Sex and Body Mass Index but Not CXCL12 801 G/A Polymorphism Determine the Efficacy of Hematopoietic Cell Mobilization: A Study in Healthy Volunteer Donors

Abstract

Analyses of healthy donors of granulocyte colony-stimulating factor (G-CSF) mobilized hematopoietic stem and progenitor cells (HSPCs) and of patients undergoing autologous stem cell transplantation have suggested that individuals harboring the CXCL12-A allele mobilize a higher number of CD34 + HSPCs after G-CSF administration. We typed 463 healthy unrelated donors (376 men and 87 women) who had received daily subcutaneous injections at a mean dose of 7.36 ± 1.71 μg/kg G-CSF for 5 days for CXCL12 801 G/A using a real-time PCR assay. Interestingly, the median concentration of mobilized CD34 + cells on day 5 was almost identical in donors with the A-allele (79/μL; range, 11 to 249/μL) and the G/G-group (82/μL; range, 15 to 268/μL). In addition, the allelic distribution was not different in donors (n = 11) who mobilized less than 20/μL CD34 + cells. No difference in the overall yield of CD34 + cells in the apheresis product and in the number of CD34 + cells/kg recipient could be detected between both groups. In a multivariate regression model for the endpoint CD34 + cells/μL at day 5, only male sex (regression coefficient, 11.5; 95% confidence interval, 1.7 to 21.2, P = .021) and body mass index as continuous variables (regression coefficient, 3.5; 95% confidence interval, 2.5 to 4.5, P = .0001) but not age, smoking status, or CXCL12 allelic status represented independent variables. Our data derived from a large well-controlled cohort contradict previous analyses suggesting an association between CXCL12 allelic status and the yield of CD34 + HSPC after G-CSF mobilization. Concentration of CD34 + cells in the peripheral blood, the most objective parameter, could not be predicted by CXCL12 genotype.

Prediction of hematopoietic stem cell yield after mobilization with granulocyte–colony‐stimulating factor in healthy unrelated donors

“…Recently published data have focused on the impact of genetic polymorphisms on the mobilization process. Two different groups have reported an association of the CLCX12‐3′A allele with a better CD34+ mobilization, although these results could not be confirmed by our group in a larger cohort of donors . Other genetic polymorphisms with potential impact include VCAM‐1 and CD44 .…”

“…Two different groups have reported an association of the CLCX12-3 0 A allele with a better CD341 mobilization, 28,29 although these results could not be confirmed by our group in a larger cohort of donors. 30 Other genetic polymorphisms with potential impact include VCAM-1 and CD44. 31 Thus, greater effort to identify important genetic polymorphisms with functional or transcriptional activity is warranted.…”

Neonatal sex and weight influence CD34+ cell concentration in umbilical cord blood but not stromal cell–derived factor 1-3′A polymorphism

“…Indeed, an association between the SDF1-3 0 A allele and high levels of CD34 þ cell mobilization has been demonstrated in peripheral blood [22,24]. Recently, Lenk et al [25] reported no impact of SDF-1a 801G/A polymorphism on efficacy of HSC mobilization in the context of allogeneic healthy donors; their results are in line with our observation. However, the rate of UCB units released in our bank is approximately 10 units per year, and this did not allow us to perform an early study of engraftment kinetics of transplanted units provided from these 180 neonates evaluated by tetra-PCR.…”

Race and Ethnicity Influences Collection of Granulocyte Colony–Stimulating Factor–Mobilized Peripheral Blood Progenitor Cells from Unrelated Donors, a Center for International Blood and Marrow Transplant Research Analysis

“…21,22 A recent report, however, found no significant effect of SCF-1 polymorphism on the mobilization efficiency in 467 healthy volunteer donors. 23 Currently, there are no published systematic investigations of genetic differences of these molecules among ethnic lines and further research in this area is warranted.…”