Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0002874 (aplastic anemia)
 5,905 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Recombinant granulocyte colony-stimulating factor (rG-CSF) is a glycoprotein hormone which has been produced in mammalian cells and, in a nonglycosylated form, in the bacterium Escherichia coli through recombinant DNA technology. It stimulates proliferation, differentiation and activation of cells of the neutrophil-granulocyte lineage and has been investigated as therapy for patients with various neutropenic conditions, both iatrogenic and disease related. rG-CSF is well tolerated, the most frequently reported adverse effect being mild to moderate bone pain. A major use for rG-CSF therapy will be in ameliorating the neutropenia which follows cytoreductive chemotherapy. rG-CSF accelerates neutrophil recovery after chemotherapy, leading to a reduction in duration of the neutropenic phase. Consequently, infection rate is diminished, as is the associated usage of antibiotics and duration of hospitalisation. The implications are that rG-CSF may allow increased dose intensity and stricter adherence to chemotherapy schedules. The increase in neutrophils produced by rG-CSF renders it a useful treatment for conditions such as congenital, acquired and cyclic neutropenias for which current therapy is not very successful. rG-CSF may be an effective therapy in myelodysplasia, although there is concern about acceleration of the possible rate of conversion of this disease to acute myelogenous leukaemia. It is also likely that rG-CSF will be useful in accelerating the recovery of transplanted bone marrow in patients with leukaemia, lymphoma and solid tumour. Furthermore, there is great potential for expansion of the role of rG-CSF as monotherapy or in combination regimens with other cell factors in various haematological disorders such as aplastic anaemia. In summary, while many aspects of its use remain to be clarified, rG-CSF must be seen as an exciting advance in therapeutics. It should rapidly find an important place as an adjunct to cancer chemotherapy, and also appears to have substantial potential in a number of other neutropenic conditions which are currently difficult to treat.
 ...
PMID:Recombinant granulocyte colony-stimulating factor (rG-CSF). A review of its pharmacological properties and prospective role in neutropenic conditions. 171 26

We investigated the effects of recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) and recombinant human granulocyte colony-stimulating factor (rhG-CSF) therapy on the natural killer (NK) cell lineage in patients with aplastic anemia and myelodysplastic syndrome. Selected bone marrow (BM) cells were prepared by the elimination of nylon wool-adherent cells and mature T and NK cells from BM cells. The frequency of BM NK progenitors relative to BM cells selected was significantly decreased 4 weeks after the start of rhGM-CSF therapy (P less than .01), while the peripheral blood NK cell count and NK activity were also significantly decreased (P less than .05). A return to the pretreatment levels was seen 4 weeks after the cessation of treatment in all cases. No suppressive effect was noted in the patients who received rhG-CSF therapy. These results suggest that rhGM-CSF therapy suppresses the generation of NK cells from human BM NK progenitors.
 ...
PMID:Inhibitory effect of granulocyte-macrophage colony-stimulating factor therapy on the generation of natural killer cells. 172 Jul

5 patients with refractory aplastic anemia (AA) received long-term administration (2-11 + months) of recombinant human G-CSF (rhG-CSF) in doses from 250-500 micrograms/body/day by intravenous infusion or 75-300 micrograms/body/d by subcutaneous injection. All 5 evaluable patients showed a substantial increase in absolute neutrophil count (ANC) with a recovery of myeloid components in the bone marrow after 1 to 2 months of treatment. Interestingly, 2 out of the 5 patients showed a dramatic improvement in severe anemia after 2 to 4 months of treatment accompanying a recovery of erythroid components in the bone marrow. In addition, there was no serious infection before or during therapy. Long-term administration of rhG-CSF was well tolerated because of its minimal toxicity. Clonal assay revealed a recovery of myeloid progenitors in all patients and a recovery of erythroid progenitors in 3 out of the 5 patients. These results suggest that long-term administration of rhG-CSF at least mobilizes residual myeloid as well as erythroid progenitor cells and induces a bilineage response in severe refractory AA.
 ...
PMID:Bilineage response in refractory aplastic anemia patients following long-term administration of recombinant human granulocyte colony-stimulating factor. 173 Feb 79

Recombinant human granulocyte macrophage colony-stimulating factor (rhGM-CSF) was one of the first of the myeloid growth factors to become available for clinical trials. Phase I studies have demonstrated that the optimal administration is by continuous intravenous infusion or subcutaneous injections at doses of 4-5 micrograms/kg/day. Phase II trials in patients with a variety of malignancies who receive rhGM-CSF after standard doses of chemotherapy have demonstrated significant reductions of the duration of leucocytopenia. Use of rhGM-CSF after high-dose chemotherapy (with or without bone marrow rescue) suggest that this agent decreases the time to recovery of a normal blood count and reduces infective complications. Results in myelodysplasia and aplastic anemia have been less encouraging. The potential value of rhGM-CSF in the treatment of a variety of other conditions including AIDS and the leukemias is being tested and the early results are discussed.
 ...
PMID:Recombinant human granulocyte macrophage colony-stimulating factor: current status of clinical trials and potential future applications. 179 89

The treatment of severe aplastic anemia has been modified recently by the demonstration that Cyclosporine A is active alone or in combination leading to more than 50% response rate. Combination or sequential treatments with ATG seem to be better than such drug separately but this must be studied in randomized studies. Long term follow-up is necessary to assess the rate of malignant transformation. Growth factors have been recently introduced. G or GM-CSF seem to be active. IL-3 has not been proven to be effective in very small non randomized study. Allogeneic bone marrow transplantation is the best treatment with a matched related donor, progress must be achieved in methods of conditioning and GVH prophylaxis when a matched unrelated donor is used.
 ...
PMID:Recent treatments of aplastic anemia. The International Group on SAA. 181 8

The aim of this study was to test whether large amounts of recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) are capable of promoting the growth of hemopoietic progenitors from patients with marrow failure. For this purpose 0.1, 100, 1000, 10,000 and 20,000 ng/ml of rhGM-CSF were added to 10(5) light-density (adherent cell-depleted) bone marrow cells from 9 normal controls and from 52 patients with aplastic anemia, 25 cases of which were transfusion-dependent (Tx-D) aplastic anemia (AA) and 27 of which were transfusion-independent (Tx-I) aplastic anemia (AA). A dose-dependent increase of granulocyte-macrophage colony-forming units (CFU-GM) was observed in healthy donors, from 81 to 247 colonies at 0.1 and 1000 ng/ml of rhGM-CSF, with a plateau thereafter. Tx-I AA patients showed the best increase of CFU-GM in response to colony-stimulating factor, from 0.1 to 32.7 mean colonies at 0.1 and 20,000 ng/ml of rhGM-CSF, and the increment was greater when compared to controls. The ratio of CFU-GM grown from these patients and controls was 1:810 at 0.1 ng/ml of rhGM-CSF and 1:7.9 at 20,000 ng/ml. Eleven patients were studied at diagnosis; there was no in vitro response to rhGM-CSF (0 and 1.8 mean colonies/10(5) cells at 0.1 and 10,000 ng/ml). Overall, Tx-D AA patients showed minimal increments of CFU-GM growth at very high doses of rhGM-CSF. Two suggestions come from this study: 1) maturation of CFU-GM from recovering AA patients appears to require larger doses of GM-CSF than normal controls, and 2) very high doses of rhGM-CSF have little or no effect on CFU-GM growth in AA patients. This may be relevant for clinical studies designed to improve hemopoiesis in patients with marrow failure.
 ...
PMID:Response of CFU-GM to increasing doses of rhGM-CSF in patients with aplastic anemia. 186 97

Colony stimulating factors and interleukins regulate proliferation, differentiation, and functional activation of hematopoietic cells of multiple lineages. These hematopoietic growth factors are proving effective in vivo in stimulation of granulopoiesis in clinical situations associated with myelosuppression. G-CSF and GM-CSF promote accelerated granulocyte recovery following chemotherapy, or allogeneic or autologous bone marrow transplantation, in patients with cancer. In congenital defects of granulocyte production or in acquired disorders such as idiopathic neutropenia or aplastic anemia, CSF administration can lead to recovery of functioning granulocytes. This has resulted in a reduction in the morbidity and mortality associated with these diseases and now permits both a dose and a schedule intensification of chemotherapy. In myeloid leukemia and myelodysplastic syndromes, CSF treatment, particularly G-CSF, has proved effective for certain patients in improving neutrophil, platelet, and occasionally red cell production while reducing blast cells. The recombinant growth factors are generally well tolerated with few limiting toxicities at dose levels that effectively stimulate hematopoiesis.
 ...
PMID:The clinical use of colony stimulating factors. 191 Jun 75

Twenty children (aged 1 to 17 years) with severe or moderate aplastic anemia were treated with recombinant human granulocyte colony-stimulating factor (rhG-CSF) at a dose of 400 micrograms/m2 per day administered as a 30-minute intravenous (IV) infusion daily for 2 weeks. This treatment increased the neutrophil counts (2.7- to 28.0-fold) in 12 of the 20 patients. Increasing doses (800 or 1,200 micrograms/m2 per day) were administered to five patients who had not responded to the initial dose, and three showed an increase in neutrophil count. Differential counts of bone marrow (BM) aspirates showed an increase in the myeloid/erythroid ratio. The response was transient, however, and the neutrophil count returned to baseline within 2 to 10 days of discontinuing treatment. No severe toxicity attributable to rhG-CSF was observed. The results suggest that this agent is effective in stimulating granulopoiesis in children with aplastic anemia. Our study also indicates that rhG-CSF will be particularly useful in managing patients with aplastic anemia complicated by bacterial or fungal infection.
 ...
PMID:Treatment of aplastic anemia in children with recombinant human granulocyte colony-stimulating factor. 199 1

Serum albumin, cholinesterase, and cholesterol were measured in ten patients with aplastic anemia and eight with myelodysplastic syndrome who received the administration of recombinant human GM-CSF. Serum albumin, cholinesterase, and cholesterol were significantly lowered by the administration of GM-CSF and recovered after the cessation of GM-CSF. These data suggest that GM-CSF impairs the biosynthesis of liver cells and that cholesterol-lowering activity of GM-CSF, which is previously reported, is due to the impairment of liver biosynthesis by GM-CSF.
 ...
PMID:GM-CSF-mediated impairment of liver to synthesize albumin, cholinesterase, and cholesterol. 199 59

The aim of the present study was to test the effect of cyclosporin A (CyA) in vitro on CFU-GM growth from patients with severe aplastic anemia (SAA). For this purpose, bone marrow (BM) cells from 9 SAA patients and 5 healthy individuals were incubated with or without CyA and then cultured for CFU-GM growth in the presence of exogenous recombinant human GM-CSF (30 ng/ml). SAA patients were tested before or after treatment with CyA, or after treatment with antilymphocyte globulin (ALG). In 3 patients responding to CyA, the addition of CyA in vitro enhanced colony growth from 13 +/- 10 to 40 +/- 20/10(5) BM cells (p = 0.01) - the median increment of colony formation was 2.4-fold. In 5 ALG responders, CyA produced no increment of CFU-GM growth (from 14 +/- 26 to 15 +/- 16/10(5) BM cells, p = 0.1). CyA did not enhance significantly CFU-GM growth in normal controls (from 57 +/- 45 to 58 +/- 81/10(5) BM cells, p = 0.9). In conclusion, it would appear that some patients with SAA can respond to CyA in vivo and in vitro, and ALG responders are not necessarily among these. This is in keeping with different mechanisms of action of CyA and ALG and possibly with the existence of distinct pathogenetic pathways in SAA.
 ...
PMID:Severe aplastic anemia (SAA): response to cyclosporin A (CyA) in vivo and in vitro. 201 76


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>