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Query: KEGG:D03343 (MDS)
 2,225 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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

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

Twenty-three patients with bicytopenia or pancytopenia were retrospectively studied. The patients with underlying disorders, blast count of more than 5% on bone marrow (BM) aspirate, blast count of more than 1% on peripheral blood or ringed sideroblast count of more than 15% on BM aspirate were excluded. According to Yoshida's criteria, 23 patients were classified into 6 subtypes [AA (aplastic anemia)1: typical AA, AA2: atypical AA, MDS (myelodysplastic syndrome)3: typical RA (refractory anemia, MDS4-6: atypical RA], and AA1 7 cases; AA2 2 cases; MDS3 5 cases; MDS4 1 case; MDS5 2 cases; MDS6 6 cases. To clarify the clinical features of atypical RA group (MDS4-6), we investigated ferrokinetics, RBC life span, karyotype, serum Epo (erythropoietin) concentration, response to therapy and prognosis. Results were as follows: 1) all three RA patients who were younger than 30 years old were included in atypical RA group, 2) in ferrokinetics study PID (plasma iron disappearance time) values of MDS4 and MDS6 patients ranged between those of AA1 and those of MDS3 patients (5 of 7 patients), 3) two cases who developed leukemia belonged to typical RA group, 4) patients with atypical RA showed response to therapy and their prognosis were better than those with typical RA. These observations suggest that atypical RA have different clinical features from typical RA.
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PMID:[Clinical features of atypical refractory anemia (RA)]. 194 25

Stem cell factor (SCF), the ligand of the c-kit receptor, is a potent enhancing cytokine for haematopoietic cells in the presence of IL-3, GM-CSF and erythropoietin (Epo). In the clonogenic assays of 63 MDS patients, the addition of rh-SCF + GM-CSF and/or IL-3 induced a significant increase (p < 0.001) in the number and size of CFU-GM. Never reaching the levels of controls, this increase was seen in all FAB subtypes, but particularly in RA. There was no significant increase in cluster formation, even in RAEB or RAEBt. Rh-SCF (10 ng/ml) led to mean increases of up to 26 times in the number of Epo-dependent BFU-E colonies, particularly in RA (p < 0.001) and RAEB (p < 0.05). Individual responses varied widely (especially in RA) from no response to supranormal levels. Added to the weekly refeed of 37 MDS LTBMC, SCF (10 ng/ml) induced only a 7% mean increase in both cell output and the number of clonogenic cells recovered in the supernatant. Immunohistochemical examination of the supernatant showed significant increases in differentiating myeloid cells in all examined cases, and in erythroid cells in 3 cases; blast cells increased in only 3 cases. These data suggest that rh-SCF is capable of at least partially reversing defective MDS myeloid haematopoiesis, and leads no overt risk of leukaemic transformation. Its potent effect on erythroid cells is encouraging for future clinical applications in patients, particularly if they are selected by means of in vitro tests.
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PMID:Effects of recombinant human stem cell factor (rh-SCF) on colony formation and long-term bone marrow cultures (LTBMC) in patients with myelodysplastic syndromes. 750 65

A novel long-term cultured interleukin (IL)-3-dependent human myelodysplastic cell line, MDS92, was shown to contain several myeloid-lineage cells such as neutrophils, macrophages, eosinophils, and a small number of megakaryocyte-lineage cells. Therefore this cell line possesses at least bipotential characteristics of myeloid- and megakaryocyte-lineages. Granulocyte colony-stimulating factor clearly promoted the neutrophil alkaline phosphatase activity of MDS92 cells. To the contrary, the incidence and growth of CD41-positive cells were hardly affected by the addition of IL-6, IL-11, c-mpl ligand (thrombopoietin, TPO) or erythropoietin. TPO slightly supported the growth of CD34-positive cell fraction, but not CD41-positive cell fraction of MDS92 cells in combination with IL-3 or Steel factor. This cell line will be a useful tool for the study of MDS stem cells, but the mechanism of commitment of differentiation in MDS stem cells remains unknown.
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PMID:A novel factor-dependent human myelodysplastic cell line, MDS92, contains haemopoietic cells of several lineages. 854 20

The use of recombinant erythropoietin for treatment of anemia in myelodysplastic patients has so far produced poorer results than expected. Most clinical studies have been conducted without any selection of patients. In the present study we report our experience with the use of rhEPO in a population of selected MDS subjects. Only patients affected by refractory anemia according to FAB criteria, without significant WBC and platelets reduction, with normal LDH and short history of disease were eligible for the study and were treated with rhEPO at a dosage of 150 mg/kg three times a week for 2 months. Among the 12 so treated patients, 7 (58.3%) achieved complete remission, 2 partial remission and 3 failed to respond. This high response rate makes more than acceptable the cost/benefit ratio for rhEPO in RA patients and may identify a subgroup of patients that can be treated successfully with rhEPO alone.
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PMID:A good response rate to recombinant erythropoietin alone may be expected in selected myelodysplastic patients. A preliminary clinical study. 859 97

Myelodysplastic syndromes [MDS] are clonal disorders of hematopoietic stem cells leading to a deregulation of proliferation and differentiation of the bone marrow cells. Clinically the patients present with symptoms and signs of anemia, thrombocytopenia, and neutropenia. About a third of the patients will develop acute myeloid leukemia. Supportive care is the mainstay of therapy in these mostly elderly patients. G-CSF should only be given in cases of neutropenia and infection, but not prophylactically. Selected patients with severe or transfusion-dependent anemia will respond to treatment with erythropoietin. In advanced MDS aggressive chemotherapy should be considered, while in patients below 50 years of age and an HLA-identical sibling donor allogeneic bone marrow transplantation is the treatment of choice.
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PMID:[Myeloproliferative syndromes]. 862 70

We measured pretreatment serum levels of tumour necrosis factor-alpha (TNF-alpha) and interleukin-1 beta (IL-1 beta) in 25 patients with myelodysplastic syndrome receiving recombinant human erythropoietin (rhEPO) at dosages up to 300 U/kg thrice weekly for 12 weeks. Both TNF-alpha and IL-1 beta levels were measured using commercially available enzyme-linked immunoassays. A complete response (CR) was defined as a rise in untransfused haemoglobin concentrations of at least 2 g/dl or a 100% decrease in RBC transfusion requirements over the treatment period; a partial response (PR) was an increase in untransfused haemoglobin values of 1-2 g/dl or a decrease in RBC transfusion requirements equal to or greater than 50%; no response (NR) was defined as a response less than a PR. After 12 weeks of rhEPO treatment, four patients showed a CR, five patients a PR, and 16 patients NR. Serum levels of both TNF-alpha (80.5 %/- 64.8 vs 8.1 +/- 4.2 ng/l, P < 0.001) and IL-1 beta (60.4 +/- 49.9 vs 8.9 +/- 4.7 ng/l, P < 0.001) were higher in MDS patients than in a group of 28 normal controls. Responders (CR + PR) showed significantly lower serum levels of TNF-alpha than non-responders (21.6 +/- 26.2 vs 106.3 +/- 60.8 ng/l, P < 0.001), whereas IL-1 beta concentrations between those who benefited from therapy and unresponsive cases were not significantly different (39.8 +/- 48.9 vs 73.4 +/- 48.2 ng/l, P = 0.120). It is noteworthy that TNF-alpha levels were within the normal range in all responsive patients but one, whereas all non-responders presented elevated cytokine concentrations. No relationship was found between TNF-alpha or IL-1 beta values and haemoglobin levels, transfusion requirement, serum EPO or ferritin concentrations. We conclude that pre-treatment TNF-alpha levels might help to select those MDS patients who are most likely to benefit from rhEPO treatment.
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PMID:Serum levels of tumour necrosis factor-alpha predict response to recombinant human erythropoietin in patients with myelodysplastic syndrome. 935 45

Immunoreactive serum erythropoietin (EPO) was measured in anemic and non-anemic patients with acquired non-severe aplastic anemia (AA; n = 22) and myelodysplastic syndromes (MDS; n = 31) receiving or not androgens to examine the effect of androgen therapy and anemia on EPO levels in these disorders. Soluble transferrin receptor (TfR) and absolute reticulocyte count (ARC) were also assayed in order to evaluate erythropoietic activity. AA and MDS patients were stratified for anemia and androgen treatment as follows: 12 untreated anemic patients; 17 anemic patients during androgen therapy; 14 non-anemic patients without any treatment (> 1 year); and 10 non-anemic patients on androgen therapy. Although EPO levels in non-anemic patients were significantly higher than in healthy controls (n = 29) no statistically significant differences in Hb and EPO values were found between non-anemic patients receiving or not androgen therapy. In the linear regression analysis between Hb and log EPO concentration, no statistically significant differences in the slopes between untreated and androgen-treated anemic groups nor between both groups and patients with iron deficiency anemia (n = 23) were observed. However, the y intercept (log EPO) of regression line was significantly higher in androgen-treated anemic patients than in the androgen therapy-free anemic group. Serum TfR levels were higher in treated than in untreated anemic patients, whereas ARC was not different between both groups. These data seemingly indicate that (1) androgens at pharmacological doses do not increase serum EPO levels in non-anemic AA and MDS patients, and (2) in patients with AA and MDS, androgen-driven EPO stimulation is appreciably enhanced by anemia.
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PMID:Effect of androgen therapy and anemia on serum erythropoietin levels in patients with aplastic anemia and myelodysplastic syndromes. 946 42

We present a case report of a 55-year-old male patient with hypoplastic myelodysplastic syndrome (MDS, refractory anemia) in which a good response to recombinant human erythropoietin (rhEPO) has been maintained for more than 60 months. There is with no evidence of progression to high risk MDS or acute leukemia, although he was predicted to be a low-responder to rhEPO therapy because of very high serum EPO levels (5,260 mU/ml), a history of multiple transfusions, chromosomal abnormalities (47,XY,+8) and severe thrombocytopenia. Since he received rhEPO with no adverse effects, it may be valuable to try rhEPO treatment at least one time for low-risk MDS patients, depending on red cell transfusion requirements.
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PMID:Sustained improvement in anemia with low-dose recombinant human erythropoietin therapy in a patient with hypoplastic myelodysplastic syndrome and chromosomal abnormalities. 961 55


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