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

Studies by other laboratories have shown that angiotensin II (AII) can affect the function of cells which comprise the immune system. In the present study, the effect of AII on the function of peritoneal macrophages and peripheral blood monocytes was assessed. In vitro exposure (4 h prior to assay) of peritoneal macrophages from mice and rats to AII increased the percentage of cells that phagocytosed opsonized yeast and the number of yeast per macrophage. Furthermore, AII increased the respiratory burst capacity of peritoneal macrophages from mice and rats and peripheral blood mononuclear cells from humans. Because of these observations, the effect of AII on host resistance to bacterial infection was assessed. Intraperitoneal administration of AII was shown to increase host resistance (reduced abscess formation) in an animal model of bacterial peritonitis. Studies were then conducted to assess whether parenteral administration of AII, a clinically relevant route, could affect peritoneal host resistance in a manner similar to that observed after peritoneal administration. These studies showed that subcutaneous administration of AII throughout the postinfection interval increased the level of host resistance to bacterial peritonitis. Furthermore, in a study which compared AII and Neupogen, an agent approved for use for the reduction of febrile neutropenia after myeloablative therapy, daily subcutaneous administration of AII reduced abscess size and incidence, whereas Neupogen did not have any therapeutic benefit in this model. These data suggest that AII may be of therapeutic benefit as an immunomodulatory agent.
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PMID:Angiotensin II increases host resistance to peritonitis. 1088 64

Granulocyte colony-stimulating factor (G-CSF) has been used to reduce the duration and/or degree of neutropenia of different etiologies in recent years. In this study, experience with the use of G-CSF (Neupogen, Roche) after 123 courses of highly myelosuppressive chemotherapy administered to 31 (20 female, 11 male) patients with pediatric solid tumors is reported. G-CSF was initiated at a white blood cell (WBC) count of 918 +/- 452/microL (100-2000), at a dose of 7.6 +/- 2.3 micrograms/kg/d (5-14) subcutaneously for 5.2 +/- 2.4 days (2-18). G-CSF was given for afebrile neutropenia after 82 and for febrile neutropenia after 41 courses. Only in two episodes where G-CSF was given for afebrile neutropenia, fever developed. The average hospitalization period for febrile neutropenia was 9.8 +/- 3.3 days (5-20). Chemotherapy could be given on scheduled time and dosage in 90% of the courses in which G-CSF was used for afebrile neutropenia. G-CSF was well tolerated. Bone pain was observed in two patients and urticaria in one patient. In conclusion, G-CSF increased the WBC count effectively, there were only two febrile episodes in 82 courses in children receiving G-CSF for afebrile neutropenia, it was well tolerated, and it was found to be feasible for use in a developing country.
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PMID:Granulocyte colony-stimulating factor in neutropenic, pediatric solid tumor patients following chemotherapy. 1089 13

This phase IIa, randomised, single-blind, placebo-controlled study was conducted to determine the dose of recombinant human granulocyte colony-stimulating factor (lenograstim) suitable for use in AIDS patients. The study was conducted at 27 European AIDS/HIV centres, and recruited 69 AIDS patients with an initial episode or relapse of cytomegalovirus infection (neurological site excluded) and an absolute neutrophil count (ANC) < or = 1.0 x 10(9)/L upon diagnosis or between days 1 and 12 of ganciclovir (GCV) treatment. The patients were randomised to placebo (n = 14) or one of four lenograstim arms: 150 microg/m2/d (the standard onco-haematology dose, n = 13) or 100 (n = 13), 50 (n = 15), or 25 microg/m2/d (n = 14). In all groups, the planned dose of GCV was 10 mg/kg/d for 21 d. Median ANC at weeks 2 and 3 was significantly higher in each lenograstim group than in the placebo group (p = 0.05). At week 3, median ANC (x 10(9)/L) was 0.7 in the placebo group, compared with 6.0, 7.4, 4.5, and 2.0 in the 150, 100, 50, and 25 microg2/d lenograstim groups, respectively. Median ANC was not significantly different between the 150, 100, and 50 microg/m2/d lenograstim groups at any time point, but significantly higher in the 50 than in the 25 microg/m2/d group at weeks 2 (p = 0.05) and 3 (p = 0.02). Lenograstim was generally well tolerated, leading to no severe adverse events. In conclusion, lenograstim 50 microg/m2/d is suitable for the treatment of ganciclovir-induced neutropenia and is safe. These results should help the physician choose an optimal and cost-efficient regimen for patients with AIDS-related neutropenia when rHuG-CSF support is indicated.
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PMID:Lenograstim for the treatment of neutropenia in patients receiving ganciclovir for cytomegalovirus infection: a randomised, placebo-controlled trial in AIDS patients. 1109 65

On the basis of preclinical and clinical data, we designed a phase II study to determine the efficacy and feasibility of high-dose epirubicin plus docetaxel (Taxotere) with lenograstim support, as first-line therapy for patients with advanced breast cancer. Patients with histologic evidence of metastatic breast cancer, without previous chemotherapy, adequate organ functions, Eastern Cooperative Oncology Group performance status less than 2, and signed informed consent entered in the trial. Treatment consisted of premedication the day before the treatment day for 3 consecutive days (dexamethasone 16 mg o.r. and 5-HT3 antagonists). On the treatment day 1, epirubicin 130 mg/m2 was administered as a 15-minute intravenous infusion followed 1 hour later by 1-hour intravenous infusion of docetaxel 100 mg/m2. Cycles were repeated every 21 days, for a maximum of 8 cycles. Lenograstim (5 microg/kg, s.c.) was started 48 hours later (day 4) and was given daily for 10 consecutive days. Response evaluation was made after the third cycle was applied, following World Health Organization criteria. Responding patients received five additional cycles. Median time to progression and survival were calculated according to the Kaplan-Meier method. A total of 32 patients have been included in the study. A total of 236 courses were delivered. A total response rate of 87.5% (95% confidence interval [CI] of 77-98) was obtained. There were 11 complete responses and 17 partial responses. Toxicity was mild, with a low incidence of undesirable effects (7 cycles, 2.9% were delayed from 3 to 6 days because of neutropenia). After a median follow-up time of 490 days (range, 131-966 days), the median time to progression was 490 days (95% CI 314-575), and the median survival was 604 days (95% CI 513-785). This epirubicin plus docetaxel regimen is an efficient treatment for patients with advanced breast cancer. The lenograstim support allows the administration of such a chemotherapy regimen with a modest incidence of side effects. A larger number of patients need to be evaluated.
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PMID:High-dose epirubicin plus docetaxel at standard dose with lenograstim support as first-line therapy in advanced breast cancer. 1131 87

Neupogen, or recombinant granulocyte colony-stimulating factor, is a neutrophil growth factor developed by Amgen. Neupogen has been used to combat the myelosuppressive effects of cancer chemotherapy, and has been approved in the United Kingdom to treat AIDS-induced neutropenia. Neutropenia filing and approval are pending in the United States. One concern is that in the rush to treat neutropenia, physicians will not carefully monitor the use of Neupogen over time, causing huge drug costs to mount (about $3,000 per month). With careful guidelines, the cost of Neupogen can be reduced dramatically. It is hoped that in the future, AIDS will not progress to the point that treatment with drugs such as Neupogen will be necessary.
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PMID:Neupogen and AIDS: the next frontier. 1136 44

Topotecan, a drug typically used to treat cancer, has shown promising in vitro results against the JC virus. The JC virus causes progressive multifocal leukoencephalopathy (PML). SmithKline Beecham is planning to announce phase II placebo-controlled trials for PML. There is currently no known treatment for PML, although it sometimes responds to anti-HIV drugs, alpha-interferon, and peptide T. AIDS advocates are questioning why SmithKline Beecham did not perform animal and pre-clinical studies to see if topotecan would be effective and tolerable among HIV/AIDS patients. Topotecan treatment has resulted in minimum success fighting ovarian cancer, however, its toxic effects are dangerous and powerful. Advocates advise that any patient considering a trial of topotecan have their blood monitored very carefully, particularly for neutropenia. Participants should consider pre- and post-treatment with G-CSF (Neupogen) to boost white blood cells.
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PMID:Topotecan and PML: the limits of pharmaceutical industry research. 1136 13

The aim of this trial was to compare the severity of neutropenia, the frequency of hospital admission for fever or infection, and the use of antibiotics among patients treated with a standard dose of lenograstim (263 microg/day of Euprotin) and others treated with half of this dose (131.5 microg/day) and the cost-effectiveness of each of the two doses. In this single-center study, 44 patients with solid tumors, who were all receiving standard-dose chemotherapy regimens following previous neutropenia or were at high risk of neutropenia, were randomized to receive lenograstim at a dose of 263 microg or 131.5 microg daily in the first cycle and then crossed over to the alternate dose for the following cycle. Crossover to the alternate dose was repeated for patients who received more than two cycles. Lenograstim was administered from day +5 to day +14. The absolute neutrophil count (ANC) was assessed on days +5, +8, +12 and +15 of each cycle. Statistical analysis was performed using a general lineal model for repeated samples. In all, 120 cycles were administered, with a median of 3 cycles (range 1-6). Only 4 patients received only 1 cycle. No statistically significant difference (P=0.324) in ANC was observed between standard-dose (mean 5.3, 10.7, 8.3, 11.4 x 10(9)/l) and low-dose (5.0, 8.6, 5.4, 7.5 x 10(9)/l) treatment at days +5, +8, +12 and + 15. Neutropenia grade III-IV was more common in patients receiving the low than in those receiving the standard dose of lenograstim (20% vs 12%, respectively), but the difference did not reach statistical significance (P=0.1). The incidence of fever and frequency of hospital admission were not affected by the dose of lenograstim: 3 patients presented with fever with the standard dose (all of those were admitted to hospital) and 2 patients with the low dose (1 was admitted). ANC in both groups (standard and low doses) was independent of chemotherapy line (first versus second or more). Lenograstim at a dose of 131.5 microg/day is as effective as the standard dose in limiting the severity of neutropenia and in preventing episodes of fever and hospital admissions after chemotherapy for solid tumors. The lower dose of lenograstim is cost-effective in neutropenia prophylaxis. Starting its administration on day +5 reduces costs while maintaining efficacy.
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PMID:A randomized, crossover comparison of standard-dose versus low-dose lenograstim in the prophylaxis of post-chemotherapy neutropenia. 1143 Apr 19

The object of this study was to determine the efficacy and safety of glycosylated recombinant human granulocyte colony-stimulating factor (rHuG-CSF; lenograstim) after combination chemotherapy consisting of ranimustine, vindesine, melphalan and prednisolone (MCNU-VMP). One hundred thirty-nine consecutive patients with newly diagnosed multiple myeloma (MM) were allocated at random to a lenograstim group (n = 70) or a placebo group (n = 69). Patients were treated with two cycles of MCNU-VMP, and either lenograstim (2 microg/kg daily, s.c.) or placebo was administered from the day neutrophils decreased to less than 1.000/microl and was discontinued when neutrophils exceeded 5,000/microl. The median duration of neutropenia (neutrophils under 1,000/microl) was significantly shorter for the lenograstim group than the placebo group (2 days vs 9 days in the first cycle; 1 day vs 13 days in the second cycle). The incidence of febrile neutropenia in the first cycle was significantly lower in the lenograstim group than in the placebo group (9.2% vs 30.4%). No life-threatening infections were observed in either group. The two cycles of MCNU-VMP therapy were completed in 90.8% of the patients, and a higher average relative dose intensity (ARDI; 0.94) was achieved in the lenograstim group. The tumor response rate of the lenograstim group (57.8%) was higher than that of the placebo group (43.1%), but the difference was not statistically significant (chi2 = 2.634, df = 1, P = 0.105). Lenograstim was well tolerated, and no unexpected adverse events occurred. Lenograstim proved effective in controlling chemotherapy-induced neutropenia in MM patients under MCNU-VMP therapy.
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PMID:Clinical benefits of lenograstim in patients with neutropenia due to chemotherapy for multiple myeloma (MM). 1149 96

The objective of this study was to determine the hematopoietic effects and toxicity of low-dose granulocyte colony-stimulating factor (G-CSF) in myelodysplastic syndrome (MDS) patients with neutropenia. Recombinant human G-CSF (Lenograstim) was administered by daily subcutaneous injection with an initial dosage of 0.5 microg/kg per day for 2 weeks. Patients not responding to the initial dosage received the escalated dosage, 1 to 2 microg/kg per day for 2 weeks. Eligibility criteria were the following: French-American-British disease classification subtype refractory anemia (RA), refractory anemia with ringed sideroblasts (RARS), or refractory anemia with excess blasts (RAEB) with an absolute neutrophil count (ANC) of <1.5 x 10(9)/L. Criteria indicating response to treatment were ANC of >1.5 x 10(9)/L and doubling of ANC on at least 2 occasions. Thirty-two MDS patients were recruited from 6 university hospitals. Eighteen patients had RA, 4 had RARS, and 10 had RAEB. Median age was 56.4 years (range, 28-87 years). Twenty-six patients (81.2%) had an increase in ANC from a median of 0.94+/-0.35 x 10(9)/L to 4.24+/-3.78 x 10(9)/L. Three of 6 patients who did not respond to the initial dosage responded to the escalated dosage of 1 microg/kg per day. Eighteen (81.8%) of 22 patients with RA or RARS responded compared with 8 (80%) of 10 patients with RAEB. The response rates in patients with ANCs of <0.5 x 10(9)/L. 0.5 to <1.0 x 10(9)/L, and 1.0 to 1.5 x 10(9)/L were 80%, 70%, and 88.2%, respectively. The side effects were minimal. No significant changes in hemoglobin levels or platelet counts were observed. In conclusion, low-dose G-CSF administered by subcutaneous injection is well tolerated and effective in improving neutropenia in MDS patients.
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PMID:Treatment of myelodysplastic syndrome with low-dose human granulocyte colony-stimulating factor: a multicenter study. 1159 13

(1) Neutropenia is frequent in patients with AIDS and is an added risk factor for infection. There is no specific treatment, except, when feasible, the withdrawal of a suspected culprit drug. (2) Filgrastim, a granulocyte growth factor, has been granted a license extension to cover the treatment of persistent neutropenia in patients at an advanced stage of HIV infection. (3) Only one comparative, unblinded trial has been published in this setting. It involved 258 patients distributed into three groups, who received daily filgrastim, intermittent filgrastim, or no treatment. Six months after the beginning of the trial, filgrastim had not reduced the number of deaths, the number of hospital days, or the risk of bacterial or fungal infection. (4) The trial report fails to show whether filgrastim influences viral load or the CD4+ lymphocyte count. (5) In the absence of published dose-finding studies there is no proof that the dose regimen recommended in the licensing terms is the one with the best risk-benefit ratio. (6) Treatment with filgrastim is costly, especially as the available unit doses are unsuitable for this indication. (7) Patients at an advanced stage of HIV infection are already heavily medicated. There is no reason to add filgrastim, which has no proven clinical value.
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PMID:Filgrastim: new indication. AIDS-associated neutropenia: another soft indication. 1171 77


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