Granulocyte-macrophage Colony-stimulating Factor In Treatment Research Articles

Efficacy of Liposomal Amphotericin B Combined with Gamma Interferon or Granulocyte-Macrophage Colony-Stimulating Factor for Treatment of Systemic Zygomycosis in Mice

Granulocyte-macrophage colony-stimulating factor enhanced the efficacy of liposomal amphotericin B (LAMB) in a murine model of disseminated infection by Rhizopus oryzae, significantly prolonging survival and reducing tissue burden. The use of gamma interferon (IFN-gamma) alone was ineffective, and IFN-gamma combined with LAMB did not improve the results obtained with LAMB alone.

Colony-stimulating factors: clinical evidence for treatment and prophylaxis of chemotherapy-induced febrile neutropenia

The hematopoietic growth factors (HGFs) are a family of glycoproteins which plays a major role in the proliferation, differentiation, and survival of primitive hematopoietic stem and progenitor cells, and in the functions of some mature cells. More than 20 different molecules of HGF have been identified. Among them, granulocyte colony-stimulating factor (G-CSF) and granulocyte-macrophage colony-stimulating factor (GM-CSF) have been demostrated to be effective in reducing the incidence of febrile neutropenia when administered inmediately after chemotherapy and as supportive therapy in patients undergoing bone marrow transplantation. Chemotherapy used for treatment of cancer often causes neutropenia, which may be profound, requiring hospitalization, and leading to potentially fatal infection. The uses of the recombinant human hematopoietic colony-stimulating factors G-CSF and GM-CSF for treatment and prophylaxis of chemotherapy-induced febrile neutropenia will be reviewed here.

Dexrazoxane for anthracycline extravasation and GM-CSF for skin ulceration and wound healing

A 38-year-old woman with breast cancer and a right partial mastectomy was given adjuvant chemotherapy according to the protocol of a clinical trial by the Breast Cancer International Research Group, called BCIRG 005. This multicentre phase III randomised trial is designed to compare treatment with docetaxel in combination with doxorubicin and cyclophosphamide with treatment with doxorubicin and cyclophosphamide followed by docetaxel as a adjuvant therapy for patients with operable breast cancer who are HER2-negative with positive axillary lymph nodes. Our patient was randomised to receive four cycles of doxorubicin and cyclophosphamide followed by four cycles of docetaxel. A port-a-cath polysite catheter was inserted into her left subclavian vein before administration of the fourth cycle of chemotherapy. During treatment, the patient accidentally received a massive doxorubicin extravasation. Halfway through doxorubicin administration, the patient complained of pain and swelling. The nurse noted tenderness and swelling around the port-a-cath entrance and immediately stopped the infusion. The Huber needle was dislodged and the region surrounding the port-a-cath was red, painful, and swollen. There was definite extravasation: half the doxorubicin dose had been infused and most of this had extravasated. Within 1 h we infused 1500 mg of dexrazoxane over 15 min through a peripheral line to avoid severe tissue necrosis of the left wall of the chest. Pain and tissue tension were relieved immediately. 5 h after extravasation, we administered a further 1500 mg of dexrazoxane. The patient improved and there were no signs of immediate tissue damage. 24 h later, a final 750 mg of dexrazoxane was given resulting in a total dose of 3750 mg. Because the patient's surface area was 1·8 m 2 Shamseddine AI Khalil AM Kibbi AG et al. Granulocytemacrophage colony-stimulating factor for treatment of chemotherapy extravasation. Eur J Gynaecol Oncol. 1998; 19: 479-481 PubMed Google Scholar , the dose received was therefore 1043 mg/m 2 Shamseddine AI Khalil AM Kibbi AG et al. Granulocytemacrophage colony-stimulating factor for treatment of chemotherapy extravasation. Eur J Gynaecol Oncol. 1998; 19: 479-481 PubMed Google Scholar once a day for 2 days. No cold compress was applied to avoid vasoconstriction and interference with diffusion of dexrazoxane. No immediate systemic side-effects of dexrazoxane were noted. We also started to apply dimethyl sulfoxide to the skin every 6 h. After three doses, application was stopped because the skin became red and the tissue swelled. Tests on liver function remained within normal limits over the next 8 weeks. Neither leucopenia nor thrombocytopenia occurred. The figure (panel shows the site 1 week after the incident.

Evaluation of granulocyte-macrophage colony-stimulating factor for treatment of pancytopenia in children with Fanconi anemia

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. (J P EDIATR 1994;124:144-50)

Granulocyte-Macrophage Colony-Stimulating Factor: Pleiotropic Cytokine with Potential Clinical Usefulness

Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a 23-kDa glycoprotein with remarkably diverse effects on immune and nonimmune cells. GM-CSF induces differentiation of granulocyte, macrophage, and eosinophil precursor cells. Proliferation of monocyte-macrophages, T lymphocytes, keratinocytes, and endothelial cells is also stimulated by GM-CSF. In addition, GM-CSF alters the functional properties of mature granulocytes, macrophages, eosinophils, and basophils. GM-CSF is produced by T lymphocytes, macrophages, and several cell types in extramedullary sites, where it may act in a paracrine manner to regulate the local response to antigenic challenge. Clinical trials of GM-CSF have been conducted in patients with AIDS, aplastic anemia, myelodysplastic syndromes, and sarcoma and following bone marrow transplantation and accidental radiation exposure. GM-CSF significantly increased circulating numbers of several myeloid cells and produced dose-dependent toxicity consisting primarily of myalgias, fever, fluid retention, and serosal effusions. Additional studies are needed to define the role of GM-CSF in treatment of patients with qualitative and quantitative dysfunction of immune cells.