Critical Reviews in Oncology/Hematology 89 (2014) 242–247 Dasatinib, large granular lymphocytosis, and pleural effusion: Useful or adverse effect? Semra Paydas ∗ Cukurova University, Faculty of Medicine, Department of Oncology, Adana, Turkey Accepted 2 October 2013 Contents 1. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 242 2. Dasatinib and clonal large granular lymphocytes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 243 2.1. Definition . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 243 2.2. Prevalence of large granular lymphocytosis associated with dasatinib . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 243 2.3. Mechanism of dasatinib-associated clonal large granular lymphocytes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 244 2.4. Large granular lymphocytes and response to therapy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 245 3. Pleural/pulmonary effusion associated with dasatinib . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 245 3.1. Prevalence. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 245 3.2. Risk factors for pleural effusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 246 3.3. Pathogenesis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 246 3.4. Management of pleural effusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 246 3.5. Pleural effusion and response to treatment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 246 4. Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 246 Conflict of interest . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 246 Reviewers . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 246 References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 246 Abstract Dasatinib is a second generation tyrosine kinase inhibitor approved for clinical use in first line and imatinib-resistant chronic myeloid leukemia and Philadelphia positive (Ph+) acute lymphoblastic leukemia. In addition to BCR-ABL1, dasatinib inhibits TEC kinases and SRC family kinases and is more potent than imatinib in the treatment of Ph+ leukemias. In the last 3 years, increases in cytotoxic T and natural-killer cells in peripheral blood samples have been reported in cases treated by dasatinib. The awareness of the clonal expansion of large granular lymphocytes and beneficial effect of these clonal cells increased the interest to dasatinib in cases receiving this drug. Clonal expansion of large granular lymphocytes is an important effect of dasatinib therapy, shown to be an off-target phenomenon associated with pleural effusion and better clinical response. The benefit of dasatinib-induced lymphocytosis and its underlying mechanism of this are important points for clinicians working in hematology and oncology. © 2013 Elsevier Ireland Ltd. All rights reserved. Keywords: Dasatinib; Large granular lymphocytosis; Immune regulation; Chronic myeloid leukemia; Pleural effusion; Response ∗ Tel.: +90 322 3386060 3142; fax: +90 322 3386572. E-mail address: sepay@cu.edu.tr 1. Introduction Dasatinib is a second generation tyrosine kinase inhibitor (TKI) with different efficacy and toxicity profiles from imat- inib mesyate. Dasatinib inhibits TEC kinases and SRC family kinases which are the key regulators in immune 1040-8428/$ – see front matter © 2013 Elsevier Ireland Ltd. All rights reserved. http://dx.doi.org/10.1016/j.critrevonc.2013.10.005