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)

This prospective multicenter study examined whether simultaneous administration of granulocyte colony-stimulating factor (G-CSF; Filgrastim) and induction chemotherapy for adult acute lymphoblastic leukemia (ALL) could prevent treatment-related neutropenia, infections, and resulting treatment delays. Seventy-six patients were randomly assigned to receive either G-CSF (n = 37) or no growth factor (n = 39) in conjunction with a uniform chemotherapy consisting of cyclophosphamide, cytarabine, mercaptopurine, intrathecal methotrexate, and cranial irradiation. The median duration of neutropenia (absolute neutrophil count < 1 x 10(9)/L) during chemotherapy was 8 days in patients receiving C-CSF, compared with 12.5 days in the control group (P < .002). A similar reduction from 11.5 to 7 days was observed in patients with T-ALL receiving additional mediastinal irradiation (P = .13). Infections occurred in 43% and 56% of patients in the G-CSF and control arm, respectively (P = .25); the incidence of nonviral infections was reduced by 50%, from 32 episodes in the control arm to 16 episodes in the G-CSF arm. Prolonged interruptions of chemotherapy administration were less frequent, with delays of 2 weeks or more occurring in only 24% of patients receiving G-CSF as opposed to 46% in the control arm (P = .01). Accordingly, chemotherapy was completed significantly earlier with the use of G-CSF (39 v 44 days, P = .008). With a median follow-up of 20 months, the probability of disease-free survival was 0.45 in the G-CSF group and 0.43 in the control group (P = .34). In conclusion, adult ALL patients appear to benefit by the simultaneous administration of G-CSF with induction chemotherapy because of a significant reduction in the duration of neutropenia, a trend to fewer infections, and a more rapid completion of chemotherapy.
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PMID:Concomitant granulocyte colony-stimulating factor and induction chemoradiotherapy in adult acute lymphoblastic leukemia: a randomized phase III trial. 754 60

The present study was designed to determine whether Filgrastim, a neutrophil-specific hematopoietic growth factor, could be administered simultaneously with intensive induction chemotherapy for adult acute lymphoblastic leukemia (ALL). The effect of Filgrastim on the severity of chemotherapy-induced neutropenia, fever, and infections was assessed in 15 patients treated according to the protocol of the German multicenter ALL (GMALL) trial 04/89. Filgrastim (5 micrograms/kg/day) was given concurrently with successive cycles of cyclophosphamide, cytosine-arabinoside (ara-C), 6-mercaptopurine (6MP), prednisone (PRD), intrathecal methotrexate, and prophylactic cranial irradiation. During the study period the median total duration of severe neutropenia (< 0.5 x 10(9)/l) in 13 evaluable patients was 8 days, individual periods of neutropenia typically were short. Infections occurred in six patients; seven patients remained fever-free during treatment with Filgrastim. We conclude that simultaneous treatment with Filgrastim and chemotherapy in this specific setting is feasible and well tolerated. The efficacy of this treatment approach in terms of overall treatment results requires further testing in a randomized trial.
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PMID:Simultaneous administration of granulocyte colony-stimulating factor (Filgrastim) and induction chemotherapy in acute lymphoblastic leukemia. A pilot study. 769 82

We evaluated the efficacy and safety of a monotherapy by piperacillin and sulbactam potentially associated to vancomycin as an empiric antimicrobial therapy in febrile neutropenic patients treated with nephrotoxic chemotherapy for solid tumors. Twenty-three patients were treated during 32 episodes with piperacillin 4 g i.v. every 8 hours and sulbactam 1 g IV every 8 hours. If the patient remained febrile after 48 hours, 1 g of vancomycin i.v. was added every 12 hours as indicated by our study design. The mean duration of neutropenia was 5.5 days (2-13 days). In ten episodes, the granulocyte nadir was < 100/mm3. Infection was microbiologically documented in seven episodes (22%) with six Gram negative bacilli and 3 Gram positive cocci. There were 19 apyrexia with piperacillin and sulbactam (59%) and further seven were resolved by the addition of vancomycin (total success: 81%). Failure was observed in six episodes consecutive to germ resistance (one episode), clinical deterioration (one episode), relapsing fever related to Pseudomonas infection (one episode), persistent fever despite withdrawal of neutropenia and no microbiological documentation (two episodes) and protocol violation (one episode). Neither septic death nor toxicity were observed. We conclude that this empirical treatment is active and safe in short period febrile neutropenic episodes in patients heavily treated with nephrotoxic chemotherapy for solid tumors.
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PMID:[Value of mono-antibiotic therapy using piperacillin associated with sulbactam and possibly followed by vancomycin in febrile neutropenia in solid tumors]. 773 70

Infection is the most frequent cause of death in patients with severe neutropenia. Fever and other signs of infection with neutrophil count below 0.5 G/L require an early and rapid treatment--the empiric antibiotic therapy. This treatment comprises various combinations of bactericidal broad-spectrum antibiotics such as ureidopenicillins, cephalosporins, quinolones and aminoglycosides. If defervescence is not attained within 3 days, modification of the treatment scheme should be done. The addition of vancomycin or teicoplanin, antibiotics active against Gram + cocci, and changing of the beta-lactams should be considered. In the case of persistent microbiologically not recognized infection after 7 days of therapy, empiric antimycotic treatment with amphotericin B is indicated. Duration of the empiric antibiotic therapy is dependent on the granulocyte recovery and the resolution of infection.
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PMID:[Empiric antibiotic therapy for treatment of infection in patients with severe neutropenia]. 774 58

Infection of naive North American horses with 10(4) cell culture infectious doses (CCID50) of virulence variants of African horsesickness virus (AHSV), designated AHSV/4SP, AHSV/9PI, and AHSV/4PI, reproduced three classical forms of African horsesickness: acute (pulmonary), subacute (cardiac), and febrile, respectively. Distinct clinicopathologic and hemostatic abnormalities were associated with each form of disease. Hemostatic abnormalities included increased concentration of fibrin degradation products and prolongation of prothrombin, activated partial thromboplastin, and thrombin clotting times. Hemostatic findings indicated activation of the coagulation and fibrinolytic systems with clotting factor consumption in acute and subacute cases of African horsesickness. Hematologic abnormalities in acute and subacute cases of African horsesickness included leukopenia, decreased platelet counts, elevated hematocrit, and increased erythrocyte counts and hemoglobin concentration. Leukopenia was characterized by lymphopenia, neutropenia, and a left shift. Increased levels of serum creatine kinase, lactate dehydrogenase, aspartate aminotransferase, and alkaline phosphatase, hypocalcemia, hypoalbuminemia, hypoproteinemia, and elevated creatinine, phosphorus, and total bilirubin levels were present in some but not all horses. Metabolic acidosis, indicated by decreased total bicarbonate and increased lactate and anion gap, was present in horses with the acute form of disease. Mild thrombocytopenia and leukopenia were occasionally associated with the febrile form of disease. These results suggest a role for intravascular coagulation in the pathogenesis of African horsesickness.
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PMID:Clinical pathology and hemostatic abnormalities in experimental African horsesickness. 777 Oct 50

The efficacy of GM-CSF was investigated in 20 neutropenic patients (< 1500 neutrophils/microliters) with acute visceral leishmaniasis due to Leishmania chagasi. Patients were randomized to receive either GM-CSF, 5 micrograms/kg daily (intravenously or subcutaneously), or placebo for ten days, in combination with pentavalent antimony, 10-20 mg/kg daily for 20 days. Neutrophil counts were significantly greater on days 5 and 10 of treatment in the GM-CSF group compared with the placebo group (p < 0.02). Eosinophil and monocyte counts were also significantly increased in the GM-CSF group at day 10 (p < or = 0.03). Interestingly, at day 30, platelet counts were significantly increased in the GM-CSF group on days 5 and 10 (p = 0.04 and 0.02, respectively). Patients in the GM-CSF group experienced fewer secondary bacterial or viral infections than placebo patients. Infections occurred in only three patients given GM-CSF compared with eight patients given placebo (p < 0.04). All patients had complete resolution of disease symptoms at three months. Few adverse events were recorded. GM-CSF given subcutaneously at a dose of 5 micrograms/kg daily for ten days was well tolerated, reversed neutropenia rapidly and reduced the number of secondary infections in patients with leishmaniasis.
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PMID:Granulocyte-macrophage colony-stimulating factor in combination with pentavalent antimony for the treatment of visceral Leishmaniasis. 787 48

Interleukin-1 beta (IL-1 beta), interleukin-6 (IL-6), interleukin-8 (IL-8) and tumor necrosis factor alpha (TNF) are important mediators of fever and inflammation, and are involved in the pathogenesis of sepsis. There is only limited data on serum concentrations of these proinflammatory cytokines in patients with fever and neutropenia, and their interrelationship and correlation with body temperature and clinical disease early in the febrile response during neutropenia have not been studied. Immunoreactive TNF, IL-1 beta, IL-6, and IL-8 in serum samples serially obtained from 14 adult patients with neutropenia and fever considered or documented to be due to infection were measured. IL-6 and Il-8 were consistently elevated in all patients, and correlated well with each other and with body temperature. Median peak concentration of IL-6 and IL-8 were 400 pg/ml (range: 100 to 41,000 pg/ml), and 1,025 pg/ml (range: 600 to 26,000 pg/ml), respectively, and levels of both cytokines rapidly declined in patients responding to antimicrobial therapy. Despite frequent sampling before and after the temperature peaks TNF and IL-1 beta, conversely, were less frequently detectable, with median peak values of < 10 pg/ml (range: < 10 to 150 pg/ml) for TNF, and 17 pg/ml (range: < 10 to 36 pg/ml) for IL-1 beta, respectively. The role of neutro- and monocytopenia with depletion of important cytokine producing and target cells in this particular cytokine response pattern needs to be further studied.
Infection
PMID:Kinetics and correlation with body temperature of circulating interleukin-6, interleukin-8, tumor necrosis factor alpha and interleukin-1 beta in patients with fever and neutropenia. 792 10

We present preliminary results of a study undertaken in previously untreated patients with non-small cell lung cancer to determine the maximum tolerated dose of paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) when administered as a 3-hour intravenous infusion in combination with cisplatin every 3 weeks; to evaluate the nature, frequency, severity, and duration of adverse events associated with this drug combination; and to evaluate the combination's antitumor efficacy. Thus far, we have treated 10 patients with cisplatin (100 mg/m2) and increasing doses of paclitaxel (135, 170, and 200 mg/m2). Among nine evaluable patients, four partial responses have been obtained, disease in three patients progressed after three courses, and no changes were seen in one patient. One patient had two cardiac arrests within 8 days of the onset of therapy, from which he recovered; he died 1 month later of massive hemoptysis. Thrombocytopenia was not seen in these patients, and neutropenia (< 1,000 granulocytes/microL) was seen in only three patients. Infections were seen in these patients and were manageable in all cases. Other toxicities consisted mainly of World Health Organization grades II and III alopecia and nausea and/or vomiting. No grade III nephrotoxicity, neurotoxicity, hypersensitivity, mucositis, or infection was seen in this series after one to three courses of chemotherapy; one patient presented with grade IV cardiotoxicity 6 days after the onset of therapy. So far, the maximum tolerated dose of the cisplatin/paclitaxel combination has not been reached; however, definitive conclusions await the full treatment of additional patients. Moreover, the possibility of cumulative and delayed toxicity must be evaluated after a sufficient duration of follow-up in adequate numbers of patients.
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PMID:Dose-finding study of paclitaxel (Taxol) plus cisplatin in patients with non-small cell lung cancer. 793 62

Patients with chronic lymphocytic leukemia (CLL) are at an increasing risk of infectious morbidity and mortality. Infections are generally due to bacteria and influenced by the degree of hypogammaglobulinemia; although, in more advanced stages of disease they may also be contributed by neutropenia due to bone marrow infiltration and/or cytotoxic therapy. Furthermore, defect in cell-mediated immunity appears to be a predisposing factor to infections in patients treated with newer purine analogues. Controversies surrounding the pathogenesis of infectious complications in CLL raise several questions on their management. Patients with advanced disease who receive cytotoxic therapy might qualify for antibacterial prophylaxis. Intravenous immunoglobulin (IVIG), although of scientific interest, may be of little relevance at the present time. The new growth factors should be tested in well-designed prospective studies.
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PMID:Infections in chronic lymphocytic leukemia: risk factors, and impact on survival, and treatment. 804 45

Examinations were made on erythrocytes, thrombocytes, leukocytes, lymph nodes, thymus, haemal nodes and bone marrow in field cases of East Coast Fever (ECF) in Tanzania. Seventy-six clinically sick short-horn Zebu and Taurine-Zebu crosses, positive for Theileria parva piroplasms and schizonts and 55 apparently healthy cattle were studied. The syndrome observed was characterised by severe pancytopenia, with massive normocytic, normochromic anaemia, panleukopenia and thrombocytopenia, but no reticulocytes in peripheral blood. The erythrocyte and leukocyte counts, haematocrit and haemoglobin concentrations were greatly decreased compared with those of the healthy cattle. The means +/- SD (with values of healthy cattle in parentheses) were 2.85 +/- 1.10 (6.04 +/- 1.58) x 10(12) l-1, 2.78 +/- 1.70 (10.59 +/- 4.16) x 10(9) l-1, 0.19 +/- 0.06 (0.31 +/- 0.054)1 l-1 and 4.07 +/- 1.62 (7.29 +/- 1.39) mmol l-1 respectively. Lymphoproliferation was low, while lymphocyte destruction (lymphocytolysis) was high. There were very few small schizonts in parotid and prescapular glands. Lymphocytes were extensively destroyed in medullary cords, germinal centres of lymph nodules in cortex and paracortical regions of lymph nodes and haemal nodes. The bone marrow was hypocellular, with only a few haematopoietic precursor erythroid, granulocytic and thrombopoietic cell series. All stages of prorubriblasts and rubricytes had granulated nuclei, some with schizonts. Infection of erythrocytes by merozoites appeared to take place in precursor stages. The destruction of erythroblasts, rubricytes and other haematopoietic cells resulted in anaemia without reticulocytosis, haemoglobinuria and jaundice, accompanied by panleukopenia of extreme neutropenia, lymphopenia and eosinopenia. This indicated that this T. parva strain differs from previously described buffalo- or cattle-derived T. parva infections in causing both haemoproliferation and lymphoproliferation by extensive haematopoietic cell destruction and lymphocytolysis. In cattle- and buffalo-derived T. parva infections, anaemia is normally mild and there are numerous large schizonts in the former.
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PMID:Severe anaemia due to haematopoietic precursor cell destruction in field cases of East Coast Fever in Tanzania. 807 8


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