Optimizing stem cell collection through CXCR4 antagonists.
Currently, nearly all the autologous stem cell transplantation and majority of allogeneic stem cell transplantation are performed using circulating peripheral blood stem cells. At steady conditions, less than 0.05 percent of the peripheral white cells are believed to be CD34+, a surrogate marker for stem cells. The content of hematopoietic CD34+ cells in the blood can be increased dramatically following recovery from myelosuppressive chemotherapy and/or the administration of hematopoietic growth factors (GM-CS or G-CSF), and an engrafting dose of stem cells can be collected by large volume apheresis following hematopoietic cytokine treatment. However these strategies fail to result in an adequate number of hematopoietic cells in 5-30 percent of the cases, limiting the ability of patients to receive high dose chemotherapy and stem cell transplantation in the treatment of their cancer. Plerixafor, a CXCR4 antagonist has been found to be a potent stem cell mobilizer and it's superiority used in combination with G-CSF over G-CSF alone has been seen in non-Hodgkin's lymphoma and multiple myeloma in double blind randomized phase III clinical trials, leading to FDA (Food and Drug Administration) approval. This review article describes the development of plerixafor to mobilize stem cells and optimal strategies for stem cell collection from peripheral blood.
Winship Cancer Institute, Emory University, Atlanta, GA, USA. hmahase@emory.edu
Hemchandra
H
Mahaseth
Jonathan
J
Kaufman
D000818:Animals; D001596:Benzylamines; D017326:Clinical Trials, Phase III as Topic; D000080027:Cyclams; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage; D019650:Hematopoietic Stem Cell Mobilization / Q000379:methods* / Q000592:standards; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods; D006412:Hematopoietic Stem Cells / Q000166:cytology; D006571:Heterocyclic Compounds / Q000008:administration & dosage*; D006801:Humans; D008228:Lymphoma, Non-Hodgkin / Q000097:blood / Q000628:therapy; D009101:Multiple Myeloma / Q000097:blood / Q000628:therapy; D016032:Randomized Controlled Trials as Topic; D019718:Receptors, CXCR4 / Q000037:antagonists & inhibitors*
D001596:Benzylamines; D000080027:Cyclams; D006571:Heterocyclic Compounds; D019718:Receptors, CXCR4; D016179:Granulocyte Colony-Stimulating Factor; C088327:plerixafor