Plasma levels of SDF-1 and expression of SDF-1 receptor on CD34+ cells in mobilized peripheral blood of non-Hodgkin's lymphoma patients

CXCR4 is the receptor for the chemokine stromal derived factor-1 (SDF-1), is expressed on CD34(+) cells, and has been implicated in the process of CD34(+) cell migration and homing. We studied the mobilization of CD34/CXCR4 cells and the plasma levels of SDF-1 and flt3-ligand (fit3-L) in 36 non-Hodgkin's lymphoma patients receiving cyclophosphamide (Cy) plus G-CSF (arm A), Cy plus GMCSF (arm B), or Cy plus GM-CSF followed by G-CSF (arm C) for peripheral blood stem cell (PBSC) mobilization and autotransplantation, We observed lower plasma levels of SDF-1 in PBSCs compared to premobilization bone marrow samples. The mean plasma SDF-1 levels were similar in PBSC collections in the three alms of the study, Zn contrast, SDF-1 levels in the apheresis collections of the "good mobilizers" (patients who collected a minimum of 2 x 10(6) CD34(+) cells/kg in one to four PBSC collections) mere significantly lon er than the apheresis collections of the 'poor mobilizers" (greater than or equal to0.4 x 10(6) CD34(+) cells/kg in the first two PBSC collections; 288 +/- 82 pg/ml versus 583 +/- 217 pg/ml; p = 0.0009), The mean percentage of CD34(+) cells expressing CXCR4 in the apheresis collections was decreased in the PBSC collections compared with premobilization values from 28% to 19.4%. Furthermore, the percentage of CD34(+) cells expressing CXCR4 in the good mobilizers was significantly lower compared with the poor mobilizers (14.7 +/- 2.1% versus 33.6 +/- 2.1%; p = 0.002), The good mobilizers had also significantly lower levels of flt3-L compared with the poor mobilizers (34 +/- 3 pg/ml versus 106 +/- 11 pg/ml; p = 0.006), Finally, the levels of flt3-L strongly correlated with SDF-1 levels (r = 0.8; p < 0.0001), We conclude: A) low plasma levels of SDF-1 and low expression of CXCR4 characterize patients with good mobilization outcome, and B) the levels of SDF-1 correlate with flt3-L, suggesting an association of these cytokines in mobilization of CD34(+) cells.