Kinetics of CXCR-4 and adhesion molecule expression during autologous stem cell mobilisation with G-CSF plus AMD3100 in patients with multiple myeloma.
AMD3100, a competitive antagonist of CXCR-4, disrupts the binding of its ligand, stromal cell-derived factor-1 (SDF-1), and facilitates stem cell mobilisation in patients with haematological malignancies. This study investigated the differential kinetics of CXCR-4 and adhesion molecule expression and their impact on stem cell yield during mobilisation with granulocyte-colony stimulating factor (G-CSF) (days 1-4) followed by AMD3100 in 10 patients with multiple myeloma. A four-colour flow cytometry-based determination of CXCR-4, VLA-4, L-selectin, PECAM, LFA-1 and CD44 expression on CD34+ cells and measurement of SDF-1 concentration were performed at different time points. After G-CSF alone, CXCR-4 expression on patients' blood and marrow CD34+ cells was significantly lower than in the healthy controls (p < 0.001), but allowed no prediction of stem cell yield. Except in the single poorly mobilising patient, AMD3100 led to a further significant decrease of CXCR4 (p = 0.001), which inversely correlated with the CD34+ counts in the blood (p = 0.005). SDF-1 level in patients' marrow was positively correlated with CXCR-4 expression on CD34+ cells (p = 0.011). It is interesting to note that the expression of adhesion molecules remained unaffected by AMD3100 administration. Further studies will define the possible prognostic role of AMD3100 mediated changes in CXCR-4 expression for the prediction of stem cell yield attainable with this new mobilisation regimen.
Oelschlaegel
Uta
U
Medical Clinic and Polyclinic I, University Hospital of the Technical University of Dresden, House 66, Fetscherstrasse 74, 01307 Dresden, Germany.
Bornhauser
Martin
M
Boxberger
Sabine
S
Kroschinsky
Frank
F
Illmer
Thomas
T
Hoelig
Kristina
K
Calandra
Gary
G
Ehninger
Gerhard
G
Platzbecker
Uwe
U
D001596:Benzylamines; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D000080027:Cyclams; D016179:Granulocyte Colony-Stimulating Factor / Q000378:metabolism / Q000494:pharmacology*; D019650:Hematopoietic Stem Cell Mobilization; D018380:Hematopoietic Stem Cell Transplantation; D006571:Heterocyclic Compounds / Q000378:metabolism / Q000494:pharmacology*; D006801:Humans; D007700:Kinetics; D009101:Multiple Myeloma / Q000378:metabolism / Q000628:therapy; D019718:Receptors, CXCR4 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D014182:Transplantation, Autologous
D001596:Benzylamines; D015815:Cell Adhesion Molecules; D000080027:Cyclams; D006571:Heterocyclic Compounds; D019718:Receptors, CXCR4; D016179:Granulocyte Colony-Stimulating Factor; C088327:plerixafor