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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)

This prospective open trial evaluated the efficacy and tolerability of recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) in patients with established neutropenia, considering as the main endpoint the clinical benefit to the patients regarding clearing of infection or resuming chemotherapy as initially planed. Adult patients (n = 28) with absolute neutrophil counts (ANC) < 10(9)/1 for 21 days were given a fixed dose (400 micrograms) of rhGM-CSF subcutaneously, for a total of 35 cycles. Causes of neutropenia were chemotherapy for acute leukaemia, lymphoma, myeloma and solid tumours, complications after bone marrow transplantation (BMT), and neutropenia associated with AIDS. Response (ANC to > 10(9)/l) occurred in 83% of rhGM-CSF cycles (29/35). Median time to response was 2.4 days (mean 6.7 days). Kinetics of response was dependent on diagnosis and treatment history. Fever abated with increasing ANC in 13/17 patients (76%) who entered the trial with hyperpyrexia. Treatment with rhGM-CSF allowed chemotherapy to be resumed on schedule in 7/9 relevant cycles. Toxicity was mild, leading to treatment interruption in only two cycles. In conclusion, rhGM-CSF was well tolerated and associated with a rise in ANC which appeared to result in immediate clinical benefit, including resolution of infection and resumption of scheduled chemotherapy.
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PMID:Recombinant human granulocyte-macrophage colony-stimulating factor in acquired or chemotherapy-induced neutropenia. An open clinical trial. 794 41

A large number of AML cases is reviewed in order to clarify biological characteristics of t(8;21) AML cells. The incidence of positivities for stem cell antigens, CD34 and HLA-DR, on blasts in t(8;21) AML is higher in comparison with those in other M2 or M3 categories. Frequent expression of CD34 and HLA-DR is indicative of the stem cell derivation of t(8;21) AML cells. The non-blastic leukemic cells in t(8;21) AML tend to lose the immature phenotype with discordant maturation such as low CD33 expression. Further, the blasts show frequent expression of the B-cell antigen, CD19, without other B-cell antigens and immunoglobulin gene rearrangements. AML cells with t(8;21) showed poorer response to granulocyte-macrophage colony-stimulating factor (GM-CSF) due to a decreased number of GM-CSF binding sites. The absence of monocytic differentiation in t(8;21) AML cells might represent the abnormal response to growth factors at the bifurcation stage of granulocyte and monocyte differentiation. Recently, breakpoint region genes for the 8;21 translocation in chromosome 8 and 21 have been isolated, 48-50 and have been named AML1 and ETO, respectively. The AML1 gene showed a strong homology with the Drosophila segmentation gene, runt, which is thought to be necessary for the Sex lethal gene expression. Since the GM-CSF receptor alpha chain gene locates in the pseudoautosomal region of the sex chromosome, the decrease of GM-CSF binding sites might be related to the AML1/ETO fusion gene expression. Further molecular genetic investigations of the breakpoint genes in the future are expected to clarify the unique biological events seen in this type of leukemia.
Leuk Lymphoma 1994 Apr
PMID:Cellular characteristics of acute myeloblastic leukemia associated with t(8;21)(q22;q22). The Japanese Cooperative Group of Leukemia/Lymphoma. 804 46

A total of 41 patients who underwent autologous bone marrow transplantation without the use of granulocyte-macrophage colony-stimulating factor were retrospectively evaluated to determine whether the infusion of peripheral blood stem cells collected during the period of recovery of bone marrow from previous disease-specific chemotherapy could shorten the time to bone marrow engraftment after transplantation. Of the 41 patients, 24 patients received bone marrow only (group 1), 8 patients received bone marrow plus steady-state peripheral blood stem cells (group 2) and 9 patients received bone marrow plus rebound peripheral blood stem cells collected during the period of recovery from disease-specific chemotherapy (group 3). Infusion of rebound peripheral blood stem cells (group 3) accelerated recovery of white blood cells and neutrophils and resulted in a white blood cell count of > 10(9)/L by day 15 compared with day 25 in group 1 (P < 0.001), and a neutrophil count of > 0.5 x 10(9)/L by day 16 versus day 26 in group 1 (P = 0.0034). Addition of steady-state peripheral blood stem cells (group 2) did not hasten myeloid engraftment, and recovery of platelets was not improved in either group given peripheral blood stem cells. Compared with patients in group 1, patients in group 3 required 7 fewer days of parenteral antibiotics (25 days versus 18 days, respectively; P = 0.0072) and were discharged about 3 weeks earlier than patients in group 1 (day + 41 verus day +21; P = 0.0002).(ABSTRACT TRUNCATED AT 250 WORDS)
Leuk Lymphoma 1993 Apr
PMID:Peripheral blood stem cells harvested during marrow recovery from disease-specific chemotherapy shorten duration of neutropenia in patients undergoing autologous bone marrow transplantation. 810 55

The mechanisms that regulate the mRNA levels of interleukin-5 (IL-5) were compared with those regulating the mRNA levels of two other coordinately expressed lymphokines in the murine T lymphoma EL4.23. Our results indicate that IL-5 mRNA levels are independently regulated from those of IL-2 and granulocyte-macrophage colony-stimulating factor (GM-CSF) mRNAs. The induction of IL-5 mRNA by phorbol 12-myristate 13-acetate (PMA) stimulation was found to be cyclosporin A-resistant, in contrast to the induction of IL-2 and GM-CSF mRNAs. Although the three lymphokine mRNAs were not detected in unstimulated cells by Northern blot analysis, the GM-CSF gene was found by nuclear run-off analysis to be constitutively transcribed. However, the IL-2 and IL-5 genes were transcriptionally inactive in the absence of PMA stimulation. The induction of IL-5 mRNA by PMA stimulation primarily involved increased transcriptional activity. In contrast, GM-CSF mRNA induction predominantly involved enhanced mRNA stability. Both transcriptional and mRNA stabilization mechanisms appeared to regulate IL-2 mRNA induction. The activation of IL-2 and IL-5 gene transcription was dependent on de novo protein synthesis. Cellular treatment with cycloheximide enhanced IL-2 gene transcription once activation was initiated, implicating the involvement of a labile repressor(s). Furthermore, IL-5 mRNA was more stable than IL-2 and GM-CSF mRNAs. These latter two species were stabilized by cycloheximide, suggesting that a labile mechanism may regulate their degradation.
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PMID:Mechanisms regulating the mRNA levels of interleukin-5 and two other coordinately expressed lymphokines in the murine T lymphoma EL4.23. 820 86

A case of non-Hodgkin's T cell lymphoma (diffuse lymphoma, large cell type) associated with marked eosinophilia and pleurisy in a 57-year-old male is reported. The leukocyte count was 12.5 x 10(3)/microliters and eosinophil count was 53% and the absolute count of 6.6 x 10(3)/microliters. The patient's serum and pleural effusion fluid, containing abundant lymphoma cells, showed eosinophil colony stimulating factor (Eo-CSF) activity. Conditioned medium (CM) prepared from patient's T cells (T-CM) produced Eo-CSF and this was enhanced by interleukin-2 (IL-2) stimulation. We demonstrated that the patient's serum contained a significant amount of interleukin-5 (IL-5) and the patient's T-CM, particularly after IL-2 stimulation contained a significant amount of granulocyte-macrophage colony-stimulating factor (GM-CSF). These findings suggest that Eo-CSF produced by neoplastic T cells or normal T cells activated by tumor antigen stimulated the production of eosinophils in this patient and that both IL-5 and GM-CSF might play a role in Eo-CSF activity.
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PMID:[Non-Hodgkin's T cell lymphoma associated with marked eosinophilia]. 823 Jul 43

Recombinant human interleukin-3 (rhIL-3) was administered to 30 patients undergoing autologous bone marrow transplant (ABMT) for treatment of lymphoma. In this phase I dose escalation study, rhIL-3 was administered from day 0 to 20 after ABMT by 2-hour intravenous infusion at dose levels of 1, 2, 5, and 10 micrograms/kg/d. Seventeen patients did not complete therapy with rhIL-3. Eleven requested early discontinuation for malaise, confusion, transplant complications, or rapid engraftment and were removed from the study, whereas six patients developed grade III toxicity, including fever (three patients), or headache (three patients) possibly attributable to rhIL3. Other common toxicities included diarrhea, rigors, mucositis, and rash. The maximum tolerated dose of rhIL-3 was 2 micrograms/kg/d. No evidence of earlier hematopoietic cell recovery was observed compared with similar historical patients treated with recombinant human granulocyte-macrophage colony-stimulating factor. Future trials will be needed to determine alternate schedules of administration of rhIL-3 or the use of rhIL-3 in combination or in sequence with other growth factors.
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PMID:Phase I trial with recombinant human interleukin-3 in patients with lymphoma undergoing autologous bone marrow transplantation. 824 99

Tumor infiltrating lymphocytes (TIL) were cultured from 17 B-cell lymphoma specimens derived from patients with predominantly low-grade malignancies. Specimens included 15 lymph-node biopsies, 1 malignant pleural effusion, and PBL from 1 patient with circulating lymphoma cells. The phenotypic and proliferative characteristics of TIL cultured in interleukin-2 (IL-2) were studied, as well as cytolysis and cytokine secretion in response to autologous tumor. Flow cytometry of fresh tumor suspensions showed that 50% of cells (median) were malignant B cells and 36% were infiltrating T lymphocytes. After culture for approximately 1 month, TIL were 75% +/- 8% CD3+ (mean +/- SEM), 47% +/- 8% CD4+ and 35% +/- 7% CD8+. TIL proliferation was modest in most cases: the median maximum expansion was 32-fold in 25 days. Lysis of autologous tumor in 4-hour 51Cr release assays was mediated by 2 of 12 TIL studied, but was nonspecific. However, these same two TIL, when cocultured with various tumor stimulators, preferentially secreted tumor necrosis factor-alpha and granulocyte-macrophage colony-stimulating factor after autologous tumor stimulation; unstimulated TIL secreted undetectable or barely detectable levels of these cytokines. In one TIL culture, cytokines were secreted by purified CD4+ TIL but not by CD8+ cells, and secretion was completely abrogated by the anti-major histocompatibility complex (MHC) class II antibody IVA12. Thus, although specific cytokine secretion by lymphoma TIL in response to autologous tumor was observed, it occurred in fewer than 20% of patients studied.
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PMID:Tumor-infiltrating lymphocytes derived from select B-cell lymphomas secrete granulocyte-macrophage colony-stimulating factor and tumor necrosis factor-alpha in response to autologous tumor stimulation. 835 84

Hematological malignancies accompanied by eosinophilia are reviewed in relation to chromosomal changes and cytokine production. Eosinophilia accompanied by hematological malignancies can be divided into two groups. In some myelogenous leukemias, including acute myelomonocytic leukemia with eosinophilia (FAB M4Eo), acute myeloblastic leukemia (FAB M2 t(8;21)) and chronic myelogenous leukemia, neoplastic cells themselves appear to differentiate into eosinophils. On the other hand, transformed tumor cells secrete some eosinophil-stimulating cytokines, including interleukin-3, interleukin-5 and granulocyte-macrophage colony-stimulating factor and these cytokines stimulate the proliferation of normal eosinophil precursors in some lymphoid malignancies, including some types acute lymphoblastic leukemia (especially with t(5;14)) or malignant lymphoma, including Hodgkin's lymphoma and adult T cell lymphoma/leukemia.
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PMID:[Hematological malignancies with eosinophilia]. 849 61

To a great extent, the risks of autologous bone marrow transplantation are related to neutropenia. Although the efficacy of the recombinant human granulocyte-macrophage colony-stimulating factor (rhu GM-CSF) on neutrophil recovery has appeared in numerous open trials, only a few randomized studies have hitherto been published. Ninety-one patients with non-Hodgkin's malignant lymphoma treated with ablative chemotherapy followed by purged or unpurged bone marrow transplantation were entered in a placebo-controlled, double-blind randomized study; 44 patients received GM-CSF (E. coli) in doses of 250 micrograms/m2/day, and 47 received a placebo. Treatment was administered daily as continuous infusion started on the day of transplantation and pursued until the absolute number of neutrophils reached 0.5 x 10(9)/l during 7 days or, if this failed, during 30 days. The median time of neutrophil recovery was 14 days in patients on rhu GM-CSF and 21 days in patients on placebo (P < 0.0001). Patients who received a mafosfamide-purged bone marrow also had a rapid neutrophil recovery (median: 16 days versus 20.5 days; P = 0.013). The stay in hospital was shorter in the rhu GM-CSF group (median: 23 days versus 28 days; P < 0.05). No significant difference in the number of days with fever, infections, antibiotics administered and overall survival was detected between the two groups. The main toxicity ascribable to rhu GM-CSF was a capillary leakage syndrome found in 3 patients. Thus, after purged or unpurged autologous bone marrow transplantation rhu GM-CSF significantly reduces the duration of both neutropenia and hospital stay.
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PMID:[Hematopoietic growth factor (GM-CSF) after autologous bone marrow transplantation. A randomized, double-blind, multicenter study in 91 cases of non-Hodgkin's malignant lymphomas]. 849 15

Granulocyte-macrophage colony-stimulating factor (GM-CSF) has been reported to induce antitumor activity in peripheral blood monocytes. We examined the role of GM-CSF on bone marrow (BM) macrophages in inducing antibody-dependent cellular cytotoxicity (ADCC) against murine and human tumor cells in vitro and in vivo with the aim of applying this approach in an autologous bone marrow transplantation (BMT) setting. GM-CSF induced a potent ADCC in BM macrophages against a murine melanoma in vitro. Treatment with GM-CSF alone or with antibody alone had no effect, whereas therapy with combination of both these agents resulted in a significant reduction in dissemination of melanoma both in a nontransplant as well as in BMT settings, with results being more optimal in the latter setting. Adoptive transfer of BM macrophages harvested from mice undergoing therapy with GM-CSF plus antibody significantly reduced the dissemination of melanoma in secondary recipients but only after irradiation, not in intact mice. GM-CSF also induced significant ADCC in human BM macrophages against a melanoma and a lymphoma in vitro and against a lymphoma implanted in nude mice in vivo. Again, these effects were more optimal after chemotherapy. These data suggest that treatment with GM-CSF plus tumor-specific monoclonal antibodies after BMT may induce an antitumor effect and help eradicate the minimal residual disease.
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PMID:Granulocyte-macrophage colony-stimulating factor-induced antibody-dependent cellular cytotoxicity in bone marrow macrophages: application in bone marrow transplantation. 850 82


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