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Published ahead of print on June 28, 2007, doi:10.1164/rccm.200705-715CR

Am. J. Respir. Crit. Care Med., Volume 176, Number 8, October 2007, 814-818

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Submitted on May 14, 2007
Accepted on June 28, 2007

Lung Abnormalities Following Dasatinib Treatment for Chronic Myeloid Leukemia: A Case Series

Anne Bergeron1*, Delphine Rea2, Vincent Levy3, Clement Picard1, Veronique Meignin4, Jerome Tamburini1, Heriberto Bruzzoni-Giovanelli3, Fabien Calvo3, Abdellatif Tazi1, and Philippe Rousselot5

1 Service de Pneumologie, Universite Denis Diderot-Paris 7, Assistance Publique-Hopitaux de Paris, Hopital Saint-Louis, Paris, France, 2 Centre d'Investigations Cliniques, INSERM CIC 9504, Paris, France; Service d'Hematologie, Universite Denis Diderot-Paris 7, Assistance Publique-Hopitaux de Paris, Hopital Saint-Louis, Paris, France, 3 Centre d'Investigations Cliniques, INSERM CIC 9504, Paris, France, 4 Service de Pathologie, Universite Denis Diderot Paris-7, Assistance Publique-Hopitaux de Paris, Hopital Saint-Louis, Paris, France, 5 Centre d'Investigations Cliniques, INSERM CIC 9504, Paris, France; Service d'Hematologie Hopital Mignot, Universite de Versailles Saint-Quentin en Yvelines, Le Chesnay, France

* To whom correspondence should be addressed. E-mail: anne.bergeron-lafaurie{at}sls.aphp.fr.

Tyrosine kinase inhibitors have revolutionized the treatment of chronic myeloid leukemia and are increasingly used for other indications. Fluid retention, however, including pleural effusions, are a significant side effect of imatinib, the first-line treatment for chronic myeloid leukemia. We investigated pleural and pulmonary complications in patients treated with dasatinib, a novel multitargeted tyrosine kinase inhibitor, as part of clinical trial protocols. Of 40 patients who received dasatinib (70 mg twice daily) for imatinib resistance or intolerance, nine (22.5%) developed dyspnea, cough, and chest pain. Of these nine patients, six had pleural effusions (all were exudates) and seven had lung parenchyma changes with either ground glass or alveolar opacities and septal thickening (four patients had both pleural effusions and lung parenchyma changes). Lymphocytic accumulations were detected in pleural and bronchoalveolar lavage fluids in all patients except for one who presented with neutrophilic alveolitis. Pleural biopsies revealed lymphocytic infiltration in one patient and myeloid infiltration in another. After dasatinib interruption, lung manifestations resolved in all cases and did not recur in three of four patients when dasatinib was reintroduced at a lower dose (40 mg twice daily). Thus, lung physicians should be aware that lung manifestations, presumably related to an immune-mediated mechanism rather than fluid retention, may occur with dasatinib treatment.


Key words: pleural effusion, tyrosine kinase, inhibition




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