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Query: UNIPROT:P04141 (granulocyte-macrophage colony-stimulating factor)
 6,790 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Clinical trials with hematopoietic growth factors (granulocyte-macrophage colony-stimulating factor [GM-CSF], granulocyte colony-stimulating factor [G-CSF], interleukin-3, erythropoietin] have been done in patients with myelodysplastic syndromes. Treatment with GM-CSF or G-CSF has resulted in an increase of neutrophil counts into the normal range in the vast majority of patients. Progression to acute leukemia does not appear to occur more frequently in the patients receiving GM-CSF or G-CSF. Increases in platelet counts and hemoglobin levels have been reported after treatment with interleukin-3 and erythropoietin, respectively, although the response is only seen in a minority of treated patients. Combination therapy with GM-CSF and low-dose cytosine arabinoside has been studied, but present data do not indicate an advantage over other treatment strategies. Cytogenetic and molecular genetic analyses demonstrate that both normal and malignant precursor cells are stimulated by cytokine therapy.
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PMID:Treatment of myelodysplastic syndromes with cytokines and cytotoxic drugs. 137 66

We examined the stimulatory effects of recombinant human granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin 6 (IL)-6 on the in vitro proliferation of leukemic blast cells from patients with acute leukemia. Bone marrow or peripheral blood leukemic blast cells were obtained from 21 patients, including 14 cases of acute myeloblastic leukemia (AML), four cases of acute lymphoblastic leukemia (ALL), two cases of acute undifferentiated leukemia, and one case of acute mixed-lineage leukemia. The proliferation of leukemic blast cells was evaluated by measuring the incorporation of 3H-thymidine into cells incubated with various concentrations of cytokines for 3 days. GM-CSF stimulated the DNA synthesis (with greater than 2.0 stimulation index) of blast cells in 9 of 14 (64%) AML cases, two cases of acute undifferentiated leukemia and one case of acute mixed-lineage leukemia. Only two cases of AML blasts responded to IL-6 to grow in the short-term suspension cultures. GM-CSF and IL-6 did not display a synergistic effect on the growth of leukemic cells. Moreover, GM-CSF and IL-6 did not stimulate the proliferation of ALL blast cells. Binding study also revealed the specific binding of GM-CSF on the blast cells of acute undifferentiated leukemia and acute mixed-lineage leukemia. Our results indicated that leukemic blast cells of acute undifferentiated leukemia and acute mixed-lineage leukemia possessed functional GM-CSF receptors.
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PMID:Effects of granulocyte-macrophage colony-stimulating factor and interleukin 6 on the growth of leukemic blasts in suspension culture. 161 67

The primary objective of this study was to compare the toxicity and hemopoietic effects of s.c. and i.v. recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) in patients with primary myelodysplasia. Twenty patients were treated in this phase I crossover-designed study. In three groups of patients, the dose of rhGM-CSF was escalated from 60 to 250 micrograms/m2/day. Each patient was to receive 2 weeks of i.v. (daily 2-h infusion) and s.c. (twice daily) rhGM-CSF separated by a 2-week rest period. The decision to start with i.v. or s.c. administration was by random selection. Toxicity was comparable between i.v. and s.c. administration. At the highest dose level, 63% (five of eight) of the patients developed moderate to severe toxicity. Increases in the absolute neutrophil count showed a dose-response relationship and were more pronounced with s.c. than i.v. administration. Failure to grow in vitro granulocyte-macrophage colonies or a hypocellular marrow (less than or equal to 30%) predicted for a poor response to therapy. No patient had a platelet or a reticulocyte response. No patient progressed to acute leukemia. Compared to a 2-h infusion of i.v. rhGM-CSF, s.c. administration is more myelostimulatory without an increase in toxicity.
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PMID:Comparison of intravenous versus subcutaneous recombinant human granulocyte-macrophage colony-stimulating factor in patients with primary myelodysplasia. 205 92

Recombinant human granulocyte-macrophage colony-stimulating factor (GM-CSF) was administered to 10 patients with refractory malignancies, 2 patients who had myelodysplastic syndromes with severe neutropenia and to a patient who had delayed marrow recovery after 3 cycles of therapy for acute leukemia. A marked neutropenia and monocytopenia was observed within 5 min after an i.v. injection of GM-CSF. This persisted for 1-2 h and seemed related to activation of an adhesive glycoprotein (MO1) on the surface of these cells. With continued daily i.v. administration of GM-CSF, all patients with refractory malignancies developed a striking leukocytosis. Total leukocyte counts reached 75,000/microliters within 2 weeks of treatment. This was due to an increase in band and segmented neutrophils, eosinophils and monocytes. Accelerated myelopoiesis required the continuous presence of GM-CSF; with pump failure for 24 h or discontinuation after 14 days, leukocyte counts returned to normal levels in 24-48 h. GM-CSF also increased myelopoiesis in the patients with myelodysplastic syndromes or following anti-leukemic treatment. These observations suggest that this growth factor should prove a useful adjunct in the treatment of patients with malignancies and bone marrow failure.
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PMID:Use of granulocyte-macrophage colony-stimulating factor in patients with malignancy and bone marrow failure. 218 42

The hematopoietic growth factors recombinant human granulocyte-macrophage colony-stimulating factor and recombinant human granulocyte colony-stimulating factor are associated with changes of the bone marrow. To evaluate the morphologic features and to differentiate them from leukemia, bone marrow specimens from 12 patients who had been treated with one of these agents were evaluated. The bone marrow displayed marked promyelocytic hyperplasia and a less striking increased percentage of myeloblasts. In each of the 11 patients without leukemia at the time of bone marrow biopsy, the percentage of promyelocytes in the bone marrow was greater than that of myeloblasts. Cytologic features of stimulated regeneration included diffuse cytoplasmic hypergranulation of immature neutrophilic precursors that had prominent perinuclear spherical clear areas representing the Golgi zones. With consideration of bone marrow composition and careful attention to cytologic detail, the distinction of bone marrow regeneration from acute leukemia can be made in most patients who are being treated with recombinant hematopoietic growth factors.
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PMID:Bone marrow changes associated with recombinant granulocyte-macrophage and granulocyte colony-stimulating factors. Discrimination of granulocytic regeneration. 751 17

We treated 115 patients in a phase I/II dose-escalation study of ifosfamide/carboplatin/etoposide (ICE) followed by autologous stem cell rescue. Patients treated had a variety of diagnoses, including breast cancer (high-risk stage II disease with eight or more positive nodes, stage III disease, and responsive metastatic disease), non-Hodgkin's lymphoma, Hodgkin's disease, acute leukemia in first remission, and various solid tumors that were responsive to induction therapy. Patients received autologous bone marrow stem cells or peripheral blood stem cells primed by one of several methods. The maximum tolerated dose of ICE was determined to be ifosfamide 20,100 mg/m2, carboplatin 1,800 mg/m2, and etoposide 3,000 mg/m2 when administered as a 6-day regimen. The dose-limiting toxicities included acute renal failure, severe central nervous system toxicity, and "leaky capillary syndrome" with hypoalbuminemia, profound fluid overload, and pulmonary insufficiency. Analysis of hematologic recovery based on stem cell source and influence of hematopoietic growth factor administration was undertaken. Hematopoietic growth factor use significantly reduced neutrophil engraftment time for patients receiving bone marrow stem cells, with evidence of earlier recovery times for patients receiving granulocyte colony-stimulating factor compared with granulocyte-macrophage colony-stimulating factor. Neutrophil recovery times varied based on the source of stem cells used, with the earliest engraftment times seen for patients receiving peripheral blood stem cells primed with cyclophosphamide and granulocyte colony-stimulating factor. Platelet recovery times were not statistically different for any of the subsets. In conclusion, the maximum tolerated dose of ICE has been defined, and the source of stem cells and the use of hematopoietic growth factors influence hematopoietic recovery.
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PMID:High-dose ifosfamide/carboplatin/etoposide: maximum tolerable doses, toxicities, and hematopoietic recovery after autologous stem cell reinfusion. 752 92

High-dose chemotherapy regimens can cure a number of otherwise incurable diseases, such as Hodgkin's disease, non-Hodgkin's lymphoma, neuroblastoma, acute leukemia (in remission), and breast cancer. Trials of high-dose chemotherapy have generally used autologous bone marrow transplant or peripheral blood stem cell support to ensure hematologic recovery after intensive chemotherapy and/or radiation. This report describes an approach in which high-dose carboplatin chemotherapy was followed initially by granulocyte-macrophage colony-stimulating factor (GM-CSF; Escherichia coli. Sandoz-Schering, East Hanover and Kenilworth, NJ) and in subsequent patients, by both GM-CSF and repeated cycles of peripheral blood progenitor cell (PBPC) collection and administration. The addition of PBPC to this regimen led to significant reductions in the duration of neutropenia and thrombocytopenia, the requirement for erythrocyte and platelet transfusions, the length of hospital stay, and the use of intravenous antibiotics in this group relative to those patients who received GM-CSF alone. In addition, laboratory studies are presented that show a direct correlation between the number of progenitor cells reinfused and the duration of neutropenia and thrombocytopenia. The report also reviews data indicating that circulating progenitor cells are depleted by this approach. This suggests that the number of progenitor cells available for mobilization is finite. Finally, the magnitude of these effects, and their implications for future trials with repetitive cycles of dose-intensive therapy, are discussed.
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PMID:High-dose carboplatin chemotherapy with GM-CSF and peripheral blood progenitor cell support: a model for delivering repeated cycles of dose-intensive therapy. 810 54

Fanconi anemia is a congenital syndrome characterized by multiple specific physical anomalies, progressive marrow failure, and a predisposition to acute leukemia. We studied the toxicity and efficacy of daily subcutaneous administration of recombinant human granulocyte-macrophage colony-stimulating factor (GM-CSF) in patients with Fanconi anemia and pancytopenia. The toxicity of GM-CSF at the doses and schedule used was minimal. Six of seven patients entered had an increase in the neutrophil count of 7- to 25-fold, which was maintained during the course of study. Despite increases in the reticulocyte count, increases in hemoglobin concentration were rare. No improvement in platelet count was evident in any patient. No patient has evidence of leukemia after up to 19 months of continuous GM-CSF exposure, and all five surviving patients remain responsive to treatment. Although the optimal dose, schedule, and choice of cytokine for patients with marrow failure and Fanconi anemia are not established by this preliminary study, the data indicate that (1) GM-CSF may be able to palliate at least the neutropenia and potentially the neutropenic complications of the disease, (2) this effect can be sustained for more than 1 year, and (3) rapid evolution of acute leukemia is unlikely to be a frequent outcome of such treatment. The clinical impact of GM-CSF or other cytokines in patients with Fanconi anemia and pancytopenia remains to be established by further studies.
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PMID:Evaluation of granulocyte-macrophage colony-stimulating factor for treatment of pancytopenia in children with fanconi anemia. 828 65

Nineteen adults with primary refractory or relapsed acute leukemia (12 ALL and 7 ANLL) were treated with an intensive salvage chemotherapy (intermediate-dose ara-C, intermediate-dose methotrexate, vindesine, cyclophosphamide, mitoxantrone and prednisolone) followed by a hematopoietic growth factor (HGF), either granulocyte colony-stimulating factor (5 micrograms/kg) or granulocyte-macrophage colony-stimulating factor (10 micrograms/kg). Both were given from the day after chemotherapy ended and until the neutrophil count rose above 1 X 10(9)/l for three consecutive days. Eleven patients (58%, 95% CI 33% to 82%) achieved complete remission, and 15 courses of salvage therapy were given to these complete responders. In a historical control group that did not receive HGF, 23 out of 38 patients (60%, 95% CI 44% to 77%) achieved complete remission, and 27 courses of therapy were delivered to complete responders. Treatment with a HGF accelerated the recovery of neutrophils to 0.5 X 10(9)/l significantly, shortening it from a mean of 28 to 22 days (p = .0002), with no effect on platelet recovery. There were no differences in the rates of documented and fatal infections, which were relatively high in both groups. In the patients with ANLL, there was no evidence that HGF accelerated leukemic regrowth. We conclude that HGF accelerates neutrophilic recovery following intensive salvage chemotherapy for acute leukemia, although no reduction in documented infections was found. Many factors, including the small patient sample, may have contributed to this latter finding.
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PMID:Hematopoietic growth factor (G-CSF or GM-CSF) after salvage chemotherapy in refractory or relapsed adult de novo acute leukemia. 862 74

High-dose methylprednisolone (HDMP, 20-30 mg/kg/day po) treatment has been shown to increase the number of bone marrow and peripheral blood CD34 positive progenitors and serum granulocyte-macrophage colony-stimulating factor (GM-CSF) levels in patients with ALL and AML. To investigate the effect of HDMP on some other hematopoietic regulatory cytokines, tumor necrosis factor-alpha (TNF-alpha), gamma-interferon (gamma-INF), granulocyte colony-stimulating factor (G-CSF) and interleukin-6 (IL-6) were studied by microplate ELISA technique in 15 chemotherapy-induced neutropenic episodes of 14 children with acute leukemia (eight with ALL and six with AML) in whom HDMP was given alone (30 mg/kg/day po) for 4 days. The absolute neutrophil counts increased significantly in all neutropenic episodes on the fourth day of HDMP treatment. The TNF-alpha was 93.5 +/- 161 pg/ml in ALL and 78.3 +/- 61.4 pg/ml in AML before treatment and 76.1 +/- 160 pg/ml in ALL and 19.1 +/- 39.8 pg/ml in AML after treatment. The gamma-INF was 204.1 +/- 210.3 pg/ml in ALL and 130.8 +/- 138.3 pg/ml in AML before treatment and 28.6 +/- 50.5 pg/ml in ALL and 23.3 +/- 20.4 pg/ml in AML after treatment (P<0.05). Serum G-CSF and GM-CSF levels increased in all episodes (100%). The GM-CSF levels increased from 12.2 +/- 10.9 pg/ml to 36 +/- 24.7 pg/ml after treatment in ALL (P<0.05) and from 13.3 +/- 4 pg/ml to 45 +/- 48.1 pg/ml in AML (P<0.05). Serum G-CSF levels increased from 13.3 +/- 11.7 pg/ml to 83.3 +/- 86.8 pg/ml after treatment in ALL (P<0.05) and from 6.6 +/- 12.1 pg/ml to 28.3 +/- 11.3 pg/ml in AML (P<0.05). However, IL-6 levels were undetectable in all patients before and after therapy. These preliminary data suggest that short-course HDMP treatment could decrease serum TNF-alpha and gamma-INF and increase G-CSF and GM-CSF levels.
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PMID:Serum TNF-alpha, gamma-INF, G-CSF and GM-CSF levels in neutropenic children with acute leukemia treated with short-course, high-dose methylprednisolone. 863 22


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