Analysis of stem cell apheresis products using intermediate-dose filgrastim plus large volume apheresis for allogeneic transplantation

Abstract

Previously, a dose-dependent influence of recombinant human granulocyte colony-stimulating factor (rhG-CSF) on CD34+ mobilization was demonstrated. In this single-center prospective analysis, 52 healthy donors were investigated to determine the efficacy of intermediate-dose rhG-CSF 2x8 microg/kg donor body weight (bw) and intermediate large volume apheresis (LVA, median 12 l) to mobilize peripheral blood progenitor cells (PBPC) for allogeneic transplantation. The median number of CD34+ cells in apheresis products was 0.45% and 2.2x10(6)/kg recipient bw per single apheresis. A total of 5.4x10(6)/kg CD34+ cells were collected with two (range: one to three) LVA. In the analysis of donor subgroups, higher peripheral blood (PB) and apheresis results were obtained in male vs female donors; however, donor weight significantly differed in both groups. Heavier donors displayed higher PB and apheresis CD34+ counts; however, when CD34+ cells/kg were adjusted to a constant bw, similar harvest results were calculated in males and females, demonstrating that gender per se does not, whereas bw does affect apheresis results. Younger donors had significantly higher PB CD34+ counts, higher CD34+ numbers per single apheresis, increased CFU, more T, B, and CD61+, comparable NK, and less CD14+ cells. A correlation analysis of donor age and apheresis results displayed an age-related decline of 0.46x10(6)/kg CD34 cells per decade of donor aging. Cell subsets in apheresis products were CD14 (49%), CD3 (22%), CD4 (13%), CD8 (7%), CD61 (20%), CD19 (5%), and CD16/56+ (3%) cells, with increasing CD14+ cells and decreasing CD3, CD4, CD8, CD61, CD19, and CD16/56+ cells on subsequent days of apheresis. Compared to our previous analysis using high- (2x12 microg) and low-dose (1x10 microg) rhG-CSF for allogeneic PBPC mobilization, the intermediate-dose showed a similar CD34+ mobilization potential to 1x10 microg rhG-CSF; however, with use of LVA, two instead of three (p<0.05) aphereses were sufficient to mobilize > or =4x10(6)/kg bw CD34+ cells in most donors. Taken together, our results demonstrate that intermediate-dose rhG-CSF sufficiently mobilizes > or =4x10(6)/kg x bw CD34+ cells with use of LVA and that especially younger donors display increased CD34+ cell numbers.

Stem cell mobilization by G‐CSF in solid and hematological malignancies: Single daily dose is better than split dose in obese patients

“…Although several studies found no correlation between the number of CD34 + cells harvested and the age, gender, or body weight of the subjects [1,7,9,11], some reports showed that higher CD34 + cell numbers were collected particularly in male [4][5][6]12] and young allogeneic donors [4,5]. In autologous transplantation, there are additional factors affecting the yield.…”

“…Although most centers use once-daily G-CSF administration, some investigators have recommended a twice daily schedule [3]. Besides the dose and schedule of G-CSF, patient characteristics, disease status, and previous therapies of diseases seem to affect the PBSC mobilization [1,[4][5][6]. In this study, we have compared two different schedules of G-CSF for mobilization of PBSC including a single daily dose of 14 lg/kg/day and twice daily doses of 7 lg/kg/12 h in two patient population (according to body mass index) undergoing autologous hematopoietic stem cell transplantation.…”

Consensus statement from European experts on the diagnosis, management, and treatment of multiple myeloma: from standard therapy to novel approaches

“…However, the prolonged use of alkylating agents, dense BM infiltration, prior irradiation, advanced age, and elevated plasma viscosity are all factors which may impair stem cell procurement and subsequent engraftment [30][31][32]. Therefore, if ASCT is contemplated, prolonged alkylating agent exposure should be avoided [30].…”

CD34+ or CD34−: which is the more primitive?

“…5 Apart from cell surface markers for isolation of HSC, numerous other assays that measure the stem cell activity have been exploited. [6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23][24][25] Clonal analyses using limiting dilution assays in Dexter-like cultures have been used (quality analysis), however, these are time-consuming due to the number of flasks that have to be analyzed. 26,27 In the past, HSC have been characterized with respect to their ability to form spleen colonies in irradiated mice (CFU-S).…”