Update on clinical experience with AMD3100, an SDF-1/CXCL12-CXCR4 inhibitor, in mobilization of hematopoietic stem and progenitor cells.
OBJECTIVE
Mobilized peripheral blood stem cells are increasingly used for the reconstitution of hematopoiesis in autologous and allogeneic transplants. New agents and approaches are emerging to improve mobilization efficacy while reducing duration and toxicity of mobilization. The purpose of this review is to overview clinical experience with AMD3100 (plerixafor) and its role in stem cell mobilization.


RESULTS
AMD3100 is a bicyclam molecule that selectively and reversibly antagonizes the binding of stromal cell-derived factor-1 (SDF-1) to its receptor CXC motif receptor-4 (CXCR4) with subsequent egress of hematopoietic stem cells to the peripheral blood. AMD3100 safely and rapidly mobilizes stem cells in patients with lymphoma, myeloma and healthy donors, and is synergistic in combination with granulocyte-colony stimulating factor. In addition, AMD3100 disrupts the interaction between mouse and human leukemic blasts and the bone marrow stroma, mobilizing blasts to the peripheral blood and sensitizing them to chemotherapy.


CONCLUSIONS
AMD3100 was recently FDA-approved for stem cell mobilization in combination with granulocyte-colony stimulating factor in patients with non-Hodgkin's lymphoma and multiple myeloma. Studies are underway testing AMD3100 as an adjunct to chemotherapy in patients with refractory acute myelogenous leukemia (and other hematologic malignancies), as a strategy to sensitize leukemic cells to chemotherapy and improve clinical outcomes.
Pusic
Iskra
I
Division of Oncology, Washington University School of Medicine, Siteman Cancer Center, St. Louis, MO 63110, USA.
DiPersio
John F
JF
D001596:Benzylamines; D054377:Chemokine CXCL12 / Q000037:antagonists & inhibitors; D002986:Clinical Trials as Topic; D000080027:Cyclams; D019650:Hematopoietic Stem Cell Mobilization / Q000379:methods*; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000187:drug effects*; D006571:Heterocyclic Compounds / Q000494:pharmacology*; D006801:Humans; D019718:Receptors, CXCR4 / Q000037:antagonists & inhibitors
D001596:Benzylamines; D054377:Chemokine CXCL12; D000080027:Cyclams; D006571:Heterocyclic Compounds; D019718:Receptors, CXCR4; C088327:plerixafor