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Query: UNIPROT:P04141 (granulocyte-macrophage colony-stimulating factor)
 6,790 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Peripheral blood cells (PBC) can hasten hematopoietic recovery after high-dose chemotherapy. To determine if PBC apheresed after mobilization further enhance hematopoietic recovery over that achieved with autologous bone marrow (ABM) and recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF), 14 patients with metastatic solid tumors were supported by ABM and rhGM-CSF during the first course of high doses of cyclophosphamide, etoposide, and cisplatin (CVP) and 11 of these 14 patients by mobilized PBC with ABM and rhGM-CSF during the second CVP. Each patient served as his or her own control. Identical doses of CVP were administered in both courses: cyclophosphamide 5.25 g/m2, etoposide 1,200 mg/m2, and cisplatin 165 to 180 mg/m2. PBC were collected on day 10 after mobilization with cyclophosphamide (3 g/m2) intravenously (IV) on day 1, doxorubicin (50 mg/m2) as a continuous IV infusion over 48 hours starting day 2, and rhGM-CSF as a daily 4-hour IV infusion starting day 4 at 0.6 mg/m2 for 14 days. Comparing recovery in the 11 patients to receive two cycles of therapy, the median days to an absolute neutrophil count of 0.1 x 10(9)/L and 0.5 x 10(9)/L were not statistically significant between the two courses; neither was there a difference in the incidence of fever and bacteremia. The median number of days to platelet count of 0.02 x 10(12)/L unmaintained by platelet transfusion was 20 from marrow infusion for course 1 and 16 for course 2 (P = .059). The median number of days to a platelet count of 0.05 x 10(12)/L was significantly shortened: 24 and 19 days for courses 1 and 2, respectively (P = .045). Patients who received PBC required fewer number of platelet transfusions. Extramedullary toxicities were not different between the groups. Our finding of enhanced early recovery of platelets and reduced platelet transfusion requirement is in concordance with other studies.
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PMID:Influence of mobilized peripheral blood cells on the hematopoietic recovery by autologous marrow and recombinant human granulocyte-macrophage colony-stimulating factor after high-dose cyclophosphamide, etoposide, and cisplatin. 159 78

Sixteen patients with relapsed non-Hodgkin's lymphoma underwent autologous bone marrow transplantation and infusion of recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF). Treatment consisted of involved-field radiotherapy, cyclophosphamide 60 mg/kg/d intravenously (IV) for 2 days, and fractionated total body irradiation (1,200 cGy). Autologous bone marrow was thawed and infused IV, followed 3 hours later by the first infusion of IV rhGM-CSF 11 micrograms/kg/d over 4 hours. Infusions of rhGM-CSF were continued daily until either both neutrophil count exceeded 1,500/microL and platelet count exceeded 50,000/microL, or until 30 days after marrow re-infusion. Toxicities encountered were mild and included fever, chills, hypertension, alopecia, rash, diarrhea, stomatitis, myalgias, and synovial (knee) effusions. Neutrophil recovery greater than 500/microL occurred a median of 14 days (range, 9 to 30 days) after marrow infusion, significantly earlier than in a comparable group of historic controls who recovered counts at a median time of 20 days (range, 12 to 51 days) (P = .00002). Median time to self-sustaining platelet counts greater than 20,000/microL was 23.5 days (range, 12 to 100 days), comparable with the historic group (P = .38). One bacteremia (central venous catheter exit site infection with Staphylococcus epidermidis) and one local infection (Giardia lamblia in stool) occurred. Patients received a median of 11.4 (range, 4.4 to 20.2) x 10(4) colony-forming unit granulocyte-macrophage (CFU-GM) progenitors per kg. Stem cell progenitors CFU-GM, CFU-granulocyte, erythroid, monocyte, megakaryocyte (CFU-GEMM), and burst-forming unit-erythroid (BFU-E) were detected in the bone marrow as early as 7 days after marrow re-infusion, and increased in proportion to peripheral blood counts, but by 30 to 60 days still remained much lower than before transplant. Neutrophils transiently decreased in 13 of 16 patients (median decrease, 42%) within 24 to 72 hours of discontinuing rhGM-CSF infusions. These data suggest that rhGM-CSF therapy enhances neutrophil recovery by forcing stem cells to produce mature elements at an enhanced rate but may not affect marrow stem cell and early progenitor population sizes.
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PMID:Recombinant granulocyte-macrophage colony-stimulating factor after autologous bone marrow transplantation for relapsed non-Hodgkin's lymphoma: blood and bone marrow progenitor growth studies. A phase II Eastern Cooperative Oncology Group Trial. 185 94

Chronic ethanol ingestion predisposes to tuberculosis and bacterial pneumonia. Mycobacterium avium complex (MAC) organisms cause bacteremia in patients with AIDS. Cultured human monocyte-derived macrophages and murine Kupffer cells were exposed to 10-100 micrograms/dl ethanol; significantly greater intracellular growth of MAC strains 100 (serovar 8) and 101 (serovar 1) occurred in ethanol-treated cells than in controls (range, 58% +/- 7%-70% +/- 5%; P less than .05 for 50 and 100 micrograms/dl ethanol vs. control). Both cell types, when treated with 10(3) units/ml recombinant tumor necrosis factor (TNF) or 10(2) units/ml granulocyte-macrophage colony-stimulating factor (GM-CSF) in the presence of 10-100 micrograms/dl ethanol, killed significantly fewer MAC than controls (49% +/- 12% decrease for GM-CSF and 57% +/- 16% for TNF; P less than .05 for all comparisons). C57BL black mice infected intravenously with MAC strain 101 were given ethanol as 4% of total calories daily; after 21 days they had greater numbers of MAC in blood, liver, and spleen than controls. Ethanol's effects on the interaction between the host and MAC favor progressive infection.
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PMID:Ethanol augments intracellular survival of Mycobacterium avium complex and impairs macrophage responses to cytokines. 203 94

We evaluated the effect of oral ciprofloxacin on neutrophil recovery in 20 consecutive patients undergoing autologous bone marrow transplantation (BMT) for malignant lymphoma and compared the results with a control group of 20 patients receiving co-trimoxazole and folinic acid. Both groups started the prophylactic antibiotic as well as granulocyte-macrophage colony-stimulating factor (GM-CSF) the day after marrow infusion and continued the former until the onset of febrile neutropenia (median duration of treatment 6 days for co-trimoxazole and 7 days for ciprofloxacin). The time of attain an absolute neutrophil count > or = 0.5 x 10(9)/L was significantly shorter in patients receiving ciprofloxacin (16 days vs 22 days; P = 0.006). There was no difference in time to attain a platelet count > or = 20 x 10(9)/L independent of transfusion or in time to the first febrile episode or incidence of bacteremia. We conclude that antibiotic prophylaxis with ciprofloxacin results in more rapid neutrophil recovery than prophylaxis with co-trimoxazole. This may result from a myelosuppressive effect of co-trimoxazole or an enhancement of neutrophil recovery by ciprofloxacin, or both.
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PMID:Effect of antimicrobial prophylaxis on hematopoietic recovery following autologous bone marrow transplantation: ciprofloxacin versus co-trimoxazole. 777 16

Group B streptococcus (GBS) continues to cause considerable morbidity and death in newborn infants despite the use of antibiotics. We investigated the use of adjunctive therapies to be used with antibiotics in the treatment of neonatal sepsis, using a neonatal rat model of established GBS disease. After the development of GBS bacteremia, a human IgG preparation hyperimmune for GBS, administered with penicillin, decreased the mortality rate compared with the use of penicillin alone (14% vs 57%; p = 0.02). Similarly, recombinant human granulocyte-macrophage colony-stimulating factor, administered in a range of doses to animals with bacteremia, decreased mortality rates. The greatest effect was noted at a dose of 0.05 micrograms/kg (mortality rate 39% in combination with penicillin vs 76% for penicillin alone; p < 0.0001). Thus adjunctive therapies such as those studied here may have the potential to improve the outcome of neonatal sepsis.
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PMID:Hyperimmune human IgG or recombinant human granulocyte-macrophage colony-stimulating factor as adjunctive therapy for group B streptococcal sepsis in newborn rats. 849 60

Many chemotherapy regimens are associated with variable periods of myelosuppression. In cancer patients, neutropenia (less than 500 neutrophils/microL) is the most important risk factor for infections. The incidence and severity of infectious complications are related to depth and duration of neutropenia, with the highest risk if neutrophils are less than 100/microL for more than a week. The period required for neutrophil recovery is usually short with standard regimens, but prolonged after high dose chemotherapy followed by autologous bone marrow transplant (-ABMT) or peripheral blood stem cell (PBSC) infusion. Under these conditions, the administration of granulocyte colony-stimulating factor (G-CSF) or granulocyte-macrophage colony-stimulating factor (GM-CSF) accelerates neutrophil recovery and shortens the duration of hospitalization. In standard chemotherapy settings, prophylactic use of CSF's is a matter of debate. Several studies have reached contrasting conclusion, but, combining effectiveness and costs, it results that this use of CSF'S is not to be recommended unless the risk of infections (elderly patients, reduced marrow reserve) is high. The administration of G-CSF or GM-CSF to a febrile neutropenic patient (cfr CSF's therapy) shortens the duration of neutropenia, although no great clinical benefits are evident. Nevertheless the identification of subsets of patients with additional risk factors (i.e. absolute neutrophil count < 100/microL at the onset of fever or delayed neutrophil recovery) should be helpful in establishing the role of CSF's therapy. When prolonged periods of severe neutropenia (less than 500 neutrophils/microL) are expected, antibiotics should be prophylactically administered. Fluoroquinolones seem to be the optimal choice in heavily myelosuppressed patients (ie. bone marrow transplant recipients). Fluoroquinolones are effective in reducing the frequency of gram-negative bacteremia, but, because of incomplete coverage, gram-positive infections are becoming increasingly problematic. The association with an agent that can be absorbed orally, active against gram-positive cocci, seems to be an effective strategy. Fungal infections are an important cause of morbility and mortality in severely neutropenic patients. Safety and efficacy of antifungal triazoles and the lipid formulations of amphotericin B used prophylactically still require investigation. In patients at high risk for fungal infections, monitoring cultures are predictive for systemic mycoses and should guide prophylactic and therapeutic choices. The standard treatment of oncologic patients with potential infectious neutropenia complications is admission to the hospital and treatment with broad-spectrum intravenous antibiotics. Until third generation cephalosporin and carbapenems became available, most neutropenic febrile patients were treated with associations of an aminoglycoside plus a beta-lactam. Monotherapy with the new antibiotics has proven to be effective as an association therapy and offers advantages in terms of cost and tolerability. Whether or not vancomycin is included in the initial antibiotic regimen should be decided on the basis of epidemiological consideration (i.e. prevalence of meticillin-resistant Staphylococcus aureus or Staphylococcus mitis in certain centers). Antifungal therapy is indicated in neutropenic patients who remain febrile after one week of broad-spectrum antibiotics or have recurrent fever. Amphotericin B should be promptly administered in patients suspected of invasive mycoses. Selected patients with fever and neutropenia, that can be identified on the basis of reduced risk of severe complications, do not need hospitalization. In the first reports, outpatient treatment has proven to be effective, cost saving and well received by patients, but further studies are needed to accurately define low risk status and the optimal home antibiotic regimens.
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PMID:[Prevention and treatment of febrile neutropenia]. 923 24

Eight AIDS patients with Mycobacterium avium complex (MAC) bacteremia were randomized to receive azithromycin with or without granulocyte-macrophage colony-stimulating factor (GM-CSF) for 6 weeks to examine the effect of GM-CSF administration on clearance of mycobacteremia and on monocyte function. Superoxide anion production was significantly increased ex vivo in monocytes from patients receiving GM-CSF but not in those from patients receiving azithromycin alone. Relative to monocytes obtained from untreated healthy controls, median differences in viable intracellular MAC at 2, 4, and 6 weeks were -0.76, -0.94, and -0.47 log10 cfu/mL of lysate for cells from patients receiving GM-CSF versus -0.15, -0.11, and -0.19 log10 cfu/mL for cells from patients receiving azithromycin alone. Although no effect on mycobacteremia was detected, the administration of GM-CSF to AIDS patients with MAC bacteremia resulted in activation of their blood monocytes, as evidenced by increased superoxide anion production and enhanced mycobactericidal activity. GM-CSF deserves further investigation in the treatment of mycobacterial infections.
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PMID:Immunomodulatory treatment of Mycobacterium avium complex bacteremia in patients with AIDS by use of recombinant granulocyte-macrophage colony-stimulating factor. 953 63

The role of human immunodeficiency virus type 1 (HIV-1) infection on the ability of human monocytes/macrophages to phagocytose Mycobacterium avium complex (MAC) in vivo and in vitro and the effect of granulocyte-macrophage colony-stimulating factor (GM-CSF) on this function were investigated. By use of a flow cytometric assay to quantify phagocytosis, HIV-1 infection was found to impair the ability of monocyte-derived macrophages to phagocytose MAC in vitro, whereas GM-CSF significantly improved this defect. Phagocytosis was not altered by exposure to a mutant form of GM-CSF (E21R) binding only to the alpha chain of the GM-CSF receptor, suggesting that signaling by GM-CSF that leads to augmentation of phagocytosis is via the beta chain of the receptor. In a patient with AIDS and disseminated multidrug-resistant MAC infection, GM-CSF treatment improved phagocytosis of MAC by peripheral blood monocytes and reduced bacteremia. These results imply that GM-CSF therapy may be useful in restoring antimycobacterial function by human monocytes/macrophages.
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PMID:Granulocyte-macrophage colony-stimulating factor augments phagocytosis of Mycobacterium avium complex by human immunodeficiency virus type 1-infected monocytes/macrophages in vitro and in vivo. 1060 95

Several studies documenting the association of bacteremia and severity of neutropenia in HIV-infected patients, as well as studies using the colony stimulating factors filgrastim or sargramostim to prevent and treat neutropenia in this patient population, are summarized. Three studies are described in which low absolute neutrophil count was associated with increased incidence of bacterial infections in patients with HIV infection. Two hematopoietic growth factors called colony stimulating factors (filgrastim and sargramostim) are available in the United States, but neither is approved by FDA for the treatment or prevention of neutropenia in HIV-infected patients. Studies have shown both filgrastim and sargramostim to be effective in treating neutropenia in HIV-infected patients without increasing the viral load. In one study, filgrastim use on a daily or intermittent basis was associated with reduction in severe neutropenia or death; in addition, filgrastim-treated patients had fewer bacterial infections, fewer hospital days (both total number of days and days associated only with bacterial infections), and a reduced need for i.v. antimicrobials compared with HIV-infected controls. In another study, neutropenia caused by zidovudine was successfully treated with sargramostim. Both filgrastim and sargramostim show promise in treating and preventing neutropenia in HIV-infected patients. More research is needed to determine the patient population who can best benefit from therapy with these agents and to determine the relative advantages and disadvantages of filgrastim and sargramostim.
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PMID:Treatment of HIV-related neutropenia. 1061 82

Staphylococcus aureus strains lacking agr- and sarA-dependent gene products or specific MSCRAMM (microbial surface components recognizing adhesive matrix molecules) adhesins were compared for the ability to activate inflammatory responses in the lung. The mutants were evaluated for virulence in a mouse model of pneumonia and by quantifying their ability to stimulate interleukin-8 (IL-8) and granulocyte-macrophage colony-stimulating factor (GM-CSF) expression in respiratory epithelial cells. In a neonatal mouse, only strains with intact agr and sarA loci were consistently associated with invasive, fatal pulmonary infection (P < 0.001) and sarA was specifically required to cause bacteremia (P < 0.001). The agr and/or sarA mutants were, nonetheless, fully capable of producing pneumonia and were as proficient as the wild-type strain in stimulating epithelial IL-8 expression, a polymorphonuclear leukocyte chemokine, in airway cells. In contrast, agr and especially sarA mutants induced less epithelial GM-CSF expression, and MSCRAMM mutants lacking fibronectin binding proteins or clumping factor A, a ligand for fibrinogen, were unable to stimulate epithelial GM-CSF production. The ability to induce IL-8 expression was independent of the adherence properties of intact bacteria, indicating that shed and/or secreted bacterial components activate epithelial responses. While conserved staphylococcal components such as peptidoglycan are sufficient to evoke inflammation and cause pneumonia, the agr and sarA loci of S. aureus are critical for the coordination of invasive infection of the lungs.
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PMID:Staphylococcus aureus agr and sarA functions are required for invasive infection but not inflammatory responses in the lung. 1174 73


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