title: The CXCR4 and adhesion molecule expression of CD34+ hematopoietic cells mobilized by "on-demand" addition of plerixafor to granulocyte-colony-stimulating factor.
abstract: BACKGROUND
  Granulocyte-colony-stimulating factor (G-CSF) is routinely used for mobilization of hematopoietic stem and progenitor cells preceding autologous transplantation after high-dose chemotherapy in hematologic malignancies. However, due to high mobilization failure rates, alternative mobilization strategies are required.
  
  
  METHODS
  Patients who poorly mobilized CD34+ hematopoietic cells (HCs) with G-CSF additionally received the CXCR4 antagonist plerixafor. The phenotype of CD34+ HCs collected after this plerixafor-induced "rescue" mobilization, in regard to adhesion molecule and CD133, CD34, and CD38 expression in comparison to CD34+ HCs collected after traditional G-CSF administration in good mobilizers, was analyzed flow cytometrically. To confirm previous studies in our patient cohort, the efficiency of mobilization and subsequent engraftment after this "on-demand" plerixafor mobilization were analyzed.
  
  
  RESULTS
  Pronounced mobilization occurred after plerixafor administration in poor mobilizers, resulting in similar CD34+ cell yields as obtained by G-CSF in good mobilizers, whereby plerixafor increased the content of primitive CD133+/CD34+/CD38- cells. The surface expression profiles of the marrow homing and retention receptors CXCR4, VLA-4, LFA-1, and CD44 on mobilized CD34+ cells and hematopoietic recovery after transplantation were similar in patients receiving G-CSF plus plerixafor or G-CSF. Unexpectedly, the expression levels of respective adhesion receptors were not related to mobilization efficiency or engraftment.
  
  
  CONCLUSIONS
  The results show that CD34+ HCs collected by plerixafor-induced rescue mobilization are qualitatively equivalent to CD34+ HCs collected after traditional G-CSF mobilization in good mobilizers, in regard to their adhesive phenotype and engraftment potential. Thereby, plerixafor facilitates the treatment of poor mobilizers with autologous HC transplantation after high-dose chemotherapy.
authors.affiliation: Laboratory for Immunological and Molecular Cancer Research, Third Medical Department with Hematology, Medical Oncology, Hemostaseology, Rheumatology and Infectiology, Paracelsus Medical University, Salzburg, Austria.
authors.forename: Tamara
authors.initials: T
authors.lastname: Girbl
authors.forename: Verena
authors.initials: V
authors.lastname: Lunzer
authors.forename: Richard
authors.initials: R
authors.lastname: Greil
authors.forename: Konrad
authors.initials: K
authors.lastname: Namberger
authors.forename: Tanja Nicole
authors.initials: TN
authors.lastname: Hartmann
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D018952:Antigens, CD34 / Q000378:metabolism*; D001596:Benzylamines; D000080027:Cyclams; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology*; D019650:Hematopoietic Stem Cell Mobilization; D006412:Hematopoietic Stem Cells / Q000187:drug effects / Q000378:metabolism; D006571:Heterocyclic Compounds / Q000494:pharmacology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D019718:Receptors, CXCR4 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D055815:Young Adult
chemical_list: D018952:Antigens, CD34; D001596:Benzylamines; D000080027:Cyclams; D006571:Heterocyclic Compounds; D019718:Receptors, CXCR4; D016179:Granulocyte Colony-Stimulating Factor; C088327:plerixafor