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)

Recombinant granulocyte-macrophage colony-stimulating factor (rGM-CSF) is a polypeptide hormone produced through recombinant DNA technologies in glycosylated (yeast or mammalian expression systems) or nonglycosylated (Escherichia coli expression system) form. It is a multilineage haematopoietin which stimulates proliferation and differentiation of bone marrow myeloid progenitors and increases peripheral white blood cell counts when administered systemically. Treatment is generally well tolerated, although mild to moderate flu-like symptoms are common and rGM-CSF-induced fever and fluid retention may be problematic in occasional patients. rGM-CSF accelerates recovery of peripheral neutrophil counts after bone marrow transplantation, and results of a placebo-controlled randomised trial correlate this with reduced infectious episodes and shortened length of hospitalisation in patients with lymphoid malignancies. A substantial number of patients with graft failure after bone marrow transplantation also respond to rGM-CSF. The duration of myelosuppression secondary to cancer chemotherapy can be significantly reduced by rGM-CSF which has permitted investigation of antineoplastic dose-intensity escalation. In some haematopoietic disorders (e.g. aplastic anaemia, myelodysplasia and neutropenia secondary to HIV infection and antiviral therapy), rGM-CSF produces clinically useful increases in peripheral blood granulocyte counts, although the effect is generally not sustained after drug withdrawal. The potential for rGM-CSF to stimulate proliferation of the abnormal clone in myelodysplasia and in acute myelogenous leukaemia following induction therapy is of concern. Available data suggest, however, that with appropriate monitoring and exclusion of high-risk patients this serious potential risk can be avoided, and that myelopoiesis is enhanced in such patients by rGM-CSF treatment. Recombinant colony-stimulating factors are a new therapeutic modality; hence many aspects of their use remain to be clarified. Nonetheless, as one of a small group of novel agents rGM-CSF has major potential in the management of myelosuppression secondary to cytoreductive therapy with or without bone marrow transplantation, and in amelioration of disturbed myelopoiesis. It represents an important application of biotechnology to a difficult area of therapeutics.
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PMID:Recombinant granulocyte-macrophage colony-stimulating factor (rGM-CSF). A review of its pharmacological properties and prospective role in the management of myelosuppression. 137 18

Levels of serum granulocyte colony-stimulating factor (G-CSF) and granulocyte-macrophage colony-stimulating factor (GM-CSF) in patients with various leukocyte disorders were estimated by enzyme-linked immunosorbent assay (ELISA). Some cases of acute myelogenous leukemia and aplastic anemia showed elevated serum levels of G-CSF and/or GM-CSF, whereas almost all of 23 healthy controls showed G-CSF and GM-CSF levels lower than 100 pg/ml. High levels of both types of CSF were noted in patients with granulocytosis due to infection. These levels became lower after resolution of the infection. Daily changes in serum CSF levels were also examined in a patient with autoimmune neutropenia, and it was found that the peripheral neutrophilic granulocyte count changed almost in parallel with the serum G-CSF level but not with GM-CSF, following the pattern with a delay of about 4-5 h, suggesting the possibility that G-CSF mainly regulates peripheral neutrophil circulation.
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PMID:Levels of human serum granulocyte colony-stimulating factor and granulocyte-macrophage colony-stimulating factor under pathological conditions. 137 27

Clinical effects of KRN8601 (recombinant human granulocyte colony-stimulating factor:rhG-CSF) were studied in 26 patients with chronic neutropenia including 4 Kostmann's disease, 1 Shwachman's syndrome, 1 Lonsdale's syndrome, 1 glycogen storage disease Ib-associated, 6 chronic benign, 5 chronic hypoplastic, 2 cyclic, 4 autoimmune and 2 miscellaneous neutropenia. The patients were given rhG-CSF intravenously at doses of 20-540 micrograms/m2 or subcutaneously at doses 20-400 micrograms/m2, over the periods of 2-32 weeks. Increases in neutrophil counts occurred after rhG-CSF administration in 23 of the 26 patients. Patients with Kostmann's disease, Shwachman's syndrome and chronic hypoplastic neutropenia responded poorly compared to patients with other types of neutropenia. There were no serious side effects which caused interruption of the study. These results indicated a beneficial effect of KRN8601 in various types of chronic neutropenia.
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PMID:[Clinical evaluation of effects of KRN8601 (rhG-CSF) on neutropenia]. 137 11

Newborns are predisposed to neutropenia and thrombocytopenia during bacterial sepsis. The presence of peripheral cytopenias during overwhelming infection may be secondary to decreased hematopoietic growth factor production during states of increased demand. We therefore examined circulating levels of granulocyte-colony stimulating factor (G-CSF) and IL-3, production of G-CSF and IL-3 from unstimulated and stimulated mononuclear cells (MNC), expression of G-CSF and IL-3 genes during unstimulated and stimulated conditions, and equilibrium and binding of G-CSF receptors on mature effector peripheral blood cells of adults and neonates. Serum from cord and adult peripheral blood contained negligible amounts of both G-CSF (less than or equal to 50 pg/mL) and IL-3 (less than or equal to 5 pg/mL). Constitutive supernatant levels of G-CSF and IL-3 from cord and adult unstimulated MNC were also undetectable. However, there was a significant difference in G-CSF and IL-3 production from stimulated cord and adult MNC. Supernatants from stimulated adult MNC had significantly more G-CSF (p less than 0.007) and IL-3 (p less than 0.02). Additionally, Northern blot hybridization and densitometry of autoradiographs demonstrated significantly more G-CSF and IL-3 mRNA transcripts from adult than from cord MNC. Lastly, affinity, binding, and number of G-CSF receptors on cord and adult peripheral effector cells were equal. These data suggest that, during states of increased demand, cord MNC produce less G-CSF and IL-3 than do adult MNC and have an associated reduction in their respective mRNA transcripts. These findings may have implications in the pathogenesis of neonatal cytopenias during states of increased demand, such as sepsis.
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PMID:Decreased G-CSF and IL-3 production and gene expression from mononuclear cells of newborn infants. 137 59

Recombinant canine granulocyte colony-stimulating factor (rcG-CSF) was administered to clinically normal dogs, cyclic-hematopoietic dogs, and dogs undergoing autologous bone marrow transplantation, to determine whether rcG-CSF could be used to stimulate WBC production and function in normal and neutropenic dogs. To the normal dogs, rcG-CSF was administered by SC injection at rates of 1 microgram/kg of body weight, q 12 h; 2 micrograms/kg, q 12 h; or 5 micrograms/kg, q 12 h. A significant dose-dependent increase in the WBC count resulted from the stimulation of bone marrow progenitor cells. The increased WBC count was characterized by mature neutrophilia and monocytosis. Neutrophil myeloperoxidase and phagocytic activity were normal in rcG-CSF-treated normal dogs, demonstrating the production of normal functional neutrophils in response to rcG-CSF treatment. Recombinant canine G-CSF prevented neutropenia and associated clinical signs but did not completely eliminate the cycling of neutrophils in cyclic-hematopoietic dogs when it was administered at rates of 1 microgram/kg, q 12 h, and 2.5 micrograms/kg, q 12 h. The time to bone marrow reconstitution was not decreased in dogs treated with rcG-CSF at a rate of 2.5 micrograms/kg, q 12 h, for 13 days following autologous bone marrow transplantation. On the basis of our findings, we suggest that treatment with rcG-CSF is an effective way to stimulate myelopoiesis in dogs, but that the dose of rcG-CSF required to stimulate WBC production will vary depending on the cause of neutropenia. Recombinant canine G-CSF should be useful in stimulating production and maintaining function of WBC for treatment of clinical diseases seen commonly in veterinary practice.
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PMID:Effects of recombinant canine granulocyte colony-stimulating factor on white blood cell production in clinically normal and neutropenic dogs. 137 21

We report a patient with congenital neutropenia or Kostmann's Syndrome who suffered many complications after presenting with Clostridium septicum enterocolitis, including absence of wound healing. Because of several reports of the use of granulocyte colony-stimulating factor (G-CSF) in patients with various complications of neutropenia, we treated this patient with recombinant human (rh) G-CSF. We found that once rhG-CSF restored neutrophil counts to normal, progressive wound healing followed. Thus, rhG-CSF therapy may be useful in treating neutropenic patients with wound complications.
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PMID:Recombinant human granulocyte colony-stimulating factor promotes wound healing in a patient with congenital neutropenia. 138 74

Anemia and neutropenia are common complications of HIV infection. Antiretroviral therapy with zidovudine exacerbates bone marrow suppression by inhibiting proliferation of blood cell progenitor cells. In addition, treatment for opportunistic infections or malignancies can involve the use of myelosuppressive drugs. As a consequence, severe anemia and neutropenia can result, thereby limiting the utilization of antiretroviral drugs. Since antiretroviral therapy can increase survival, drugs that ameliorate myelosuppression are important adjuncts in the treatment of HIV-infected patients. Three hematopoietic growth factors are effective in the treatment of anemia or neutropenia. In four placebo-controlled trials, erythropoietin (EPO) at doses up to 600 U/kg/wk decreased mean transfusion requirements by 37%, increased mean hematocrit by 4.5% and corrected anemia in the majority of patients receiving zidovudine over a 12-week period. In a separate study, granulocyte colony-stimulating factor (G-CSF) corrected leukopenia and isolated neutrophil defects in 22 patients with AIDS without altering HIV expression. When erythropoietin was added to the regimen, combined G-CSF and EPO corrected both anemia and leukopenia and lessened subsequent zidovudine toxicity. Similarly, granulocyte macrophage-colony-stimulating factor (GM-CSF) corrected leukopenia and pre-existing neutrophil defects in patients with HIV infection. In controlled and uncontrolled trials, GM-CSF also appears to reduce toxicity from zidovudine, ganciclovir, and antineoplastic therapy. New combinations of hematopoietic stimulants are being used to decrease the toxicity from combination antiretroviral therapy with alpha interferon and cytotoxic chemotherapy in the treatment of AIDS-related malignancies.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Hematopoietic growth factors as adjuncts to antiretroviral therapy. 138 Feb 56

Fifty-six children with various malignancies were treated subcutaneously with recombinant human granulocyte colony-stimulating factor (rhG-CSF, KRN 8601) for neutropenia induced by cancer chemotherapy. Patients received the first chemotherapy without rhG-CSF (control course). In the second course, rhG-CSF was given once daily, starting 3 days after completion of identical chemotherapy (day 3) and continuing until day 12. At day 12, the white blood counts and neutrophil counts were found to be 6.8 and 30 times higher in the rhG-CSF course than in the control course (P = .0001) Nadirs of white blood counts and neutrophils were significantly elevated in the rhG-CSF course (P = .003 and .0001, respectively). rhG-CSF administration shortened the neutropenic period in the majority of patients. Children tolerated the rhG-CSF administration well and we have hereby confirmed that rhG-CSF administration is useful for proceeding with chemotherapy in children with cancer.
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PMID:Treatment of chemotherapy-induced neutropenia in children with subcutaneously administered recombinant human granulocyte colony-stimulating factor. 138 41

Recently biotechnologic progress has, through the technique of the recombinant DNA, allowed a low cost production of large amount of several growth factors. Such a large availability has made possible to either carry out deeper investigations on the physiopathology of the hemopoietic regulation and perform new therapeutic approaches under different pathologic conditions. The most interesting acquisition concerning the biology of hemopoiesis to which such investigations have addressed us is the inadequacy of the protocols adopted till now. Such protocols considered only a simple vision of an elective action of a given growth factor during an exact maturation period of a determined cell colony. On the contrary, it was possible to point out a close network of inter-relationship among the different factors, which sometime impedes a clear distinction for each single factor, between actions of competence and progression in the cell maturation phenomena. However, the present uncertainty pertaining to the regulation of hemopoiesis has not impede the performance of clinical trials with positive findings in several pathologic conditions. The administration of recombinant erythropoietin has for example allowed to intervene in a resolutive way on the anemia in uremic subjects, and seems giving satisfactory results also in subjects with non renal origin anemic conditions. Satisfactory results were also obtained through the use of the Granulocyte-Macrophage CSF and of the Granulocyte-CSF, which by preventing neutropenia have allowed the performance of more adequate chemotherapeutic protocols in neoplastic subjects. New interesting perspectives are now coming for the use of Interleukin-3 in the treatment of the aplastic anaemia.
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PMID:[Growth factors and hematopoiesis. Physiopathology and clinical applications]. 138 4

The neutropenia-related morbidity and mortality occurring after autologous bone marrow transplantation (ABMT) is increased by marrow purging procedures. While phase I through III clinical trials showed the enhancing activity of recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) on neutrophil recovery after ABMT with unpurged marrow, controversial results have been reported when purged marrow was used. Therefore, it was the aim of the present study to evaluate the efficacy of rhGM-CSF administration in a group of patients (n = 15) with lymphoid malignancies transplanted in complete remission with mafosfamide-purged (n = 10) or unpurged (n = 5) marrow. Mafosfamide concentrations used for marrow purging were evaluated on an individual basis by means of a recently described technique that destroys the granulocyte-macrophage (granulocyte-macrophage colony-forming units [CFU-GM]) compartment, but spares 50% of the more primitive stroma adherent colony-forming cells (CFU-Blast). rhGM-CSF (10 micrograms/kg/d) was started within 24 hours of ABMT and administered in a 4-hour infusion daily until the absolute neutrophil count (ANC) reached 500 x 10(6)/L and then for 7 more days. Patients receiving mafosfamide-purged or unpurged marrow failed to show any difference in terms of median number of days required to achieve an ANC > or = 500 x 10(6) (13 v 14.0, P > .4) cells/L. As compared with retrospective controls, granulocytic recovery was reduced by a median time of 11 (P < or = .0005) and 5 (P < or = .0005) days for patients grafted with purged and unpurged marrow, respectively. The number of CFU-GM (mean +/- SD) infused per kilogram of body weight was significantly lower in patients who received purged autografts as compared with those receiving unpurged autografts (0.85 +/- 0.79 x 10(4) v 15.7 +/- 9.2 x 10(4), P < or = .0005). The dose of CFU-GM progenitors infused per kilogram of body weight did not correlate (r = .031, P > .05) with the time required to reach an ANC > or = 500 x 10(6) cells/L. The number of CFU-Blast (mean +/- SD) infused per kilogram of body weight was not significantly different between patients who received purged or unpurged autografts (5.05 +/- 2.51 x 10(3)/kg v 6.18 +/- 2.66 x 10(3)/kg, P < or = .375). A statistically significant correlation (r = -.658, P < or = .05) was observed between the number of CFU-Blast infused and the number of days required to reach an ANC > or = 500 x 10(6) cells/L.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Use of recombinant human granulocyte-macrophage colony-stimulating factor in patients with lymphoid malignancies transplanted with unpurged or adjusted-dose mafosfamide-purged autologous marrow. 142 13


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