Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0002874 (aplastic anemia)
 5,905 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Recombinant human granulocyte macrophage colony-stimulating factor (rhGM-CSF) was one of the first of the myeloid growth factors to become available for clinical trials. Phase I studies have demonstrated that the optimal administration is by continuous intravenous infusion or subcutaneous injections at doses of 4-5 micrograms/kg/day. Phase II trials in patients with a variety of malignancies who receive rhGM-CSF after standard doses of chemotherapy have demonstrated significant reductions of the duration of leucocytopenia. Use of rhGM-CSF after high-dose chemotherapy (with or without bone marrow rescue) suggest that this agent decreases the time to recovery of a normal blood count and reduces infective complications. Results in myelodysplasia and aplastic anemia have been less encouraging. The potential value of rhGM-CSF in the treatment of a variety of other conditions including AIDS and the leukemias is being tested and the early results are discussed.
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PMID:Recombinant human granulocyte macrophage colony-stimulating factor: current status of clinical trials and potential future applications. 179 89

We describe a patient with viral induced aplastic anemia who developed severe bone pain after treatment with multiple courses of antithymocyte globulin, cyclosporine A, recombinant human granulocyte macrophage colony stimulating factor and deferoxamine. Radiographs and bone biopsy revealed extensive new trabecular bone formation in long bone diaphyses and adjacent periosteal reaction. The effects of hematopoietic growth factors, cyclosporine A and deferoxamine on bone metabolism are reviewed.
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PMID:Bone remodelling after growth factor and cyclosporine A therapy for aplastic anemia. 186 22

Granulocyte-macrophage colony stimulating factor (GM-CSF) has been tested for tolerability and efficacy on a compassionate need case basis in 17 patients (5 females, 12 males aged 4-72 years, median 35 years). GM-CSF was given at the rate of 3.5-32 micrograms/kg for 2-64 days as a continuous infusion for the following indications: impending rejection following bone marrow transplantation (5 patients), severe neutropenia secondary to chemotherapy in tumor patients (5), severe aplastic anemia (3), immune granulocytopenia (2) and accidental overdose with cytostatic agents (2 patients). Tolerance of GM-CSF was good in regard to doses of up to 16 micrograms/kg. Fever, myalgia and eosinophilia were the most frequent side effects. The patient treated with 32 micrograms/kg developed thrombosis of the vena cava. Efficacy is more difficult to assess in this heterogenous population, but 11 of 17 patients showed increased granulocyte counts and 3 patients clearly recovered from severe neutropenia. The role of GM-CSF in this recovery, however, cannot be proven. The results further indicate that GM-CSF cannot reverse ongoing rejection following allogenic BMT and cannot correct immune neutropenia. The value of GM-CSF therapy in patients with severe aplastic anemia and in the context of chemotherapy still needs to be defined. It is certainly indicated in patients with an accidental overdose of chemotherapeutic agents.
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PMID:[Emergency therapy with granulocyte-macrophage colony-stimulating factor (GM-CSF)]. 202 44

The colony-stimulating factors (CSF) are a class of glycoprotein hormones that regulate the production and function of blood cells. Human sequences encoding four of the factors active on myeloid cells--granulocyte-macrophage colony-stimulating factor (GM-CSF), granulocyte colony-stimulating factor (G-CSF), macrophage colony-stimulating factor (M-CSF), and interleukin-3 (IL-3)--have been molecularly cloned and the biosynthetic (recombinant) products introduced into clinical trials. Sufficient clinical data have accumulated regarding G-CSF and GM-CSF to allow insight into their potential use in clinical practice. Both molecules have shown some impact in the prevention of chemotherapy-induced neutropenia and in the treatment of cytopenias associated with myelodysplastic syndromes and aplastic anemia. G-CSF has shown promise in the treatment of congenital and idiopathic neutropenias.
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PMID:The colony-stimulating factors: biology and clinical use. 214 19

The family of colony stimulating factors and interleukins influence all aspects of hematopoietic cell proliferation and differentiation. In most instances these hematopoietic growth factors have overlapping, pleiotropic effects and frequently regulate early progenitor cell proliferation and mature cell function. Currently, seven of these factors are in clinical trial: erythropoietin for treatment of anephric anemia, IL-2 in conjunction with LAC therapy, and IL-1, IL-3, G-CSF, GM-CSF, and M-CSF for stimulation of myelopoiesis and granulocyte-macrophage function after chemotherapy, irradiation, or bone marrow transplantation in patients with cancer. G-CSF and GM-CSF have also proved effective in treatment of congenital and idiopathic neutropenias and have had some efficacy in treatment of myeloid leukemias, myelodysplastic disorders, aplastic anemia, and acquired immunodeficiency syndrome (AIDS).
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PMID:Hematopoietic growth factors in cancer. 240 5

[3H]thymidine uptake by NFS-60 cells in microcultures was found to increase in a linear fashion with the increasing doses of purified recombinant human granulocyte colony-stimulating factor (rhG-CSF). Such increases were found neither with rhG-CSF samples pretreated with rabbit anti-rhG-CSF serum nor with other human colony-stimulating factors such as granulocyte-macrophage colony-stimulating factor (hGM-CSF) or macrophage colony-stimulating factor (hM-CSF). Based on these findings, sera from normal persons and patients with severe infections or various hematological disorders were tested after dialysis using this system in order to determine whether G-CSF levels in sera can be estimated or not. In ten normal persons, five patients with acute myelogenous leukemia (AML M1, M2, and M3), five with myelodysplastic syndrome, and four with chronic myelogenous leukemia, no increases in [3H]thymidine uptake were found within the dose range of 0.4 microliters to 50 microliters. In contrast, linear dose responses parallel to a G-CSF standard curve were observed in one patient with a severe bacterial infection, four with aplastic anemia, two with acute myelomonocytic leukemia (AMMoL) (M4), and two with idiopathic neutropenia tested. From the standard curve, the probable levels of G-CSF were calculated as follows: approximately 200 pg/ml with infection, 130-220 pg/ml with aplastic anemia, 150 and 200 pg/ml with AMMoL, and 1120 and 1200 pg/ml with idiopathic neutropenia. The activities of sera were reduced by the anti-rhG-CSF serum pretreatment in the same way as documented in the case of rhG-CSF. Furthermore, the level in a patient with a severe infection became undetectable soon after elimination of the infection and blood neutrophil counts had returned to normal. These findings indicate that the microbioassay system will be useful for measuring circulating G-CSF levels which would fluctuate in accord with requirements for stimulating neutrophil production or with abnormal production of hG-CSF.
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PMID:A new bioassay for human granulocyte colony-stimulating factor (hG-CSF) using murine myeloblastic NFS-60 cells as targets and estimation of its levels in sera from normal healthy persons and patients with infectious and hematological disorders. 246 30

The myeloid growth factors are a promising new class of therapeutic agents with the potential for broad clinical application. Four recombinant myeloid growth factors, granulocyte macrophage colony-stimulating factor (GM-CSF), granulocyte colony-stimulating factor (G-CSF), macrophage colony-stimulating factor (M-CSF), and interleukin (IL)-3 are available for clinical trials. GM-CSF has been studied in leukopenia related to acquired immunodeficiency syndrome (AIDS), aplastic anemia, and myelodysplasia, as well as in patients receiving chemotherapy and those undergoing autologous bone marrow transplantation. In these trials, GM-CSF was demonstrated to increase the number of neutrophils, eosinophils, and monocytes with corresponding bone marrow changes. Toxicity is dose-related, and maximum tolerated dosages are in the range of 16 to 32 micrograms/kg/day. The effects of daily subcutaneous administration of GM-CSF appear to be similar to those of intravenous (IV) administration. G-CSF, studied mainly in the treatment of neutropenia following cytotoxic chemotherapy, was found to decrease the duration of severe neutropenia as well as the risk of infections. G-CSF causes prominent increases in neutrophil levels without affecting eosinophils or monocytes. Associated toxicity is minimal, and subcutaneous administration is efficacious. Preliminary evidence suggests that G-CSF may also have a therapeutic role in indolent lymphoid neoplasms complicated by neutropenia. Administration of natural M-CSF to patients receiving chemotherapy and those with chronic childhood neutropenia has shown modest neutrophil increases. Preclinical data on IL-3 suggest that this agent increases neutrophils, eosinophils, basophils, reticulocytes, and possibly platelets.
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PMID:Clinical applications of the myeloid growth factors. 247 Dec 74

Recombinant DNA technology has allowed for the production of large quantities of several hematopoietic growth factors as cloned gene products. Three of these factors--recombinant human erythropoietin (r-HuEPO), granulocyte macrophage colony-stimulating factor (GM-CSF), and granulocyte colony-stimulating factor (G-CSF)--are currently undergoing clinical trials and appear to offer considerable promise for the treatment of a variety of hematopoietic abnormalities. Therapy with r-HuEPO can raise the hematocrit levels of patients with end-stage renal disease. Therapy with GM-CSF in patients undergoing marrow transplantation results in acceleration of granulocyte and platelet recovery by 1 to 2 weeks, leading to fewer infections and earlier discharge from the hospital. Other demonstrated uses of GM-CSF include treatment for aplastic anemia, myelodysplastic syndromes, chemotherapy-induced neutropenia, and neutropenia associated with the acquired immunodeficiency syndrome (AIDS). Similar beneficial effects have been reported with G-CSF. Other hematopoietic growth factors, including the interleukins (IL)-1, -3, and -6, will soon be entering clinical trials. For the first time, the availability of a large number of hematopoietic growth factors may allow physicians to regulate closely the entire hematopoietic system of their patients.
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PMID:The clinical use of hematopoietic growth factors. 247 5

In order to maintain adequate circulating numbers of blood cells, the bone marrow must produce billions of cells each day and must be able to rapidly increase production by 10-20-fold in response to infection and hemorrhage. The existence of circulating factors that regulate this process has been suspected for over 100 years. Recently, the genes encoding these growth factors were cloned and their functions are now identified. Interleukin-3 (IL-3) acts on the most primitive hematopoietic stem cell, driving this self-renewing cell to produce progeny of all hematopoietic lineages. Granulocyte-macrophage colony-stimulating factor (GM-CSF) stimulates the granulocyte-macrophage progenitor cell, as well as cells committed to the erythroid lineage, to differentiate. G-CSF and M-CSF stimulate the most differentiated myeloid progenitors to produce granulocytes and monocytes/macrophages, respectively. Erythropoietin stimulates the differentiation of late erythroid progenitors. In the lymphoid progenitor lineage, IL-2 stimulates T cell differentiation; IL-4 and IL-6 stimulate differentiation of B cells. The colony-stimulating factors also enhance function and cause activation of the mature cells whose production they induce. In clinical trials, these hormones have successfully ameliorated anemia in renal failure, chronic disease, and in prematurity. They have improved pancytopenias in aplastic anemia, myelodysplastic syndromes, and congenital cytopenias, and they have hastened recovery from chemotherapy and bone marrow transplantation.
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PMID:Hematopoietic hormones: from cloning to clinic. 267 59

The characteristics and clinical uses of recombinant colony-stimulating factors (CSFs) are described, and the pharmacist's role as a consultant and educator on biotherapeutic substances is discussed. CSFs stimulate the formation and differentiation of the erythrocytes, neutrophils, eosinophils, basophils, monocytes, and platelets that compose the blood cell population. Recombinant CSFs represent a means by which the numbers of hematopoietic cells can be modulated, thus making these agents potentially useful in treating hematologic and immunologic deficiencies. CSFs also can increase the ability of neutrophils and monocyte-macrophages to protect the body against foreign invasion. Granulocyte macrophage colony-stimulating factor (GM-CSF) has increased host defenses in acquired immunodeficiency syndrome patients with Kaposi's sarcoma; increased neutrophil, platelet, and erythrocyte counts in preleukemic patients; and increased neutrophil counts in patients with aplastic anemia. GM-CSF and granulocyte colony-stimulating factor (G-CSF) have appeared to alleviate the drastic decrease in neutrophil counts associated with cytotoxic chemotherapy. G-CSF also has shown promise in stimulating neutrophil production in patients with transitional cell carcinoma, congenital agranulocytosis, and hairy-cell leukemia. Mild adverse effects such as fever, chills, rash, fatigue, myalgia, and bone pain are associated with GM-CSF therapy; G-CSF therapy is associated mostly with mild to moderate bone pain. Areas of education for pharmacists working with biotherapeutic substances include stability, storage temperature, drug interactions, novel drug-delivery systems such as monoclonal antibodies or liposomes, variations in biologic activity, and the evolving nature of the information about these investigational drugs. The pharmacist can anticipate an increasing role as a consultant on the use of CSFs and other biotherapeutic substances.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Colony-stimulating factors and tomorrow's pharmacy: why we must be ready. 269 Jun 7


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