title: 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.
authors.affiliation: Medizinische Klinik und Poliklinik I, University Hospital, Dresden, Germany.
authors.forename: Juliane
authors.initials: J
authors.lastname: Lenk
authors.forename: Martin
authors.initials: M
authors.lastname: Bornhauser
authors.forename: Michael
authors.initials: M
authors.lastname: Kramer
authors.forename: Kristina
authors.initials: K
authors.lastname: Hölig
authors.forename: Kirsten
authors.initials: K
authors.lastname: Poppe-Thiede
authors.forename: Helmuth
authors.initials: H
authors.lastname: Schmidt
authors.forename: Markus
authors.initials: M
authors.lastname: Wiesneth
authors.forename: Kerstin
authors.initials: K
authors.lastname: Schaefer-Eckart
authors.forename: Peter
authors.initials: P
authors.lastname: Schlenke
authors.forename: Michael
authors.initials: M
authors.lastname: Punzel
authors.forename: Sonja
authors.initials: S
authors.lastname: Martin
authors.forename: Frank
authors.initials: F
authors.lastname: Kroschinsky
authors.forename: Alexander H
authors.initials: AH
authors.lastname: Schmidt
authors.forename: Gerhard
authors.initials: G
authors.lastname: Ehninger
authors.forename: Christian
authors.initials: C
authors.lastname: Thiede
mesh_terms: D000293:Adolescent; D000328:Adult; D015992:Body Mass Index; D054377:Chemokine CXCL12 / Q000235:genetics* / Q000276:immunology; D005260:Female; D064368:Healthy Volunteers; D019650:Hematopoietic Stem Cell Mobilization / Q000379:methods*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D012737:Sex Factors; D014019:Tissue Donors; D055815:Young Adult
chemical_list: C515255:CXCL12 protein, human; D054377:Chemokine CXCL12
keywords: CD34+ mobilization; CXCL12; G-CSF; Healthy volunteer donors; Hematopoietic cell mobilization; Hematopoietic stem and progenitor cells