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)

The haemopoietic growth factor granulocyte colony-stimulating factor (G-CSF; filgrastim) substantially shortens the period of severe neutropenia that follows high-dose chemotherapy and autologous bone-marrow infusion by stimulating granulopoiesis. Filgrastim also increases numbers of circulating progenitor cells. We have studied the ability of filgrastim to mobilise peripheral-blood progenitor cells and assessed their efficacy when infused after chemotherapy on recovery of neutrophil and platelet counts. 17 patients with non-myeloid malignant disorders received filgrastim (12 micrograms/kg daily for 6 days) by continuous subcutaneous infusion. Numbers of granulocyte-macrophage progenitors in peripheral blood increased a median of 58-fold over pretreatment values, and numbers of erythroid progenitors increased a median of 24-fold. Three leucapheresis procedures collected a mean total of 33 (SEM 5.7) x 10(4) granulocyte-macrophage progenitors per kg body weight. After high-dose chemotherapy in 14 of the patients (busulphan and cyclophosphamide), these cells were used to augment autologous bone-marrow rescue and post-transplant filgrastim treatment. Platelet recovery was significantly faster in these patients than in controls who received the same treatment apart from the infusion of peripheral-blood progenitors; the platelet count reached 50 x 10(9)/l a median of 15 days after infusion of haemopoietic cells in the study patients compared with 39 days in controls (p = 0.0006). The accelerated neutrophil recovery associated with filgrastim treatment after chemotherapy was maintained. This method may be widely applicable to aid both neutrophil and platelet recovery after high-dose chemotherapy; it will allow investigation of peripheral-blood progenitor-cell allotransplantation.
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PMID:Effect of peripheral-blood progenitor cells mobilised by filgrastim (G-CSF) on platelet recovery after high-dose chemotherapy. 137 71

Filgrastim (granulocyte colony stimulating factor) recently became commercially available for the treatment of chemotherapy-induced neutropenia. Studies have shown that filgrastim induces a dose-dependent granulocytosis in humans, thereby shortening the period of neutropenia in patients treated conventionally with submarrow ablative doses of chemotherapy, as well as with marrow ablative therapy given in the bone marrow transplant setting. By reducing the incidence and severity of infections and mucositis in patients treated with chemotherapy, it has a significant economic impact since it shortens the duration of antibiotic administration and hospitalization. Adverse reactions reported are limited to mild to moderate bone pain. Several other potential applications are being investigated for filgrastim, including treatment of patients with myelodysplastic syndrome and congenital neutropenia.
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PMID:Topics in clinical pharmacology: filgrastim, a myeloid colony stimulating factor. 137 51

A patient with neutropenia and life-threatening infections secondary to T-gamma lymphoproliferative disease, who did not respond to treatment with recombinant human G-CSF (filgrastim), was treated with filgrastin plus cyclosporine A (CyA). The patient achieved a good response in the absolute neutrophil count and subsequently required a dose reduction in the filgrastim. The patient was eventually discontinued from the CyA but continues on filgrastim alone. While on therapy, the large granular lymphocytes disappeared from the circulation and the beta-TCR rearrangement, which was present prior to beginning therapy, became undetectable. The patient had no significant toxicity to the CyA or the filgrastim and he has not experienced any serious infections or required hospitalization. Filgrastim has proven to be relatively nontoxic and of some benefit to patients with this disease and should probably be utilized first when treatment is necessary. However, if improvement is not observed, these findings suggest that a trial of the combination of CyA plus filgrastim may be beneficial.
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PMID:Treatment of chronic neutropenia associated with large granular lymphocytosis with cyclosporine A and filgrastim. 748 4

Haemopoietic growth factors are accepted as accelerating haemopoietic recovery after bone-marrow grafting, yet no large randomised trials have been published that convincingly show benefit. Lenograstim (glycosylated recombinant human granulocyte colony-stimulating factor) was given to 315 patients after bone-marrow transplantation in a prospective randomised placebo-controlled multicentre trial. 1 day after bone-marrow infusion, 163 patients received lenograstim 5 micrograms/kg per day by 30-min infusion, and 152 patients received placebo daily for 28 days or until neutrophil recovery. 137 patients had lymphoma, 35 myeloma, 85 acute lymphoblastic leukaemia, and 58 a solid tumour. Patients were stratified by age and by type of bone-marrow transplantation (BMT). Neutrophil recovery to above 10(9)/L for 3 consecutive days was seen earlier in lenograstim-treated patients (16 vs 27 days, p < 0.001). Time to neutrophil recovery above 0.5 x 10(9)/L was reduced (14 vs 20 days, p < 0.001). The difference was significant both in autograft (20 vs 14 days, p < 0.001) and allograft (20 vs 14 days, p < 0.01) patients, in children (20 vs 13 days, p < 0.001), and adults. Lenograstim-treated patients had fewer days of infection, and of antibiotic administration, and also spent less time in hospital. However, clinical and microbiological sepsis was similar in both groups. There was no significant toxicity ascribed to lenograstim. Survival was the same at days 100 and 365. In patients undergoing autologous or allogeneic BMT for neoplastic disease, lenograstim significantly reduced duration of neutropenia and led to earlier hospital discharge.
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PMID:Placebo-controlled phase III trial of lenograstim in bone-marrow transplantation. 751 Aug 13

Seven patients with glycogen storage disease type Ib suffering from severe and/or recurrent bacterial infections were treated with glycosylated recombinant G-CSF (Lenograstim). Mean follow up was 20.8 months (range 9-30 months). In all cases a median dose of 5 micrograms/kg/day resulted in rapid clinical improvement, associated in 6/7 with an increase in absolute polymorphonuclear (PMN) count. In the remaining subject, a striking amelioration of infectious status contrasted with a persistently low PMN count. Liver transplantation in one patient resolved metabolic complications but did not improve PMN count or the infectious status, while neutropenia was corrected by G-CSF. Prevention of recurrent infections was achieved in all cases with intermittent therapy. Short term treatment was well tolerated, thrombocytopenia in two patients (WHO grade 0 and grade 3) recovering after decrease of G-CSF dosage.
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PMID:Recombinant human G-CSF (Lenograstim) for infectious complications in glycogen storage disease type Ib. Report of 7 cases. 751 58

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

No published data are available concerning the activity and tolerability of intramuscularly administered granulocyte colony-stimulating factor (G-CSF) in humans. To fill this gap, 19 patients with advanced ovarian cancer previously treated with at least one first-line chemotherapy cycle received the following myelosuppressive regimen: mitoxantrone (DHAD) 12 mg m-2 i.v. on day 1; ifosfamide (IFO) 4 g m-2 i.v. on days 1 and 2; mesna 800 mg m-2 i.v. t.i.d. on days 1 and 2. G-CSF (Filgrastim) was given at a dose of 5 micrograms/kg/day i.m. from day 6 to day 19, its pharmacokinetics being assessed in five patients. The neutrophil nadir was observed after a mean period of 8 days, and the neutrophil count was < 1.0 x 10(3) mm-3 for a mean of 6 days during the cycle of chemotherapy. The neutrophil count fell after the withdrawal of G-CSF on the 19th day of treatment. The difference in absolute neutrophil count between day 19 and day 21 was statistically significant (P = 0.0001); nevertheless, at day 21 no WHO grade 3-4 neutropenia was reported. DHAD and IFO were respectively given at 95% and 93% of the planned dose. The pharmacokinetics of G-CSF i.m. seems to be similar to that of the drug given subcutaneously. No evidence of cumulative myelosuppression was observed. G-CSF was well tolerated and no complications were observed at the injection sites. In conclusion, if the results obtained in this pilot study regarding the activity of i.m. G-CSF are confirmed by a randomised trial, the intramuscular administration of G-CSF could become a valid alternative for patients who dislike the subcutaneous route and who are being treated with chemotherapy that does not induce profound thrombocytopenia.
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PMID:The intramuscular administration of granulocyte colony-stimulating factor as an adjunct to chemotherapy in pretreated ovarian cancer patients: an Italian Trials in Medical Oncology (ITMO) Group pilot study. 751 30

Clinical application of glycoproteins stimulating the growth (G-CSF), differentiation and activity of the cells of granulocyte line has become a landmark in the treatment of patients with neutropenia. It has been proved that filgrastim (rHU G-CSF) applied after intensive chemotherapy shortens the duration of neutropenia and decreases the frequency of occurrence of infections. The paper discusses the efficiency and tolerance of filgrastim in children treated for NHL. Filgrastim was applied in children with NHL T cell and B cell treated according to BFM 86 protocols. It was given in a dose of 5 micrograms/kg daily i.v. The duration of therapy ranged from 5-20 days. Altogether 47 cycles were performed. 25 cycles were performed in 12 children during granulocytopenia (< 1 x 10(9)/l). The median time of neutropenia recovery, the frequency of severe infection and chemotherapy retardation were significantly lower in the examined than in the control group (p < 0.05). In 6 children 22 courses of filgrastim were given prophylactically after the cycles of intensive chemotherapy of NHL. Only during two courses due to neutropenia the chemotherapy retardation was necessary. Toleration of filgrastim was good. Application of filgrastim right after the intensive chemotherapy in children with NHL has considerably improved persistent realization of treatment programmes. Tolerance of the drug was good.
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PMID:[Use of filgrastim (RHU G-CSF) in supplemental treatment of non Hodgkin's lymphoma (NHL) in children]. 752 59

The clinical usefulness of Recombinant Human Granulocyte Colony Stimulating Factor (rhG-CSF, Filgrastim, GRAN) was evaluated in patients with leukopenia and neutropenia following chemotherapy for non-Hodgkin's lymphoma, lung cancer and breast cancer. During chemotherapy when patients' leukocyte count (WBC) fell below 4.0 x 10(9)/L.rhG-CSF(GRAN) at a dose of 75 micrograms/body.day was given subcutaneously 48 hours after the termination of chemotherapy. The results indicated that rhG-CSF(GRAN) could elevate nadirs of WBC and significantly shortened leukopenic period with WBC below 4.0 x 10(9)/L and expedited the recovery of WBC. rhG-CSF (GRAN)'s side effects were mild.
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PMID:[Clinical study of recombinant human granulocyte colony stimulating factor (rhG-CSF) on leukopenia induced by chemotherapy in cancer patients]. 752 73

The economic cost of treating febrile neutropenic cancer patients in Canada has not been defined. Amgen Canada Inc., the distributor of filgrastim (Neupogen Amgen Canada Inc.) was interested in determining this cost in order to evaluate the potential economic impact of filgrastim in the Canadian healthcare setting. Filgrastim is indicated to decrease the incidence of infection, as manifested by febrile neutropenia, in patients with nonmyeloid malignancies who receive myelosuppressive antineoplastic drugs. In addition, the company sought to determine which demographic factors influenced the cost. This was done to characterize which patients could derive clinical benefit from filgrastim while at the same time producing cost offsets through anticipated reductions in hospitalizations. In order to address these issues a study was commissioned to collect demographic data on patients diagnosed with both cancer and neutropenia in Canadian acute care hospitals. This cancer/neutropenia database was created from patient discharge abstracts contained in the 1990/91 Hospital Medical Records Institute national acute-care hospital database. The data presented in the HMRI report are consistent with the concept that subgroups of cancer patients exist in whom clinical benefits and cost off-sets may be realized from the use of growth factors.
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PMID:A cancer and neutropenia database study. 752 29


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