title: Rapid and sustained increase of large granular lymphocytes and rare cytomegalovirus reactivation during dasatinib treatment in chronic myelogenous leukemia patients.
abstract: We retrospectively investigated increases in large granular lymphocytes (LGL) in peripheral blood during dasatinib treatment in 25 chronic myelogenous leukemia patients. Fifteen of 25 patients (60 %) showed an increase in LGL. All 15 of these patients also showed an increase in NK cells, and 11 showed an increase in CD8(+) T cells. High frequencies of clonal rearrangements of TCR-β, -γ, and -δ genes were observed in LGL (+) patients, and at lower frequencies in LGL (-) patients as well. Clinical responses were favorable for all. With respect to their newly obtained complete molecular response after dasatinib treatment, LGL (+) patients showed higher response rates than did LGL (-) patients. In contrast, pleural effusions were more commonly observed in LGL (+) patients (60 %) than in LGL (-) patients (20 %). LGL counts significantly increased at 2 h after oral intake of dasatinib in all 25 patients. This was not observed in treatment with imatinib or nilotinib. Cytomegalovirus (CMV) C7-HRP tests were negative in all patients. Serum CMV-IgM antibodies were positive in only 2 of 25 patients without symptom of infection. Thus, LGL lymphocytosis during dasatinib treatment may be correlated with favorable molecular response, and with increased incidence of pleural effusions. In the clinical setting, CMV reactivation appears uncommon.
authors: Department of Hematology, Hiroshima City Asa Hospital, 2-1-1 Kabeminami, Asakita-ku, Hiroshima 731-0293, Japan. hd-tanaka@asa-hosp.city.hiroshima.jp
authors: Hideo
authors: H
authors: Tanaka
authors: Shizuka
authors: S
authors: Nakashima
authors: Miyuki
authors: M
authors: Usuda
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D003587:Cytomegalovirus / Q000276:immunology*; D000069439:Dasatinib; D005260:Female; D015329:Gene Rearrangement, T-Lymphocyte; D006801:Humans; D016130:Immunophenotyping; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy / Q000276:immunology* / Q000821:virology*; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000378:metabolism; D018655:Lymphocyte Count; D008214:Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D016066:Pleural Effusion, Malignant / Q000209:etiology; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D011743:Pyrimidines / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D011948:Receptors, Antigen, T-Cell / Q000235:genetics; D013844:Thiazoles / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D016896:Treatment Outcome; D014775:Virus Activation / Q000276:immunology*; D055815:Young Adult
chemical_list: D000970:Antineoplastic Agents; D007166:Immunosuppressive Agents; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D011948:Receptors, Antigen, T-Cell; D013844:Thiazoles; D000069439:Dasatinib