Lung abnormalities after dasatinib treatment for chronic myeloid leukemia: a case series

Am J Respir Crit Care Med. 2007 Oct 15;176(8):814-8. doi: 10.1164/rccm.200705-715CR. Epub 2007 Jun 28.

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.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Bronchoalveolar Lavage Fluid / chemistry
  • Chest Pain / chemically induced
  • Cough / chemically induced
  • Dasatinib
  • Dyspnea / chemically induced
  • Female
  • Humans
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / drug therapy*
  • Lung / diagnostic imaging*
  • Lung / drug effects*
  • Lung / metabolism
  • Lymphocytes / metabolism
  • Male
  • Middle Aged
  • Myeloid Cells / metabolism
  • Neutrophils / metabolism
  • Pleural Effusion / diagnostic imaging
  • Protein Kinase Inhibitors / administration & dosage
  • Protein Kinase Inhibitors / adverse effects*
  • Pyrimidines / administration & dosage
  • Pyrimidines / adverse effects*
  • Radiography
  • Thiazoles / administration & dosage
  • Thiazoles / adverse effects*

Substances

  • Protein Kinase Inhibitors
  • Pyrimidines
  • Thiazoles
  • Dasatinib