Innovative strategies for PBPC mobilization.
Stem cell transplantation, whether autologous or allogeneic, improves the outcome of patients with a number of hematologic malignancies or solid tumors. A relevant proportion of these patients are excluded from this treatment because sufficient numbers of hematopoietic stem cells cannot be obtained by standard cytokine-assisted mobilization. In this article we review the physiology of peripheral blood progenitor cell (PBPC) mobilization and discuss the role of adhesion molecules, such as integrins and selectins, chemokines and their ligands, such as SDF-1alpha and CXCR4, and proteolytic enzymes. Based on this knowledge, several innovative pharmacologic approaches have been proposed to boost the stem cell harvest. Some of them (CTCE, C3a receptor agonist and GrobetaT) are still subject of pre-clinical development, others, such as chemokine receptor ligand AMD3100, have recently been introduced in clinical trials and already deliver promising results. It appears possible to harvest PBPC successfully in poor mobilizers and to cut down the number of collections required in the remaining PBPC donors.
Fruehauf
S
S
Department of Internal Medicine V, University of Heidelberg, Im Neuenheimer Feld 410, 69120 Heidelberg, Germany.
Seeger
T
T
Topaly
J
J
D019380:Anti-HIV Agents / Q000494:pharmacology; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001559:Benzhydryl Compounds / Q000494:pharmacology; D001596:Benzylamines; D015815:Cell Adhesion Molecules / Q000378:metabolism; D054377:Chemokine CXCL12; D054426:Chemokine CXCL2; D019743:Chemokines, CXC / Q000378:metabolism / Q000494:pharmacology; D000080027:Cyclams; D019650:Hematopoietic Stem Cell Mobilization; D006412:Hematopoietic Stem Cells / Q000187:drug effects / Q000502:physiology; D006571:Heterocyclic Compounds / Q000494:pharmacology; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000494:pharmacology; D008024:Ligands; D018448:Models, Immunological; D036102:Peripheral Blood Stem Cell Transplantation; D019718:Receptors, CXCR4 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D014182:Transplantation, Autologous; D014184:Transplantation, Homologous
D019380:Anti-HIV Agents; D001559:Benzhydryl Compounds; D001596:Benzylamines; C500221:CTCE-0021; C515255:CXCL12 protein, human; C499706:CXCL2 protein, human; D015815:Cell Adhesion Molecules; D054377:Chemokine CXCL12; D054426:Chemokine CXCL2; D019743:Chemokines, CXC; D000080027:Cyclams; D006571:Heterocyclic Compounds; D036341:Intercellular Signaling Peptides and Proteins; D008024:Ligands; D019718:Receptors, CXCR4; C431907:SB 290157; D001120:Arginine; C088327:plerixafor