title: Lung abnormalities after dasatinib treatment for chronic myeloid leukemia: a case series.
abstract: 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.
authors.affiliation: Université Denis Diderot-Paris 7, Assistance Publique-Hôpitaux de Paris, Service de Pneumologie, Hôpital Saint-Louis 1, Avenue Claude Vellefaux, 75475 Paris, Cedex 10, France. anne.bergeron-lafaurie@sls.aphp.fr
authors.forename: Anne
authors.initials: A
authors.lastname: Bergeron
authors.forename: Delphine
authors.initials: D
authors.lastname: Réa
authors.forename: Vincent
authors.initials: V
authors.lastname: Levy
authors.forename: Clément
authors.initials: C
authors.lastname: Picard
authors.forename: Véronique
authors.initials: V
authors.lastname: Meignin
authors.forename: Jérome
authors.initials: J
authors.lastname: Tamburini
authors.forename: Heriberto
authors.initials: H
authors.lastname: Bruzzoni-Giovanelli
authors.forename: Fabien
authors.initials: F
authors.lastname: Calvo
authors.forename: Abdellatif
authors.initials: A
authors.lastname: Tazi
authors.forename: Philippe
authors.initials: P
authors.lastname: Rousselot
mesh_terms: D000328:Adult; D000368:Aged; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D002637:Chest Pain / Q000139:chemically induced; D003371:Cough / Q000139:chemically induced; D000069439:Dasatinib; D004417:Dyspnea / Q000139:chemically induced; D005260:Female; D006801:Humans; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy*; D008168:Lung / Q000000981:diagnostic imaging* / Q000187:drug effects* / Q000378:metabolism; D008214:Lymphocytes / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D022423:Myeloid Cells / Q000378:metabolism; D009504:Neutrophils / Q000378:metabolism; D010996:Pleural Effusion / Q000000981:diagnostic imaging; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage / Q000009:adverse effects*; D011743:Pyrimidines / Q000008:administration & dosage / Q000009:adverse effects*; D011859:Radiography; D013844:Thiazoles / Q000008:administration & dosage / Q000009:adverse effects*
chemical_list: D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D013844:Thiazoles; D000069439:Dasatinib