scholarly journals Collection of peripheral blood hematopoietic progenitors (PBHP) from patients with severe aplastic anemia (SAA) after prolonged administration of granulocyte colony-stimulating factor

Blood ◽  
1993 ◽  
Vol 82 (5) ◽  
pp. 1410-1414 ◽  
Author(s):  
A Bacigalupo ◽  
G Piaggio ◽  
M Podesta ◽  
MT Van Lint ◽  
M Valbonesi ◽  
...  
Keyword(s):  
Peripheral Blood ◽  
Autologous Transplantation ◽  
Colony Growth ◽  
Median Number ◽  
Granulocyte Colony Stimulating Factor ◽  
Colony Stimulating Factor ◽  
Hematopoietic Progenitors ◽  
Prolonged Administration ◽  
Stimulating Factor

Abstract The aim of this study was to test whether prolonged administration of granulocyte colony-stimulating factor (G-CSF) would allow the collection by leukapheresis of PBHP in patients with SAA. For this purpose, nine SAA patients, 7 to 46 years old, six of whom were enrolled at diagnosis of their disease and three after previous immunosuppression had failed, were treated with antilymphocyte globulin (ALG) (day 1 to 5), cyclosporin A (5 mg/kg/d orally) (day 6 to 90) and G-CSF 5 micrograms/kg/d (day 6 to 90). A total of 40 leukaphereses were performed, (range 2 to 7 per patient), between days +10 and +168 from G- CSF treatment. White blood cell count at the time of harvest ranged from 1.2 to 18.1 x 10(9)/L. Results can be summarized as follows: the median number of cells collected per patient was 5.0 x 10(8)/kg (range 2.6 to 18.7), the median number of CD34+ cells was 1.8 x 10(6)/kg (range 0.27 to 3.8) and the median number of colony-forming units granulocyte-macrophage (CFU-GM) was 3.9 x 10(4)/kg (range 0 to 39). Twenty leukaphereses performed between days +33 and +77 of G-CSF treatment grew granulocyte macrophages and erythroid colonies in vitro. No colony growth was obtained from 20 leukaphereses performed before day +33 or after day +80. In six patients the total number of CFU-GM recovered were in the range described for autologous peripheral blood stem cell grafts. (2.6 to 39 x 10(4)/kg). In conclusion, this study suggests that circulating hematopoietic progenitors can be recovered after ALG priming and after at least 1 month of G-CSF treatment in a proportion of patients with SAA. Whether these cells will be suitable for autologous transplantation remains to be determined.

scholarly journals Collection of peripheral blood hematopoietic progenitors (PBHP) from patients with severe aplastic anemia (SAA) after prolonged administration of granulocyte colony-stimulating factor

Blood ◽  
1993 ◽  
Vol 82 (5) ◽  
pp. 1410-1414
Author(s):  
A Bacigalupo ◽  
G Piaggio ◽  
M Podesta ◽  
MT Van Lint ◽  
M Valbonesi ◽  
...  
Keyword(s):  
Peripheral Blood ◽  
Autologous Transplantation ◽  
Colony Growth ◽  
Median Number ◽  
Granulocyte Colony Stimulating Factor ◽  
Colony Stimulating Factor ◽  
Hematopoietic Progenitors ◽  
Prolonged Administration ◽  
Stimulating Factor

The aim of this study was to test whether prolonged administration of granulocyte colony-stimulating factor (G-CSF) would allow the collection by leukapheresis of PBHP in patients with SAA. For this purpose, nine SAA patients, 7 to 46 years old, six of whom were enrolled at diagnosis of their disease and three after previous immunosuppression had failed, were treated with antilymphocyte globulin (ALG) (day 1 to 5), cyclosporin A (5 mg/kg/d orally) (day 6 to 90) and G-CSF 5 micrograms/kg/d (day 6 to 90). A total of 40 leukaphereses were performed, (range 2 to 7 per patient), between days +10 and +168 from G- CSF treatment. White blood cell count at the time of harvest ranged from 1.2 to 18.1 x 10(9)/L. Results can be summarized as follows: the median number of cells collected per patient was 5.0 x 10(8)/kg (range 2.6 to 18.7), the median number of CD34+ cells was 1.8 x 10(6)/kg (range 0.27 to 3.8) and the median number of colony-forming units granulocyte-macrophage (CFU-GM) was 3.9 x 10(4)/kg (range 0 to 39). Twenty leukaphereses performed between days +33 and +77 of G-CSF treatment grew granulocyte macrophages and erythroid colonies in vitro. No colony growth was obtained from 20 leukaphereses performed before day +33 or after day +80. In six patients the total number of CFU-GM recovered were in the range described for autologous peripheral blood stem cell grafts. (2.6 to 39 x 10(4)/kg). In conclusion, this study suggests that circulating hematopoietic progenitors can be recovered after ALG priming and after at least 1 month of G-CSF treatment in a proportion of patients with SAA. Whether these cells will be suitable for autologous transplantation remains to be determined.

Circulating Primitive Stem Cells in Paroxysmal Nocturnal Hemoglobinuria (PNH) Are Predominantly Normal in Phenotype But Granulocyte Colony-Stimulating Factor Treatment Mobilizes Mainly PNH Stem Cells

Blood ◽  
1998 ◽  
Vol 91 (12) ◽  
pp. 4504-4508 ◽  
Author(s):  
Roderick J. Johnson ◽  
Andy C. Rawstron ◽  
Steve Richards ◽  
Gareth J. Morgan ◽  
Derek R. Norfolk ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Peripheral Blood ◽  
Paroxysmal Nocturnal Hemoglobinuria ◽  
Autologous Transplantation ◽  
Hemopoietic Stem Cell ◽  
Granulocyte Colony Stimulating Factor ◽  
Colony Stimulating Factor ◽  
Peripheral Blood Stem Cells ◽  
Stimulating Factor

Abstract Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired hemolytic anemia resulting from a somatic mutation in a hemopoietic stem cell. In most cases of hemolytic PNH, the majority of the marrow cells are derived from the PNH clone. Recent evidence has indicated, however, that the majority of the most primitive peripheral blood stem cells (PBSCs) in PNH appear to be of normal phenotype. This has led to tentative suggestions that normal PBSCs could be collected and used for autologous transplantation. We have investigated this possibility in four PNH patients by treating them with granulocyte colony-stimulating factor (G-CSF) in an attempt to mobilize normal progenitors. The expression of glycosylphosphatidylinositol (GPI)-linked proteins was analyzed by flow cytometry on mature neutrophils, late stem cells (CD34+/CD38+), and primitive stem cells (CD34+/CD38−). The phenotyping and stem cell quantitation was performed in steady-state blood and post–G-CSF administration. The most primitive PBSCs (CD34+/CD38−) were almost all normal before G-CSF treatment, even when the patients' neutrophils were mainly PNH. However, after G-CSF, the cells that were mobilized into the peripheral blood were of a similar phenotype to the mature neutrophils, ie, mainly PNH. It is possible that PNH-stem cells are preferentially destroyed by complement in the peripheral blood leaving only normal cells in the circulation. After G-CSF, the PNH cells in the marrow are released into the blood. Our findings suggest that it would be difficult to collect sufficient numbers of normal stem cells for autologous transplantation.

Successful Hematopoietic STEM CELL Mobilization with GRANULOCYTE Colony Stimulating FACTOR PLUS Plerixafor (MOZOBIL, AMD3100) IN POOR Mobilizers: A Single CENTER STUDY

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 4444-4444
Author(s):  
Despina Mallouri ◽  
Ioanna Sakellari ◽  
Chrisa Apostolou ◽  
Panayotis Baliakas ◽  
Apostolia Papalexandri ◽  
...  
Keyword(s):  
Stem Cells ◽  
Peripheral Blood ◽  
Median Number ◽  
Granulocyte Colony Stimulating Factor ◽  
Colony Stimulating Factor ◽  
Hematopoietic Stem ◽  
Cd 34 ◽  
Healthy Donors ◽  
Stimulating Factor ◽  
Poor Mobilizers

Abstract Abstract 4444 Background: According to published data mobilization of sufficient number of CD 34+ cells with cytokines alone or with chemo-mobilization fails in 5–30% of patients. Plerixafor is a novel chemokine receptor 4 antagonist (CXCR4) that reversibly inhibits the interaction with its ligand SDF-1 (Stromal Derived Factor 1). Phase III studies have demonstrated that plerixafor combined with granulocyte-colony stimulating factor (GCSF) improves CD 34+ cell collection in patients with Multiple Myeloma (MM) or Non Hodgkin Lymphoma (NHL). It has been shown to be efficacious in combination with GCSF to mobilize adequate number of CD 34+ cells in patients proven to be poor mobilizers yielding a success rate of 60–100% in several reports. Plerixafor is currently approved for administration in combination with GCSF to enhance mobilization of hematopoietic stem cells in patients with lymphoma and MM whose cells mobilize poorly. Patients/methods: We administered plerixafor in combination with GCSF in 14 patients (in 4/14 as part of compassionate use protocol) and 2 sibling donors after an informed consent was obtained. Individuals were defined as poor mobilizers either due to unsuccessful collection of CD34+ >2×106/kg or due to peripheral blood CD34+ peak <20/μ l in spite of adequate mobilization treatment. Data of the individuals were collected retrospectively. Eight patients suffered from MM, 3 of NHL, 3 of H°dgkin Lymphoma (HL). Marrow involvement was present in 1 patient suffering from MM. The median number of previous chemotherapy regimens was 4(1-8). Two patients had a history of previous autologous hematopoietic cell transplantation (autoHCT) and 4 patients had received multiple radiotherapy courses. Patients had a median of 2 (1-3) previous unsuccessful attempts of mobilization before plerixafor plus GCSF administration. Nine patients had received GCSF alone and 5 patients chemotherapy plus GCSF. Patients received GCSF for 4 consecutive days and plerixafor was administered at the evening of the forth day, 10–11 hours before the scheduled aphaeresis procedure. In case of not sufficient or suboptimal number of CD34+ cells collection the procedure was repeated for maximum of 3 days plerixafor administration (7 days of GCSF). Results: Mobilization with plerixafor plus GCSF and collection of adequate number of CD 34+ cells was successful in 12/14 patients. The median number of CD 34+ cells collected was 2.5×106/kg in a median of 2 (1-4) apheresis days. Two of 14 patients proceeded to a second mobilization with plerixafor plus GCSF, eventually succeeding a sufficient cell dose graft collection. In 2 sibling female donors, aged 47 and 54 years, after administration of GCSF 10μ g/kg/day for 5 consecutive days mobilization was poor and collection of a graft with an acceptable CD 34+ cell dose was not possible. Administration of plerixafor improved mobilization and eventually grafts consisting of 2.55 ×106 and 5.34×106 CD34+/kg were collected by apheresis. Patients reported a grade ≤ II according to WHO scale toxicity following plerixafor administration. Most common side effects were hyperhidrosis, facial numbness and abdominal pain. None of the two healthy donors reported any adverse side effect. Engraftment was uneventfully in predictive time according to our historical data. Discussion: In our experience mobilization with either cytokines alone or cytokines following chemotherapy fails in a number of otherwise eligible for transplantation patients, mostly heavily pretreated or with advanced disease. In addition a small minority of healthy donors with no identifiable risk factors for poor mobilization, also fail mobilization with GCSF. The combination of plerixafor and GCSF seems to augment peripheral blood stem cells mobilization in poor mobilizers and offers a new treatment to collect sufficient CD 34+ cells and benefit from the transplantation procedure Disclosures: Off Label Use: Plerixafor was used for the mobilization of two healthy sibling donors after a signed concept was optained, due to poor mobilization with GCSF and failure of addequate graft collection.

scholarly journals In Vivo Effects of Flt3/Flk2 Ligand on Mobilization of Hematopoietic Progenitors in Primates and Potent Synergistic Enhancement With Granulocyte Colony-Stimulating Factor

Blood ◽  
1997 ◽  
Vol 90 (2) ◽  
pp. 620-629 ◽  
Author(s):  
Thalia Papayannopoulou ◽  
Betty Nakamoto ◽  
Robert G. Andrews ◽  
Stewart D. Lyman ◽  
Minako Y. Lee
Keyword(s):  
Functional Properties ◽  
Peripheral Blood ◽  
Combined Treatment ◽  
Mast Cell Activation ◽  
Granulocyte Colony Stimulating Factor ◽  
Colony Stimulating Factor ◽  
Synergistic Enhancement ◽  
Stimulating Factor

The Flt3 receptor is expressed in primitive hematopoietic cells and its ligand exerts proliferative effects on these cells in vitro in synergy with other cytokines. To expand on the functional properties of Flt3 ligand (FL) in vivo we treated nonhuman primates with FL and tested its ability to mobilize stem/progenitor cells when given alone or in combination with granulocyte colony-stimulating factor (G-CSF ) treatment. FL alone (200 μg/kg/day) mobilizes progenitors with slow kinetics and with a peak effect at the end of 2 weeks of treatment. The spectrum of mobilized progenitors includes myeloid, lymphoid, megakaryocytic, and osteoclastogenic but a low proportion of burst-forming unit (BFU)e. Bone marrow (BM) studies before and during the treatment suggested that proliferative effects in BM may have preceded effects on peripheral blood mobilization. To assess the synergy of FL with G-CSF in mobilization of progenitors we used two schemes: one in which G-CSF was used for the last 5 days of a 12-day treatment with FL; the other in which both cytokines were given concurrently for 5 days only (FL, 200 μg/kg; G-CSF, 100 μg/kg). Both schemes yielded much higher progenitor mobilization levels (peak levels of colony-forming cells [CFSs] 41,000 to 95,000/mL blood) than observed with either FL (CFC 4,600 to 7,300/mL) or G-CSF (8,405 ± 3,024/mL) used alone at the same doses. Furthermore, there was a progressive and significant expansion of progenitors in vitro during 2 weeks in suspension cultures of mononuclear cells or of CD34+ cells only in the animal with the combined treatment. Likewise, substantial mobilization of osteoclastogenic progenitors was documented only with the combined treatment. Given the functional properties of FL, its synergistic mobilization with G-CSF, and its anticipated good tolerance (because of the absence of an effect on mast cell activation), a clinical use is projected for this cytokine in peripheral blood transplantation settings, as well as in experiments with ex vivo gene transfer.

scholarly journals Granulocyte colony-stimulating factor induces hFc gamma RI (CD64 antigen)-positive neutrophils via an effect on myeloid precursor cells

Blood ◽  
1993 ◽  
Vol 81 (6) ◽  
pp. 1457-1464 ◽  
Author(s):  
JM Kerst ◽  
JG van de Winkel ◽  
AH Evans ◽  
M de Haas ◽  
IC Slaper-Cortenbach ◽  
...  
Keyword(s):  
Peripheral Blood ◽  
Precursor Cells ◽  
Polymorphonuclear Neutrophil ◽  
Granulocyte Colony Stimulating Factor ◽  
Colony Stimulating Factor ◽  
Final Maturation ◽  
Vitro Effect ◽  
Stimulating Factor

Abstract In this study we have examined hFc gamma RI expression during myelopoiesis. Normal bone marrow (BM) cells were found to express hFc gamma RI up to the metamyelocyte stage. A different Fc gamma RI expression pattern was observed in an in vitro model of myelopoiesis. Purified CD34-positive BM cells, cultured for 12 to 14 days with granulocyte colony-stimulating factor (G-CSF), differentiate into a population of mature granulocytic cells. In these cultures, in which hFc gamma RI was virtually absent on the initial CD34-positive BM cells, hFc gamma RI was strongly induced by G-CSF after only 5 days. During final maturation the cells remained hFc gamma RI positive. This expression was confirmed functionally by antibody-sensitized erythrocytes (EA)-rosette assays. Moreover, the mature myeloid cells were found to express mRNA encoding for hFc gamma RI, whereas reverse- transcriptase polymerase chain reaction analysis showed that both hFc gamma RIA and hFc gamma RIB genes were expressed. In contrast, on peripheral blood (PB) polymorphonuclear neutrophil leukocytes (PMN) the in vitro effect of G-CSF as to hFc gamma RI induction was limited. Therefore, we conclude that, with respect to hFc gamma RI expression on PMN, G-CSF acts on myeloid precursor cells rather than on mature cells. This conclusion could be strengthened by in vivo administration of a single dose of G-CSF to a healthy volunteer. After a 12-hour lag time, hFc gamma RI expressing PMNs were detected in the peripheral blood. This study shows that hFc gamma RI is an early myeloid differentiation marker that is lost during normal final maturation. However, committed myeloid progenitor cells can be strongly induced by G-CSF to express hFc gamma RI, ultimately resulting in mature granulocytic cells expressing the high-affinity receptor for IgG. This expression may have important consequences for the functional capacity of these cells.

Harvest of Autologous Peripheral Blood Stem Cells Using Ifosfamide/Etoposide Regimen Combined with Granulocyte Colony-Stimulating Factor.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 5218-5218
Author(s):  
Mitsuho Noguchi ◽  
Haruko Tashiro ◽  
Moritaka Goto ◽  
Kazuo Kawasugi ◽  
Naoki Shirafuji
Keyword(s):  
Stem Cells ◽  
Peripheral Blood ◽  
Hemorrhagic Cystitis ◽  
Median Number ◽  
Granulocyte Colony Stimulating Factor ◽  
Colony Stimulating Factor ◽  
Peripheral Blood Stem Cells ◽  
Blood Stem Cells ◽  
Wbc Count ◽  
Stimulating Factor

Abstract Aim: To make clear the feasibility of Ifosfamide/Etoposide (IE) regimen combined with granulocyte colony-stimulating factor (G-CSF) for the collection of autologous peripheral blood stem cells (APBSC), we evaluated the number of the collected CD34 positive cells, and the regimen-related toxicities. Patients’ characteristics and Methods: 19 Patients (male 12, female 7) were received APBSC harvest in our hospitals during Aug. 2000 to Dec. 2003 with age of 54.3 years on average (30–66). Diagnoses were included HD (n=2), NHL (n=13), MM (n=3), and malignant synovioma (n=1). IE regimen was included with Ifomide 2000 mg/m2 (day 1), and Etoposide 200 mg/m2 (day 1–3) (4cases) or 500 mg/m2 (day 1,2) (15 cases). For the prevention of hemorrhagic cystitis patients were administered with Mesna, and NaHCO3 during and after 1 day of the administration of Ifosfamide. G-CSF was administered at the dose of 10 ug/kg (lenograstim) or 300 ug/m2 (filgrastim) when blood absolute neutrophil count came down to 1000/mm3. When the suppression of bone marrow was recovered and blood WBC count came up to 5000/m3, CD34-positive cells were counted in blood, and APBSC was harvested when blood CD34-positive cells were determined above 0.1 %. APBSC was harvested with CS-3000 plus (Fenwall). Result: The median duration from the start of the administration of G-CSF to the finish of APBSC harvest was 6.5 days (4–11). The median number of CD34-positive cells of the harvested was 4.32 x 106/kg (1.10–13.50). All cases were harvested. The toxicities during from the conditioning to the harvest were included with grade 1 headache (2 cases), grade 2 nausea (6 cases), grade 1 bleeding (1 case), grade 1 constipation (1 case), grade 1 fever (1 case), and grade 1 thrombocytopenia (1 case). Conclusion: IE regimen combined with G-CSF was feasible to harvest APBSC on the yield of the collection of the transplantable stem cells, and on the regimen-related toxicities.

Circulating Primitive Stem Cells in Paroxysmal Nocturnal Hemoglobinuria (PNH) Are Predominantly Normal in Phenotype But Granulocyte Colony-Stimulating Factor Treatment Mobilizes Mainly PNH Stem Cells

Blood ◽  
1998 ◽  
Vol 91 (12) ◽  
pp. 4504-4508
Author(s):  
Roderick J. Johnson ◽  
Andy C. Rawstron ◽  
Steve Richards ◽  
Gareth J. Morgan ◽  
Derek R. Norfolk ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Peripheral Blood ◽  
Paroxysmal Nocturnal Hemoglobinuria ◽  
Autologous Transplantation ◽  
Hemopoietic Stem Cell ◽  
Granulocyte Colony Stimulating Factor ◽  
Colony Stimulating Factor ◽  
Peripheral Blood Stem Cells ◽  
Stimulating Factor

Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired hemolytic anemia resulting from a somatic mutation in a hemopoietic stem cell. In most cases of hemolytic PNH, the majority of the marrow cells are derived from the PNH clone. Recent evidence has indicated, however, that the majority of the most primitive peripheral blood stem cells (PBSCs) in PNH appear to be of normal phenotype. This has led to tentative suggestions that normal PBSCs could be collected and used for autologous transplantation. We have investigated this possibility in four PNH patients by treating them with granulocyte colony-stimulating factor (G-CSF) in an attempt to mobilize normal progenitors. The expression of glycosylphosphatidylinositol (GPI)-linked proteins was analyzed by flow cytometry on mature neutrophils, late stem cells (CD34+/CD38+), and primitive stem cells (CD34+/CD38−). The phenotyping and stem cell quantitation was performed in steady-state blood and post–G-CSF administration. The most primitive PBSCs (CD34+/CD38−) were almost all normal before G-CSF treatment, even when the patients' neutrophils were mainly PNH. However, after G-CSF, the cells that were mobilized into the peripheral blood were of a similar phenotype to the mature neutrophils, ie, mainly PNH. It is possible that PNH-stem cells are preferentially destroyed by complement in the peripheral blood leaving only normal cells in the circulation. After G-CSF, the PNH cells in the marrow are released into the blood. Our findings suggest that it would be difficult to collect sufficient numbers of normal stem cells for autologous transplantation.

Pharmacologic doses of granulocyte colony-stimulating factor affect cytokine production by lymphocytes in vitro and in vivo

Blood ◽  
2000 ◽  
Vol 95 (7) ◽  
pp. 2269-2274 ◽  
Author(s):  
Elaine M. Sloand ◽  
Sonnie Kim ◽  
Jaroslaw P. Maciejewski ◽  
Fritz Van Rhee ◽  
Aniruddho Chaudhuri ◽  
...  
Keyword(s):  
Peripheral Blood ◽  
Mononuclear Cells ◽  
Th2 Cells ◽  
Granulocyte Colony Stimulating Factor ◽  
Colony Stimulating Factor ◽  
Cd4 Cells ◽  
Ifn Γ ◽  
Stimulating Factor

Peripheral blood stem cell (PBSC) transplantation is successful in improving engraftment without increasing acute graft-versus-host disease (GVHD), despite much larger numbers of T cells in unmanipulated PBSCs than in bone marrow grafts. In mouse models and retrospective human studies, granulocyte colony-stimulating factor (G-CSF) therapy has been associated with less acute GVHD. We studied the effect of G-CSF on interferon (IFN)-γ and IL-4 expression in CD4+lymphocytes. CD4+ cells co-cultivated with G-CSF and stimulated with PHA or CD3 monoclonal antibodies showed significant decreases in IFN-γ and increases in IL-4 expression (n = 13;P < .01). G-CSF appeared to have a direct effect on CD4+ cells independent of monocytes present in the culture because purified CD4+ cells exposed to G-CSF, washed, and cocultivated with untreated monocytes demonstrated similar changes in IFN-γ and IL-4 expression, whereas untreated CD4+ cells cocultured with G-CSF–stimulated monocytes behaved as controls. We then studied peripheral blood mononuclear cells (PBMCs) from G-CSF–mobilized PBSC donors. When their PBMCs were cultured with PHA or CD3 monoclonal antibody, the percent of IFN-γ–expressing cells decreased by a mean of 55% and 42%, respectively, whereas the percent of IL-4–containing cells increased by a mean of 39% and 58%, respectively, following G-CSF stimulation. Increased apoptosis of IFN-γ–producing CD4+ cells was not responsible for the shift in TH1/TH2 subsets. G-CSF-R mRNA was present in both CD4+ and CD8+ cells. These results suggest that G-CSF decreases IFN-γ and increases IL-4 production in vitro and in vivo and likely modulates a balance between TH1 and TH2 cells, an effect that may be important in PBSC transplantation.

scholarly journals A Specific Stimulator of Granulocyte Colony-Stimulating Factor Accelerates Recovery From Cyclophosphamide-Induced Neutropenia in the Mouse

Blood ◽  
1997 ◽  
Vol 90 (2) ◽  
pp. 795-802
Author(s):  
Jay S. Fine ◽  
Xiao-Yan Cai ◽  
Luminita Justice ◽  
Carl P. Gommoll ◽  
Linda D. Hamilton ◽  
...  
Keyword(s):  
Peripheral Blood ◽  
Mononuclear Cells ◽  
Human Peripheral Blood ◽  
Granulocyte Colony Stimulating Factor ◽  
Colony Stimulating Factor ◽  
Small Molecular Weight ◽  
Peripheral Blood Mononuclear ◽  
Stimulating Factor

We have identified a small molecular weight compound, SCH 14988, which specifically stimulates in vitro granulocyte-colony stimulating factor (G-CSF ) production from activated human peripheral blood mononuclear cells and monocytes but not other cytokines or CSFs with hematoregulatory activity. In vivo administration of SCH 14988 to mice rendered neutropenic by cyclophosphamide treatment resulted in the accelerated recovery of the peripheral neutrophil compartment. This activity correlated with increased in vivo G-CSF levels and stimulation of marrow granulopoiesis, and was comparable to that of exogenously administered recombinant human G-CSF. No alterations to other leukocyte populations in peripheral blood, spleen, or the peritoneal cavity were observed. These findings suggest that SCH 14988 may be clinically useful to enhance neutrophil granulopoiesis, as well as to study the mechanisms involved in G-CSF gene regulation.

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