Thrombopoietin Levels During Tyrosine Kinase Inhibitor Therapy for Chronic Myeloid Leukemia.

Abstract

Although it is well known that platelet depletion is one of the major adverse events related to tyrosine kinase inhibitor (TKI) therapy, the effect of TKIs on thrombopoietin (TPO), a stimulating factor for thrombopoiesis, has not been examined to date. In this study, we investigated the effect of TKIs on the levels of plasma TPO concentration in patients with well-controlled chronic myeloid leukemia receiving imatinib or dasatinib and those in treatment-free remission (TFR). Blood samples for blood cell counts and plasma TPO levels were obtained from 23 dasatinib-treated patients before and 1 h after intake, 11 patients treated with imatinib before and 2h after intake, and nine TFR patients. Levels of plasma TPO were determined by using enzyme-linked immunosorbent assays. Levels of TPO were significantly inversely correlated with platelet counts in the entire cohort (r = - 0.568, p < 0.0001). Dasatinib intake, but not imatinib, significantly reduced platelet counts after intake (p = 0.0009 in dasatinib and p = 0.5431 in imatinib). However, imatinib and dasatinib intake increased the levels of TPO in these patients (p = 0.0024, dasatinib; p = 0.0098, imatinib). Our study results suggest that neither dasatinib nor imatinib therapy inhibits TPO production. Rather, transient increases in TPO levels seen with these two treatments might be a result of the decrease in TPO clearance these TKIs confer. However, further investigations are required to clarify the effect of TKIs on thrombopoiesis.