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Query: UMLS:C0026986 (myelodysplastic syndrome)
 14,926 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Chromosomes of bone marrow cells obtained from nine patients with myelodysplastic syndrome (MDS) were assessed after in vitro co-culture (48 hours culture) with recombinant human granulocyte colony-stimulating factor (rhG-CSF), recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF), or recombinant human erythropoietin. Three of the nine MDS cases showed no cytogenetic abnormalities with or without any recombinant human hematopoietic growth factors; one MDS patient with a t(3;4) did not show any change in the proportion of cells with this cytogenetic change. The remaining five cases exhibited changes in the frequency of subclones after the treatment. An increasing number of metaphase cells with less complex chromosome abnormalities was observed in two of the five cases by treatment with rhG-CSF; one of them also showed an increasing number of cells with normal karyotypes. After rhGM-CSF treatment, cells with nonclonal hyperdiploid abnormalities appeared in one MDS patient. After erythropoietin treatment, an increasing number of cells with a prototypic change was observed in one MDS patient, whereas one patient showed an increasing number of cells with an additional chromosome abnormality. These observations indicate that hematopoietic growth factors possibly modify the constitution of marrow cells with multiple chromosome abnormalities and the degree is different in each MDS patient. Furthermore, a chromosome analysis using an in vitro culture system with human recombinant hematopoietic growth factors may be able to detect metaphase cells with additional chromosome abnormalities in some MDS patients.
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PMID:In vitro cytogenetic effects of recombinant human hematopoietic growth factors on cells derived from myelodysplastic syndromes. 169 82

The effects of four recombinant hemopoietic growth factors (HGF) and of the impure factor HTB9 on proliferation and maturation of marrow myeloid (CFU-GM) and erythroid (BFU-E) progenitor cells were studied in 22 cases of myelodysplastic syndromes (MDS). In most cases, IL-3, GM-CSF and G-CSF increased significantly the number of myeloid colonies, the best combination being IL-3 + GM-CSF. A significant increase in the myeloid colony/cluster ratio was also noted, but cytological examination of colony cells showed little maturation. The analysis of myeloid colony surface markers with four monoclonal antibodies (to CD13, CD15, CD33 and CD34) showed minor modifications with an increase of CD13 and CD15 in about one third of cases when compared to control without HGF. Erythroid colonies were obtained in one case with erythropoietin alone, and in 19 cases with the addition of GM-CSF and/or IL-3. In short-term liquid cultures, IL-3, GM-CSF and G-CSF increased 3H-thymidine incorporation. We conclude that progenitor cells of most MDS are able to proliferate in the presence of HGF, with wide case-to-case variations. However, the pattern of growth remains abnormal when compared to normal marrow. Although the combination of IL-3 and GM-CSF is the most efficient, there is a large overlap in the stimulating effects of all factors studied.
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PMID:In vitro effects of recombinant hemopoietic growth factors on progenitor cells from patients with myelodysplastic syndromes. 170 6

Hematopoietic growth factors have now been purified, cloned, and produced in bacteria and yeast. Those that are currently in clinical study include erythropoietin, GM-CSF, G-CSF, M-CSF (also called CSF-1), and multi-CSF (also called interleukin 3). Growth factor appear likely to enhance the recovery and function of circulating white cells after standard-dose cancer therapy and high-bone-dose cancer therapy with marrow transplant and to restore leukocyte numbers and competence in the acquired immune deficiency syndromes and myelodysplastic syndromes. Phase I, II trials in AIDS, in cancer patients receiving chemotherapy, in cases of myeloproliferative disease, and after bone marrow transplant have been published. The results of phase III studies are just becoming available.
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PMID:G-CSF and GM-CSF in clinical trials. 170 37

The serum erythropoietin (EPO) concentration in patients with myelodysplasia (MDS) varies widely at similar hemoglobin concentrations, although the reasons for this variation are unclear. We have studied the pharmacokinetics of an i.v. bolus of recombinant human EPO in ten subjects with myelodysplasia. Basal serum EPO concentration varied from 210 to 5984 mU/ml. Plasma half-time clearance (t1/2) varied from 3.9 to 20.0 h. A significant positive correlation was found between t1/2 and basal EPO concentration. An increase in immature peripheral blood reticulocytes was found on days 1 and 2 after EPO treatment; this may represent either an effect on hemopoiesis or on reticulocyte release from the bone marrow.
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PMID:The clearance of a single i.v. bolus of recombinant human erythropoietin from the serum of patients with myelodysplastic syndromes and its effects on erythropoiesis. 171 88

In the paper the role of interleukin-3, granulocyte-macrophage colony stimulating factor (GM-CSF), granulocyte-colony stimulating factor (G-CSF) and macrophage colony stimulating factor (M-CSF), in the proliferation and differentiation of haemopoietic cells and pathogenesis of leukaemia are reviewed. Role of erythropoietin, thrombopoietin and other thrombopoiesis-stimulating factors in the development of hematopoietic is presented. Potential applications of recombinant haemopoietic growth factors in the treatment of myelodysplastic syndromes. AIDS and other haematologic, infections and neoplastic disorders are also discussed.
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PMID:[Hematopoietic growth factors]. 172 24

We have used recombinant human erythropoietin (rHuEPO) in a phase I/II clinical trial to evaluate its ability to reverse refractory anemia in hematologic disorders. rHuEPO was administered subcutaneously 5 days per week at escalating doses (50 to 150 U/kg per day). The aim of treatment was a hemoglobin (Hb) level greater than or equal to 10 g/dL without blood transfusion. Of 25 patients treated, 17 were evaluable, most of them with a regular need for transfusion. Eight of these had lymphoproliferative disorders (three cases of malignant lymphoma and five of monoclonal gammopathy) and were exposed to cytotoxic therapy. The other nine patients had hematopoietic stem cell disorders (four cases of myelodysplastic syndrome, three of idiopathic myelofibrosis, and two of chronic myelogenous leukemia). All patients with lymphoproliferative disorder had serum EPO levels inappropriately low for the degree of anemia, while patients with stem cell disorder showed variable values. Erythroid marrow activity was inadequate in all cases. Seven of eight patients with lymphoproliferative disorder responded to treatment maintaining Hb above 10 g/dL without transfusion. The median dose of rHuEPO required for correction of anemia was 75 U/kg. In four cases response was maintained with 50 U/kg, three times per week. There was no complete response among patients with hematopoietic stem cell disorder, although transfusion requirement was eliminated or reduced in four cases. Four patients developed functional iron deficiency during rHuEPO treatment and required iron supplementation to obtain response. Aggravation of splenomegaly was observed in two cases of myeloproliferative disorder. We conclude that: (1) subcutaneous administration of rHuEPO can be effective and safe in patients with lymphoproliferative disorder exposed to chemotherapy and showing inappropriate EPO response to anemia; (2) this is less likely in hematopoietic stem cell disorders, although favorable responses may be observed in occasional patients; and (3) functional iron deficiency as a cause of nonresponse to rHuEPO is frequent also in nonrenal anemia.
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PMID:Subcutaneous erythropoietin for treatment of refractory anemia in hematologic disorders. Results of a phase I/II clinical trial. 163 33

The clinical and ferrokinetic effects of escalating doses of subcutaneously administered recombinant human erythropoietin (rh-EPO) were studied in ten patients with myelodysplastic syndromes and severe transfusion-dependent anemia. Red blood cell transfusion requirements diminished in four patients, and one of the patients eventually became transfusion independent with an EPO-induced rise of Hb from 7.7 g/dl to 12.3 g/dl. Endogenous serum levels of EPO were significantly increased in all patients (100-5700 mU/ml), but three of four responders had a relatively low baseline level. The effective red cell iron turnover (RCIT) improved in two responding patients and even normalized in one patient. This increase in RCIT was accompanied with a decline in the ineffective red cell iron turnover (IIT). The other responding patients had a relatively preserved RCIT before EPO treatment. EPO therapy further increased the fraction of IIT in the latter patients. Red cell survival time did not increase during EPO therapy, even in the responding patients. One transient and one maintained increase in platelet count were observed. Disease progression with a sustained increase in blast cells in one patient and a transient elevation of blasts in another patient was seen. No other side effects of EPO therapy were observed. These results suggest that anemic MDS patients with low serum EPO levels and relatively spared effective erythropoiesis as measured by ferrokinetic studies may be the best candidates for treatment with recombinant human EPO.
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PMID:Recombinant human erythropoietin for the treatment of anemia in the myelodysplastic syndromes: a clinical and erythrokinetic assessment. 173 54

The serum concentration of erythropoietin in 79 cases with various blood diseases, uremia, chronic obstructive pulmonary disease etc was determined. At comparable degrees of anemia, patients with myelodysplastic syndrome and aplastic anemia had the highest levels of erythropoietin in our study. The high level of erythropoietin titer in patients with aplastic anemia should be taken as the nom for renal synthesis and release of this hormone. The erythropoietin level in patients with uremic anemia was lower than the level in patients with anemia of other causes but still higher than that of the normal controls. Patients suffering from polycystic kidney disease with or without uremia had a high level of erythropoietin due to local hypoxia of remnant kidney tissue resulting from the pressure of cystic formation. Different methods are used to determine the erythropoietin level, which varies with the stage and etiology of the diseases. There are other stimulating or inhibitory factors of erythropoiesis when the assay is processed. Transfusion and administration of certain drugs also influence the growth of erythroid cells, thus the serum titers of erythropoietin differed markedly between patients at comparable hemoglobin concentration.
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PMID:[The difference of erythropoietin concentration in various disease]. 175 56

12 patients with myelodysplastic syndromes were treated with recombinant human erythropoietin (r-epo). 5 patients had stable anemia, 78-92 g/l, and 7 were transfusion-dependent. In 11 patients, r-epo was given intravenously three times a week, with dose escalation after 4 and 8 wk if hemoglobin did not increase more than 15 g/l. The doses were 600, 1500 and 3000 U/kg bodyweight/wk. The 12th patient was treated subcutaneously with a dose of 560 U/kg/wk. 3 patients showed a significant response with an increase in hemoglobin of greater than or equal to 15 g/l. 2 of these had stable anemia before treatment and increased in hemoglobin from 87 to 116 g/l and from 80 to 99 g/l, respectively. The 3rd patient was transfusion-dependent and rose to a stable hemoglobin level between 76 and 80 g/l without transfusions. 2 patients showed a reduction of their transfusion need. Mean initial serum erythropoietin in the responding group was 366 U/l compared to 1049 among the non-responders (p = 0.367). Response was observed in 5/7 patients without bone marrow sideroblasts and in 0/5 patients with sideroblasts (p = 0.027). Erythropoietin seems to be an effective and well-tolerated treatment for a certain proportion of patients with MDS. A larger patient material might provide a model for predicting responses.
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PMID:Treatment of myelodysplastic syndromes with recombinant human erythropoietin. 176 Nov 22

Erythropoietin is a glycoprotein hormone that plays a vital role in erythropoiesis. It is mainly produced in the fetal liver till the third trimester of pregnancy. At that point, the kidney interstitium takes over this function and becomes the main source of erythropoietin. Hypoxia stimulates erythropoietin production by a mechanism that may require a heme protein as a second messenger. Erythropoietin stimulates the maturation of erythroid precursors (colony-forming unit-erythroid and burst-forming unit-erythroid) via at least two types of cell surface receptors. The higher-affinity receptors appear to be more important in modulating the effects of erythropoietin in vivo. Changes in intracellular calcium may ultimately mediate the action of erythropoietin on erythroid precursors. A specific and sensitive radioimmunoassay is now available for accurately measuring erythropoietin levels. All forms of erythrocytosis except polycythemia vera are associated with elevated erythropoietin levels. Levels are also high in cord blood obtained following fetal asphyxia. Reduced levels are seen in patients with anemia due to renal diseases. The response of erythropoietin to the degree of anemia appears to be attenuated in patients with cancer, chronic diseases, and human immunodeficiency virus (HIV) infection. Erythropoietin has been successfully used for treating patients with anemia due to renal failure. Its use has also been approved for the treatment of anemia patients receiving zidovudine for HIV infection. Encouraging results have been observed when erythropoietin was used to treat anemia due to rheumatoid arthritis, hematological malignancies, and prematurity. It has also been used to increase the yield of autologous blood collected prior to an elective surgical procedure. However, it has not proved to be useful in sickle cell anemia and myelodysplastic syndromes.
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PMID:Erythropoietin. Biology and clinical applications. 178 66


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