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)

In acute lymphoblastic leukemia (ALL), treatment with granulocyte colony stimulating factor (G-CSF) during remission induction shortens granulocytopenia and may decrease morbidity due to infections. However, the optimal timing of G-CSF administration after chemotherapy is not known. In a prospective randomized multi-center study, adult ALL patients were treated with high-dose ARA-C [HDAC, 3 g/m(2) bid (1 g/m(2) bid for T-ALL) days 1-4] and mitoxantrone (MI 10 mg/m(2) days 3-5). They were randomized to receive recombinant human G-CSF (Lenograstim) 263 micro g/day SC starting either from day 12 (Group 1) or day 17 (Group 2). Fifty-five patients (41 male, 14 female) with a median age of 34 years (range: 18-55 years) were enrolled into the study; 50 patients were evaluable. The median duration of neutropenia <500/ micro l after HDAC/MI was 12 days (range: 7-22 days) in the early G-CSF Group 1 and also 12 days (range: 4-22 days) in the late G-CSF Group 2; this was shorter than in the historical control group (15 days, range: 4-43 days, n=46) where the patients received identical cytotoxic treatment without G-CSF. Seventeen infections were observed in 14 patients in Group 1 (47%) and 13 infections in 10 patients in Group 2 (50%) compared to 27 infections in 49 patients of the historical control (54%). In Group 1, the patients received a median of 11 injections with G-CSF (range: 7-22) compared to 7 injections (range: 4-19) in Group 2. The total administered dose of G-CSF in Group 2 was significantly reduced by 40% ( P<0.0001). The delayed start of G-CSF after HDAC/MI in ALL achieves the same clinical benefit compared to the earlier initiation of G-CSF. The reduction of treatment costs by reducing the total G-CSF dose may be important in future treatment with this hematopoietic growth factor.
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PMID:Prospective randomized trial to evaluate two delayed granulocyte colony stimulating factor administration schedules after high-dose cytarabine therapy in adult patients with acute lymphoblastic leukemia. 1242 38

More than 4 million people in the United States are infected with hepatitis C virus (HCV). During the next 20-30 years, the burden of HCV-related mortality and morbidity will likely double. To date, the most effective treatment for chronic HCV infection is the combination of either interferon (IFN)-alpha or pegylated IFN-alpha and ribavirin. For a sustained virologic response, treatment adherence and dose maintenance are essential. However, both IFN-alpha and ribavirin induce hematologic toxicity, such as anemia, neutropenia, and thrombocytopenia, which can compromise treatment adherence and dose maintenance and could, therefore, potentially influence outcomes. Although there are currently no approved treatments for hematologic complications of HCV therapy, studies have shown that hematopoietic growth factors can provide significant benefits. This review highlights the pharmacology, risks, and benefits of recombinant hematopoietic growth factor therapy in HCV-infected patients.
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PMID:Hematologic disorders associated with hepatitis C virus infection and their management. 1503 43

Granulocyte-colony stimulating factor (G-CSF), a hematopoietic growth factor, is widely used to accelerate recovery from neutropenia after severe chemotherapy, both decreasing the risk of infection and mobilizing peripheral blood stem cells. Adverse effects occur with G-CSF use in approximately 30% of cases, comprised predominantly of bone pain, headache, and general fatigue. Pulmonary toxicity is very rare. Here, we describe a healthy donor for allogeneic hematopoietic stem cell transplantation who developed acute lung injury (ALI) after 4 days of G-CSF administration. Among the serum cytokines examined, only Interleukin (IL)-1beta level was elevated in this case. As a high level of IL-1beta was detected at the onset of ALI, on day 4 after G-CSF administration, and decreased to below the level of detection on day 11, it is possible in a certain part that IL-1beta was involved in the onset of G-CSF-related ALI in the present case. Granulocyte-colony stimulating factor (G-CSF) is commonly administered to healthy donors to mobilize peripheral blood stem cells (PBSC) for allogeneic hematopoietic stem cell transplantation (allo-HSCT). Adverse events from G-CSF use in healthy donors have been described in approximately 30% of cases, and are comprised predominantly of bone pain, headache, and general fatigue. Pulmonary complications caused by G-CSF include cough, dyspnea, and interstitial or alveolar pulmonary edema with mild-to-severe deterioration of blood oxygen level. Few cases of acute respiratory distress syndrome (ARDS) following G-CSF administration have been reported. The present report describes a healthy donor for allo-HSCT with acute lung injury (ALI) after 4 days of G-CSF administration. The cytokine-related mechanisms of G-CSF administration that contribute to ALI are discussed.
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PMID:Acute lung Injury in a healthy donor during mobilization of peripheral blood stem cells using granulocyte-colony stimulating factor alone. 1575 51

This report summarizes recent data on neutropenia-related quality of life (QOL), including measures and interventions. Neutropenia is a common adverse effect of cytotoxic chemotherapy. The clinical significance of QOL in patients with chemotherapy-induced neutropenia (CIN) remains largely unexplored, although recent studies have shown a correlation between severe CIN and impaired QOL. Neutropenia typically occurs at the same time as other adverse effects. Data indicate that other toxicities are worse in the presence of febrile neutropenia and that these concurrent events may have a greater effect on QOL. Precautions that are taken to minimize the incidence of infection in patients with neutropenia may also affect their QOL. Future research should focus on accurately defining and measuring QOL in patients with CIN as well as on assessing ways to manage CIN more effectively and thus improve QOL. A number of interventions may have a positive influence on QOL in patients with cancer and neutropenia. Hematopoietic growth factor support, for example, reduces the incidence and sequelae of neutropenia and may provide a QOL benefit. To assess the effect of such interventions, neutropenia-specific QOL instruments, such as the Functional Assessment of Cancer Therapy-Neutropenia (FACT-N), may be valuable tools.
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PMID:Quality of life and chemotherapy-induced neutropenia. 1591 58

Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a hematopoietic growth factor, that has been used as a therapeutic agent in facilitating bone marrow and stem cell transplantation and in other clinical cases like neutropenia. Although biologically active recombinant GM-CSF has been successfully produced in Escherichia coli, the reported levels are extremely poor. In this study we looked into the possible reasons for poor expression and found that protein toxicity coupled with protease-based degradation was the principal reason for low productivity. To overcome this problem we attached a signal sequence, as well as an amino-terminal His-tag fusion to the GM-CSF gene. This combination had a dramatic effect on expression levels, which increased from 0.8 microg/mL in the control to 40 microg/mL. When a larger fusion partner, such as the Maltose-binding protein (MBP-tag), was used the expression levels increased further to 69.5 microg/mL, which along with the MBP-tag represented approx 12% of the total cellular protein.
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PMID:Combined effect of protein fusion and signal sequence greatly enhances the production of recombinant human GM-CSF in Escherichia coli. 1592 Feb 80

The adverse effects of antiviral drugs are dose dependent and often reversible. The major side effects include influenza-like symptoms, hematologic abnormalities and neuropsychiatric symptoms. The influenza-like syndrome can be prevented by paracetamol taken at the time of the injection. Psychiatric adverse effects range from irritability to a severe depressive syndrome. Antidepressants, such as selective serotonin reuptake inhibitors, may be useful in the management. Adverse hematologic effects can occur very early during treatment. The platelet count often stabilizes rapidly, but neutropenia can deteriorate throughout treatment. In selected patients treatment with hematopoietic growth factor (filgrastim) may be useful. Ribavirin therapy may result in a dose-dependent reversible intravascular hemolytic anemia in 10% of patients. Adjunctive therapy with erythropoietin for ribavirin-induced anemia is currently under evaluation. Interferons and ribavirin are contraindicated in pregnancy. Contraception must be continued for 4 months (women) and 7 months (men) after ribavirin cessation. Lactic acidosis may be a rare complication of combination therapy in patients undergoing therapy for HIV and HCV. Any sign of mitochondrial DNA depletion syndrome calls for blood lactate measurement and, possibly, a modification of antiretroviral treatment. Lamivudine is well tolerated but the emergence of lamivudine-resistant (YMDD) HBV mutants is associated with the loss of clinical response. Adefovir dipivoxil effectively suppresses lamivudine-resistant HBV in chronic hepatitis B.
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PMID:[Treatment of the side effects of antiviral therapy]. 1638 Dec 45

Granulocyte-macrophage colony-stimulating factor (GM-CSF) is an important hematopoietic growth factor and immune modulator. GM-CSF also has profound effects on the functional activities of various circulating leukocytes. It is produced by a variety of cell types including T cells, macrophages, endothelial cells and fibroblasts upon receiving immune stimuli. Although GM-CSF is produced locally, it can act in a paracrine fashion to recruit circulating neutrophils, monocytes and lymphocytes to enhance their functions in host defense. Recent intensive investigations are centered on the application of GM-CSF as an immune adjuvant for its ability to increase dendritic cell (DC) maturation and function as well as macrophage activity. It is used clinically to treat neutropenia in cancer patients undergoing chemotherapy, in AIDS patients during therapy, and in patients after bone marrow transplantation. Interestingly, the hematopoietic system of GM-CSF-deficient mice appears to be normal; the most significant changes are in some specific T cell responses. Although molecular cloning of GM-CSF was carried out using cDNA library of T cells and it is well known that the T cells produce GM-CSF after activation, there is a lack of systematic investigation of this cytokine in production by T cells and its effect on T cell function. In this article, we will focus mainly on the immunobiology of GM-CSF in T cells.
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PMID:Granulocyte-macrophage colony-stimulating factor (GM-CSF) and T-cell responses: what we do and don't know. 1647 24

Chemotherapy used to treat lymphoma can cause severe neutropenia. Risk models have identified factors that predict neutropenia across all chemotherapy cycles. We used clinical information obtained during pretreatment evaluation to develop a predictive model for severe neutropenia in the first cycle of cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP) chemotherapy. This case series study included lymphoma patients receiving CHOP chemotherapy with or without rituximab who did not receive pre-emptive hematopoietic growth factor. Risk factors for neutropenia were identified from previously published models and included age >or=65 years, hypoalbuminemia, renal/cardiovascular disease, anemia, abnormal bone marrow and increased lactate dehydrogenase (LDH). A composite score equal to the number of pretreatment risk factors was used to predict severe neutropenia in cycle 1. Fifty-three percent of patients (47 of 89) had severe neutropenia, with 70% of first episodes occurring during cycle 1. Eighty-two percent of first-cycle, severe neutropenia events occurred in patients >or=65-years-old. In univariate analysis, age >or=65 years and increased baseline LDH were significantly associated with increased risk for severe neutropenia in cycle 1. In logistic regression modeling, the probability of severe neutropenia in cycle 1 increased as the number of pretreatment risk factors increased, with a one-unit increase in risk score resulting in a 2.3-fold increase in severe neutropenia. The study results suggest that data obtained before initiating CHOP-based chemotherapy can be used to identify those patients who are at risk for severe neutropenia in cycle 1. If validated, our model could be used to identify patients who would benefit from early use of growth factors.
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PMID:Severe neutropenia in CHOP occurs most frequently in cycle 1: a predictive model. 1675 58

The hematopoietic growth factors (HGFs) are a family of glycoproteins which plays a major role in the proliferation, differentiation, and survival of primitive hematopoietic stem and progenitor cells, and in the functions of some mature cells. More than 20 different molecules of HGF have been identified. Among them, granulocyte colony-stimulating factor (G-CSF) and granulocyte-macrophage colony-stimulating factor (GM-CSF) have been demostrated to be effective in reducing the incidence of febrile neutropenia when administered inmediately after chemotherapy and as supportive therapy in patients undergoing bone marrow transplantation. Chemotherapy used for treatment of cancer often causes neutropenia, which may be profound, requiring hospitalization, and leading to potentially fatal infection. The uses of the recombinant human hematopoietic colony-stimulating factors G-CSF and GM-CSF for treatment and prophylaxis of chemotherapy-induced febrile neutropenia will be reviewed here.
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PMID:Colony-stimulating factors: clinical evidence for treatment and prophylaxis of chemotherapy-induced febrile neutropenia. 1707 71

Extensive small-cell lung cancer (SCLC) is commonly treated with multiple cycles of chemotherapy. Reducing the time interval between cycles of chemotherapy (dose-dense chemotherapy) may improve outcomes in the treatment of extensive SCLC, as it has in other chemosensitive malignancies. To evaluate the feasibility of dose-dense chemotherapy in patients with extensive SCLC, this study evaluates a dose-dense doxorubicin/cyclophosphamide/etoposide (ACE) regimen, supported by the once-per-cycle administration of the hematopoietic growth factor pegfilgrastim. Patients received up to six 14-day cycles of ACE chemotherapy (doxorubicin 40 mg/m,(2) cyclophosphamide 1000 mg/m(2), etoposide 120 mg/m(2) on day 1 IV, plus oral etoposide 240 mg/m(2) daily on days 2-3). On day 4 of each cycle, patients received pegfilgrastim 6 mg by subcutaneous injection. Of 30 patients enrolled, 27 started chemotherapy and received pegfilgrastim. Full-dose, on-schedule chemotherapy was given to all 22 patients starting cycle 2, and in 107 (88%) of 121 cycles. Eighteen of the 27 patients (67%) received full-dose, on-schedule chemotherapy for all 6 cycles. The overall response rate was 17/27 (63%). Nine patients (33%) experienced hematologic toxicities that investigators considered severe or life-threatening. Four patients (15%) had febrile neutropenia. Full-dose, on-schedule dose-dense ACE chemotherapy is feasible with once-per-cycle pegfilgrastim support in extensive SCLC.
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PMID:Achieving full-dose, on-schedule administration of ACE chemotherapy every 14 days for the treatment of patients with extensive small-cell lung cancer. 1723 28


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