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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)

The treatment of patients with relapsed or refractory acute myeloid leukemia (AML) with high dose cytosine arabinoside (ara-C) results in short-lived complete response rates of 30-50%. We have previously shown that entry of myeloid leukemic cells into S phase can be accelerated in vitro through the use of recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF), resulting in enhancement of ara-C-mediated cytotoxicity. In order to evaluate the in vivo biological and clinical effects of this strategy in patients with high risk AML, we treated three patients with either refractory or relapsed disease with a continuous infusion of rhGM-CSF (0.45 micrograms/kg/h aglycoprotein) for 18 h, followed by the institution of high dose ara-C and continuation of rhGM-CSF throughout the 4 day duration of ara-C treatment. Prior to therapy, no patient had detectable levels of circulating rhGM-CSF, and there was no evidence of GM-CSF receptor occupancy in leukemic myeloblasts. After 18 h of rhGM-CSF therapy, all patients had biologically active levels of circulating rhGM-CSF (7.9-12.0 ng/ml), and two patients showed a significant degree of leukemic GM-CSF receptor occupancy without evidence of GM-CSF receptor down-regulation. A significant rise in the S phase fraction of leukemic myeloblasts was observed at 18 h of rhGM-CSF treatment in all three patients (29-56% increment). The toxicity of combined rhGM-CSF/ara-C therapy included pericarditis and cerebellar degeneration in one patient, fever and mild renal dysfunction in two patients, and mild hepatic dysfunction in all three patients. Each patient showed a transient rise in the absolute neutrophil and blast count during rhGM-CSF/ara-C administration, followed by profound, but clinically tolerable, myelosuppression. No patient developed clinical evidence of leukostasis. There was one death related to pericardial tamponade, one death related to refractory disease, and one clinical and cytogenetic remission. These results suggest that exogenously administered rhGM-CSF is capable of rapidly mobilizing leukemic cells into S phase in vivo and theoretically should be useful in overcoming kinetic resistance to ara-C. Clinical trials of this regimen in patients with high risk AML who are not already pharmacologically resistant to ara-C are warranted.
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PMID:Simultaneous administration of granulocyte-macrophage colony-stimulating factor and cytosine arabinoside for the treatment of relapsed acute myeloid leukemia. 182 36

A number of human hematopoietic growth factors have been genetically cloned and recombinant proteins produced. Several phase I and II clinical trials have already been published and results from phase III studies are becoming available. The use of erythropoietin to alleviate chemotherapy-induced myelosuppression is being tested. Granulocyte colony-stimulating factor and granulocyte-macrophage colony-stimulating factor have been extensively studied in patients receiving chemotherapy at standard or escalated doses and after bone marrow transplantation and appear to ameliorate chemotherapy-induced neutropenia and to speed bone marrow engraftment after high-dose cancer therapy. Interleukin-3 and interleukin-6 are quite early in their clinical development, but appear able to alleviate post-chemotherapy thrombocytopenia.
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PMID:Hematopoietic growth factors as supportive therapy for cancer- and chemotherapy-induced conditions. 193 23

Patients with relapsed Hodgkin's disease who respond to salvage therapy are successfully treated with cyclophosphamide, carmustine (BCNU), and etoposide (VP-16) (CBV) followed by autologus bone marrow transplantation (ABMT). Because of heavy pretreatment including radiation to the pelvic site, marrow harvest was not feasible in those patients. We therefore used blood-derived hemopoietic precursor cells as an alternative stem-cell source to rescue them after superdose chemotherapy. Hemopoietic precursor cells were mobilized into the peripheral blood either by chemotherapeutic induction of transient myelosuppression followed by an overshooting of blood stem-cell concentration, or by continuous intravenous (IV) granulocyte-macrophage colony-stimulating factor (GM-CSF) administration. The median time to reach 1,000 WBC per microliter, 500 polymorphonuclear cells (PMN) per microliter, or 20,000 platelets per microliter was 10, 20.5, and 38 days, respectively, for 50% of all patients. The platelet counts of two patients never dropped below 20,000/microL following autologous blood stem-cell transplantation (ABSCT), whereas two other patients had to be supported with platelets for 75 and 86 days posttransplant until a stable peripheral platelet count of 20,000/microL was attained. Among the 11 assessable patients, seven are in unmaintained complete remission (CR) at a median follow-up of 318 days. This is a first report on a series of ABSCTs in patients with advanced Hodgkin's disease proving that, despite prior damage to the marrow site, the circulating stem-cell pool is still a sufficient source of hemopoietic precursor cells for stem-cell rescue.
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PMID:Autologous blood stem-cell transplantation in patients with advanced Hodgkin's disease and prior radiation to the pelvic site. 197 51

Based on in vitro data suggesting that recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) is capable of stimulating acute myeloid leukemia (AML) blast cells to become more sensitive to cell-cycle-specific drugs we conducted a phase I/II study in de novo AML patients (pts). rhGM-CSF (250 micrograms/m2/d, continuous intravenous infusion) was administered in 18 pts suffering from de novo AML in combination with standard induction chemotherapy (3 + 7 = daunorubicin 45 mg/m2 days 1 through 3, cytosine-arabinoside [Ara-C] 200 mg/m2 continuous infusion days 1 through 7). GM-CSF was started 48 or 24 hours before chemotherapy (prephase) in 14 pts. In four pts with high white blood cell counts (WBC) rhGM-CSF was started after chemotherapy-induced cell reduction (WBC less than 30,000/mm3). During prephase GM-CSF induced an increase in neutrophil and blast cell counts in 13 of 14 and 10 of 14 pts, respectively. In vivo recruitment of leukemic cells into drug-sensitive phases of the cell cycle could be demonstrated by multiparameter cell-cycle analyses in peripheral blood (n = 7) and bone marrow (n = 4) specimens. On day 14, complete aplasia was evident in 17 of 18 pts. GM-CSF was administered until recovery from chemotherapy-induced myelosuppression (absolute neutrophil counts, [ANC] greater than 500/mm3). Fifteen pts (83%) achieved complete remission, 12 did so with one cycle. A shorter duration of neutropenia was evident in these pts compared with historical controls (n = 39), (ANC greater than 500/mm3, day 22.5 +/- 3.4 v 25.2 +/- 3.7, P less than .05). Three pts achieved complete remission after a second cycle (same combination of rhGM-CSF and 3 + 7). Two pts died during bone marrow aplasia because of invasive pulmonary aspergillosis. Clinical side effects possibly related to GM-CSF, mainly fever, diarrhea, and weight gain were mild and tolerable (World Health Organization toxicity grade less than or equal to 2). Together, rhGM-CSF recruits kinetically quiescient AML cells in vivo to enter drug-sensitive phases of the cell cycle and promotes early myeloid recovery from aplasia after exposure to standard induction chemotherapy for AML.
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PMID:Recombinant human granulocyte-macrophage colony-stimulating factor in combination with standard induction chemotherapy in de novo acute myeloid leukemia. 199 13

The ability of recombinant murine granulocyte-macrophage colony-stimulating factor (rmGM-CSF) to protect myelosuppressed mice against lethal infections was evaluated. In mice myelosuppressed by cyclophosphamide, subcutaneously administered rmGM-CSF was a potent stimulus of granulopoiesis by increasing the number of GM-CSF-responsive precursor cells in bone marrow followed by a profound neutrophilia. Neutrophil recovery was augmented by rmGM-CSF in a dose-dependent manner at daily doses of 0.6-5.0 micrograms/mouse. In addition, rmGM-CSF increased the functional activity of circulating neutrophils at similar doses. When rmGM-CSF was administered to neutropenic mice before experimentally induced Pseudomonas aeruginosa, Staphylococcus aureus, or Candida albicans infections, it protected against these lethal infections, resulting in increased numbers of survivors. These data suggest that rmGM-CSF protects neutropenic mice from lethal infections, probably by augmenting neutrophil recovery after myelosuppression and activation of mature cells.
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PMID:Recombinant murine granulocyte-macrophage colony-stimulating factor augments neutrophil recovery and enhances resistance to infections in myelosuppressed mice. 199 31

To evaluate the efficacy of recombinant murine granulocyte-macrophage colony-stimulating factor (rGM-CSF) in attenuating the myelosuppression associated with chemotherapy, the effects of 100 and 300 ng rGM-CSF, administered twice daily by intraperitoneal injection for 6 consecutive days to mice 24 hours after a dose of 200 mg/kg cyclophosphamide, were measured. Six days after the initial injection of rGM-CSF, a significant increase occurred in the absolute myeloid count compared to that of vehicle-treated animals. The difference was most pronounced on day 7, attaining levels of 327% and 428% of the control; these increases slowly declined to that of the control level by day 19. No significant effect was produced by rGM-CSF on the packed red cell volume or on the platelet count. Furthermore, the administration of rGM-CSF did not alter bone marrow cellularity or increase the number of marrow-derived hematopoietic stem cells. In contrast, a significant splenomegaly occurred, starting on day 6 and continuing until day 17. This was characterized by a pronounced increase in splenic-derived granulocyte (CFU-G), granulocyte-macrophage (CFU-GM), macrophage (CFU-M), megakaryocyte (CFU-MK), and erythroid (BFU-E, CFU-E) stem cells. The increases occurred between days 6 and 9 following the initial administration of rGM-CSF. These findings indicated that the administration of rGM-CSF to cyclophosphamide-treated animals causes an absolute increase in circulating myeloid cells and that these increases are derived from the spleen. The use of recombinant hematopoietic growth factors may permit the administration of more intensive chemotherapy through amelioration of chemically induced leukopenia.
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PMID:Effects of recombinant murine granulocyte-macrophage colony-stimulating factor in cyclophosphamide-treated mice. 201 56

Myelosuppression is the main limiting factor in cancer chemotherapy. The development of recombinant hematopoietic growth factors which stimulate myeloid progenitors and mainly neutrophil precursor cells leads to the evaluation of their potential activity in numerous fields of oncology. The available clinical trials have demonstrated the ability of G-CSF (granulocyte colony-stimulating factor) and GM-CSF (granulocyte-macrophage colony-stimulating factor) to accelerate neutrophil recovery following cytotoxic chemotherapy, and therefore to reduce the incidence of neutropenic febrile episodes and thereby improve the quality of life of patients receiving chemotherapy. The main goals of the future studies will be to determine to what extent the increase of dose intensity may lead to higher response rates and survival at least in patients with chemosensitive tumors.
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PMID:[Use of hematopoietic growth factors in oncology]. 203 83

Recombinant technology has been harnessed to produce sufficient quantities of colony-stimulating factors (CSFs)--also known as hematopoietic growth factors--to make clinical trials with these agents possible. Endogenous CSFs are hormone-like glycoproteins that bind to receptors on target cells and stimulate processes within these cells that mediate their proliferation, maturation, differentiation, and functional activation. Several such CSFs cloned by recombinant DNA technology now are being tested clinically. Some are multilineage growth factors, such as interleukin-3 (IL-3) and granulocyte-macrophage colony-stimulating factor (GM-CSF), which tend to affect cells early in the hematopoietic hierarchy. Others, such as granulocyte colony-stimulating factor (G-CSF), primarily stimulate the formation of neutrophilic granulocytes. Macrophage CSF predominantly affects monocytes/macrophages. These are late-stage, single-lineage growth factors. Numerous clinical trials with all of these agents are under way. The granulopoietic agents, including GM-CSF and G-CSF, are being tested for their potential use in preventing or ameliorating myelosuppression related to AIDS, antineoplastic chemotherapy, bone marrow transplantation, myelodysplastic syndromes, and aplastic anemia. Clinical trial results on G-CSF and GM-CSF are encouraging thus far. However, it is too early to characterize the effects of IL-3, which is just entering clinical trials.
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PMID:Future strategies in the control of myelosuppression: the use of colony-stimulating factors. 204 96

Interleukin 3 (IL-3) is one of a family of cytokines believed to be important in regulating the growth and development of cells of both the hematopoietic and immune systems. In comparison with other hematopoietic growth factors, IL-3 preferentially supports the proliferation and differentiation of progenitors at early stages of hematopoietic development. In addition, IL-3 exerts a wide spectrum of biological activities on various target cell populations, including T cells, B cells, eosinophils, basophils and monocytes. The direct interaction between IL-3 and early multipotential progenitors has been confirmed in the primate model in which pretreatment of IL-3 primed the animals to become more responsive to late-acting hematopoietic growth factors, like granulocyte-macrophage colony-stimulating factor and erythropoietin. Furthermore, administration of IL-3 can diminish myelosuppression and accelerate hematopoietic recovery in primates treated with various chemotherapeutic drugs. These studies suggest that IL-3 alone or in combination with other hematopoietins may prove to be useful in treating myelosuppressed patients.
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PMID:Human interleukin 3: analysis of the gene and its role in the regulation of hematopoiesis. 218 33

Over the last decade, the key role of specific glycoproteins (hematopoietic growth factors) in the proliferation and maturation of hematopoietic cells (in conjunction with some of their particular functional activities) has been demonstrated through in vitro and in vivo studies. These glycoproteins have been evaluated for their potential application in reducing the duration of myelosuppression following conventional chemotherapy and autologous bone marrow transplantation. Preliminary results using granulocyte-macrophage colony-stimulating factor to restore neutrophil competence seem to be encouraging.
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PMID:Clinical use of GM-CSF in autologous bone marrow transplantation. 218 40


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