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Plasma Levels of SDF-1 and Expression of SDF-1 Receptor on CD34⁺ Cells in Mobilized Peripheral Blood of Non-Hodgkin's Lymphoma Patients

University of Texas Health Science Center, San Antonio, Texas, USA

Key Words. Mobilization • CD34⁺ • CXCR4 • SDF-1

Yair Gazitt, Ph.D., Department of Medicine/Hematology, University of Texas Health Science Center, 7703 Floyd Curl Drive, San Antonio, Texas 78284, USA. Telephone: 210-567-4848; Fax: 210-567-1956; e-mail: gazitt{at}uthscsa.edu

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 (flt3-L) in 36 non-Hodgkin's lymphoma patients receiving cyclophosphamide (Cy) plus G-CSF (arm A), Cy plus GM-CSF (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 arms of the study. In contrast, SDF-1 levels in the apheresis collections of the "good mobilizers" (patients who collected a minimum of 2 x 10⁶ CD34⁺ cells/kg in one to four PBSC collections) were significantly lower than the apheresis collections of the "poor mobilizers" (0.4 x 10⁶ 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 ± 4 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.

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