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 2h 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.