Impact of constitutional polymorphisms in VCAM1 and CD44 on CD34(+) cell collection yield after administration of granulocyte colony-stimulating factor to healthy donors

Background The number of CD34(+) cells mobilized from bone marrow to peripheral blood after administration of granulocyte colony-stimulating factor varies greatly among healthy donors. This fact might be explained, at least in part, by constitutional differences in genes involved in the interactions tethering CD34(+) cells to the bone marrow. Design and Methods We analyzed genetic characteristics associated with CD34(+) cell mobilization in 112 healthy individuals receiving granulocyte colony-stimulating factor (filgrastim; 10 mu g/kg; 5 days). Results Genetic variants in VCAM1 and in CD44 were associated with the number of CD34(+) cells in peripheral blood after granulocyte colony-stimulating factor administration (P=0.02 and P=0.04, respectively), with the quantity of CD34+ cells x10(6)/kg of donor (4.6 versus 6.3; P<0.001 and 7 versus 5.6; P=0.025, respectively), and with total CD34(+) cells x10(6)(355 versus 495; P=0.002 and 522 versus 422; P=0.012, respectively) in the first apheresis. Of note, granulocyte colony-stimulating factor administration was associated with complete disappearance of VCAM1 mRNA expression in peripheral blood. Moreover, genetic variants in granulocyte colony-stimulating factor receptor (CSF3R) and in CXCL12 were associated with a lower and higher number of granulocyte colony-stimulating factor-mobilized CD34(+) cells/mu L in peripheral blood (81 versus 106; P=0.002 and 165 versus 98; P=0.02, respectively) and a genetic variant in CXCR4 was associated with a lower quantity of CD34(+) cells x10(6)/kg of donor and total CD34(+) cells x10(6) (5.3 versus 6.7; P=0.02 and 399 versus 533; P=0.01, respectively). Conclusions In conclusion, genetic variability in molecules involved in migration and homing of CD34(+). cells influences the degree of mobilization of these cells.