rhG-CSF in Healthy Donors: Mobilization of Peripheral Hemopoietic Progenitors and Effect on Peripheral Blood Leukocytes

Abstract

Recombinant human granulocyte colony-stimulating factor (rhG-CSF) 16 micrograms/kg/day was given to 9 healthy donors to recruit hemopoietic progenitors (HP) for allogeneic transplantation or donor leukocyte infusion. rhG-CSF was administered s.c. for 5 days. No side effects were encountered except for moderate bone pain and lumbago. Mobilization was effective, reaching a peak median value of 187 x 10(3) CD34+ cells/ml (range 51.2-1127) and 2170 x 10(3) colony-forming units-granulocyte macrophage (CFU-GM)/ml (range 1138-4190). Peak values were obtained at a median of 4 days of rhG-CSF and represented, respectively, a 13-fold and a 37-fold increase from baseline values (p = 0.0007 and p = 0.006). White blood cell (WBC) counts increased 6-fold from baseline values (p < 0.0007) and reached a median peak of 34 x 10(6)/ml (23.5-59). Polymorphonuclear (PMN), and mononuclear (MNC) cells increased 10-fold and 2-fold, respectively (p = 0.0039 and p = 0.0026) and reached a median peak of 32.1 x 10(6)/ml (18.2-52) and 4.42 x 10(6)/ml (3.14-12.42). Absolute lymphocyte and monocyte counts increased at peak day in all donors 1.5-fold and 5.7-fold from baseline values (p = 0.0017 and p = 0.0018). In 7 of 9 donors, lymphocyte subsets were analyzed in detail. CD3+ and CD19+ lymphocytes increased 1.5-fold and 3-fold, respectively (p = 0.032 for both). NK and activated T lymphocytes doubled at a median of 4 days of rhG-CSF (p = 0.032 and p = NS, respectively). Similar changes were observed in lymphocytes collected in leukapheresis product. T helper and T suppressor subsets displayed a similar increase. Thus, besides the anticipated priming effect on HP and PMN, rhG-CSF in healthy donors produced an unexpected and still unexplained modification of lymphocyte subsets in peripheral blood.

Granulocyte colony-stimulating factor (G-CSF) transiently suppresses mitogen-stimulated T-cell proliferative response

“…As expected, G-CSF administered to our patients was associated with a large increase on absolute number of leucocytes and neutrophils from peripheral blood (Sica et al, 1996). As previously described, we observed a rise in monocyte counts induced by G-CSF (Hartung et al, 1995;Pollmacher et al, 1996;Sica et al, 1996).…”

“…As expected, G-CSF administered to our patients was associated with a large increase on absolute number of leucocytes and neutrophils from peripheral blood (Sica et al, 1996). As previously described, we observed a rise in monocyte counts induced by G-CSF (Hartung et al, 1995;Pollmacher et al, 1996;Sica et al, 1996). Although it has been reported that lymphocyte production in humans and mice is not affected by G-CSF (Bronchud et al, 1987;Pollmacher et al, 1996), we have observed that G-CSF induces a significant increase in peripheral blood lymphocyte counts.…”

“…However, several findings indicate that the immunological variations were due to G-CSF treatment (Sica et al, 1996). Before G-CSF treatment, the phenotypical and functional analysis of PBMC from the patients did not show substantial differences with respect to those found in healthy controls.…”

rhG-CSF does not affect the phenotype of adult donor peripheral blood NK cells

“…20,22,23 There are contradictory reports on changes in the absolute numbers of NK cells and their proportion within total lymphocytes, following rhG-CSF administration. 20,22,23,[29][30][31][32][33] Functional assays produced equally contradictory results, 31,[33][34][35][36][37][38] although in most instances impaired natural cytotoxic activity against NK-sensitive cell lines was evidenced after rhG-CSF treatment. Two studies reported a decreased expression of proinflammatory cytokines such as IFN-g, IL-2 and TNF-a 31,39 after rhG-CSF mobilization; interestingly, they observed no change in perforin, Fas and Fasligand expression on allogeneic NK cells, a result consistent with our observations.…”

Mirimostim (macrophage colony‐stimulating factor; M‐CSF) improves chemotherapy‐induced impaired natural killer cell activity, Th1/Th2 balance, and granulocyte function

“…32) In a trial involving the administration of M-CSF to ovarian cancer patients for 5 days from day 14 after chemotherapy, Suzuki et al observed improved NK cell activity during the administration of M-CSF, 33) which agrees with the results of the present study. Although the administration of G-CSF to healthy individuals to recruit hemopoietic progenitors for allogeneic transplantation or donor leukocyte infusion has been reported to increase leukocyte and peripheral blood NK cell counts markedly, 34,35) those studies did not confirm that the effect of G-CSF on the percentage of NK cells was independent of the increase in the leukocyte count. A G-CSF-induced decrease in NK cell activity has also been reported, 2,3) but in our study, no significant decrease in NK cell activity occurred after the use of G-CSF.…”