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

A number of studies have illustrated the effectiveness of hematopoietic growth factors in managing treatment-related cytopenias in patients with human immunodeficiency virus (HIV) infection. One of these factors, granulocyte-macrophage colony-stimulating factor, has been shown to restore absolute neutrophil counts in patients with acquired immunodeficiency syndrome (AIDS) and Kaposi's sarcoma receiving a combination of zidovudine (AZT) and interferon alfa. A combination of granulocyte colony-stimulating factor and erythropoietin has also been demonstrated to alleviate both neutropenia and anemia in patients with advanced AIDS or AIDS-related complex receiving zidovudine. Hematopoietic growth factors, in combination with each other and with antiretroviral agents, thus have an important supportive role to play in the treatment of patients with HIV disease.
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PMID:Antiretroviral therapy and immunomodulators in patients with AIDS. 201 46

In clonogenic assays, high concentrations of erythropoietin (epo) result in reduced generation of neutrophils from progenitors. Fetal progenitors appear to be more sensitive to this effect than are those of adults. Neutropenia has not been observed, however, as a complication of epo administration to anemic adults. Nevertheless, we remained concerned that diminutions in the neutrophil proliferative or storage pools might occur in epo-treated neonates. Therefore, after establishing that epo induces down-modulation of neutrophil generation in vitro from progenitors of weanling rats, we administered high doses of epo and subsequently performed neutrophil kinetic studies. Six pairs of 8-9-d-old rats were given three daily injections of 2000 IU/kg of either epo or a control Forty-eight h later, the epo recipients had elevations in reticulocytes, circulating normoblasts, and hematocrits, as well as in splenic and femoral normoblasts and mature erythroid progenitors. However, no changes were observed in concentrations of circulating neutrophils, monocytes, or lymphocytes. In addition, no changes were observed in the splenic or marrow neutrophil storage or proliferative pools, or the pools of granulocyte-macrophage progenitors or multipotent progenitors. Thus, although in vitro high concentrations of epo resulted in diminished generation of neutrophils from progenitors, no reductions were observed in vivo using epo doses 4- to 40-fold higher than those generally administered to humans.
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PMID:Effect of erythropoietin on granulocytopoiesis: in vitro and in vivo studies in weanling rats. 235 2

The genes for a number of growth factors that stimulate human hematopoietic and lymphoid cells in vitro have recently been cloned and recombinant molecules provided for clinical trials. For three of these (erythropoietin, G-CSF, and GM-CSF), phase I and II studies have been completed and promising results have been obtained. Of particular relevance to the field of bone marrow transplantation (BMT) has been the finding that G-CSF and GM-CSF could shorten the period of neutropenia in patients treated with chemotherapy, including regimens requiring BMT support. Doses of up to 240 micrograms/m2 of GM-CSF have been well tolerated and have increased the peripheral blood neutrophil count in a dose-dependent manner. At higher doses, eosinophils and monocytes were also increased. A continuous infusion over at least 2 h was found to be superior to bolus administration in terms of both efficacy and reduced side effects. These have usually been mild, but bone pain, headache, fatigue and elevated temperature have been encountered. The rise in neutrophil numbers shortly after initiating treatment with GM-CSF is probably due to neutrophil demargination. After a few days increased bone marrow cellularity has also been noted. In addition to these effects on cell numbers, enhancement of granulocyte and monocyte functions has been documented. However, a major concern with the use of G-CSF and GM-CSF in cancer patients, particularly those with hematopoietic malignancies, is the potential of these molecules to stimulate malignant cells.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Colony stimulating factors. 245 88

Clinical trials of recombinant biologic agents have resulted in new treatment options for hematologic, oncologic, and cardiologic disorders. These agents include the interferons, recombinant human erythropoietin (r-HuEPO), colony-stimulating factors (CSFs), interleukins (ILs), and tissue plasminogen activator (t-PA). Interferon alfa has proven efficacious in treating certain hematologic malignancies and solid tumors and has recently been indicated for acquired immunodeficiency syndrome (AIDS)-related Kaposi's sarcoma. Treatment with r-HuEPO has relieved the chronic anemia of hemodialysis patients. Recombinant human granulocyte CSF (G-CSF) or human granulocyte macrophage CSF (GM-CSF) has been used to treat patients after autologous bone marrow transplantation for lymphoid or solid malignancies, resulting in increased production of granulocytes and platelets. G-CSF and GM-CSF have been used to treat aplastic anemia, myelodysplastic syndromes, chemotherapy-induced neutropenia, and neutropenia associated with AIDS. In patients with evolving myocardial infarction, the recombinant agent t-PA has proved more efficacious than streptokinase in terms of average coronary artery patency rates and survival rates in patients with evolving myocardial infarction. While these agents all offer promising therapeutic advances, the expenses associated with developing and testing biotherapeutic substances have resulted in high treatment costs. Since in many instances investigational therapy is the best treatment option available, physicians, patients, the pharmaceutical industry, the government, and insurance carriers must work together to ensure that these therapies are financially available to those in need.
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PMID:New directions in hematologic biotherapy. 247 3

Recombinant DNA technology has allowed for the production of large quantities of several hematopoietic growth factors as cloned gene products. Three of these factors--recombinant human erythropoietin (r-HuEPO), granulocyte macrophage colony-stimulating factor (GM-CSF), and granulocyte colony-stimulating factor (G-CSF)--are currently undergoing clinical trials and appear to offer considerable promise for the treatment of a variety of hematopoietic abnormalities. Therapy with r-HuEPO can raise the hematocrit levels of patients with end-stage renal disease. Therapy with GM-CSF in patients undergoing marrow transplantation results in acceleration of granulocyte and platelet recovery by 1 to 2 weeks, leading to fewer infections and earlier discharge from the hospital. Other demonstrated uses of GM-CSF include treatment for aplastic anemia, myelodysplastic syndromes, chemotherapy-induced neutropenia, and neutropenia associated with the acquired immunodeficiency syndrome (AIDS). Similar beneficial effects have been reported with G-CSF. Other hematopoietic growth factors, including the interleukins (IL)-1, -3, and -6, will soon be entering clinical trials. For the first time, the availability of a large number of hematopoietic growth factors may allow physicians to regulate closely the entire hematopoietic system of their patients.
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PMID:The clinical use of hematopoietic growth factors. 247 5

Shwachman's syndrome is a rare congenital disorder associated with neutropenia and exocrine pancreatic insufficiency. We describe the development of acute myeloid leukemia in a 38-year-old patient with Shwachman's syndrome following three years of pancytopenia. After chemotherapy the leukemic clone was eradicated, however, the patient's bone-marrow hypoplasia persisted beyond 180 days with neutropenia that responded to administration of granulocyte colony-stimulating factor. Despite the patient's low erythropoietin levels, administration of erythropoietin did not improve his hemoglobin. We review previously reported cases of leukemia complicating Shwachman's syndrome with emphasis on the persistent risk of complications in patients with congenital bone-marrow failure syndromes.
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PMID:Acute leukemia complicating bone marrow hypoplasia in an adult with Shwachman's syndrome. 751 52

In this study, we determined in vivo interactions between hemopoietic growth factors and etoposide (VP-16) to assess whether normal blood cell production could be maintained during chemotherapy if hemopoietic growth factors were simultaneously administered. Groups of mice were treated for 7 consecutive days with four different doses of VP-16 in combination with three different doses of erythropoietin (EPO) or granulocyte colony-stimulating factor (G-CSF). In total, 12 combinations of VP-16 plus EPO and 12 combinations of VP-16 plus G-CSF were thus evaluated. Intricate dose-response surfaces of the effects of the different treatments on colony-forming units-erythroid, reticulocytes, hematocrit, colony-forming units-granulocyte/macrophage, and absolute neutrophil count were obtained, which revealed that: (a) simultaneous EPO administration was able to maintain reticulocyte production and to protect mice from VP-16 induced anemia; (b) simultaneous G-CSF administration was able to maintain granulocyte production and to protect mice from VP-16 induced neutropenia; (c) VP-16 dose escalation was feasible when EPO or G-CSF were simultaneously administered; and (d) no increased myelotoxicity on erythroid or granuloid progenitors was observed when EPO or G-CSF was simultaneously administered with VP-16. These results suggest that in vivo either individual hemopoietic progenitors can become resistant against VP-16-induced cell death by appropriate simultaneous growth factor administration or that the loss of overall cell amplification, induced by VP-16, can be compensated by extra amplification of surviving progenitors. Furthermore, these data indicate that a strict separation in time of cytostatic drug and growth factor treatment is not necessarily the optimal schedule with respect to the reduction of hemotoxicity.
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PMID:Hemotoxicity by prolonged etoposide administration to mice can be prevented by simultaneous growth factor therapy. 752 32

The use of the recombinant hematopoietic growth factors G-CSF and GM-CSF have shortened the period of neutropenia, or avoided this problem, in many cancer patients who have received cytotoxic therapy. Although these benefits have been particularly striking in the autologous bone marrow and/or autologous peripheral blood progenitor cell transplant setting, most data suggest that the use of G-CSF and GM-CSF only marginally enhance recovery of the neutrophil count when administered after allogeneic bone marrow infusion. Furthermore, in the allograft setting these expensive agents have not provided benefit in the form of enhanced platelet count recovery, lessening the incidence of graft-versus-host disease, or improvement in overall survival. These data do not justify routine widespread use of G-CSF and GM-CSF and suggest that these agents should be reserved for patients who experience delay in engraftment after allogeneic bone marrow infusion. Administration of erythropoietin, on the other hand, may reduce the need for homologous red blood cell transfusions, and may increase the safety margin for both the allogeneic bone marrow recipient and as well as the donor. Recombinant hematopoietic growth factors targetted specifically to enhance platelet recovery after transplantation (such as interleukin-3, interleukin-6, and interleukin-11) have shown promise after autotransplantation and after conventional dose chemotherapy, and likely will be evaluated in the allogeneic transplant patient.
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PMID:Clinical use of hematopoietic growth factors in allogeneic bone marrow transplantation. 752 6

Haematopoiesis is regulated by unrelated, pleiotropic, and diverse regulatory molecules, cytokines, whose membrane receptors are related and restricted to a few families manifesting sequence homology. Most members of the cytokine receptor family which lack tyrosine kinase activity are composed of multiple chains. An accessory signal transducer can be shared by members of the receptor family. Cytokine receptor oligomerisation is required for signal transduction, which includes phosphorylation of receptors and cytoplasmic proteins. Upon ligand binding, the receptors for erythropoietin and G-CSF form homodimers, whereas other members of the receptor family form hetero-oligomers in order to generate high-affinity receptor and signal transduction. In their cytoplasmic part, cytokine receptors contain distinct functional domains, proximal and distal to the membrane, that generate separate signals. Cytokines can be used to minimise chemotherapy-induced neutropenia and treat chronic neutropenia, and to shorten the period of aplasia following bone marrow transplantation.
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PMID:[Hematopoiesis. Biological mass production closely regulated by cytokines]. 770 97

HIV-infected patients commonly experience haematological disturbances including anemia, neutropenia or thrombocytopenia. Bone marrow failure may be caused by HIV itself, or by secondary involvement by opportunistic pathogens and malignancy. The need for multiple concomitant suppressive treatments may increase the risk of cytopenias. Strategy to reduce both anemia and neutropenia as well as to improve the haematological tolerance to myelotoxic agents have been developed by using haematological growth factors. So far, erythropoietin and granulocyte(macrophage) colony-stimulating factors have been successfully used in clinical trials including HIV-patients with either zidovudine-associated anemia or severe HIV or drug-induced neutropenia. However, according to the cost of these palliative approaches, there is a need for more reliable data showing that these growth factors could really have a major impact on the patient's compliance to therapy, reduction of hospitalization and infection rate and improvement of the overall survival.
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PMID:Clinical use of haematological growth factors in patients with human immunodeficiency virus (HIV-1) infection. 791 7


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