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

Treatment results of Hodgkin's disease have been improved by polychemotherapy. The overall cure rate for adults is about 70%. For advanced stages of Hodgkin's disease (IIIB-IV), the results of treatment are less satisfactory. One approach to improving the cure rates for patients with advanced stages is the intensification of chemotherapy. The German Hodgkin Study Group (GHSG) will apply this treatment strategy by introducing a new protocol (BEACOPP) in combination with growth factor (G-CSF) support to prevent prolonged neutropenia and severe infections. In a currently initiated "run-in"-study the maximal tolerable dose of cyclophosphamide, adriamycin, and etoposide will be defined within a multicenter setting. The subsequent trial will consist of a randomized study of BEACOPP baseline vs. BEACOPP dose-intensified vs. COPP/ABVD standard, in order to evaluate the role of dose intensification for the improvement of treatment outcome.
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PMID:Dose-escalation study for the treatment of Hodgkin's disease. The German Hodgkin Study Group (GHSG). 768 48

Cyclic neutropenia is a rare hematological disorder characterized by periodical severe granulocytopenia. A stem cell defect and/or immunological abnormalities are considered to play a role in this disease. Here we describe the case of an adult woman who was diagnosed as having both cyclic neutropenia and severe hypogammaglobulinemia. Her clinical history revealed that one or both abnormalities had been present since childhood. Normal in vitro growth of the patient's bone marrow CFU-GM was observed, while immunological analysis revealed the presence of a persistent excess of activated (HLA-DR+) CD8+ T lymphocytes in both bone marrow and peripheral blood. These T lymphocytes have been shown to be polyclonal by DNA analysis, and their role in determining the clinical picture of our patient remain uncertain since they could not be shown to produce inhibitors of in vitro CFU-GM growth. Intermittent low doses of human recombinant G-CSF were able to improve neutropenia and completely prevent infectious symptoms, thus confirming the efficacy of this cytokine in cyclic neutropenia patients.
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PMID:Cyclic neutropenia and severe hypogammaglobulinemia in a patient with excess of CD8-positive T lymphocytes: response to G-CSF therapy. 768 13

Neutropenia in Felty's Syndrome predisposes patients to recurrent bacterial infections. We have treated a patient for more than one year with G-CSF and ascertained that this growth factor can safely correct neutropenia over a long period of time. G-CSF may constitute a new agent for the treatment and prophylaxis of infection in Felty's syndrome.
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PMID:Long-term correction of neutropenia in Felty's syndrome with granulocyte colony-stimulating factor. 768 94

Haematopoietic growth factors are a family of genetically determined low molecular weight glycoproteins which regulate the proliferation and differentiation of haemopoietic cells through specific membrane receptors. GCSF and GMCSF reduce the morbidity from infections associated with the neutropenia induced by chemotherapy of onco-haematological neoplasia; EPQ totally corrects not only the anaemia of patients with chronic renal failure, but also 50 percent of anaemias related to chemotherapy; finally, the activity of IL 3 on platelet production seems to control the thrombocytopenia which restricts the use of therapeutics.
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PMID:[Hematopoietic growth factors]. 768 23

We studied the effects of several cytokines on the development of granulocyte-macrophage (GM) progenitors using the serum-deprived culture. SCF plays an important role in the GM-CSF- or IL-3-dependent production of neutrophils and macrophages. In vitro colony assay also suggests an increase in sensitivity of GM progenitors to cytokines (GM-CSF, IL-3, G-CSF and/or SCF) in a patient with juvenile chronic myelogenous leukemia. A high level of serum IFN-gamma was associated with leukopenia and thrombocytopenia in a patient with hemophagocytic syndrome. Based on the evidence that IFN-gamma significantly inhibited the proliferation of GM progenitors, IFN-gamma-mediated suppression was suggested as one of the mechanisms causing cytopenia. In patients with aplastic anemia and neutropenia, an increase of serum G-CSF levels was observed when neutrophils decreased remarkably in number. However, the serum SCF levels were constant in these patients. A failure of SCF to enhance colony growth in some patients with aplastic anemia implies qualitative abnormalities of hematopoietic progenitors.
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PMID:[Abnormalities in regulation system of granulopoiesis]. 768 32

Our purpose was to evaluate the ability of recombinant human granulocyte colony-stimulating factor (r-metHuG-CSF) as an adjunct to induction chemotherapy of acute lymphoblastic leukemia (ALL) to ameliorate chemotherapy-induced neutropenia and thus allow patients to receive full doses of chemotherapy on time. Sixteen consecutive patients with adult ALL (13 de novo, three relapsed) were treated with induction chemotherapy according to the BMFT protocol and received in addition r-metHuG-CSF (200 micrograms/m2/day). Patients who were treated with the same induction chemotherapy but without G-CSF between 1982 and 1990 served as controls. Fifteen of the 16 patients achieved complete hematological remission. One patient died because of fungal septicemia. Compared with historical controls, G-CSF-treated patients had a significantly faster neutrophil recovery in phase I, resulting in neutrophil counts > 1000/microliters at day 17 vs day 26 (in median) in controls. In phase II, the onset of severe leukocytopenia (< 1500/microliters) was significantly (p = 0.01) delayed and the degree of leukocytopenia less pronounced (mean nadir 3300/microliters) in G-CSF-treated patients compared with controls (1880/microliters). The number of days of febrile neutropenia was not different in phase I. In phase II it was lower in study patients (0 vs 1.1 days), but the difference did not reach statistical significance (p = 0.09). Full doses of chemotherapy could be given on time to 11/13 (85%) G-CSF patients but to only 7/30 (23%) controls. These data indicate that (a) G-CSF can be given along with chemotherapy in induction treatment of ALL without compromising efficacy; (b) the duration of neutropenia in phase I is markedly shortened and the degree of leukocytopenia in phase II ameliorated; (c) these beneficial effects allow patients to receive full doses of chemotherapy on time.
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PMID:Granulocyte colony-stimulating factor (G-CSF) as an adjunct to induction chemotherapy of adult acute lymphoblastic leukemia (ALL). 768 4

Recombinant methionyl human granulocyte colony-stimulating factor (r-metHuG-CSF, hereafter G-CSF) has been demonstrated in clinical trials to be effective in correcting iatrogenic neutropenia by stimulating the production of neutrophils. Not surprisingly, G-CSF has also been found to induce neutrophilia in non-neutropenic hosts. Experimental data suggest that G-CSF leads to the enhancement of neutrophil function. Endogenous G-CSF levels are elevated over a broad spectrum of serious infectious diseases, suggesting the clinical importance of G-CSF in these settings. These findings have stimulated research on the use of G-CSF alone or as an adjunct to conventional antimicrobial therapy in a number of non-neutropenic animal models of infections. In total these studies suggest that G-CSF may be useful in the prevention or therapy of infections in both non-neutropenic and neutropenic clinical settings.
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PMID:Recombinant methionyl human granulocyte colony-stimulating factor for the prevention and treatment of non-neutropenic infectious diseases. 769 89

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

Agranulocytosis developed in a 63-year-old patient with myelodysplasia 6 weeks after commencing treatment with the oral iron chelator deferiprone (L1, 1,2-dimethyl-3-hydroxypyrid-4-one, CP20) at a daily dose of 79 mg/kg. This was the 3rd case of agranulocytosis (neutrophils 0 x 10(9)/l) in clinical trials of L1 at the Royal Free Hospital. The neutrophil count recovered 7 days after stopping L1 and commencing G-CSF at a dose of 300 micrograms daily. Three other patients with milder degrees of neutropenia (neutrophils < 1.5 x 10(9)/l) have also been observed in our trials. The case histories of these 4 patients are described here; other reported cases of neutropenia or agranulocytosis are reviewed. Based on worldwide long-term clinical trials the incidence of agranulocytosis is about 1.6% and of neutropenia 2%.
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PMID:Deferiprone-associated myelotoxicity. 781 10

The search for new active agents and strategies to improve the prognosis for patients with stage IV breast cancer has led to examination of paclitaxel. Several clinical trials have been undertaken to determine its optimal use and clarify its role in the treatment of breast cancer and other malignancies. Several phase II trials involving breast cancer patients with limited prior therapy have yielded overall response rates (complete response and partial response) of 44% to 62% among women receiving paclitaxel. Treatment was generally well tolerated, with febrile neutropenia the most common side effect. An interim analysis of the European-Canadian Randomized Trial in Metastatic Breast Cancer demonstrated safety and efficacy of paclitaxel in a multicenter setting. Among the 234 patients evaluable for response, 29% (34/117) responded at 175 mg/m2 paclitaxel and 22% responded (26/117) at 135 mg/m2. Treatment was well tolerated at both dose levels; responses continue to evolve in patients who remain on study. Among patients with extensive prior therapy (> 2 prior regimens for stage IV disease), paclitaxel also has demonstrated safety and efficacy. At Memorial Sloan-Kettering Cancer Center, responses were noted among 36% of patients who had received two prior treatments and 21% of those who had received 3 or more. Paclitaxel was administered at 200 mg/m2 plus G-CSF. Other studies involving heavily pretreated patients yielded overall response rates as high as 53%. The concerns about cross-resistance between paclitaxel and doxorubicin (or other agents for which resistance is thought to be at least partly due to P-glycoprotein-mediated pleiotropic drug resistance) also are addressed.
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PMID:Single-agent use of Taxol (paclitaxel) in breast cancer. 786 28


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