Plasmatic Levels of FLT-3 Ligand and SDF-1 and Expression of FLT-3 and CXCR4 in CD34+ Cells Population Prior and Post Mobilization of Peripheral Blood Stem Cell.

Introduction: Peripheral blood stem cells (PBSC) became the main source of cells for autologous and allogeneic marrow transplantation. FLT3L is capable to inducing multi-lineage hematopoietic cell differentiation in vivo and in vitro. It was postulated that an increase in FLT-3 levels correlated with a compensatory mechanism to boost the amount of PBSC. The stromal-derived- factor-1 (SDF-1) is a member of the family of α-chemokines that binds to the seven-span transmembrane G-protein-couple CXCR4. Mobilized human CD34+ progenitors cells express reduced levels of the SDF-1 receptor of CXCR4, which correlates with improved mobilization, suggesting the involvement of SDF-1/CXCR4 interactions in the trafficking of CD34+ cells from marrow to peripheral blood. Objective: To determine the behavior of the of FLT-3-L and SDF-1 plasma concentration, prior and post mobilization of PBSC. The cellular expression of the FLT-3 and CXCR4 in the CD34+ cell population in the bone marrow (BM) prior and post mobilization and in the apheresis product and to evaluate its association with the good and bad yield of CD34+cells.

Material and Methods: The plasma concentration of SDF-1 and FLT3-L was determined by ELISA, prior and after PBSC mobilization in 48 individuals, being 12 donors and 36 patients. The cellular expression of CXCR4 and FLT-3 in the CD34+ cell population, was estimated as the mean fluorescence intensity (MFI), in material of bone marrow (BM), prior and after mobilization and in the apheresis product. It was considered success of mobilization who had reached in the peripheral blood (PB), 15 or more CD34+cells and in the apheresis product ≥5x 10⁶/Kg CD34+cells.

Results: Considering globally the total of individuals, it was observed a plasma concentration variation of FLT3L and SDF-1, prior and post mobilization of PBSC (p=0.001 and 0,012, respectively), even this, did not have influenced the good yield of CD34+ cells. When evaluated the cellular expression of the CXCR4, it was observed variations in the BM, prior and post mobilization of PBSC, for the myeloma group (p<0.001), however when the total of individuals was considered, the behavior was different. There was a variation between the measures prior and post mobilization, only to the success mobilization group(p=0.036). For the FLT-3, we find variations between BM mobilized and not mobilized for all studied groups, however it did not have relation with the yield of CD34+ cells.

Conclusion: Although, FLT-3L and SDF-1 prior and post mobilization showed variations in the plasmatic concentration in this study, the only variable that had association with the good yield of CD34+ cells was the cellular expression of the CXCR4.