy: Molecularly targeted agents".)

EPIDEMIOLOGY AND RISK FACTORS

Symptomatic pulmonary injury is thought to occur in fewer than 8 percent of patients who receive busulfan; the incidence of pulmonary toxicity appears to be similar in children and adults [2-16]. However, the true incidence is unknown; most of the early data in patients treated with busulfan alone for chronic myelogenous leukemia (CML) consisted of single case reports [3-7,9,10]. Such treatment is no longer considered a standard approach since the introduction of oral tyrosine kinase inhibitors. (See "Overview of the treatment of chronic myeloid leukemia".)

At present the utility of busulfan is limited to preparative regimens prior to hematopoietic cell transplantation (HCT). Modern data examining the risk of pulmonary toxicity in such patients are derived from series in which patients received busulfan in addition to other myelosuppressive chemotherapy agents and/or radiation therapy prior to HCT. The incidence has been variable, and interpretation complicated by competing causes of pulmonary toxicity, particularly cytomegalovirus (CMV) pneumonitis:

In one report, 2 of 78 patients (2.5 percent) who received a conditioning regimen of busulfan and cyclophosphamide prior to autologous HCT developed pulmonary fibrosis [14].

          

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Literature review current through: Nov 2016. | This topic last updated: Wed Dec 23 00:00:00 GMT+00:00 2015.
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References
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