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Published ahead of print on June 28, 2007, doi:10.1164/rccm.200705-715CR
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American Journal of Respiratory and Critical Care Medicine Vol 176. pp. 814-818, (2007)
© 2007 American Thoracic Society
doi: 10.1164/rccm.200705-715CR


Original Article

Lung Abnormalities after Dasatinib Treatment for Chronic Myeloid Leukemia

A Case Series

Anne Bergeron1, Delphine Réa2,3, Vincent Levy2, Clément Picard1, Véronique Meignin4, Jérome Tamburini1, Heriberto Bruzzoni-Giovanelli2, Fabien Calvo2, Abdellatif Tazi1 and Philippe Rousselot2,5

1 Université Denis Diderot–Paris 7, Assistance Publique-Hôpitaux de Paris, Service de Pneumologie, Hôpital Saint-Louis, Paris, France; 2 INSERM CIC 9504, Centre d'Investigations Cliniques, Paris, France; 3 Université Denis Diderot–Paris 7, Assistance Publique-Hôpitaux de Paris, Service d'Hématologie, Hôpital Saint-Louis, Paris, France; 4 Université Denis Diderot–Paris 7, Assistance Publique-Hôpitaux de Paris, Service de Pathologie, Hôpital Saint-Louis, Paris, France; and 5 Université de Versailles Saint-Quentin en Yvelines, Service d'Hématologie Hôpital Mignot, Le Chesnay, France

Correspondence and requests for reprints should be addressed to Anne Bergeron, M.D., Ph.D., Service de Pneumologie, Hôpital Saint-Louis 1, Avenue Claude Vellefaux, 75475 Paris, Cedex 10, France. 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, 9 (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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