In vivo effects of imatinib mesylate on human haematopoietic progenitor cells

Abstract

Imatinib mesylate has considerable antineoplastic activity in patients with chronic myeloid leukaemia (CML) and some solid tumours. Although originally regarded as nontoxic for normal haematopoiesis, mild to moderate myelosuppression is a commonly observed side-effect of this treatment. Recently, this molecule has been shown to suppress normal haematopoietic progenitor cells in vitro. This is the first study that has investigated the effect of imatinib on haematopoietic progenitor cells in vivo. We investigated the number of circulating haematopoietic progenitor cells in 79 patients with CML and five patients with solid tumours who were treated with imatinib for at least 3 months. Bone marrow progenitor cells were assessed in a subgroup of 18 patients with CML after 12 months of imatinib treatment. Results were compared with haematopoietic progenitor cell numbers of normal controls. Circulating progenitors of all classes were significantly decreased in CML up to 24 months of imatinib therapy compared with healthy controls (median progenitor cells in CML after 12 months: CFU-GM 62, range 0-2543; BFU-E 216, range 0-3259; CFU-GEMM 0, range 0-139; versus controls: CFU-GM 208, range 50-936; BFU-E 690, range 120-1862; CFU-GEMM 20, range 4-77; P < 0.001). Similar reductions in the number of progenitor cells derived from bone marrow were found in a subgroup of 18 patients with CML. In patients with solid tumours the number of circulating progenitor cells was significantly lower under treatment with imatinib when compared with the controls. Withdrawal of imatinib in a patient with a malignant brain tumour resulted in a prompt normalization of circulating progenitors. This study suggests that imatinib exerts myelosuppressive effects through inhibition of haematopoietic progenitor cells.