Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027947 (neutropenia)
 17,527 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

RhGM-CSF is a hematopoietic growth factor which stimulates the proliferation, differentiation and functional activity of neutrophils, monocytes and macrophages. It also stimulates proliferation of endothelial cells and induces the production of other cytokines, such as interleukin (IL-1), tumor necrosis factor (TNF), interferon, prostaglandin E2, and plasminogen activating factor which affects both hematopoietic and non-hematopoietic cell activities. Initial clinical studies in 1987 generally excluded experimental therapy with rhGM-CSF in pediatric patients (age < or = 17 years) unless life threatening illness related to neutropenia and infection developed (i.e., patients with graft failure). Serious complications of patients undergoing autologous bone marrow transplantation (BMT) related to pancytopenia include infection and hemorrhage. Other regimen related complications include venooclusive disease, pneumonitis and mucositis. As a result of these complications, patients require intensive medical support including antibiotics and hyperalimentation. Initial hospital duration following marrow reinfusion is generally 4 to 5 weeks. Hematopoietic growth factors have been administered to patients undergoing autologous BMT as an attempt to reduce regimen related toxicity.
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PMID:RhGM-CSF in bone marrow transplantation: experience in pediatric patients. 130 85

Ten dogs were given mitoxantrone at a dose of 5 mg/m2 body surface area intravenously. Recombinant canine granulocyte colony-stimulating factor (rcG-CSF) was administered subcutaneously daily for 20 days after an infusion of mitoxantrone in five of these dogs to determine the effect of the hematopoietic growth factor on the duration and severity of myelosuppression. The median neutrophil counts dropped below normal (less than 3,000/uL) for 2 days in the dogs that received rcG-CSF, and for 5 days in the dogs that received only mitoxantrone. Four of five dogs not treated with rcG-CSF and none of those receiving rcG-CSF developed serious neutropenia (less than 1,500/uL). The neutrophil counts were significantly (P less than 0.05) higher in the rcG-CSF treated dogs at all time points except before the administration of the colony-stimulating factor, and the sixth day after the mitoxantrone was administered. These findings demonstrate that rcG-CSF is capable of reducing the duration and severity of mitoxantrone-induced myelosuppression.
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PMID:Use of recombinant canine granulocyte colony-stimulating factor to decrease myelosuppression associated with the administration of mitoxantrone in the dog. 137 55

Newborns are predisposed to neutropenia and thrombocytopenia during bacterial sepsis. The presence of peripheral cytopenias during overwhelming infection may be secondary to decreased hematopoietic growth factor production during states of increased demand. We therefore examined circulating levels of granulocyte-colony stimulating factor (G-CSF) and IL-3, production of G-CSF and IL-3 from unstimulated and stimulated mononuclear cells (MNC), expression of G-CSF and IL-3 genes during unstimulated and stimulated conditions, and equilibrium and binding of G-CSF receptors on mature effector peripheral blood cells of adults and neonates. Serum from cord and adult peripheral blood contained negligible amounts of both G-CSF (less than or equal to 50 pg/mL) and IL-3 (less than or equal to 5 pg/mL). Constitutive supernatant levels of G-CSF and IL-3 from cord and adult unstimulated MNC were also undetectable. However, there was a significant difference in G-CSF and IL-3 production from stimulated cord and adult MNC. Supernatants from stimulated adult MNC had significantly more G-CSF (p less than 0.007) and IL-3 (p less than 0.02). Additionally, Northern blot hybridization and densitometry of autoradiographs demonstrated significantly more G-CSF and IL-3 mRNA transcripts from adult than from cord MNC. Lastly, affinity, binding, and number of G-CSF receptors on cord and adult peripheral effector cells were equal. These data suggest that, during states of increased demand, cord MNC produce less G-CSF and IL-3 than do adult MNC and have an associated reduction in their respective mRNA transcripts. These findings may have implications in the pathogenesis of neonatal cytopenias during states of increased demand, such as sepsis.
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PMID:Decreased G-CSF and IL-3 production and gene expression from mononuclear cells of newborn infants. 137 59

Recently biotechnologic progress has, through the technique of the recombinant DNA, allowed a low cost production of large amount of several growth factors. Such a large availability has made possible to either carry out deeper investigations on the physiopathology of the hemopoietic regulation and perform new therapeutic approaches under different pathologic conditions. The most interesting acquisition concerning the biology of hemopoiesis to which such investigations have addressed us is the inadequacy of the protocols adopted till now. Such protocols considered only a simple vision of an elective action of a given growth factor during an exact maturation period of a determined cell colony. On the contrary, it was possible to point out a close network of inter-relationship among the different factors, which sometime impedes a clear distinction for each single factor, between actions of competence and progression in the cell maturation phenomena. However, the present uncertainty pertaining to the regulation of hemopoiesis has not impede the performance of clinical trials with positive findings in several pathologic conditions. The administration of recombinant erythropoietin has for example allowed to intervene in a resolutive way on the anemia in uremic subjects, and seems giving satisfactory results also in subjects with non renal origin anemic conditions. Satisfactory results were also obtained through the use of the Granulocyte-Macrophage CSF and of the Granulocyte-CSF, which by preventing neutropenia have allowed the performance of more adequate chemotherapeutic protocols in neoplastic subjects. New interesting perspectives are now coming for the use of Interleukin-3 in the treatment of the aplastic anaemia.
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PMID:[Growth factors and hematopoiesis. Physiopathology and clinical applications]. 138 4

To define the maximum tolerated dose and to study whether recombinant human interleukin-3 (rhIL-3) reduced chemotherapy-induced neutropenia and thrombocytopenia, 20 chemotherapy-naive patients with advanced ovarian cancer eligible for treatment with 6 cycles of carboplatin-cyclophosphamide every 4 weeks (day 1) were entered in a phase I/II open, single-center trial. Cohorts of five patients received during 7 days 1, 5, 10, or 15 micrograms/kg/d rhIL-3 (days 5 through 11) in cycles 1, 3, and 5 by continuous intravenous (IV) infusion or once daily subcutaneous (SC) administration. In control cycles 2, 4, and 6, no rhIL-3 was administered. rhIL-3 significantly increased the recovery of leukocyte, neutrophil, and platelet counts, especially at 5, 10, and 15 micrograms/kg rhIL-3. rhIL-3 also increased basophil, eosinophil, monocyte, and lymphocyte counts at this dose steps. Effects on reticulocytes were limited. No difference in efficacy between SC and IV rhIL-3 treatment was found. Chemotherapy postponement for insufficient bone marrow recovery was necessary in 22 of 45 control cycles versus 2 of 49 rhIL-3 cycles (P less than .001). Platelet transfusions were required in 7 of 45 control cycles versus 3 of 50 rhIL-3 cycles (P less than .5). rhIL-3 up to 10 micrograms/kg/d could be administered without severe side effects. At 15 micrograms/kg/d, rhIL-3 headache was dose-limiting. Other side effects were fever, flu-like symptoms, nausea, skin rash, flushing, facial erythema, and urticaria. Liver toxicity occurred in rhIL-3 and control cycles. rhIL-3 slightly increased tumor necrosis factor alpha, C-reactive protein, and serum amyloid A plasma levels, whereas no effect on IL-6 plasma levels was observed. rhIL-3 administered SC appears to be an interesting hematopoietic growth factor for reduction of chemotherapy-induced myelotoxicity.
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PMID:Effects of interleukin-3 after chemotherapy for advanced ovarian cancer. 151 36

Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a hematopoietic growth factor that stimulates myeloid cell proliferation and maturation and enhances the function of terminally differentiated effector cells. Phase I and II clinical trials have demonstrated mild to moderate toxicities at doses of less than 30 micrograms/kg/day. These studies suggest a potential role for this growth factor to stimulate myelopoiesis in patients with aplastic anemia, myelodysplastic syndromes, AIDS, chemotherapy-induced myelosuppression, chronic neutropenia, and following bone marrow transplantation. The potential clinical uses of GM-CSF will depend on results of studies designed to optimize its therapeutic efficacy.
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PMID:Clinical applications of human granulocyte-macrophage colony-stimulating factor. 177 Feb 27

The human recombinant GM-CSF (hrGM-CSF) is a glycosylated hematopoietic growth factor, derived from CHO cells (Schering Plough/Sandoz) used in these studies. The hrGM-CSF can be given intravenously (i.v.) in 4- to 24-h infusions or subcutaneously (scx) once or twice a day. Many patients (more than a thousand) have been treated with the hrGM-CSF in various pathologies, in association with anti-cancer chemotherapy, after bone marrow transplants or for myelodysplasias, refractory anemias, some neutropenias and infections. The reversion of neutropenia is dose-dependent with either a sc or i.v. administration. Recommended doses are from 5.0 to 10.0 micrograms/kg/per day. When the product is given sc the effect is delayed by one day but is more prolonged than with the i.v. route. The treatment duration has been investigated in different studies: a minimal duration of 5 days seems appropriate. When given in association with high doses of cytotoxic chemotherapeutic agents 10 to 14 days are required. In bone marrow transplants (autologous or allogenic with T-cell depletion), the hrGM-CSF has been shown to significantly reduce the time necessary for engraftment. Contrary to some fears, it was not shown that hrGM-CSF increased the risk of blastic transformation in myelodysplastic syndromes. In association with cytosine-arabinoside a certain number of partial and complete responses have been obtained. The toxic effects of the product are also dose-dependent. At doses greater than 11 micrograms/kg per day, there is a risk of stimulating inflammatory phenomena whereas at lower doses, more moderate side effects (myalgia, fever, injection site reaction) occur in only 30% of the cases. The GM-CSF will certainly be important in the future in haematology, oncology and for the treatment of infectious diseases.
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PMID:Recombinant human GM-CSF: present clinical results and potential use in oncologic and hematologic disorders. 178 28

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

Combined zidovudine (ZDV) and interferon-alpha (IFN) is an appealing therapy for AIDS-associated Kaposi's sarcoma because of the antiretroviral as well as antitumor potential of this combination. Overlapping myelotoxicity of these agents, however, frequently complicates their clinical use. This phase I/II study was undertaken to test the safety and efficacy of granulocyte-macrophage colony stimulating factor (GM-CSF) in those patients who became neutropenic while receiving ZDV (1,200 mg/day) and IFN (9 MU/day). Despite a "high-risk" population of patients, the tumor response rate among evaluable patients was 50% (33% overall). Sixty-four percent of patients required GM-CSF and all patients receiving GM-CSF had a prompt improvement in their absolute neutrophil count (ANC). The use of GM-CSF was associated with an improved end of study ANC (p less than 0.05), but was not associated with tumor response, CD4 count improvement, or improved change in hemoglobin concentration. GM-CSF/ZDV/IFN was not associated with increased toxicity over ZDV/IFN; however, two unusual events occurred in the GM-CSF/ZDV/IFN group: erythema multiforme and glucose intolerance. Dose-limiting thrombocytopenia and anemia were seen in two patients and anemia in one patient on GM-CSF/ZDV/IFN. No consistent alterations in serum HIV p24 antigenemia were noted in either group. The use of GM-CSF mitigated the neutropenia of combined ZDV and IFN. Further study evaluating the utility of this hematopoietic growth factor in combination therapies for AIDS patients is warranted.
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PMID:GM-CSF as an alternative to dose modification of the combination zidovudine and interferon-alpha in the treatment of AIDS-associated Kaposi's sarcoma. 204 63

Interleukin-3 (IL-3) is a hematopoietic growth factor that supports the growth of early hematopoietic progenitors in vitro. In vivo administration of recombinant human interleukin-3 (rhIL-3) to normal primates results in a modest and delayed leukocytosis secondary to increases in neutrophils, basophils, and eosinophils. We postulated that the effects of rhIL-3 might be more pronounced in hematologically stressed primates, and therefore administered rhIL-3 to primates after intensive myelosuppressive therapy. Primates received either cyclophosphamide (CPM) at 60 mg/kg or 5-fluorouracil (5-FU) at 75 mg/kg i.v. on two consecutive days. Subsequently, rhIL-3 was administered intravenously or subcutaneously at 20 micrograms/kg per d for 14 d. Compared to controls, all rhIL-3 treated primates experienced higher absolute neutrophil count (ANC) nadirs and dramatic decreases in the period of severe neutropenia (ANC less than 500) after myelosuppressive therapy. RhIL-3 administration resulted in a significant basophilia and eosinophilia, which resolved after discontinuation of the drug. RhIL-3 did not enhance erythroid recovery. Platelet recovery was earlier in rhIL-3-treated animals. However, variations in the platelet recovery observed in control animals, precluded accurate estimation of this effect or its significance. Our results indicate that the administration of rhIL-3 following intensive myelosuppressive therapy dramatically enhances myeloid recovery and ablates the predicted period of prolonged severe neutropenia.
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PMID:Effects of interleukin-3 on hematopoietic recovery after 5-fluorouracil or cyclophosphamide treatment of cynomolgus primates. 233 7


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