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)

Management of fungal infections is a major medical problem. The risk of developing a fungal infection is higher for patients who are undergoing dose-intensive therapy, are immunocompromised, have neutropenia, are receiving prophylactic antibiotics, have other infections, have invasive catheters, or have a history of severe trauma or burns. Survival is decreased among patients who develop fungal infection in these situations. In view of the high morbidity and mortality associated with fungal infections in transplant recipients, cytokines that enhance cell function, such as macrophage colony-stimulating factor (M-CSF), have been investigated. M-CSF enhances cytotoxicity, superoxide production, phagocytosis, chemotaxis, and secondary cytokine production in monocytes and macrophages. Animal models and clinical data suggest efficacy of M-CSF in controlling fungal infection.
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PMID:Use of macrophage colony-stimulating factor in the treatment of fungal infections. 963 46

The use of hematopoietic growth factors, although well established for the management of chemotherapy-induced neutropenia, remains controversial for the treatment of aplastic anemia and inherited bone marrow failure syndromes. The most commonly used factors are granulocyte colony-stimulating factor, granulocyte macrophage colony-stimulating factor, and erythropoietin. Newer growth factors such as stem cell factor, thrombopoietin, Flt3 ligand, and interleukins have shown promising results in the laboratory, and some have been used in clinical trials. This article reviews the clinical use of old and new hematopoietic growth factors in acquired and inherited bone marrow failure, and discusses emerging concerns about long term toxicity of these factors.
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PMID:Hematopoietic growth factors for the treatment of aplastic anemia. 966 65

Peptide growth factors involved in the regulation of haematopoiesis (HPGF), for example granulocyte-colony-stimulating factor (G-CSF) and granulocyte/macrophage-colony-stimulating factor (GM-CSF), are of clinical importance in the treatment of testicular germ cell tumour (GCT) patients with modern chemotherapy regimens since they ameliorate chemotherapy-induced neutropenia. Aberrant expression of and/or response to HPGF has been reported in several solid tumour types although no data are available on GCT with the exception of those on stem cell factor (SCF). The aims of this pre-clinical study were twofold: (1) to screen a panel of human non-seminomatous (NS)GCT for the production of HPGF and (2) to test the effects of G-CSF or SCF on the growth of NSGCT cell lines in vitro, and on the growth kinetics of two human NSGCT xenograft models. HPGF concentrations in cell culture supernatant from 11 NSGCT cell lines growing under routine culture conditions were measured by enzyme-linked immunosorbent assay. The growth kinetics of cell lines was quantified in vitro using the sulphorhodamine B assay. The growth kinetics of nude mouse NSGCT xenografts was followed by measuring tumour volumes every 2-3 days over days 1-30, following daily subcutaneous injection of nude mice (days 1-14). The cell lines produced G-CSF (1/11 cell lines), GM-CSF (2/11), SCF (2/11), M-CSF (6/11). and interleukin-6 (9/11). Growth stimulation of cell line H12.1 by SCF was observed in vitro, but no statistically significant differences in NSGCT xenograft tumour volume (VT) or relative VT (r VT) in treated groups were observed on days 14 or 29 compared to the control. The change in rVT of H12.1 xenografts treated with G-CSF alone compared to control (rVT/rVT,c) was 0.96 on day 29. The values for rVT/rVT,c for H12.1 xenografts treated with G-CSF in combination with low- or high-dose SCF were, respectively, 1.67 or 1.7 compared to 1.19 for SCF-treated mice. The results are in agreement with clinical data to date where no observations have been reported of stimulation or inhibition of tumours in patients receiving treatment with G-CSF. Before any clinical trials are initiated in GCT patients treated with G-CSF in combination with SCF, further pre-clinical experiments with this tumour type are recommended to investigate this phenomenon further in a greater number of NSGCT cell lines in vitro and in vivo and with a wider range of SCF/G-CSF schedules. The potential relevance of secretion of HPGF in NSGCT cell lines in vitro to the pathobiology of GCT in patients is also a subject of interest for future research.
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PMID:Production and pre-clinical significance of haematopoietic peptide growth factors (HPGF) in human non-seminomatous germ cell tumour cell lines. 975 20

The role of G-CSF, GM-CSF and M-CSF in the treatment of AML and ALL was reviewed. These CSFs significantly accelerate the neutrophil recovery after intensive chemotherapy, and reduce febrile neutropenia and documented infections. There is no clear evidence that CSFs accelerate early regrowth of AML cells at the doses and schedules presently used clinically except one study. Patients who have received CSFs tend to have a higher CR rate, which does not seem to be translated into definite survival benefit. There has been no prospective randomized study showing any beneficial priming effect of CSFs on AML cells with better clinical outcomes.
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PMID:Granulocyte colony-stimulating factor, granulocyte-macrophage colony-stimulating factor and macrophage colony-stimulating factor in the treatment of acute myeloid leukemia and acute lymphoblastic leukemia. 992 78

This paper discusses the analysis of randomized clinical trials where the primary endpoint is a recurrent event observed during a time period which can vary among patients. In particular it describes a method of estimating robust confidence limits for clinically relevant parameters. As an illustrative example, a clinical trial of a macrophage colony stimulating factor (M-CSF) for patients with acute myeloblastic leukaemia (AML) is introduced where the endpoint is the incidence and duration of febrile neutropenia. The causal effects in the framework of Rubin's deterministic model are defined as estimands. A non-parametric method based on the permutation test, using an accelerated search procedure proposed by Garthwaite, is compared with other standard methods by simulation and by application to the AML trial data.
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PMID:Analysis of recurrent events: application to a clinical trial of colony stimulating factor with the endpoint of febrile neutropenia. 1047 49

Colony stimulating factors reduce the duration of neutropenia following intensive chemotherapy in a variety of settings, but the advantages in the management of leukemia are inconclusive. The variations in clinical results and the high costs of granulocyte colony-stimulating factor (G-CSF) and granulocyte macrophage colony-stimulating factor (GM-CSF) have led to confusion over appropriate use for leukemia patients. In this paper, we reviewed published information on costs and cost-effectiveness of growth factors for childhood and adult leukemia patients. Medline and Healthstar databases were searched for original research articles that contain cost or cost-effectiveness analyses of G-CSF (filgrastim) and GM-SCF (sargramostim) in oncology cooperative group trials. Published manuscripts and abstracts presented at national or international oncology conferences were included. The cost of adjunct treatment was evaluated in two studies of pediatric ALL, one study of adult AML, and two studies of AML in older adults (>55 years). The use of G-CSF for children with ALL was associated with reductions in days to ANC recovery, fewer documented infections, a shorter duration of hospitalization, and small (but not significant) additional costs. In adult AML patients, benefits included a shortening of the duration of neutropenia and hospital stays, a lower incidence of infection and febrile episodes, less use of antibiotics, and cost savings of $2,230 and $2,310 in two studies and an increase if $120 in the third study. This summary suggests that economic analyses can provide useful information to assist clinical decision-making. For pediatric ALL patients, this information indicates that G-CSF use is unlikely to have significant cost implications, and its use should be based on clinical considerations. In studies of adult and older adult AML patients, both GM-CSF and G-CSF have clinical benefits and can be expected to lead to a decrease in overall costs.
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PMID:Cost analyses of adjunct colony stimulating factors for acute leukemia: can they improve clinical decision making. 1072 70

Neutropenia in neonates is often associated with sepsis, prematurity and maternal hypertension with increased risk of mortality. We describe two neonates with neutropenia treated with granulocyte macrophage colony stimulating factor. The total and absolute neutrophil counts showed a marked response and led to a favourable outcome. Human granulocyte macrophage colony stimulating factor may be used as an adjuvant therapy for neonatal neutropenia of different aetiologies.
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PMID:Granulocyte macrophage-colony stimulating factor (GM-CSF) in neonatal neutropenia. 1083 25

Gemcitabine and paclitaxel (PTX) are among the most active new drugs in advanced breast and ovarian cancer. In this Phase I study, we used fixed doses of gemcitabine administered on days 1 and 8 and escalating doses of paclitaxel on day 1 of a 21-day cycle in patients with pretreated metastatic breast or ovarian cancer. The dose of gemcitabine was fixed at 1,000 mg/m2; PTX was commenced in the first small patient group at a dose of 90 mg/m2, which was then escalated in subsequent groups by 30 mg/m2 per step. From the third dose level onwards, all patients received granulocyte colony-stimulating factor 300 microg by subcutaneous injection on days 5 and 6, and granulocyte macrophage colony-stimulating factor on days 15-18. Cohorts of at least 3 patients were treated at each dose level. Dose escalation was stopped if at least a third of the patients in a given cohort had dose-limiting toxicity (DLT), which was defined as grade 4 neutropenia or thrombocytopenia, or grade 3-4 non-haematological toxicity. The maximum tolerated dose (MTD) was defined as the dose level immediately below that causing DLT in one-third of the patients or more. Evaluation of the tumour response was performed every three cycles. Forty-five patients (31 with breast cancer, 14 with ovarian cancer) were treated at seven different dose levels. Only at the seventh PTX dose level was DLT observed after the first course of therapy: three grade 4 neutropenia, one grade 4 thrombocytopenia, and one grade 4 anaemia. DLT occurred in 5/6 patients at at PTX dose of 270 mg/m2; therefore dose escalation was stopped at that level and the dose immediately before it (PTX 240 mg/m2) was considered as the MTD and recommended for further studies. No toxic deaths occurred. Grade 3-4 uncomplicated neutropenia was observed in four patients. Three had uncomplicated grade 3-4 thrombocytopenia. One patient had grade 3 and one grade 4 anaemia. Nonhaematological side effects were generally mild. Among 30 evaluable patients with metastatic breast cancer, four complete responses (CR) (13%) and 12 partial responses (PR) (40%) were observed, for an overall response rate of 53% (95% confidence interval (CI) 34-72). The median duration of response was 31 weeks. Among 13 evaluable patients with advanced ovarian cancer, one CR (8%) and five PRs (38%) were observed, for an overall response rate of 46% (95% CI 19-78). The median duration of response was 32 weeks. Our study shows that gemcitabine and PTX can be administered in combination in patients with breast and ovarian cancer without unexpected toxicities and with encouraging therapeutic results.
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PMID:Phase I dose escalation study of gemcitabine and paclitaxel plus colony-stimulating factors in previously treated patients with advanced breast and ovarian cancer. 1100 95

We describe a patient with Felty's syndrome and chronic renal failure due to secondary amyloidosis in a periodic haemodialysis programme, who was successfully treated for neutropenia with sequential administration of colony-stimulating factors: granulocyte colony-stimulating factor and granulocyte macrophage colony-stimulating factor.
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PMID:[G-CSF versus GM-CSF in the treatment of neutropenia in a patient with Felty's syndrome on hemodialysis]. 1110 Jun 68

We conducted a phase II randomized trial of recombinant granculocyte-macrophage colony-stimulating factor (GM-CSF) administered before topotecan chemotherapy to determine whether it could prevent myelosuppression and to determine the antitumor activity of this topoisomerase I inhibitor in 53 patients with metastatic malignant melanoma and renal cell cancer. All patients received GM-CSF after topotecan at a dose of 250 microg/m(2) daily for at least 8 days. Patients randomly assigned to receive GM-CSF priming were treated with GM-CSF at 250 microg/m(2) twice daily for 5 days before treatment. Twenty-five patients were randomly assigned to receive GM-CSF priming and 28 to receive topotecan without priming. The primary analysis was restricted to the protective effects seen during the first cycle of therapy. Grade 4 neutropenia occurred in 8 of 23 patients (35%) and grade 3 neutropenia in 5 of 23 patients (22%) randomized to GM-CSF priming, whereas 18 of 26 (69%) and 5 of 26 (19%) patients experienced grade 4 or 3 neutropenia, respectively, without GM-CSF priming (P =.0074). The mean duration of neutropenia was reduced by GM-CSF priming: grade 3 neutropenia from 5.2 +/- 0.7 to 2.8 +/- 0.7 days (P =.0232) and grade 4 neutropenia from 2.7 +/- 0.6 to 1.1 +/- 0.4 days (P = 0.0332). The protective effects of GM-CSF extended to the second cycle of treatment. The incidence of febrile neutropenia was also reduced. Chemotherapy-induced anemia and thrombocytopenia were similar in both groups. One partial response was seen in a patient with melanoma, and one patient with renal cell cancer had complete regression of pulmonary metastases and was rendered disease-free by nephrectomy. (Blood. 2001;97:1942-1946)
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PMID:A prospective randomized phase II trial of GM-CSF priming to prevent topotecan-induced neutropenia in chemotherapy-naive patients with malignant melanoma or renal cell carcinoma. 1126 56


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