Relative increase in lymphocytes from as early as 1 month predicts improved response to dasatinib in chronic-phase chronic myelogenous leukemia

Abstract

Lymphocytosis in response to dasatinib for chronic myelogenous leukemia (CML) may be associated with favorable response. However, it occurs at varying times and in a limited subset of patients. To identify early clinical markers for favorable responses applicable to all patients with or without lymphocytosis, we prospectively analyzed lymphocyte profiles of 50 Japanese CML patients treated with dasatinib after intolerance/resistance to imatinib. Although absolute lymphocyte counts did not differ significantly until 3 months between patients with complete molecular response (CMR) at 12 months and those without it, relative increases in lymphocyte compared with baselines differed significantly from 1 month. Patients with relative lymphocyte counts >150 % at 1 month or >200 % at 3 months had higher CMR rates at 12 months than others (57.9 vs. 23.3 %, P = 0.015, and 76.5 vs. 16.1 %, P < 0.0001, respectively). A relative increase in lymphocyte subset of CD57(+)CD14(-), CD8(+)T, or NK cells >200 % at 1 month was also significantly associated with a higher CMR rate. There were significant negative correlations between relative lymphocyte increases and BCR/ABL transcript levels. CD57(+)CD14(-) cells were a highly specific focus of proliferation. Relative increases in lymphocyte count and its subsets from 1 month are reliable early markers of favorable responses to dasatinib.