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PubMed1994

The efficacy of recombinant human granulocyte colony-stimulating factor and recombinant human granulocyte macrophage colony-stimulating factor in permitting the administration of higher doses of cyclophosphamide in a doxorubicin-cyclophosphamide combination. An NSABP pilot study in patients with metastatic or high-risk primary breast cancer. National Surgical Adjuvant Breast and Bowel Project.

Colony-stimulating factors (CSFs) shorten the duration of myelosuppression following chemotherapy and, thus, allow the administration of higher doses. This study evaluates the efficacy of granulocyte macrophage colony-stimulating factor (GM-CSF) and granulocyte colony-stimulating factor (G-CSF) in allowing administration of high-dose cyclophosphamide in combination with doxorubicin. Ninety women with metastatic, locally advanced, or high-risk (> or = 10 positive nodes) breast cancer and no prior anthracycline treatment were given doxorubicin (60 mg/m2) with progressively increased doses of cyclophosphamide (1,200 mg/m2, 1,800 mg/m2, and 2,400 mg/m2). The first 60 patients received GM-CSF; the remaining 30, G-CSF. The maximum tolerated dose was not reached with 2,400 mg/m2 of cyclophosphamide. When compared to GM-CSF, G-CSF significantly reduced the duration of granulocytopenia (P < .001). No differences in duration of thrombocytopenia were noted. The results were not sufficiently consistent to indicate a trend toward reduction in rates of febrile neutropenia with one CSF versus the other. However, patients who received G-CSF were hospitalized less frequently than those receiving GM-CSF. With CSFs, high-dose cyclophosphamide in combination with doxorubicin can be safely administered on an outpatient basis. A shorter duration of granulocytopenia resulted from the use of G-CSF than from GM-CSF.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1997

Effects of granulocyte colony-stimulating factor and granulocyte-macrophage colony-stimulating factor on the bactericidal functions of neutrophils.

The hematopoietic growth factors granulocyte colony-stimulating factor (G-CSF) and granulocyte-macrophage colony-stimulating factor (GM-CSF) not only regulate the numbers of circulating neutrophils but also modulate the function of mature cells. Additionally, newly developed neutrophils subsequently released from the bone marrow in response to colony-stimulating factors (CSFs) also have enhanced function. A variety of different functions are affected, including changes in adherence, movement, phagocytosis, priming and stimulation of the respiratory burst, secretion, and degranulation. These effects also can cause increased microbicidal capacity in vitro, ex vivo, and in vivo. Both G-CSF and GM-CSF have such effects on neutrophil function, but there are differences that may result in precise modulation of the immune responses and may have implications for choice of agents for immune-based therapy for different conditions.

Blood Bactericidal Activity↗
PubMed1997

Safety of concomitant use of granulocyte colony-stimulating factor or granulocyte-macrophage colony-stimulating factor with cytotoxic chemotherapy agents.

Most studies that use recombinant granulocytopoietic cytokines, such as granulocyte colony-stimulating factor (G-CSF) and granulocyte-macrophage colony-stimulating factor (GM-CSF), with the intent of attenuating neutropenia generally have delayed the administration of the cytokine until 24 to 72 hours following completion of chemotherapy. This practice was initiated out of theoretic concern that colony-stimulating factor administration may cycle and differentiate a population of normal cells, thus increasing their susceptibility to cycle-specific antineoplastic agents. The theory, in fact, has been substantiated by evidence from several clinical trials of concurrent administration. Thus, simultaneous administration of chemotherapy and G-CSF or GM-CSF should be limited to investigational protocols with scientific objectives, such as cycle compression or malignant cell sensitization.

Animals↗
PubMed2000

Granulocyte colony-stimulating factor versus granulocyte-macrophage colony-stimulating factor for collection of peripheral blood progenitor cells from healthy donors.

The harvesting of peripheral blood progenitor cells (PBPCs) after granulocyte colony-stimulating factor or granulocyte-macrophage colony-stimulating factor stimulation instead of bone marrow in healthy donors has become increasingly popular. Donors, given the choice between bone marrow and PBPC donation, often prefer cytapheresis because of the easier access, no necessity for general anesthesia, and no multiple bone marrow punctures. In addition, accelerated engraftment and immunomodulation by granulocyte colony-stimulating factor-mobilized PBPCs are advantageous for the recipient. However, because of donor inconvenience and poor mobilization, there is a need to develop improved procedures. Aspects such as durability of hematopoietic engraftment, characterization of the earliest stem cell, and composition of PBPCs are not yet well defined, and international donor registration and follow-up must be considered when evaluating long-term safety profiles in healthy donors. This review concentrates on the most significant developments on mobilization of PBPCs published during the past year.

Consumer Product Safety↗
PubMed1999

Comparative effects of three cytokine regimens after high-dose cyclophosphamide: granulocyte colony-stimulating factor, granulocyte-macrophage colony-stimulating factor (GM-CSF), and sequential interleukin-3 and GM-CSF.

PURPOSE: To compare the toxicity and effects on hematologic recovery and circulating progenitor cell mobilization of three cytokine regimens administered after high-dose cyclophosphamide (HD-CTX; 6 g/m(2)), given as the first step of a high-dose sequential chemotherapy. PATIENTS AND METHODS: Forty-eight patients with breast cancer or non-Hodgkin's lymphoma were randomized to receive granulocyte colony-stimulating factor (G-CSF) alone (arm 1), granulocyte-macrophage colony-stimulating factor (GM-CSF) alone (arm 2), or sequential interleukin-3 (IL-3) and GM-CSF (arm 3). Cytokines were administered as a single daily subcutaneous injection at a dose of 5 to 6 microg/kg/d. Progenitor cells were evaluated in peripheral blood as well as in apheretic product as both CD34(+) cells and granulocyte-macrophage colony-forming units (CFU-GM). RESULTS: Neutrophil recovery was faster in arm 1 as compared with arms 2 and 3 (P <.0001); no significant differences were observed between arms 2 and 3. In arm 3, a moderate acceleration of platelet recovery was observed, but it was statistically significant only as compared with arm 1 (P =.028). The peak of CD34(+) cells was hastened in a median of 2 days in arm 1 compared with arms 2 and 3 (P =.0002), whereas the median peak value of CD34(+) cells and CFU-GM was similar in the three patient groups. Administration of IL-3 and GM-CSF resulted in more significant toxicity requiring pharmacologic treatment in 90% of patients. CONCLUSION: The three cytokine regimens administered after HD-CTX are comparably effective in reducing hematologic toxicity and mobilizing the hematopoietic progenitor cells. G-CSF accelerates leukocyte recovery and progenitor mobilization. Although G-CSF-treated patients have somewhat slower platelet recovery, they definitely have fewer side effects.

Adult↗
PubMed2000

Randomized cross-over trial of progenitor-cell mobilization: high-dose cyclophosphamide plus granulocyte colony-stimulating factor (G-CSF) versus granulocyte-macrophage colony-stimulating factor plus G-CSF.

PURPOSE: Patient response to hematopoietic progenitor-cell mobilizing regimens seems to vary considerably, making comparison between regimens difficult. To eliminate this inter-patient variability, we designed a cross-over trial and prospectively compared the number of progenitors mobilized into blood after granulocyte-macrophage colony-stimulating factor (GM-CSF) days 1 to 12 plus granulocyte colony-stimulating factor (G-CSF) days 7 to 12 (regimen G) with the number of progenitors after cyclophosphamide plus G-CSF days 3 to 14 (regimen C) in the same patient. PATIENTS AND METHODS: Twenty-nine patients were randomized to receive either regimen G or C first (G1 and C1, respectively) and underwent two leukaphereses. After a washout period, patients were then crossed over to the alternate regimen (C2 and G2, respectively) and underwent two additional leukaphereses. The hematopoietic progenitor-cell content of each collection was determined. In addition, toxicity and charges were tracked. RESULTS: Regimen C (n = 50) resulted in mobilization of more CD34(+) cells (2.7-fold/kg/apheresis), erythroid burst-forming units (1.8-fold/kg/apheresis), and colony-forming units-granulocyte-macrophage (2.2-fold/kg/apheresis) compared with regimen G given to the same patients (n = 46; paired t test, P<.01 for all comparisons). Compared with regimen G, regimen C resulted in better mobilization, whether it was given first (P =.025) or second (P =.02). The ability to achieve a target collection of > or =2x10(6) CD34(+) cells/kg using two leukaphereses was 50% after G1 and 90% after C1. Three of the seven patients in whom mobilization was poor after G1 had > or =2x10(6) CD34(+) cells/kg with two leukaphereses after C2. In contrast, when regimen G was given second (G2), seven out of 10 patients failed to achieve the target CD34(+) cell dose despite adequate collections after C1. Thirty percent of the patients (nine of 29) given regimen C were admitted to the hospital because of neutropenic fever for a median duration of 4 days (range, 2 to 10 days). The higher cost of regimen C was balanced by higher CD34(+) cell yield, resulting in equivalent charges based on cost per CD34(+) cell collected. CONCLUSION: We report the first clinical trial that used a cross-over design showing that high-dose cyclophosphamide plus G-CSF results in mobilization of more progenitors then GM-CSF plus G-CSF when tested in the same patient regardless of sequence of administration, although the regimen is associated with greater morbidity. Patients who fail to achieve adequate mobilization after regimen G can be treated with regimen C as an effective salvage regimen, whereas patients who fail regimen C are unlikely to benefit from subsequent treatment with regimen G. The cross-over design allowed detection of significant differences between regimens in a small cohort of patients and should be considered in design of future comparisons of mobilization regimens.

Adolescent↗
PubMed2005

Granulocyte colony-stimulating factor and granulocyte-macrophage colony-stimulating factor have differential effects on neonatal and adult neutrophil survival and function.

Neutropenia is a common sequela of neonatal sepsis. Recent clinical trials have shown the beneficial effects of colony-stimulating factors (CSFs) on outcome in this group, but the exact mechanism remains unknown. Neonates and mothers who were at high-risk for infection were recruited for cord blood sampling in a university tertiary referral maternity hospital. Neonatal and adult neutrophils were evaluated for their ability to combat bacterial infection by examining their functional activity (CD11b and reactive oxygen intermediates) and their persistence at inflammatory sites (apoptosis). The mechanism for altered apoptotic responses was assessed by caspase activation assays, X chromosome-linked inhibitor of apoptosis protein expression, and cytosolic cytochrome c release. Although granulocyte colony-stimulating factor (G-CSF) and granulocyte-macrophage colony-stimulating factor (GM-CSF) significantly delayed neutrophil apoptosis in normal adults, only G-CSF had a similar effect in normal neonates. Neutrophils from neonates who are at high risk for infection are unresponsive to the antiapoptotic effects of G-CSF or GM-CSF, unlike maternal neutrophils, which have delayed apoptosis in response to GM-CSF. However, CD11b expression and reactive oxygen intermediate production were significantly increased in normal neonatal neutrophils that were incubated with GM-CSF versus controls but not G-CSF or lipopolysaccharide. Decreased cytosolic cytochrome c release and caspases 3 and 9 activity are associated with the CSF-mediated delay in apoptosis in adults but not in newborns. The antiapoptotic X chromosome-linked inhibitor of apoptosis protein is up-regulated in neonates compared with adults and may mediate their differential spontaneous apoptosis. These results have important implications for the use of CSFs in neonatal sepsis, as responses differ from those seen in adults. Further delineation of neonatal neutrophil responses to CSFs may improve their therapeutic potential.

Adult↗
PubMed1998

Psoriasiform eruption triggered by recombinant granulocyte-macrophage colony stimulating factor (rGM-CSF) and exacerbated by granulocyte colony stimulating factor (rG-CSF) in a patient with breast cancer.

Colony-stimulating factors (CSFs) are commonly used for the treatment of neutropenia following chemotherapy and for the mobilization of peripheral blood stem cells (PBSC). We recently experienced a rare case of a new onset of psoriasiform eruption by GM-CSF (granulocyte-macrophage colony-stimulating factor) which was exacerbated by G-CSF (granulocyte colony-stimulating factor) in a patient with breast cancer. A 36-year-old woman had received neoadjuvant chemotherapy (cyclophosphamide, epirubicin and 5-fluorouracil), modified radical mastectomy and adjuvant chemotherapy with paclitaxel and mitoxantrone followed by GM-CSF administration for the treatment of locally advanced breast cancer. She had developed a psoriatic skin lesion on face and both upper arms during leukocyte recovery in spite of no previous history of psoriasis. Next, the chemotherapy course was complicated by a flare of mild psoriatic skin lesion, although CSF was changed into G-CSF due to GM-CSF-associated psoriasis. Subsequently, she had had high-dose chemotherapy and autologous peripheral blood stem cell transplantation for consolidation therapy. GM-CSF was administered for the mobilization of PBSC and post-transplant period, but psoriatic skin lesion did not appear. During 6 months after PBSCT, psoriasiform eruption did not appear.

Adult↗
PubMed1999

Granulocyte colony-stimulating factor and drugs elevating extracellular adenosine act additively to enhance the hemopoietic spleen colony formation in irradiated mice.

The effects of combined administration of two drugs elevating extracellular adenosine, namely dipyridamole (DP) and adenosine monophosphate (AMP), and granulocyte colony-stimulating factor (G-CSF) on hemopoietic stem cells in vivo were investigated. The experiments were performed on mice using the endogenous spleen colony formation in gamma-irradiated animals as an endpoint. The results have shown that DP and AMP act additively with G-CSF to enhance spleen colony formation and thus the erythroid repopulation of the spleen. These findings indicate that the signaling pathways of G-CSF and drugs elevating extracellular adenosine can interact at the level of primitive hemopoietic stem cells. The enhancement of hemopoiesis-stimulating effects of G-CSF by DP and AMP, which are low-priced and clinically available drugs, could improve the cost-effectiveness of the therapy with G-CSF.

Adenosine↗
PubMed2004

[Low-dose granulocyte colony-stimulating factor combined with granulocyte-macrophage colony-stimulating factor for mobilizing peripheral CD34+ hematopoietic progenitor cells].

OBJECTIVE: To study the efficacy of combined use of low-dose granulocyte colony-stimulating factor (G-CSF) and granulocyte-macrophage colony-stimulating factor (GM-CSF) in mobilizing hematopoietic stem/progenitor cells. METHODS: Twenty adult patients with malignant hematologic diseases were paired using statistical methods, and the 10 pairs were divided into 2 equal groups. For non-Hodgkin lymphoma, the treatment regimen adopted intravenous infusion of cytoxan (2 g/d for 1 or 2 d) and VP16 (0.2 g/d for 1 to 3 d), while for acute non-lymphocytic leukemia, Ara-C (2 g/d for 1 to 3 d) and VP16 (0.2 g/d for 1 to 3 d) were used. When the while blood cell count (WBC) was below 1.0 x10(9)/L, G-CSF and GM-CSF were administered subcutaneously at the same dose of 2.5 microg/d.kg in the 10 patients in the experimental group, while the patients in the control group received only 5 microg/d.kg G-CSF, both for 5 to 6 d. After WBC>5.0 x 10(9)/L, the peripheral blood mononuclear cells (PBMNC) were separated by CS-3000 pluse separator and CD34+ cells were determined by flow cytometry. RESULTS: The purity of the isolated PBMNC was 95%-99%. In the experimental group, the mean number of CD34+ cells acquired was 9.4 x 10(6)/kg ranging from 8.4 x 10(6) to 10.2 x 10(6)/kg, and granulocyte-macrophage colony-forming unit (CFU-GM) was 42.4 x 10(4)/kg on average ranging from 21.9 x 10(4) to 72.8 x 10(4)/kg, as compared with 4.8 x 10(6)/kg [(4.1-8.3) x10(6)/kg] for CD34+ cells and 28.1 x 10(4)/kg [(7.1-60.2) x 10(4)/kg] for CFU-GM in the control group (P<0.05). No obvious difference was observed between the two groups in terms of the adverse effects of the treatment (P>0.05). CONCLUSION: Combined use of G-CSF and GM-CSF can be more effective than the exclusive use of GM-CSF for mobilizing CD34+ cells.

Adult↗
PubMed1991

Granulocyte colony-stimulating factor, not granulocyte-macrophage colony-stimulating factor, co-operates with retinoic acid on the induction of functional N-formyl-methionyl-phenylalanine receptors in HL-60 cells.

The interaction of colony-stimulating factors (CSF) and retinoic acid (RA) in the proliferation and differentiation of HL-60 cells was examined. Granulocyte-macrophage colony-stimulating factor (GM-CSF) stimulated the proliferation of HL-60 cells in a dose-dependent manner at concentrations of 0.01-100 ng/ml; however, the proliferation due to GM-CSF was suppressed by 100 nM RA. Granulocyte colony-stimulating factor (G-CSF) slightly stimulated the proliferation of HL-60 cells at concentrations above 10 ng/ml. Neither G-CSF nor GM-CSF alone induced 12-o-tetra-decanoyl-phorbol-13-acetate (TPA)- or N-formyl-methionyl-phenylalanine (FMLP)-stimulated nitro-blue tetrazolium (NBT) reduction at concentrations of 0.01-100 ng/ml. G-CSF induced TPA- and FMLP-stimulated NBT reduction in the presence of 100 nM RA, but GM-CSF induced only TPA-stimulated NBT reduction. RA in addition to G-CSF synergistically increased FMLP binding to HL-60 cells, accompanied by increased NBT reduction in response to FMLP. RA in addition to GM-CSF markedly increased FMLP binding to HL-60 cells more than that induced by RA alone, but the combined treatment with RA and GM-CSF did not increase FMLP-stimulated NBT reduction more than that induced by RA alone. The results suggest that G-CSF stimulates RA-induced morphological and functional differentiation of HL-60 cells, but the differentiation-enhancing effects of GM-CSF are limited, whereas the growth-stimulating effect of GM-CSF on HL-60 cells is greater than that of G-CSF.

Cell Differentiation↗
PubMed1991

Granulocyte-macrophage colony-stimulating factor (GM-CSF) and granulocyte colony-stimulating factor (G-CSF) in serum in bone marrow transplanted patients.

Colony-stimulating factors (CSF) are being increasingly used to accelerate hematopoietic recovery after bone marrow transplantation. To study the endogenous serum levels of CSF in bone marrow transplanted patients we have used immunoassays measuring granulocyte-macrophage colony-stimulating factor (GM-CSF) with a sensitivity of 0.10 ng/ml and granulocyte colony-stimulating factor (G-CSF) with a sensitivity of 0.05 ng/ml. Serum samples, taken from the conditioning treatment until engraftment, were analysed in 13 patients receiving allogeneic transplants and in eight patients receiving autologous transplants. Ten patients had acute myeloid leukemia, seven acute lymphoblastic leukemia, one acute undifferentiated leukemia, two non-Hodgkin's lymphoma and one multiple myeloma. Samples were taken 1-2 times before transplantation and 1-2 times per week after transplantation (median of 46 days in allotransplant recipients and 32 days in autotransplant recipients); 17% of the allogeneic transplanted patients and 35% of the autologous transplanted patients had detectable levels of G-CSF. In both types of transplantation the G-CSF concentrations were low: median 0.06 (range 0.05-0.14) and 0.08 (range 0.05-0.40) ng/ml respectively. GM-CSF was detected only in one analysed sample in all patients. There was no evidence of increased CSF levels related to engraftment or documented infections.

Acute Disease↗
PubMed1989

Growth of human hematopoietic colonies from patients with myelodysplastic syndromes in response to recombinant human granulocyte-macrophage colony-stimulating factor.

The in vitro effect of recombinant human GM-CSF (rHuGM-CSF) was tested on bone marrow-derived multilineage (CFU-GEMM) as well as megakaryocytic (CFU-Mk), erythroid (BFU-E), and granulocyte-macrophage (CFU-GM) progenitors in a group (n = 16) of patients with myelodysplastic syndromes (MDS). Hematopoietic progenitor cell growth was markedly impaired in MDS patients as compared to normal controls (p less than 0.05, at least). Recombinant HuGM-CSF supported the growth of CFU-GEMM, CFU-Mk, and BFU-E at lower, equivalent, or slightly higher frequencies that those found in cultures plated with medium conditioned by peripheral blood leukocytes (PHA-LCM), but it was invariably ineffective in improving growth values. Recombinant HuGM-CSF supported the growth of granulocyte-macrophage colonies in 15 of 16 cases. The overall incidence (mean +/- SEM) of CFU-GM in cultures containing rHuGM-CSF (5 ng/ml) was significantly higher than the one found in cultures stimulated with PHA-LCM (40 +/- 15 vs. 17 +/- 7, p less than 0.05). Upon culture with rHuGM-CSF (5 ng/ml), in 5 of 15 patients de novo colony formation was observed (8 +/- 4) and in 4 of 15 patients CFU-GM growth (129 +/- 33) fell within normal range. Doses of rHuGM-CSF higher than 5 ng/ml did not result in a further increase of MDS-derived colony formation. It is concluded that rHuGM-CSF (a) does not improve the growth of CFU-GEMM, CFU-Mk, and BFU-E; (b) may completely restore the growth of CFU-GM in a subgroup of MDS patients; (c) while ineffective in improving anemia and thrombocytopenia, its in vivo in MDS may correct leukopenia through an effect at the level of granulocyte-macrophage progenitor cell compartment, at least in a subset of highly responsive patients.

Adult↗
PubMed1981

Stromal colony-stimulating activity production and myeloid colony-forming cells in human hemopoietic and nonhemopoietic bone marrow.

In order to evaluate the role of the stromal bone marrow microenvironment in regulating granulopoiesis, we have examined the capacity of adult human proximal hemopoietic (PH) and distal nonhemopoietic (DNH) long bone to produce colony-stimulating activity (CSA), characterized the cellular sources of CSA, and quantitated the colony-forming cells (CFU-GM) of marrow from these sites. Stromal elements were obtained from slices of cancellous bone. PH bone marrow stroma contained CFU-GM concentrations similar to aspirated PH marrow and significantly more CFU-GM than DNH bone marrow: 20.7 +/- 4.8/10(5) cells and 25.8 +/- 12.0/mg bone versus 0.81 +/- 0.34/10(5) cells and 0.02 +/- 0.01/mg bone (p less than 0.001). Conditioned media prepared from PH and DNH bone were quantitated for CSA by their ability to promote in vitro granulocyte colony formation of nonadherent human marrow cells. Stromal CSA production was destroyed by freeze--thawing and was radioresistant (4400 rad). Of DNH stromal cells, 15%--30% were monocyte-macrophage, but the slow absolute numbers of these cells suggested alternative CSA cellular sources in distal bones. PH stroma produced significantly more CSA than DNH bone stroma: 0.72 +/- 0.10 versus 0.30 +/- 0.06 U/mg bone (p less than 0.01). The CSA concentration gradient between PH and DNH bones may contribute to the regulation of granulopoiesis in marrow and to the absence of hemopoiesis distally.

Bone Marrow Cells↗
PubMed1981

Evaluation of radioimmunoassay and in vitro colony assay techniques for determination of colony-stimulating factor and inhibitory activity in murine serum and tissue.

These studies have evaluated a newly developed radioimmunoassay (RIA) for the measurement of colony-stimulating factor (CSF) in murine serum and other biologic fluids. The routine in vitro agar gel bioassay for CSF is influenced by high molecular weight serum lipoproteins and low molecular weight tissue-derived materials that are inhibitory to colony formation. Studies with normal serum revealed that in all cases, the levels of CSF detected by the RIA were equal to or greater than levels measured by the bioassay. Dose curves with varying quantities of serum had linear responses in the RIA but not the colony assay. Using Sephadex G-150 chromatography, the murine serum was separated into CSF active and CSF inhibitory peaks as determined by bioassay. Evaluation of these fractions by RIA indicated that the assay was unaffected by the serum inhibitors. Likewise, experiments with tissue lysates indicated that the RIA was not influenced by the low molecular weight tissue inhibitors. Instead, the radioimmunoassay revealed low levels of CSF that were not detectable by bioassay. These observations indicate that the RIA is superior to the bioassay for the estimation of CSF in murine serum and other biologic materials.

Agar↗
PubMed1994

Kinetic response of human marrow myeloid progenitor cells to in vivo treatment of patients with granulocyte colony-stimulating factor is different from the response to treatment with granulocyte-macrophage colony-stimulating factor.

We previously demonstrated that granulocyte-macrophage colony-stimulating factor (GM-CSF) induced sustained increases in cycling of myeloid progenitors in patients with sarcoma. However, decreased proliferation of these cells to a slow- or noncycling state, below pretreatment levels, occurred within 1 to 2 days and maintained for at least 1 week after discontinuation of GM-CSF. To assess possible biological differences in GM-CSF and granulocyte (G)-CSF in such kinetic effects, we evaluated cycling status of marrow progenitors before, during, and after administration of recombinant human G-CSF (5 micrograms/kg/d subcutaneously [s.c.]) to six patients with sarcoma for 8 days. On the last (8th) day of G-CSF treatment, cycling rates of colony-forming units-granulocyte/macrophage (CFU-GM), burst-forming units-erythroid (BFU-E), and multipotent colony-forming units (CFU-GEMM) were enhanced 1.5- to 1.9-fold, to values of 40 +/- 10% to 58 +/- 5%. In sharp contrast to patients receiving GM-CSF, however, progenitor cells from patients off G-CSF treatment for 2 to 4 days were still rapidly proliferating. These differences in proliferative kinetics may be of use for design of clinical trials to efficaciously utilize these growth factors.

Bone Marrow↗
PubMed1994

Granulocyte-macrophage colony-stimulating factor and granulocyte colony-stimulating factor: differential action on incisional wound healing.

BACKGROUND: Granulocyte-macrophage colony-stimulating factor (GM-CSF) specifically stimulates granulocyte, macrophage, and eosinophil colonies; granulocyte colony-stimulating factor (G-CSF) acts directly on neutrophil-restricted progenitor cells in their proliferation. Those cells have been implicated in the process of wound healing. METHODS: Paired 6 cm incisions were made on rats; GM-CSF or G-CSF was given systemically (100 micrograms/kg/dose) or locally (30 micrograms/wound). The controls received vehicle alone. Impaired healing was induced by injection of methylprednisolone (30 mg/kg). White blood cells (WBC) were counted at day 2 after treatment. Tissue strips were evaluated for tensiometry and histologic features at days 7 and 14 after wounding. RESULTS: For local GM-CSF treated incisions, the breaking strength was 25% stronger than controls at day 7 (p = 0.004), 36% at day 14 (p < 0.0001), and 42% at day 7 (p = 0.012) in impaired animals. Local G-CSF and systemic GM-CSF and G-CSF increased circulating WBC (p < 0.05), but they had no effects on healing. Histologic studies revealed an increase of wound cellulity at day 7 and day 14 in topical GM-CSF treated wounds. CONCLUSIONS: These results suggest GM-CSF is an activator of tissue macrophages and that increasing circulating WBC did not affect wound healing.

Animals↗
PubMed1994

Effects of in vivo recombinant methionyl human granulocyte colony-stimulating factor on the neutrophil response and peripheral blood colony-forming cells in healthy young and elderly adult volunteers.

Recombinant granulocyte colony stimulating factor (G-CSF) was administered daily for 14 days to healthy young (Y) (20 to 30 years) and elderly (O) (70 to 80 years) volunteers to evaluate the effects of age on the neutrophil (polymorphonuclear leukocytes, PMN) responses. Thirty-eight volunteers were randomized to receive 0 micrograms, 30 micrograms, or 300 micrograms per day. Baseline neutrophil counts (ANC), peak ANCs, and the rate of attaining the peak ANC were similar in both age groups at both doses. The peak ANC was increased 5-fold at 30 micrograms and 15-fold at 300 micrograms in both the young and elderly. Daily tests of PMN function, as measured by an automated chemiluminescence system, showed nearly identical responses to several agonists for both age groups. Marrow proliferative activity as reflected by the percentage of cells in the marrow neutrophil mitotic pool also increased similarly for both age groups at both doses. In contrast, there was an age-related change in blood colony formation as measured by the blood CFU-GM assay. Compared with controls at the 30 micrograms dose, mean colony formation was increased 2-fold in the young versus no change in the elderly and at the 300 micrograms dose 24-fold in the young versus 12-fold in the elderly. These studies indicate that neutrophil responses to rhG-CSF are equivalent in healthy young and elderly volunteers but the mobilization of progenitor cells, as measured by the CFU-GM assay appears to differ substantially.

Adult↗