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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)

Infections during granulocytopenia are major complications of autologous bone marrow transplantation (ABMT). Since recombinant human granulocyte-macrophage colony-stimulating factor (rhuGM-CSF) has proved to accelerate bone marrow recovery after cytostatic chemotherapy, we studied its effects on hematopoietic regeneration and on infectious complications after total body irradiation (TBI) and high-dose chemotherapy followed by ABMT. Eighty-one patients with acute lymphoblastic leukemia (ALL) in complete remission (CR) or with non-Hodgkin's lymphoma (NHL) in CR or partial remission were randomized in a double-blind, placebo-controlled trial. They received either rhuGM-CSF 250 micrograms/m2 (Escherichia coli-derived) daily by continuous infusion after ABMT, or placebo. Treatment was continued until the neutrophil counts reached greater than 500/microL for 1 week. The maximum treatment duration was 30 days. Thirty-nine patients in the rhuGM-CSF group and 40 patients in the placebo group were evaluable. The median time needed to reach a neutrophil count of 500/microL was 15 days with rhuGM-CSF and 28 days with placebo (P = .0001). Bacterial infections occurred in 14 (35.9%) of the patients with rhuGM-CSF and in 25 (62.5%) of the patients given the placebo (P = .024). Nine of the 14 bacterial infections in the rhuGM-CSF group and 20 of the 25 infections in the placebo group were diagnosed within the first 10 days after ABMT. Capillary leakage and a reversible fluid retention were seen in five of the rhuGM-CSF-treated patients. Patients treated with rhuGM-CSF had lower serum protein and albumin levels than patients in the placebo group. There was no statistically relevant difference in overall survival between the two groups (P = .47). Relapse occurred in 14 (34%) patients with rhuGM-CSF and in 18 (45%) patients with placebo. We conclude that continuous infusion of rhuGM-CSF after ABMT accelerates the regeneration of granulocytes and reduces the number of bacterial infections.
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PMID:A controlled trial of recombinant human granulocyte-macrophage colony-stimulating factor after total body irradiation, high-dose chemotherapy, and autologous bone marrow transplantation for acute lymphoblastic leukemia or malignant lymphoma. 142 90

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

High-dose methylprednisolone therapy (HDMP) induces acceleration of leukocyte recovery in acute lymphoblastic leukemia (ALL) and the differentiation of myeloblasts to mature granulocytes in acute myeloblastic leukemia (AML). These effects of corticosteroids have been shown to be due to the enhanced colony-stimulating activity (CSA) and responses to corticosteroids in some patients with aplastic anemia and myelodysplastic syndromes (MDS) have been related to increased CSA activity. We measured the serum (granulocyte-macrophage colony-stimulating factor (GM-CSF) levels by a sandwich linked immunoabsorbent assay (ELISA) in patients with ALL and AML at presentation and following high-dose methylprednisolone (HDMP) therapy. Serum GM-CSF levels at presentation in the ten cases studied ranged between 160 and 700 pg/ml (mean 418.5 +/- 252.5). One week following HDMP therapy GM-CSF levels increased to between 260 and 950 pg/ml (733.5 +/- 203.2). Four weeks after therapy the GM-CSF levels increased to between 470 and 1350 pg/ml (911 +/- 278.7). GM-CSF levels were markedly elevated one week after HDMP in the patients with ALL, suggesting that in addition to the lymphotoxic effects on leukemic blasts, the acceleration in neutrophil recovery may be due to release of GM-CSF induced by HDMP and its effects on myeloid progenitors.
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PMID:The effect of high-dose methylprednisolone treatment on GM-CSF level in children with acute leukemia: a pilot study. 163 79

The production of colony-stimulating activity (CSA) by phytohemagglutinin (PHA)-stimulated peripheral blood mononuclear cells (PBMC) from patients receiving maintenance chemotherapy for acute lymphoblastic leukemia (ALL) was examined. Supernatants from only 14 of 22 patient PBMC cultures (64%), but all supernatants from normal PBMC cultures, supported myeloid colony growth. When present, colony-stimulating activity always included granulocyte-macrophage colony-stimulating factor (GM-CSF). In addition, in nine of ten patient studies and in all control studies, stimulated PBMC produced interleukin-1 (IL-1). These results show that the chemotherapy administered to children with ALL can damage the cytokine production mechanisms in PBMC; the diminished ability to produce GM-CSF and IL-1 may contribute to the increased risk of overwhelming infection in these patients.
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PMID:Defective production of granulocyte-macrophage colony-stimulating factor and interleukin-1 by mononuclear cells from children treated for acute lymphoblastic leukemia. 164 Jul 33

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.
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PMID:Granulocyte-macrophage colony-stimulating factor (GM-CSF) and granulocyte colony-stimulating factor (G-CSF) in serum in bone marrow transplanted patients. 172 Mar 39

Thirty-four adults with refractory acute lymphocytic leukemia received salvage therapy with mitoxantrone 5 mg/m2 intravenously over 1 hour daily for 5 days and cytosine arabinoside (ara-C) 3 g/m2 intravenously over 2 hours every 12 hours for six doses, followed by granulocyte-macrophage colony-stimulating factor (GM-CSF) 125 microgram/m2 intravenously over 4 hours daily until recovery of granulocytes above 2.0 x 10(3)/microL. Their outcome was compared with 29 prognostically similar historical control patients treated with the identical chemotherapy without GM-CSF. Overall, the complete response rates were similar in the treatment and control groups (13 of 34 [38%] v 11 of 29 [38%]). There was a trend for less remission induction mortality in the GM-CSF-treated patients (2 of 34 [6%] v 6 of 29 [21%]; P = .08), but, conversely, a higher rate of resistant disease (19 of 34 [56%] v 10 of 29 [34%]; P = .09). Recovery of granulocyte counts above 500/microL was significantly faster in the GM-CSF-treated group (25 days v 33 days; P less than .01), but there was no reduction in the incidence of febrile episodes (91% v 93%) or of documented infections (59% v 59%). Survival was prolonged in the GM-CSF-treated patients but was not of clinical relevance (31 v 20 weeks; P = .05). In summary, the addition of GM-CSF to intensive chemotherapy in refractory adult ALL was associated with a reduction in the remission induction mortality, probably secondary to a shorter duration of granulocytopenia, but not with an improvement in complete response rates.
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PMID:Intensive chemotherapy with mitoxantrone and high-dose cytosine arabinoside followed by granulocyte-macrophage colony-stimulating factor in the treatment of patients with acute lymphocytic leukemia. 173 98

We investigated the effect of recombinant human interleukin-4 (rhIL-4) on the in vitro growth of human leukemia cells in liquid culture and 3H-thymidine incorporation and found inhibitory effects on the growth of leukemic cells from patients with Ph1-positive acute lymphoblastic leukemia (Ph1 ALL) and three Ph1 ALL cell lines. However, no inhibitory effects were seen in Ph1-positive leukemic cell lines derived from patients with chronic myelogenous leukemia in blast crisis and various types of Ph1-negative leukemia cells, including B-lineage leukemia cells. In a flow cytometry assay of IL-4 receptor (IL-4R), all three Ph1-positive ALL cell lines showed the presence of IL-4R on their cell surfaces, and the IL-4-dependent inhibition on the growth of Ph1-positive ALL cells was abrogated by the addition of either monoclonal or polyclonal antibodies against rhIL-4. Other cytokines, including IL-2, IL-3, granulocyte-macrophage colony-stimulating factor (CSF), granulocyte-CSF, and IL-6, showed no inhibitory effects on the growth of Ph1-ALL cells, but tumor necrosis factor-alpha (TNF-alpha) and interferon (IFN)-alpha, -beta, and -gamma displayed slight inhibitory effects in a high concentration. The growth inhibition induced by rhIL-4 in the Ph1-positive ALL cells was not abrogated by the addition of antibodies against either IFN-gamma or TNF-alpha. Furthermore, these cells showed no significant production of IFN-alpha, -beta, or -gamma or TNF-alpha after exposure to rhIL-4, thus indicating that the growth inhibition of Ph1-positive ALL cells by rhIL-4 is not associated with IL-4-stimulating production of these factors. rhIL-4 caused significant inhibition of the tyrosine kinase activity in these Ph1-positive ALL cells, similar to Herbimycin A, an inhibitor of tyrosine kinase that inhibited the tyrosine kinase activity in these cells. Our finding suggests that the clinical evaluation of rhIL-4 may offer promising therapeutic possibilities for patients with Ph1-positive ALL.
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PMID:Inhibitory effect of interleukin-4 on the in vitro growth of Ph1-positive acute lymphoblastic leukemia cells. 188 23

An in vitro colony assay was used to examine the growth stimulatory effects of a variety of recombinant human lymphohemopoietic cytokines on human precursor-B acute lymphoblastic leukemia (ALL) cells. Of 23 cases evaluated, 16 formed significant numbers of colonies (mean 280, range 36-939) when cultured in 10% fetal calf serum in 0.8% methylcellulose containing 10% partially purified B-cell growth factor (BCGF). Immunoperoxidase staining of cells from cultures confirmed a precursor-B phenotype (HLA-DR+, CD-10+, CD-19+, CD-34+, Ig-, CD-3-, CD-11C-). When these cases were cultured with recombinant human cytokines (but without BCGF) only a minority showed colony formation, in all instances less than seen with BCGF. Three cases were stimulated both by interleukin 3 (IL-3) and the putative pre-B growth factor interleukin 7 (IL-7). One case was stimulated both by tumor necrosis factor alpha and by interleukin 6 (IL-6); these results were confirmed on highly purified CD-10+, CD-19+ cells prepared by fluorescence-activated cell sorting. A further case was stimulated by granulocyte-macrophage colony-stimulating factor (GM-CSF), including CD-10+, CD-19+ purified cells. All cases responding to recombinant cytokines were heavily pretreated patients at relapse, whereas none of the newly diagnosed untreated cases showed any response. These results confirm that activities present in BCGF are the major stimulant for precursor-B ALL proliferation in vitro. None of the recombinant cytokines examined, including IL-7, appeared to have consistent activity under these culture conditions. The molecules regulating growth of ALL remain to be more precisely defined.
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PMID:Effects of recombinant human cytokines on precursor-B acute lymphoblastic leukemia cells. 189 54

Myeloid colony growth by bone marrow cells obtained from pediatric cancer patients was stimulated by granulocyte-macrophage colony-stimulating factor (GM-CSF) and/or interleukin 1 (IL-1). Although patients recovering from cyclic high-dose chemotherapy showed normal colony growth in response to GM-CSF, patients with acute lymphoblastic leukemia (ALL) receiving continuous maintenance chemotherapy at moderate dose had variable but often severe decreases in myeloid colony growth compared with controls. Marrow from all patients and controls demonstrated enhanced colony growth in GM-CSF-stimulated cultures which also contained IL-1. For patients on continuous daily maintenance therapy for ALL, enhancement of myeloid colony growth in response to IL-1 was proportional to the decrease in colony growth in response to GM-CSF. These observations support a possible clinical role for GM-CSF or other direct stimulators of myeloid growth in the patients receiving episodic high doses of chemotherapy, but suggest that alternative strategies may be more effective for those patients receiving chronic moderate-dose chemotherapy.
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PMID:Differential effect of continuous versus cyclic maintenance chemotherapy on cytokine-induced myeloid colony growth. 219 67

The effects of recombinant human granulocyte colony-stimulating factor (rhG-CSF) and recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) on primary human leukemic cells were studied. Phagocyte-depleted mononuclear cells containing more than 88% blasts were obtained from peripheral blood of 11 AML and 2 ALL patients and from bone marrow aspirates from 2 ALL patients. The leukemic cells were incubated with these CSF in suspension cultures or in methylcellulose cultures. In suspension cultures, the spontaneous proliferation was observed in 1 M4 patient. RhG-CSF stimulated the leukemic cell proliferation in 5 AML, cases and rhGM-CSF that in 4 AML cases. In methylcellulose cultures, spontaneous colony formation occurred in 3 M4 patients. RhG-CSF and rhGM-CSF stimulated the leukemic colony formation in 8 AML cases. The CSFs had an additive effect in both cultures. Neither CSF induced O2- production or phagocytic activity. From these results, we concluded that both CSFs stimulated the proliferation of leukemic cells without inducing differentiation.
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PMID:Effects of recombinant human G-CSF and GM-CSF on primary human leukemic cells. 248 49


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