Dasatinib, large granular lymphocytosis, and pleural effusion: useful or adverse effect?

Crit Rev Oncol Hematol. 2014 Feb;89(2):242-7. doi: 10.1016/j.critrevonc.2013.10.005. Epub 2013 Oct 12.

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.

Keywords: Chronic myeloid leukemia; Dasatinib; Immune regulation; Large granular lymphocytosis; Pleural effusion; Response.

Publication types

  • Review

MeSH terms

  • Animals
  • Dasatinib
  • Humans
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / drug therapy*
  • Lymphocytosis / chemically induced*
  • Pleural Effusion / chemically induced*
  • Protein Kinase Inhibitors / adverse effects*
  • Protein Kinase Inhibitors / therapeutic use*
  • Pyrimidines / adverse effects*
  • Pyrimidines / therapeutic use*
  • Thiazoles / adverse effects*
  • Thiazoles / therapeutic use*

Substances

  • Protein Kinase Inhibitors
  • Pyrimidines
  • Thiazoles
  • Dasatinib