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)

Selection of a drug for formulary inclusion involves evaluation of safety, efficacy, and cost. The colony-stimulating factors (CSFs) sargramostim and filgrastim have a broad range of potential indications and represent a costly formulary addition when acquisition price alone is considered; their comparative safety is unclear. These factors suggest that the CSFs should be closely scrutinized prior to formulary addition. In the absence of direct comparative studies, an assessment of the safety of CSFs involves evaluation of information provided in the product circular, official drug compendia, adverse biologic reports submitted to the United States Food and Drug Administration, and data from key clinical trials. Data in the product circulars report on adverse events in small numbers of patients treated for chemotherapy-induced neutropenia (filgrastim) or neutropenia subsequent to bone marrow transplantation (sargramostim). The official compendia and clinical trials include experience with CSFs produced in a variety of expression systems; these data are not limited to sargramostim and filgrastim. Importantly, there was a similar incidence of adverse events in patients who received sargramostim or filgrastim and in those who took placebo reported in the product circulars and the pivotal trials, suggesting that the underlying disease may have an important role in determining the side-effect profile of these agents. Adverse biologic reports represent experience with sargramostim and filgrastim obtained under actual clinical conditions and suggest that the same types of adverse events are seen with sargramostim as with filgrastim. This analysis suggests that a decision to select filgrastim over sargramostim for formulary inclusion based on the safety profile is not appropriate because currently available data are equivocal and that such decisions would more appropriately be based on efficacy and cost.
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PMID:Drug formulary review process for sargramostim and filgrastim: focus on analysis of adverse drug reactions. 750 17

Treatment of neoplastic diseases is followed by a variety of infectious complications. Neutropenia and functional defects of phagocytes are common consequences of cancer and its treatment and contribute to an increased susceptibility to infections. Cytokines with hematopoietic growth stimulatory and/or immunoenhancing properties, such as granulocyte-macrophage colony-stimulating factor (GM-CSF), granulocyte colony-stimulating factor (G-CSF), interleukin-3, interferon-gamma, macrophage colony-stimulating factor, interleukin-1, and interleukin-6 have been shown to either have clinical utility in patients with cancer and neutropenia or offer the promise to do so. GM-CSF and G-CSF, for example, have been shown to reduce the incidence of fever and infectious complications in patients with cancer and neutropenia. The role of cytokines for the treatment of defined infections (e.g., invasive mycoses) is under investigation.
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PMID:Perspectives on the use of cytokines in the management of infectious complications of cancer. 750 61

We have previously demonstrated that protein production and mRNA expression of granulocyte-macrophage colony-stimulating factor (GM-CSF), granulocyte colony-stimulating factor (G-CSF), and IL-3 are decreased in activated mononuclear cells (MNC) from human umbilical cord compared with adult peripheral blood. Reduced production of these colony-stimulating factors (CSF) during states of increased demand, as occurs during overwhelming bacterial infection, may play a role in the pathogenesis of neutropenia and thrombocytopenia in the newborn. To determine whether the reduced mRNA expression and CSF production from activated cord MNC is secondary to the decreased transcriptional activity of the corresponding genes, we determined the transcriptional rate of GM-CSF, G-CSF, IL-3, and M-CSF by nuclear run-on assays. Cord and adult MNC were isolated by Ficoll-Hypaque density centrifugation. A total of 10(8) MNC from cord and adult blood were stimulated as follows: GM-CSF and G-CSF [32 nmol/L phorbol-12-myristate-6-acetate (20 micrograms/L) + 2 mg/L phytohemagglutinin for 6 h]; IL-3 [32 nmol/L phorbol-12-myristate-6-acetate (20 micrograms/L) + 0.5 mumol/L A 23187 for 6 h]; and macrophage CSF (2 micrograms/L recombinant human GM-CSF for 24 h). The nuclei from unstimulated and stimulated cells were isolated and labeled with 32P-uridine triphosphate. Newly elongated 32P-labeled RNA transcripts were hybridized to slot blots of CSF DNA. To minimize cross hybridization artifacts, short fragments (0.5-1.0 kb) of cDNA were used.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Transcriptional rates of granulocyte-macrophage colony-stimulating factor, granulocyte colony-stimulating factor, interleukin-3, and macrophage colony-stimulating factor genes in activated cord versus adult mononuclear cells: alteration in cytokine expression may be secondary to posttranscriptional instability. 750 24

Several clinical trials have demonstrated that granulocyte colony-stimulating factor (G-CSF) accelerates the recovery of neutropenia in chemotherapy-induced bone marrow suppression. In this report, we describe a 46-year-old female with glioblastoma multiforme who developed interstitial pneumonia due to administration of G-CSF during the phase of immunochemoradiotherapy-induced neutropenia. Thirty-three days after starting immunochemoradiotherapy (ACNU, VCR, IFN -beta, radiation), she developed neutropenia (1,000/microliters). Administration of G-CSF at doses of 125-250 micrograms/day led to an increase of peripheral neutrophil counts. Eleven days later, the patient developed sudden severe respiratory failure and cyanosis with worsening of lung shadows. Blood gas levels on room air were PaO2 49.3mmHg, PaCO2 28.0mmHg, and pH 7.46. At this time, her neutrophil count had risen to 26,080/microliters. LDH and alpha - HBD had also increased to 1,439 IU/l and 1,117IU/l respectively. Chest radiograph and CT scan demonstrated interstitial pneumonia. After treatment with methyl prednisolone, her respiratory symptoms were gradually resolved. A number of side-effects have been reported with granulocyte-macrophage colony-stimulating factor (GM-CSF). These include fluid retention with pericardial and pleural effusion, fever, bone pain, fatigue, and rash. This report also suggests that G-CSF might be a cause of interstitial pneumonia during the phase of immunochemoradiotherapy-induced neutropenia.
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PMID:[A case report of interstitial pneumonia caused by granulocyte colony-stimulating factor]. 750 62

Human recombinant colony-stimulating factors may be used to treat or prevent neutropenia caused by marrow toxic chemotherapeutic agents administered to patients with cancer. Despite their common clinical use, little is known about the potential adverse effects that these cytokines may have on the growth of malignant cells. Indeed, several in vitro reports have indicated that colony-stimulating factors may act as stimulating growth factors in some human malignancies. To evaluate these effects in ovarian cancer, we investigated the possible growth effects of granulocyte colony-stimulating factor (G-CSF/Filgrastim) and granulocyte-macrophage colony-stimulating factors (GM-CSF/Sargramostim) on four established ovarian cancer cell lines, as well as five primary ovarian cancer cultures over a wide range of pharmacologic doses. Cell viability was measured by an ATP bioluminescence assay and expressed as a percentage of untreated control cultures. G-CSF showed no growth-stimulating effects in any of the four established cell lines tested. In the OVCAR-3 cell line, a decrease in growth (> 10%) was seen at 10, 100, and 1000 ng/ml after 5 days of continuous treatment. In the same cell line, GM-CSF caused an increase (> 10%) in growth at the same doses. However, these changes did not demonstrate statistical significance in a dose-dependent fashion. In the five primary cultures treated with G-CSF, only one demonstrated statistically significant increases in growth in a dose-dependent manner. GM-CSF treatment had no significant growth alterations in these same five primary cultures. These results would suggest that colony-stimulating factors may act as growth factors in some but not all ovarian cancer cells. Further investigations into the receptor status of ovarian cancer cells for these cytokines are underway to clarify this issue.
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PMID:In vitro growth effects of colony-stimulating factors in ovarian cancer. 751 21

In high-grade malignant non-Hodgkin's lymphomas (hNHL) recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) was evaluated as support to chemotherapy. In a phase III trial, 172 patients (age 18-73 years, stage II-IV) were risk-stratified according to LDH levels and lymphoma size and randomized to receive rhGM-CSF (400 micrograms) (87 patients) or placebo (85 patients) subcutaneously days 8-14 of each cycle of an intensified COP-BLAM regimen. RhGM-CSF significantly reduced the length and nadir of neutropenia, the length of fever episodes, the frequency of all and of severe infections, and of hospitalization and antibiotic requirements. Complete response rates were 63% for all patients and 64% vs. 61% (n.s.) in the rhGM-CSF vs. the control group. Deviations from protocol in applied dosages of myelotoxic drugs and in cycle intervals maintained differed slightly in favor of the rhGM-CSF arm. However, there were no significant differences in overall survival between the GM-CSF treatment and control groups (21 vs. 23 months). Early relapse rates were markedly lower than in the standard-dose COP-BLAM/IMVP-16 regimen. Thus, GM-CSF abates toxic side effects of chemotherapy and may help to maintain dose intensity in high-risk hNHL.
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PMID:Cytokine efficiency in the treatment of high-grade malignant non-Hodgkin's lymphomas: results of a randomized double-blind placebo-controlled study with intensified COP-BLAM +/- rhGM-CSF. 751 44

Granulocyte colony-stimulating factor (G-CSF) and granulocyte-macrophage colony-stimulating factor (GM-CSF) have recently been introduced in the treatment of chemotherapy-induced neutropenia. Effects of these CSFs on the cellular immune system were evaluated in 38 neutropenic gynecological cancer patients during chemotherapy. In addition to restoring the leukocyte count, GM-CSF--to a greater extent than G-CSF--also induced neopterin, a sensitive marker of macrophages activated by interferons. This effect was confirmed in vitro by investigating the effects of these CSFs on interferon-gamma-mediated pathways in THP-I human myelomonocytic cells. The results suggest activation of immune effector cells by GM-CSF.
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PMID:Increased production of immune activation marker neopterin by colony-stimulating factors in gynecological cancer patients. 751 25

Colony-stimulating factors (CSFs) shorten the duration of myelosuppression following chemotherapy and, thus, allow the administration of higher doses. This study evaluates the efficacy of granulocyte macrophage colony-stimulating factor (GM-CSF) and granulocyte colony-stimulating factor (G-CSF) in allowing administration of high-dose cyclophosphamide in combination with doxorubicin. Ninety women with metastatic, locally advanced, or high-risk (> or = 10 positive nodes) breast cancer and no prior anthracycline treatment were given doxorubicin (60 mg/m2) with progressively increased doses of cyclophosphamide (1,200 mg/m2, 1,800 mg/m2, and 2,400 mg/m2). The first 60 patients received GM-CSF; the remaining 30, G-CSF. The maximum tolerated dose was not reached with 2,400 mg/m2 of cyclophosphamide. When compared to GM-CSF, G-CSF significantly reduced the duration of granulocytopenia (P < .001). No differences in duration of thrombocytopenia were noted. The results were not sufficiently consistent to indicate a trend toward reduction in rates of febrile neutropenia with one CSF versus the other. However, patients who received G-CSF were hospitalized less frequently than those receiving GM-CSF. With CSFs, high-dose cyclophosphamide in combination with doxorubicin can be safely administered on an outpatient basis. A shorter duration of granulocytopenia resulted from the use of G-CSF than from GM-CSF.
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PMID:The efficacy of recombinant human granulocyte colony-stimulating factor and recombinant human granulocyte macrophage colony-stimulating factor in permitting the administration of higher doses of cyclophosphamide in a doxorubicin-cyclophosphamide combination. An NSABP pilot study in patients with metastatic or high-risk primary breast cancer. National Surgical Adjuvant Breast and Bowel Project. 752 93

Serum samples from 76 patients with neutropenia and 34 control subjects were analyzed for levels of granulocyte colony-stimulating factor, granulocyte-macrophage colony-stimulating factor, interleukin 1 alpha, and tumor necrosis factor beta. Clinical correlates and duration of neutropenia were determined insofar as possible. Systemic acute inflammatory disease was present in only two patients. In most cases, the neutropenia was considered idiopathic or medication related. Significantly elevated serum granulocyte colony-stimulating factor levels were found in the patient group, regardless of the apparent cause of the neutropenia. Increased levels of granulocyte-macrophage colony-stimulating factor, interleukin 1, and tumor necrosis factor were seen in only one patient with sepsis.
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PMID:Serum cytokine levels in patients with neutropenia. 752 20

The application of hematopoietic growth factors in the treatment on acute myeloid leukemia (AML) may principally aim at shortening the period of treatment associated neutropenia and reducing the rate of infectious complications by their post-therapeutic administration but may also be used to increase the sensitivity of leukemic blasts to antileukemic therapy by pretherapeutic growth stimulation. Both aspects were addressed in subsequent clinical phase II studies and preclinical investigations. In a first clinical trial, 36 patients with high-risk AML received granulocyte-macrophage colony-stimulating factor (GM-CSF) after successful cytoreductive chemotherapy and experienced a shortening of the period of post-therapeutic neutropenia by 6 to 9 days, leading to a significant reduction of treatment-associated deaths from 39% to 14%. In preclinical studies an enhancement of the cytotoxicity of cytosine arabinoside (AraC) on leukemic blasts could be shown by pretreatment with GM-CSF or IL-3. Investigations on the impact of hematopoietic growth factors on the intracellular metabolism of AraC indicated that this effect was primarily mediated by an increase in the activity of DNA-polymerase-alpha. The evaluation of different doses of AraC showed the most marked increase after the combination of GM-CSF with conventional rather than high doses of AraC. Based on these preclinical experiments, a prospective randomized trial was subsequently initiated investigating the effect of GM-CSF before and during induction, consolidation, and the first two cycles of maintenance chemotherapy in newly diagnosed AML. This ongoing trial has enrolled 67 patients at the current time. An early interim analysis showed no differences in remission rates but a tendency toward a longer remission duration in patients receiving GM-CSF. These data indicate that hematopoietic growth factors like GM-CSF in particular may provide a new perspective in the treatment of acute myeloid leukemia with the possibility of reducing treatment associated mortality and perhaps of increasing the efficacy of antileukemic treatment.
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PMID:New perspectives in the treatment of acute myeloid leukemia by hematopoietic growth factors. 752 49


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