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)

We have previously demonstrated that continuous administration of dose-escalation zidovudine (AZT) in either normal or LP-BM5 MuLV immunodeficient virus-infected mice (MAIDS) was associated with the development of anemia, neutropenia, and thrombocytopenia. Hematopoietic growth factors/cytokines are being evaluated to determine their efficacy in ameliorating the hematopoietic toxicity associated with AZT. In normal mice receiving AZT, an increase in only plasma erythropoietin and not GM-CSF, Meg-CSF or TNF-alpha has been reported. This article describes studies that investigated the effect of combination interleukin-3 (IL-3) and granulocyte-macrophage colony stimulating factor (GM-CSF) administered in normal non-viral, viral-infected, and viral-infected C57BL6 mice receiving dose-escalation AZT, i.e. 0.1 mg/ml, 1.0 mg/ml, and 2.5 mg/ml placed in the drinking water. Non-viral control mice responded to IL-3/GM-CSF by increasing erythropoiesis, myelopoiesis and platelet production measured by increased bone marrow and spleen derived erythroid, myeloid and platelet precursor stem cells cultured in semi-solid media. Virus-infected control mice not receiving IL-3/GM-CSF developed pancytopenia. Administration of IL-3/GM-CSF to virus-infected mice receiving dose-escalation AZT did not ameliorate the peripheral pancytopenia associated with immunodeficiency disease and AZT treatment, even though erythroid, myeloid and platelet precursor progenitor cells were increased at certain times when compared to either normal or viral-infected mice receiving IL-3/GM-CSF. These results indicate that the combination use of IL-3 and GM-CSF in vivo is only a partially effective growth factor/cytokine treatment to ameliorate the hematopoietic toxicity associated with the use of the anti-viral drug zidovudine.
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PMID:Effect of combination interleukin-3 (IL-3) and granulocyte-macrophage colony stimulating factor (GM-CSF) on hematopoiesis administered to retrovirus-infected immunodeficient mice receiving dose-escalation zidovudine (AZT). 878 16

To verify whether the association of granulocyte-macrophage colony-stimulating factor (GM-CSF) and erythropoietin (EPO) would allow both the acceleration and the dose escalation of the cyclophosphamide/epidoxorubicin/5-fluorouracil (CEF) regimen as first-line therapy in advanced breast cancer patients, we conducted a dose-finding study. Cohorts of three consecutive patients received cyclophosphamide (Ctx, dose range 800-1400 mg/m2), epidoxorubicin (Epidx, dose range 70-100 mg/m2), and 5-fluorouracil (5-Fu, 600 mg/m2, fixed dose) given as an intravenous bolus on day 1 every 14 days; GM-CSF at 5 micrograms/kg given as a subcutaneous injection from day 4 to day 11; and EPO at 150 IU/kg given as a subcutaneous injection three times a week. In no single patient was any dose escalation allowed. A total of 14 patients entered the study. At the 4th dose level (Ctx 1400 mg/m2, Epidx 100 mg/m2, 5-Fu 600 mg/m2), two patients had dose-limiting mucositis and one patient developed dose-limiting neutropenia. Therefore, the 3rd cohort received the maximum tolerated dose, i.e. Ctx at 1200 mg/m2, Epidx at 90 mg/m2, and 5-Fu at 600 mg/m2, given every 18.5 (+/-2.5) days. Toxicity was moderate and manageable in an outpatient setting. Only 1 admission at the 4th dose level was required. Throughout the 4 dose levels there was no toxicity-related death; grade IV leukopenia ranged from 24% to 75% of cycles and grade IV thrombocytopenia ranged from 6% to 8%. No grade IV anemia was recorded. Increasing the doses of Ctx and Epidx while maintaining a fixed dose of 5-Fu with the support of both EPO and GM-CSF allows safe acceleration and dose escalation of CEF chemotherapy. Further controlled studies will evaluate the activity and efficacy of this strategy.
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PMID:Erythropoietin and granulocyte-macrophage colony-stimulating factor allow acceleration and dose escalation of cyclophosphamide/epidoxorubicin/5-fluorouracil chemotherapy: a dose-finding study in patients with advanced breast cancer. 882 88

Cytokines are involved in hematopoiesis by regulating proliferation, differentiation and cellular functions of various lineages of hematopoietic cells. There is an increasing range of clinical conditions in which cytokines are involved as therapeutic agents. One of the most advanced and successful applications is the stimulation of hematopoiesis by the colony stimulating factors (GM-CSF and G-CSF) and erythropoietin. Hematopoietic growth factors are effective in accelerating recovery from neutropenia after chemotherapy and bone marrow transplantation and in reducing incidence of infections. Interferon alpha (IFN-alpha) proved a useful therapeutic agent for chronic myelogenous and hairy cell leukemias as well as for multiple myeloma and non-Hodgkin's lymphoma. Interleukin 2 is the only cytokine apart from IFN-alpha accepted as antineoplastic agent. It may be useful as adjuvant therapy in the hematological malignancies. It may be supposed that in the near future new recombinant cytokines will be introduced in the treatment of blood diseases.
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PMID:Cytokines in the treatment of hematological disorders: recent progress and perspectives. 887 63

To date, six hematopoietic growth factors, granulocyte colony-stimulating factor (G-CSF), granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin-3 (IL-3), interleukin-1 (IL-1), interleukin-6 (IL-6) and erythropoietin (Epo), have been used in the treatment of patients with aplastic anemia (AA). Among them, G-CSF and GM-CSF are effective in correcting neutropenia in some patients with AA, but in general, patients with very severe hypoplasia do not respond to conventional doses of either agent. These factors have been used in the treatment of AA as follows: (1) as adjuvant therapy for severe infections; (2) as adjuvant therapy to immunosuppressive therapy (IS); and (3) as second-line therapy for patients refractory to IS. The results of clinical trials with antilymphocyte globulin, cyclosporine combined with G-CSF have been remarkable both in Europe and in Japan. Ongoing randomized studies with long-term follow-up will reveal the effects of hematopoietic growth factors on both hematopoiesis and the long-term course of the disease, including the later development of clonal disorders.
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PMID:Use of hematopoietic growth factors for treatment of aplastic anemia. 897 6

The hematologic manifestations of HIV infection and AIDS are common and may cause symptoms that are life-threatening and impair the quality of life of these patients. The most important of these manifestations are cytopenias. Anemia and neutropenia are generally caused by inadequate production because of suppression of the bone marrow by the HIV infection through abnormal cytokine expression and alteration of the bone marrow microenvironment. Thrombocytopenia is caused by immune-mediated destruction of the platelets, in addition to inadequate platelet production. The incidence and severity of cytopenia are generally correlated to the stage of the HIV infection. Other causes of cytopenia in these patients include adverse effects of drug therapy, the secondary effects of opportunistic infections or malignancies, or other preexisting or coexisting medical problems that may be prevalent in the HIV-infected population. Diagnosis of the mechanism and cause of the cytopenia may allow for specific management. Optimal management of the underlying HIV infection is essential, and mild cytopenia in asymptomatic patients may need no specific management. Supportive care for anemia includes the use of erythropoietin in addition to the judicious use of red blood cell transfusions. Therapy for neutropenia includes the use of the myeloid growth factors G-CSF and GM-CSF. Immune-mediated thrombocytopenia may be treated with a combination of zidovudine, corticosteroids, IVGG, and splenectomy. Platelet transfusions are sometimes needed for the treatment of thrombocytopenia caused by decreased production. Other hematologic manifestations such as hypergammaglobulinemia and lupus anticoagulants are commonly asymptomatic and usually require no specific therapy, but they can rarely cause morbidity and require specific interventions.
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PMID:Hematologic complications of human immunodeficiency virus infection and the acquired immunodeficiency syndrome. 909 37

The present report describes the non-haematological toxicity and the influence of growth factor administration on haematological toxicity and haematopoietic recovery observed after high-dose carboplatin (1200 mg m(-2)), etoposide (900 mg m(-2)) and melphalan (100 mg m(-2)) (CEM) followed by peripheral blood progenitor cell transplantation (PBPCT) in 40 patients with high-risk cancer during their first-line treatment. PBPCs were collected during the previous outpatient induction chemotherapy programme by leukaphereses. CEM administration with PBPCT was associated with low non-haematological toxicity and the only significant toxicity consisted of a reversible grade III/IV increase in liver enzymes in 32% of the patients. Haematopoietic recovery was very fast in all patients and the administration of granulocyte colony-stimulating factor (G-CSF) plus erythropoietin (EPO) or granulocyte-macrophage colony-stimulating factor (GM-CSF) plus EPO after PBPCT significantly reduced haematological toxicity, abrogated antibiotic administration during neutropenia and significantly reduced hospital stay and patient's hospital charge compared with patients treated with PBPCT only. None of the patients died early of CEM plus PBPCT-related complications. Low non-haematological toxicity and accelerated haematopoietic recovery renders CEM with PBPC/growth factor support an acceptable therapeutic approach in an adjuvant or neoadjuvant setting.
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PMID:High-dose carboplatin, etoposide and melphalan (CEM) with peripheral blood progenitor cell support as late intensification for high-risk cancer: non-haematological, haematological toxicities and role of growth factor administration. 909 71

The effect of granulocyte-macrophage colony stimulating factor (GM-CSF) on reticulocytes, haemoglobin and haematocrit levels of patients receiving chemotherapy for solid tumours was assessed. Forty-two patients were randomized into two groups who either did or did not receive GM-CSF 300 U/d on days 8 and 15 post-chemotherapy for neutropenia prophylaxis. Patients were stratified according to tumour type (non small-cell lung cancer, small-cell lung cancer, ovarian and breast cancer). Eight patients with progressive disease were excluded. The 34 patients evaluated completed six chemotherapeutic cycles of 21 days. They did not receive transfusions or erythropoietin. The estimated dose intensities (mg/m2/d) for each drug used were significantly higher in the group on GM-CSF compared to the group without. Haemoglobin and haematocrit were measured by the H * 1 (Bayer) haematology analyser and reticulocyte counts by the flow-cytometric reticulocyte analyser, R-1000 (Sysmex). Measurements were conducted on days 1 and 12 of every cycle for six cycles. At the beginning of therapy there were no significant differences between the two groups. However, red cell and reticulocyte counts fell significantly in the group without GM-CSF compared to the group on GM-CSF. Reticulocyte differences preceded those of haemoglobin and haematocrit. The data indicate a positive in vivo effect of GM-CSF on the erythroid tissue of patients receiving chemotherapy for solid tumours.
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PMID:The effect of GM-CSF on reticulocytes, haemoglobin and haematocrit in patients receiving chemotherapy for solid tumours. 911 14

In myelodysplastic syndromes (MDS), pancytopenia and defective function of neutrophils and platelets lead to a high risk of infectious and hemorrhagic complications. The progression to acute myeloid leukemia adds to morbidity and mortality. Supportive care including red blood cell and platelet transfusions are still the cornerstone of therapeutic management. However, the clinical use of the recombinant hematopoietic growth factors has enlarged the range of therapeutic applications in patients with MDS. It is possible to reverse neutropenia in MDS patients by administration of G-CSF (granulocyte colony stimulating factor) or GM-CSF (granulocyte-monocyte colony stimulating factor). Because of the lower incidence of adverse events, G-CSF is preferable. However, neither G-CSF nor GM-CSF have been shown to reduce the rate of severe infection or mortality from infection when given prophylactically. In the case of a severe infection, therapeutic administration of G-CSF together with antibiotics might be justified in otherwise neutropenic MDS patients. Preliminary data suggest it to be possible to identify MDS patients with a higher than 50% chance of reversal of anemia or transfusion dependency by treatment with high-dose erythropoietin (EPO). Since patients with only slight impairment of erythropoiesis and no transfusion dependency have the highest response rates but need EPO the least, pharmacoeconomic analyses are urgently needed. Controlled randomized trials will have to ascertain whether combinations of EPO with G-CSF or GM-CSF are of benefit. Clinical studies with thrombopoietin (megakaryocyte growth and differentiation factor) have to be initiated to find out whether thrombocytopenia in MDS can be reversed.
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PMID:Clinical use of hematopoietic growth factors in patients with myelodysplastic syndromes. 919 74

Haematopoietic growth factors are glycosylated proteins involved in the differentiation of pluripotent stem cells into committed progenitor cells, which eventually give rise to distinct haematopoietic cell lineages. Three recombinant hematopoietic growth factors--G-CSF, GM-CSF and erythropoietin--are currently commercially available for clinical use. G-CSF and GM-CSF are lineage-specific growth factor that regulate the production and function of granulocytic and monocytic cells. They have been shown to reduce the incidence of febrile neutropenia. Primary prophylactic administration is reserved for patients in which the expected incidence of febrile neutropenia is greater than 40% without haematopoietic growth factor. After a documented occurrence of febrile neutropenia in an earlier cycle, the secondary prophylactic administration of G-CSF or GM-CSF may be considered. However, in the absence of clinical data supporting maintenance of chemotherapy dose-intensity, dose reduction should be considered as an alternative to the use of haematopoietic growth factors. G-CSF and GM-CSF also shorten the period of neutropenia in patients undergoing high-dose chemotherapy with autologous bone marrow support. Erythropoietin is currently approved for treatment of anemia associated with cisplatin-based chemotherapy with the aim to reduce transfusion requirements.
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PMID:[Haematopoietic growth factors and solid tumors]. 936 42

Hematopoietic growth factor (HGF) administration following autologous peripheral blood progenitor cell transplantation (APBPCT) is a current approach for shortening the duration of high-dose chemotherapy-induced transient peripheral pancytopenia. Several published clinical experiences and a retrospective study reported here show that recombinant human granulocyte colony stimulating factor (rhG-CSF) or recombinant human granulocyte-macrophage colony stimulating factor (rhGM-CSF) administration potentiates polymorphonuclear leukocyte (PMN) and white blood cell (WBC) recovery with some clinical benefits mainly related to the reduction of infectious complications during the shortened period of neutropenia. However, this therapeutic strategy does not produce any enhancement of platelet (PLT) recovery or potentiation of red cell production. Conversely, a recent phase I/II study carried out in our institution showed that the combined administration of rhG-CSF and recombinant human erythropoietin (rhEPO) is able to potentiate trilineage hematopoietic recovery with a reduction of PLT transfusions and to considerably simplify the clinical management of patients as compared to patients treated with APBPCT alone. The post-APBPCT administration of rhEPO with rhGM-CSF decreased the number of days with WBC < 1 x 10(9)/L but failed to produce any appreciable effect on PLT recovery. Both combined treatments significantly reduced the patients' hospital stay and allowed the abrogation of systemic antibiotic administration following APBPCT. A further group of patients were treated with the combined administration of rhEPO, rhG-CSF and rhGM-CSF; they did not show a faster hematopoietic recovery than rhG-CSF plus EPO treated patients and a consistent hyperthermia was observed in most patients as a prominent side effect. Future prospective randomized studies will clarify the efficacy of HGF administration following APBPCT. Moreover, further improvements in the hematopoietic support of transplanted patients may be obtained when stem cell factor, flt3/flk2 tyrosine kinase ligands or megakaryocyte growth and development factor will become clinically available.
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PMID:Growth factor administration following autologous peripheral blood progenitor cell transplantation. 937 97


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