title: Lymphocytosis after treatment with dasatinib in chronic myeloid leukemia: Effects on response and toxicity.
abstract: BACKGROUND
  The proliferation of clonal cytotoxic T-cells or natural killer cells has been observed after dasatinib treatment in small studies of patients with chronic myeloid leukemia (CML).
  
  
  METHODS
  The incidence of lymphocytosis and its association with response, survival, and side effects were assessed in patients from 3 large clinical trials. Overall, 1402 dasatinib-treated patients with newly diagnosed CML in chronic phase (CML-CP), CML-CP refractory/intolerant to imatinib, or with CML in accelerated or myeloid-blast phase were analyzed.
  
  
  RESULTS
  Lymphocytosis developed in 32% to 35% of patients and persisted for >12 months. This was not observed in the patients who received treatment with imatinib. Dasatinib-treated patients in all stages of CML who developed lymphocytosis were more likely to achieve a complete cytogenetic response, and patients who had CML-CP with lymphocytosis were more likely to achieve major and deep molecular responses. Progression-free and overall survival rates were significantly longer in patients with CML-CP who were refractory to or intolerant of imatinib and had lymphocytosis. Pleural effusions developed more commonly in patients with lymphocytosis.
  
  
  CONCLUSIONS
  Overall, lymphocytosis occurred and persisted in many dasatinib-treated patients in all phases of CML. Its presence was associated with higher response rates, significantly longer response durations, and increased overall survival, suggesting an immunomodulatory effect. Prospective studies are warranted to characterize the functional activity of these cells and to assess whether an immunologic effect against CML is detectable. Cancer 2016;122:1398-1407. © 2016 The Authors. Cancer published by Wiley Periodicals, Inc. on behalf of American Cancer Society.
authors.affiliation: Barbara Ann Karmanos Cancer Institute, Wayne State University, Detroit, Michigan.
authors.forename: Charles A
authors.initials: CA
authors.lastname: Schiffer
authors.affiliation: The University of Texas M.D. Anderson Cancer Center, Houston, Texas.
authors.forename: Jorge E
authors.initials: JE
authors.lastname: Cortes
authors.affiliation: Jena University Hospital, Jena, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Hochhaus
authors.affiliation: San Luigi Gonaga Hospital, University of Turin, Orbassano-Turin, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Saglio
authors.affiliation: Charite-Campus Virchow Clinic, Berlin Medical University, Berlin, Germany.
authors.forename: Philipp
authors.initials: P
authors.lastname: le Coutre
authors.affiliation: Department of Hematology and Hematology Research Unit, Helsinki University Central Hospital Comprehensive Cancer Center, University of Helsinki, Helsinki, Finland.
authors.forename: Kimmo
authors.initials: K
authors.lastname: Porkka
authors.affiliation: Department of Hematology and Hematology Research Unit, Helsinki University Central Hospital Comprehensive Cancer Center, University of Helsinki, Helsinki, Finland.
authors.forename: Satu
authors.initials: S
authors.lastname: Mustjoki
authors.affiliation: Bristol-Myers Squibb, Princeton, New Jersey.
authors.forename: Hesham
authors.initials: H
authors.lastname: Mohamed
authors.affiliation: University of California, San Francisco School of Medicine, San Francisco, California.
authors.forename: Neil P
authors.initials: NP
authors.lastname: Shah
mesh_terms: D000970:Antineoplastic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D017326:Clinical Trials, Phase III as Topic; D000069439:Dasatinib / Q000009:adverse effects*; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D000068877:Imatinib Mesylate / Q000627:therapeutic use; D015994:Incidence; D007694:Killer Cells, Natural; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy; D015465:Leukemia, Myeloid, Accelerated Phase / Q000188:drug therapy* / Q000401:mortality; D015466:Leukemia, Myeloid, Chronic-Phase / Q000188:drug therapy* / Q000401:mortality; D008218:Lymphocytosis / Q000139:chemically induced* / Q000453:epidemiology / Q000401:mortality; D008297:Male; D008875:Middle Aged; D010996:Pleural Effusion / Q000139:chemically induced; D047428:Protein Kinase Inhibitors / Q000009:adverse effects* / Q000627:therapeutic use; D016032:Randomized Controlled Trials as Topic; D012189:Retrospective Studies; D013602:T-Lymphocytes, Cytotoxic
chemical_list: D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; D000068877:Imatinib Mesylate; D000069439:Dasatinib
keywords: T-lymphocytes; chronic myeloid; dasatinib; killer cells; leukemia; lymphocytosis; natural