G-CSF versus GM-CSF for stimulation of peripheral blood progenitor cells (PBPC) and leukocytes in healthy volunteers: comparison of efficacy and tolerability

Abstract

This study compared two recombinant human (rh) hematopoietic growth factors in healthy volunteers for stem cell stimulation. Granulocyte colony-stimulating factor (G-CSF, n=9) or granulocyte-macrophage colony-stimulating factor (GM-CSF, n=8) was given subcutaneously for 5 days (5 microg/kg/day). Controls (n=5) received no growth factor. Laboratory parameters and side effects were monitored for 8 days. Within 24 h, both cytokines led to a rapid increase of leukocytes, the majority of which were granulocytes. Compared with the controls (n=5), the increase on day 5 in the G-CSF/GM-CSF groups was 37-/10-fold (CD34+ cells), 5.2-/2.4-fold (leukocytes), 7.2-/3.0-fold (granulocytes), 7.4-/4.4-fold (monocytes), 1.7-/1.1-fold (lymphocytes), 9.8-/2.7-fold (basophils), 2.3-/9.6-fold (eosinophils), and 1.9-/1.6-fold (reticulocytes). The mobilization of myeloblasts, promyelocytes, myelocytes, and metamyelocytes coincided with the pronounced increase of CD34 + PBPC observed on day 4. Serum levels of uric acid (UA) and lactic dehydrogenase (LDH) increased under G-CSF, and platelets decreased after G-CSF discontinuation. Rash at the injection site occurred in 50% of the GM-CSF-treated volunteers. Seven volunteers in the GM-CSF group and six in the G-CSF cohort complained of flu-like symptoms, including musculoskeletal pain. We conclude that, in terms of tolerance and mobilization of CD34+ cells and leukocytes, G-CSF is superior to GM-CSF, but higher levels of UA and LDH and late decrease in platelets make monitoring of these parameters necessary.

Reduced risk of acute GVHD following mobilization of HLA-identical sibling donors with GM-CSF alone

“…Our results, as well as those reported previously from other groups, demonstrate that GM-CSF used as a single agent is less effective than G-CSF for mobilization in normal donors. [16][17][18] Allografts mobilized by GM-CSF alone contained significantly fewer CD34 þ cells in comparison with G or G/GM and the donors required more LP procedures to obtain both the minimum and target CD34 þ cell doses. Further, several donors failed to reach a target of 5.0 Â 10 6 CD34 þ cells/kg and three of 31 (9.7%) mobilized less than 2.0 Â 10 6 CD34 þ cells/kg.…”

“…GM-CSF has been used previously to mobilize autologous PBPC either in combination with chemotherapy or as a single agent. [13][14][15][16] It is effective for these purposes, although does not appear to stimulate the mobilization of as many CD34 þ cells as G-CSF. Our results, as well as those reported previously from other groups, demonstrate that GM-CSF used as a single agent is less effective than G-CSF for mobilization in normal donors.…”

“…14,16,17 Of note, several studies have demonstrated wide differences in the profile of monocytes, lymphocytes, and dendritic cells mobilized by the two agents. 14,16,[18][19][20] Since these graft constituents are likely to exert an influence on the development of GVHD and graft-versus-malignancy effects, we sought to determine the clinical impact of donor PBPC mobilization regimens using GM-CSF alone or in combination with G-CSF. In this retrospective analysis of uniformly treated and supported patients, we found that the transplantation of PBPC from HLA identical sibling donors mobilized with GM-CSF alone was associated with similar engraftment kinetics compared to G-CSF alone, but lower rates of moderate to severe acute GVHD.…”

“…Granulocyte-macrophage colony stimulating factor (GM-CSF; sargramostim) given singly or combined with G-CSF has been effective in mobilizing sufficient autologous CD34 þ cells to support prompt hematopoietic recovery following high-dose therapy. [13][14][15][16] However, it appears that as a single agent, G-CSF is more effective than GM-CSF in mobilizing CD34 þ cells. 14,16,17 Of note, several studies have demonstrated wide differences in the profile of monocytes, lymphocytes, and dendritic cells mobilized by the two agents.…”

“…[13][14][15][16] However, it appears that as a single agent, G-CSF is more effective than GM-CSF in mobilizing CD34 þ cells. 14,16,17 Of note, several studies have demonstrated wide differences in the profile of monocytes, lymphocytes, and dendritic cells mobilized by the two agents. 14,16,[18][19][20] Since these graft constituents are likely to exert an influence on the development of GVHD and graft-versus-malignancy effects, we sought to determine the clinical impact of donor PBPC mobilization regimens using GM-CSF alone or in combination with G-CSF.…”