Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0026986 (myelodysplastic syndrome)
 14,926 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Erythropoietin can be successfully used in the treatment of anaemia induced by chemotherapy and radiotherapy as well as for the treatment of anaemia induced by malignant disease without previous chemotherapy of radiotherapy. Erythropoietin administered during chemotherapy is effective in 50-70% patients, it has a more marked effect as a supplement to chemotherapy with cisplatinum and carboplatinum than non-platinum regimens. Erythropoietin reduces the consumption of red cell concentrates during chemotherapy on average by one half. Long-term administration of erythropoietin in anaemia caused by malignant disease alone proves most effective in multiple myeloma and in chronic lymphatic leukaemia or in non-Hodgkin lymphomas with a low malignity. The therapeutic responses defined as independence on transfusions and a rise of the haemoglobin level by at least 20 g/l, as compared with the pretreatment value, can be achieved in 60 to 80% of the patients. Erythropoietin is much less effective (10-20% therapeutic responses) in myelodysplastic syndrome, in myeloproliferative diseases or in aplastic anaemia. The authors give an account on the effectiveness of erythropoietin in different indications.
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PMID:[Erythropoietin in oncology. II. Evaluation of the effectiveness of erythropoietin in hematologic and oncologic diseases]. 876 96

Anemia is a frequent complication in hematologic malignancies. In advanced stages of chronic lymphocytic leukemia, non-Hodgkin's lymphoma, and myeloma, anemia usually develops in parallel with marrow involvement. However, anemia may occur in the absence of overt infiltration of bone marrow by malignant cells. When all other causes of anemia (such as chronic bleeding, vitamin deficiency, hemolysis, and pure red blood cell aplasia) are eliminated, anemia can be related to "anemia of chronic disorders." Myelodysplastic syndromes are characterized by cytopenias. Anemia is very frequent, and nearly 90% of patients present with anemia during the evolution of the disease. In this disorder, erythroid progenitors are defective for their proliferation and maturation, as shown by in vitro culture techniques. Moreover, these patients often have a high endogenous serum erythropoietin level. The rationale for treating these patients with epoetin alfa is the possibility of overcoming the defective proliferation by pharmacologic doses of epoetin alfa. The response rate was rather low with epoetin alfa alone. Combinations with earlier-acting cytokines, such as recombinant human granulocyte colony-stimulating factor, have been tested in an attempt to improve response rates.
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PMID:Update on the role of epoetin alfa in hematologic malignancies and myelodysplastic syndromes. 967 24

Epoetin alfa is being used to treat patients with symptomatic anemia of cancer and to prevent or postpone chemotherapy-induced anemia in cancer treatment. As only approximately 50% of unselected anemic cancer patients respond sufficiently to epoetin alfa treatment, careful patient selection according to reliable prediction criteria is of great importance. Predictions of response to epoetin alfa treatment are based either on the degree of blunted erythropoietin response to the anemic condition or on indicators of responsiveness during the early treatment phase. The most accurate predictions of responsiveness, however, are derived from combinations of predictive factors. Combinations of synergistically acting hematopoietic growth factors, particularly epoetin alfa and granulocyte colony-stimulating factor, are beneficial to selected patients with myelodysplastic syndrome and may prolong survival in certain cases. Correction of anemia in cancer patients is particularly important because highly significant correlations have been reported between hemoglobin levels and quality of life in these patients.
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PMID:Anemia of cancer patients: patient selection and patient stratification for epoetin treatment. 967 28

First used successfully to correct the anemia associated with chronic renal failure, epoetin alfa has been shown to be highly effective in many patients with either hematologic or nonhematologic malignancies. Multiple studies have demonstrated effective response rates, with increases in hemoglobin concentration and reduction or elimination of transfusion requirements in up to 75% or 80% in such patients. Nevertheless, as clinical experience has grown, several issues have arisen. First, not all cancer patients respond to epoetin alfa and, consequently, it is important to identify those patients most likely to respond to make early clinical decisions regarding dose adjustment or drug withdrawal. Second, experience in patients with renal failure has revealed a state of "functional iron deficiency" and, thus, highlighted the importance of iron supplementation to optimize the response to epoetin alfa. Does "functional iron deficiency" complicate epoetin alfa therapy of patients with the anemia of cancer, and could such patients benefit from iron supplementation? Finally, some hematologic malignancies, especially myelodysplastic syndromes, can be resistant to epoetin alfa monotherapy. Can the effective response rates in such patients be improved by combining epoetin alfa therapy with the administration of other hematopoietic growth factors? Epoetin alfa has made substantial contributions to the care of patients with cancer and, with time, additional uses for this very valuable drug will become apparent.
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PMID:Epoetin alfa: into the new millennium. 967 36

To evaluate the effect of recombinant human erythropoietin (rHuEpo) on the haemoglobin level and transfusion requirement in low-risk myelodysplastic syndromes (MDS), 87 patients were enrolled in a randomized double-blind placebo-controlled study, 44 patients were assigned to epoetin alpha (150 U/kg/d s.c. for 8 weeks) and 43 to placebo arms. MDS types were homogenous in both groups: refractory anaemia (RA) 47.7-48.8%. refractory anaemia with ringed sideroblasts (RAS) 20.5-25.6%, refractory anaemia with excess of blasts (RAEB) (blasts < 10%) 31.8-25.6%, 14/38 evaluable patients responded to epoetin alpha versus 4/37 to placebo (P=0.007). 50% of RA responded to epoetin alpha versus 5.9% to placebo (P=0.0072), RAS 37.5% v 18.2% (P=0.6) and RAEB 16.7% v 11.1% (P=1.00). 60% of non-pretransfused patients responded to epoetin alpha (Hb 8.35< or = 0.73 to 10.07+/-1.87 g/dl), whereas a slight decrease was observed in the placebo group (8.4+/-0.66 to 8.19+/-0.92 g/dl) (P=0.0004). Percentage of transfused patients was similar in both arms. Basal erythropoietin (Epo) serum levels > 200 mU/l predicted for a non-response. At week 4 sTfR levels were increased > 50% in responders (P=0.013), whereas an increase < 18% predicted for non-response (P=0.006). Leucocyte and platelet counts were not influenced by epoetin alpha treatment. Adverse events occurred in 31.8% of the rHuEpo-treated versus 42.99%) of the placebo-treated patients (P=0.2), and seven patients did not complete the course. In conclusion, rHuEpo was effective in the treatment of low-risk MDS. RA subtype, no transfusions prior to rHuEpo therapy, and low basal Epo levels were associated with higher probability of response. Soluble transferrin receptor level at the fourth week was an early predictor of response.
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PMID:A randomized double-blind placebo-controlled study with subcutaneous recombinant human erythropoietin in patients with low-risk myelodysplastic syndromes. 1046 Jun 28

The myelodysplastic syndromes (MDS) are a heterogeneous group of disorders characterized by peripheral blood cytopenias with a hypercellular bone marrow exhibiting dyspoiesis. The MDS range from those with a relatively indolent course (e.g., refractory anemia with or without ringed sideroblasts) to more aggressive disorders (e.g., refractory anemia with excess blasts [RAEB], and RAEB in transformation [RAEB-T]), which may exhibit a clinical course indistinguishable from acute myeloid leukemia (AML). Supportive care is the standard treatment for most patients, particularly those who are elderly, with the judicious use of blood components and antibiotics. For younger patients with RAEB and RAEB-T, antileukemic therapy might be considered, since the outcome is similar to that of patients with AML. Promising new chemotherapy agents currently in clinical trials include the topoisomerase I inhibitor, topotecan. The only curative treatment for MDS is allogeneic bone marrow transplantation, with long-term survival in approximately 40%, but with treatment-related deaths in 25%-40%. Factors predicting outcome include age, cytogenetics, number of blasts, and others. Myeloid growth factors (e.g., G-CSG, GM-CSF), increase the granulocyte count in most patients and may be useful in the setting of an active infection, although the prophylactic use of these agents does not improve survival. Erythropoietin increases the hematocrit in about 20% of patients. Growth factors being evaluated for their role in enhancing platelet counts include interleukin 11, stem cell factor, and megakaryocyte growth and development factor (thrombopoietin). Newer strategies to improve the outcome of patients with MDS should be based on an increased understanding of the biology of these disorders.
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PMID:The Myelodysplastic Syndromes. 1038 27

Ineffective erythropoiesis in myelodysplasia is characterized by a defect in erythroid progenitor growth and by abnormal erythroid differentiation. Increased apoptosis of erythroid, granulocytic and megakaryocytic lineages is thought to account for cytopenias. Erythropoietin (Epo)-induced BFU-E and CFU-E growth was studied in 25 myelodysplastic syndrome (MDS) marrow specimens and found to be drastically diminished. To investigate the functionality of Epo-R in MDS marrow, we focused on Epo-induced STAT5 activation. Epo was able to stimulate STAT5 DNA binding activity in all normal and 12/24 MDS marrows tested, with no correlation between the level of STAT5 activation and the development of erythroid colonies in response to Epo. In contrast, impaired proliferation of erythroid progenitors was related to an increased expression of the transmembrane mediator of apoptotic cell death Fas/CD95 on the glycophorin A+ subpopulation. Therefore we conclude that the stimulation of pro-apoptotic signals rather than the defect of anti-apoptotic pathways resulting from Epo-stimulated Jak2-STAT5 pathway, predominantly accounts for ineffective erythropoiesis in myelodysplasia.
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PMID:Ineffective erythropoiesis in myelodysplastic syndromes: correlation with Fas expression but not with lack of erythropoietin receptor signal transduction. 1046 Jun 7

The myelodysplastic syndromes (MDS) are a heterogenous family of hematologic disorders characterized by ineffective hematopoiesis. Because of the variability between patients regarding prognosis and morbidity related to the disease, consensus regarding the management of these patients has been difficult. Over the past several years, new prognostic scoring systems such as the International Prognostic Scoring System (IPSS) have attempted to provide a projection for long-term stability of the percentage of patients who have "low-grade" or indolent MDS. Unfortunately, its lack of prospective use in clinical trials and other settings has thus far failed to validate it as a functional decision-making tool. Thus, investigators have hypothesized that separating patients based on more simplistic treatment-oriented guidelines may be more efficient. For the majority of patients with MDS, no curative option exists. Patients who are young enough and have an available matched sibling or matched unrelated donor may undergo an allogeneic bone marrow transplant (BMT) with a potential cure rate of 30% to 50%. The major issue regarding this approach is the relatively high morbidity and the risk that the patient's lives may be shortened, that their quality of life will be worsened, or that no overall benefit will occur (relapse). Compounding the issue of selection and timing for BMT is the fact that the best results in terms of relapse-free survival appear to be in the subset of patients with early or low-grade MDS, characterized by refractory anemia with or without ringed sideroblasts. For these patients, lacking a donor for BMT, the major issue has become the consideration of induction chemotherapy. While dose-intensive chemotherapy may improve outcome in a small percentage of patients, the majority of elderly patients with MDS are not optimal candidates for such an approach. As a result, supportive care has a major role for patients with MDS and depending on the French-American-British (FAB) presentation and comorbid illnesses may be the preferred approach. Erythropoietin, a growth factor, is perhaps the most commonly used supportive care after transfusion. The use of colony-stimulating growth factors to support leukopenia is currently under investigation. The use of thrombopoietic agents has lagged behind in the management of MDS patients. Investigation of interleukin-6 (IL-6), a thrombopoietic cytokine, showed some ability to increase platelets through significant toxicity. Investigation of IL-11, an approved thrombopoietic growth factor, is preparing to start and should aid in determining its role in this setting.
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PMID:Advances in supportive care of myelodysplastic syndromes. 1053 Jul 13

This randomized, placebo-controlled trial was designed to assess the efficacy and safety of therapy with granulocyte-macrophage colony-stimulating factor (GM-CSF) and erythropoietin (epoetin alfa) in anemic, neutropenic patients with myelodysplastic syndrome. Sixty-six patients were enrolled according to the following French-American-British classification: refractory anemia (20), refractory anemia with excess blasts (35), refractory anemia with ringed sideroblasts (9), and refractory anemia with excess blasts in transformation (2). Patients were stratified by their serum erythropoietin levels (less than or equal to 500 mU/mL, n = 37; greater than 500 mU/mL, n = 29) and randomized, in a 2:1 ratio, to either GM-CSF (0.3-5.0 microg/kg.d) + epoetin alfa (150 IU/kg 3 times/wk) or GM-CSF (0.3-5.0 microg/kg.d) + placebo (3 times/wk). The mean neutrophil count rose from 948 to 3831 during treatment with GM-CSF +/- epoetin alfa. Hemoglobin response (increase greater than or equal to 2 g/dL, unrelated to transfusion) occurred in 4 of 45 (9%) patients in the GM-CSF + epoetin alfa group compared with 1 of 21 (5%) patients with GM-CSF + placebo group (P = NS). Percentages of patients in the epoetin alfa and the placebo groups requiring transfusions of red blood cells were 60% and 92%, respectively, for the low-endogenous erythropoietin patients and 95% and 89% for the high-endogenous erythropoietin patients (P = NS). Similarly, the average numbers of units of red blood cells transfused during the 12-week study in the epoetin alfa and the placebo groups were 5.9 and 9.5, respectively, in the low-endogenous erythropoietin patients and 9.7 and 8.6 in the high-endogenous erythropoietin patients (P = NS). GM-CSF +/- epoetin alfa had no effect on mean platelet count. Treatment was well tolerated in most patients, though 10 withdrew from the study for reasons related predominantly to GM-CSF toxicity. (Blood. 2000;95:1175-1179)
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PMID:Effect of recombinant human erythropoietin combined with granulocyte/ macrophage colony-stimulating factor in the treatment of patients with myelodysplastic syndrome. GM/EPO MDS Study Group. 1066 87

The myelodysplastic syndromes are a heterogeneous family of hematologic disorders characterized by ineffective hematopoiesis. Because of the interpatient variability regarding prognosis and morbidity, management of myelodysplastic syndromes continues to be a challenge to clinical hematologists. Pancytopenia and defective function of neutrophils and platelets carry a high risk of infectious or hemorrhagic complications. Erythropoietin is perhaps the most commonly used therapeutic option, second only to transfusion; improvement of erythropoiesis is seen in approximately 20% of patients, mainly in those with relatively preserved erythroid function and no or low transfusion requirements. Coadministration of erythropoietin with either granulocyte colony-stimulating factor or granulocyte-macrophage colony-stimulating factor may increase the response rate up to 50%. Although prophylactic administration of granulocyte- or granulocyte-macrophage colony-stimulating factor cannot be recommended, treatment of febrile neutropenia might benefit from administration of granulocyte- or granulocyte-macrophage colony-stimulating factor in addition to antibiotics.
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PMID:Cytokine therapy for myelodysplastic syndrome. 1078 52


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