Plerixafor: a peripheral blood stem cell mobilizer

Abstract

Autologous hematopoietic stem cell (HSC) transplantation is a treatment strategy for restoring normal hematopoietic function in patients with select hematologic malignancies. The number of CD34(+) cells available for transplantation has been reported to be the strongest predictor of transplantation success, as measured by rapid and durable hematopoietic recovery. Currently, granulocyte colony-stimulating factor (G-CSF) alone or G-CSF plus chemotherapy are the most commonly used methods for stem cell mobilization. Unfortunately, 5-30% of patients do not respond to these agents. Plerixafor is a new HSC mobilizing drug that antagonizes the binding of chemokine stromal-cell-derived factor-1alpha (SDF-1alpha) to CXC chemokine receptor 4 (CXCR4). It is indicated in combination with G-CSF to mobilize HSC to the peripheral blood for collection and subsequent autologous transplantation in patients with non-Hodgkin's lymphoma (NHL) and multiple myeloma (MM). Results of clinical trials have shown that plerixafor plus G-CSF allow for the collection of a high yield of HSC with fewer apheresis sessions in patients with NHL and MM. Plerixafor has also shown promising results in small studies enrolling patients with Hodgkin's lymphoma. Moreover, for patients who fail G-CSF mobilization alone, plerixafor with G-CSF may be useful as a salvage mobilization strategy. Overall, plerixafor has been generally well tolerated with adverse effects classified as mild to moderate. The most common adverse effects reported in randomized clinical trials were injection site reactions and diarrhea, with approximately 33% of patients experiencing these effects. To our knowledge, clinical trials comparing G-CSF plus plerixafor with G-CSF plus chemotherapy and cost-effectiveness analyses have not been published; therefore, questions remain regarding the optimal role of plerixafor in the clinical practice setting.