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Query: UMLS:C0027947 (neutropenia)
 17,527 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The haematopoietic growth factor (HGF), 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 (PBPC) and assessed their efficacy when infused after chemotherapy on recovery of neutrophil and platelet counts. Seventeen patients with non-myeloid malignant disorders received filgrastim (12 micrograms/kg daily for six 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 leukapheresis 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 haematopoietic 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. Subsequently, 10 patients received filgrastim-mobilised PBPC without marrow after high-dose chemotherapy. The rate of platelet and neutrophil recovery in these patients was at least equal to that observed in the patients receiving PBPC and bone marrow.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effect of peripheral blood progenitor cells mobilised by filgrastim (G-CSF) on platelet recovery after high-dose chemotherapy. 833 35

The recombinant hG-CSF Filgrastim was used in severe cases of neutropenia in the dog caused by parvovirosis, hyperestrogenism, treatment with antineoplastic agents, an aplastic syndrome and in the cat in cases of infectious panleukopenia. Increases of the numbers of leukocytes were observed in all groups of diseases in the dog, but not in feline infectious panleukopenia. Filgrastim is indicated in neutropenias associated with disturbance of the general condition accompanied by fever, but not in cases of transitory leukopenias.
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PMID:[Treatment of severe neutropenias in dogs and cats with filgrastim]. 858 81

Severe chronic neutropenia (SCN) include a heterogeneous group of diseases characterized by blood neutrophil counts chronically less than 0.5 x 10(9)/ L. In phase I-III studies in SCN patients, treatment with recombinant human granulocyte colony stimulating factor (r-metHuG-CSF; Filgrastim) resulted in a rise in the absolute neutrophil counts (ANC) to above 1.0 x 10(9)/L associated with a reduction in bacterial infections. Long-term treatment with filgrastim up to 8 years demonstrate a sustained ANC response, a significant reduction of the need for intravenous antibiotics and a dramatic improvement in the quality of life. In 1994 an international registry for severe chronic neutropenia (SCNIR) was established to improve care for chronic neutropenia and for further understanding the pathophysiology of this rare disease. Three-hundred and ten patients have been enrolled to this registry so far. Worldwide phase I-III studies with filgrastim and SCNIR provide information on 424 patients with severe chronic neutropenia. Adverse events include the development of acute myeloid leukemia in approximately 7% of the patients within the cohort of patients with congenital neutropenia (Kostmann's syndrome) suggesting that congenital neutropenia is a preleukemic syndrome. None of the patients with cyclic of idiopathic neutropenia developed leukemia suggesting that filgrastim is not involved in the development of leukemia.
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PMID:Pathophysiology and treatment of severe chronic neutropenia. 862 68

Neutropenia in solid organ transplant recipients may be caused by immunosuppressive therapy, antimicrobial therapy, as well as bacterial and viral infections. Filgrastim, a human granulocyte colony stimulating factor (G-CSF) is used for the reversal of neutropenia. Although its influence is principally restricted to neutrophil progenitors, the safety of G-CSF in terms of percipitating or aggravating allograft rejection and its efficacy in reversing neutropenia in kidney and combined kidney and pancreas transplant patients has not been studied or reported. In this study we retrospectively analyzed the use of G-CSF between March 1992 and May 1994 at the University of Cincinnati Medical Center, in patients who received either a kidney or a combined kidney and pancreas transplant. A total of 25 patients developed 35 episodes of neutropenia and received an average of 2.9 doses of G-CSF per episode. The mean WBC nadir was 2.6 x 10(3)/cu mm with an average peak WBC count of 15.5 x 10(3)/cu mm following treatment (p = < 0.00001). The average number of days to peak WBC after initiation of treatment was 4.6 days. The mean pre-treatment serum creatinine level was 2.3 mg/dl and the peak serum creatinine in the week following treatment remained the same. We conclude that G-CSF is an effective treatment in reversing neutropenia in renal transplant recipients and does not precipitate or aggravate allograft rejection.
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PMID:Role of granulocyte colony stimulating factor (G-CSF) in reversing neutropenia in renal allograft recipients. 865 92

We performed a dose escalation study to evaluate the maximum tolerated dose of paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) given over 3 hours plus bolus epirubicin 90 mg/m2. The starting dose of paclitaxel, 135 mg/m2, was escalated by 20-mg/m2 increments in cohorts of three to six patients. Courses were repeated every 3 weeks. Filgrastim (5 micrograms/kg/d) was administered to shorten the duration of grade 4 neutropenia lasting longer than 72 hours. Twenty-nine patients have been treated, 86% of whom had failed adjuvant chemotherapy (with anthracyclines in 14 cases). One hundred forty-eight courses have been administered, and the paclitaxel dose has been escalated to 225 mg/m2 without reaching the maximum tolerated dose. The most frequent dose-related toxicity has been grade 4 neutropenia, which occurred in 59% of courses. The median duration of grade 4 neutropenia was 4 days, which was shortened with filgrastim only in patients treated with paclitaxel 225 mg/m2. Eleven episodes of febrile neutropenia (7% of courses) have been observed. Nonhematologic toxicities were mild or moderate: grade 1 or 2 peripheral neuropathy was reported by 41% and 10% of patients, respectively. The cardiac toxicities of this regimen were surprisingly low: median left ventricular ejection fraction was 57% at study entry and 56% after six courses. Only two patients showed a decrease of left ventricular ejection fraction below 50% after six courses, and no signs of anthracycline-induced congestive heart failure were noted. The activity of this novel combination is encouraging: the overall response rate is 80%, with 16% complete responses. We have demonstrated that the combination of epirubicin plus paclitaxel given over 3 hours is feasible with acceptable toxicities, does not appear to be associated with clinically relevant cardiotoxicity, and is active in a population of patients who have failed adjuvant chemotherapy.
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PMID:A dose-finding study of epirubicin in combination with paclitaxel in the treatment of advanced breast cancer. 889 96

This phase II study combined paclitaxel (Taxol; Bristol Myers Squibb Company, Princeton, NJ) 135 mg/m2 by 3-hour infusion on day 1 and vinorelbine 25 mg/m2 on days 1 and 8 (in the first 14 patients) or on days 1 and 3 (in the subsequent 20 patients). The courses were repeated every 3 weeks. The second vinorelbine dose (on days 3 or 8) was reduced or omitted according to the toxicities encountered. Thirty-four patients have been treated to date; 21 had received one prior regimen of chemotherapy, 11 had two prior regimens, and two had three prior regimens. Only two patients (6%) had not been exposed to anthracyclines. One hundred twenty-six courses have been administered: 52 with vinorelbine given on days 1 and 8, and 74 with vinorelbine administered on days 1 and 3. The most frequent toxicity was grade 4 neutropenia, which occurred in 64% of the courses; 13 episodes of febrile neutropenia have been reported in eight patients. Filgrastim was administered in 43% of the courses because of febrile neutropenia or delayed recovery (> 72 hours) from grade 4 neutropenia. Mucositis was observed in 18% of the courses (12% grade 1, 3% grade 2, and 3% grade 3). The dose of vinorelbine was reduced or omitted in 86% of courses with the days 1 and 8 schedule, and in 48% of courses with the days 1 and 3 schedule. Among 28 evaluable patients, two complete and 10 partial responses have been observed (response rate, 43%, 95% confidence interval, 19% to 51%). Median duration of response is 5+ months (range, 1 to 15 months). In conclusion, this combination is active and has acceptable toxicities in anthracycline-pretreated breast cancer patients. The delivered dose intensity of vinorelbine is higher with the schedule adopted later in the study, with vinorelbine given on days 1 and 3.
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PMID:Paclitaxel in combination with vinorelbine in pretreated advanced breast cancer patients. 889 98

Given their known activity against non-small cell lung cancer, paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) and carboplatin were combined in this phase I study of patients with metastatic disease to determine the maximum tolerated dose and the dose-limiting toxicity of the combination. The initial dose of paclitaxel was fixed at 135 mg/m2 given as a 24-hour infusion with carboplatin administered in escalating doses in cohorts using Calvert's formula-dose (mg) = target AUC x (GFR + 25), where AUC is area under the concentration-time curve and GFR is glomerular filtration rate-based on target AUCs of 5, 7, 9, or 11 mg/mL.min. Dose escalations were based on cycle 1 toxicities. Filgrastim was not administered with the first cycle until two or more patients developed grade 4 or febrile neutropenia at the preceding dose level. Dose-limiting toxicity occurred in two patients at level 2 (cycle 1), and filgrastim was administered thereafter for the next four dose levels. Grade 4 thrombocytopenia was seen at level 4; thus, the carboplatin dose was de-escalated thereafter, and the paclitaxel dose escalated. Rare nonhematologic toxicities include fatigue, diarrhea, and nausea and vomiting. Among the first 30 patients, one had a complete response and 14 had partial responses, for an overall response rate of 50%. The combination of paclitaxel and carboplatin is active in non-small cell lung cancer, and the recommended phase II dose without filgrastim support is paclitaxel 175 mg/m2 via a 24-hour infusion with the carboplatin dose targeted to achieve an AUC of 7 mg/ mL.min.
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PMID:Paclitaxel and carboplatin in metastatic non-small cell lung cancer: preliminary results of a phase I study. 894 6

Low-dose, subcutaneous recombinant human granulocyte colony-stimulating factor (rHuG-CSF, Lenograstim) was administered to 40 cancer patients (17 men, 23 women) enrolled from two medical centers to verify its clinical effectiveness and safety. The patients' mean age was 50.3 +/- 14.9 years. In this study, there were 20 patients with non-Hodgkin's lymphoma, 10 with breast cancer and 10 with various other solid tumors. The patients first received a course of chemotherapy without rHuG-CSF (control cycle). All patients had at least one episode of neutropenia or leukopenia during the control cycle. rHuG-CSF (2 micrograms/kg/day) was given subcutaneously for 10 days during the study cycle starting on the fourth day of chemotherapy. The nadirs of absolute neutrophil counts (ANC) were 1.8 +/- 0.25 x 10(9)/L and 0.27 +/- 0.05 x 10(9)/L for the rHuG-CSF cycle and pre-rHuG-CSF control cycle, respectively. The number of days of ANC < 1 x 10(9)/L were 1.03 +/- 0.29 and 7.38 +/- 0.58 for rHuG-CSF and control cycles, respectively. The duration from nadir to recovery of ANC (> or = 2 x 10(9)/L) was 9.68 +/- 1.15 days in the rHuG-CSF cycle, vs 22.53 +/- 1.03 days in the control cycle (p < 0.0001). No patient withdrew from the study. Adverse events were mild, with 12.5% to 40% of patients developing myalgia, general malaise, back pain, anorexia or fever. These side-effects were tolerable in all cases. The biochemical abnormalities were subtle and negligible. rHuG-CSF 2 micrograms/kg/day given subcutaneously for 10 days beginning on the fourth day of chemotherapy is very effective (90%), safe and convenient.
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PMID:Clinical trial of low-dose rHuG-CSF in neutropenic cancer patients following anti-cancer chemotherapy. 899 Jul 72

A modified technique of two-dimensional gel electrophoresis (2-DE) was used to investigate differences in the pattern of cytosolic proteins of neutrophilic granulocytes from patients with severe congenital neutropenia, cyclic neutropenia, and idiopathic neutropenia in comparison with healthy donors. At the time of study, all patients tested received treatment with a recombinant human granulocyte colony-stimulating factor (r-metHuG-CSF; Filgrastim, Amgen). Using the Investigator 2-D Electrophoresis System (Millipore) we were able to detect more than 1000 protein spots in the cytosol of neutrophilic granulocytes from both patients and healthy controls. We investigated six patients with severe congenital neutropenia, five patients with cyclic neutropenia, four patients with idiopathic neutropenia, and 13 healthy donors. In the cytosol of neutrophilic granulocytes from patients we found an additional protein spot. This protein spot (molecular mass approximately 32.4 kDa, pI about 5.5) could be identified by internal sequencing after in-gel digestion with endoproteinase Lys-C as tropomyosin. The importance of the overexpression of tropomyosin in neutrophilic granulocytes from patients with severe chronic neutropenia is not yet understood.
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PMID:Cytosolic proteins from neutrophilic granulocytes: a comparison between patients with severe chronic neutropenia and healthy donors. 905 36

Recently, point mutations in the gene of the granulocyte colony-stimulating factor (G-CSF) receptor have been reported in two patients with severe congenital neutropenia who developed acute myeloid leukemia (AML). We investigated the frequency of these specific G-CSF receptor mutations in patients with congenital neutropenia undergoing treatment with r-metHuG-CSF (Filgrastim) and the clinical relevance of these mutations. Nucleotides 2306 to 2561 including the critical region (nucleotides 2384-2429) from the intracellular domain of the G-CSF receptor gene were amplified by reverse transcriptase-polymerase chain reaction. Detection of point mutations was performed with specific restriction enzyme analysis, as well as sequencing of PCR products. Both genomic DNA and cDNA from neutrophils and mononuclear cells were analyzed from 28 patients with severe congenital neutropenia. Four of 28 patients with congenital neutropenia displayed a point mutation in the tested cytoplasmic region of the G-CSF receptor gene. The point mutations replace a glutamine codon by a stop codon of the G-CSF receptor gene. Among these four congenital neutropenia patients with a mutated G-CSF receptor, two developed AML. All four patients were investigated regularly and no correlation between occurrence of G-CSF receptor mutation and time or dose of r-metHuG-CSF treatment was found. No point mutations in the G-CSF receptor critical domain could be detected in cells from the other 24 congenital neutropenia patients. Furthermore, we tested six family members of the two patients with AML including mothers and fathers, one sister, and one brother who suffers from congenital neutropenia, as well. All family members displayed a normal G-CSF receptor gene. After the acquisition of the G-CSF receptor mutations, the congenital neutropenia patients continued to respond to G-CSF therapy with an increase in absolute neutrophils in the peripheral blood. We conclude that the point mutations in the critical region of the intracellular part of the G-CSF receptor occur spontaneously and are not inherited. From our data, we suggest that the described G-CSF receptor point mutations do not alter the response to treatment with r-metHuG-CSF and are not the cause of severe congenital neutropenia.
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PMID:Clinical relevance of point mutations in the cytoplasmic domain of the granulocyte colony-stimulating factor receptor gene in patients with severe congenital neutropenia. 932 53


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