Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0026764 (multiple myeloma)
 36,148 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The efficacy of recombinant human erythropoietin (r-HuEPO) in patients with multiple myeloma (MM) has been confirmed in several clinical trials. We report our experience of r-HuEPO treatment in 5 myeloma patients with renal failure. The therapy with r-HuEPO (Eprex, Janssen-Cilag or Recormon, Boehringer, Mannheim) was started after 4-8 months from diagnosis, the drug was administered intravenously (in one patient subcutaneously after cessation of hemodialysis treatment), two or three times weekly. The initial doses were 4-12,000 units/week (mean 8,400). In all patients good response during the first month of therapy was observed. Median Hb and hematocrit increased from 70 g/l and 20.8% to 87 g/l and 26% after 1 month and to 105 g/l and 30.3% after 4-6 months, respectively. The need for blood transfusion decreased significantly--from 2.72 TU/month to 0.13 TU/month. WHO performance status and patients self-assessment of quality of live improved substantially after r-HuEPO. No serious adverse events, including hypertension and/or thromboembolic events were observed. In accordance with some previous reports we conclude r-HuEPO is effective and safe treatment in patients with MM and renal failure. Moreover, lower doses of growth factor could be effective in this particular group of patients.
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PMID:[Effect of treatment with recombinant erythropoietin in patients with multiple myeloma and kidney failure]. 960 5

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

Recombinant human erythropoietin (EPO; epoetin) has been shown to be effective in improving anemia in a proportion of cancer patients. The response rate is approximately 60%, but varies considerably according to baseline hematocrit and transfusion needs, as well as the response criteria used. Response is not greatly influenced by the type of tumor, except in situations of major marrow involvement and limited residual hematopoiesis, or in the presence of specific mechanisms of anemia, such as hemolysis, splenomegaly, bleeding, hemodilution, or ineffective erythropoiesis. Stem cell damage by previous therapy as well as marrow suppression by current intensive chemotherapy can impair response. Besides its intensity, the type of chemotherapy may not be critical, although patients undergoing platinum-based chemotherapy may respond faster than those receiving non-platinum regimens. Complications, such as infections, bleeding, or nutritional deficiencies, may have a major negative impact on outcome. An important response-limiting factor is functional iron deficiency (ie, an imbalance between iron needs in the erythropoietic marrow and iron supply), which depends on the level of iron stores and its rate of mobilization. Functional iron deficiency is best monitored by the percentage of hypochromic red blood cells, and oral or intravenous iron supplements should be given when this percentage increases above 10%. All these factors explain why the response rate to epoetin is only approximately 60%. Therefore, it would be interesting to develop models that could help predict response to epoetin to help select the most appropriate cancer patients for this therapy. Few baseline parameters have been shown to be highly predictive of response in patients with solid tumors, although most studies in patients with myeloma or lymphoma have indicated that patients with a low baseline serum EPO level will respond better. Early changes after 2 to 4 weeks of treatment are also of great interest. Among these early changes, increments of soluble transferrin receptor, reticulocytes, and hemoglobin, as well as the persistence of elevated ferritin or EPO levels, have all shown some predictive value. Combination of baseline serum EPO and the 2-week increment of soluble transferrin receptor or hemoglobin may provide the best prediction of response.
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PMID:Prediction of response to optimize outcome of treatment with erythropoietin. 967 27

The key role of a blunted production of endogenous erythropoietin (EPO) in determining anemia of patients with multiple myeloma (MM) has been definitively established. Thus, several clinical trials have investigated the effects of recombinant EPO (r-EPO) in anemic MM patients. The results of these studies have demonstrated that r-EPO is a safe and effective drug, which results in an increase in Hb levels in the majority of treated patients. However, several factors, such as serum levels of endogenous EPO, severity of anemia, presence of normal erythroid progenitors, serum levels of some cytokines with inhibitory activity on erythroid function and previous treatments, may significantly affect the possibility of response, thereby suggesting the need for careful selection of MM patients for treatment with r-EPO.
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PMID:The role of recombinant erythropoietin for the treatment of anemia in multiple myeloma. 968 26

Recombinant human erythropoietin has been recently introduced as an important alternative for treatment of anaemia in multiple myeloma and non-Hodgkin's lymphoma. In the present paper we review the basis for its use in the anaemia of both entities, and the most relevant clinical trials showing the effect of erythropoietin. In MM patients the response rate (assessed by an increase of at least 2g/dl in the Hb level) ranges between 60%-80% while in NHL patients it ranges from 50% to 61%. The most appropriate EPO dose is around 5000 units per day, which is equivalent to 150 u/kg, three times per week. In addition, this review provides tools to decide the best candidates for this treatment and a guideline to monitor its efficacy.
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PMID:Recombinant human erythropoietin in the anaemia of multiple myeloma and non-Hodgkin's lymphoma. 978 34

The anaemia associated with cancer can be effectively treated with recombinant human erythropoietin (rHuEpo) in about 60% of the patients. However, the response rate varies according to treatment modalities as well as the response criteria used. A number of disease- or chemotherapy-related factors determines the probability of response. Several specific mechanisms of anaemia, such as haemolysis, splenomegaly, bleeding, haemodilution, or ineffective erythropoiesis can seriously interfere with response. However, the type of tumor, in particular haematologic versus non-haematologic, is not critical, except in situations of major marrow involvement and limited residual haematopoiesis. Stem cell damage by previous therapy, reflected by low platelet counts or high transfusion needs, will impair response. In addition, marrow suppression by current intensive chemotherapy will also have a negative impact. Besides its intensity, the type of chemotherapy may not be critical, although patients undergoing platinum-based chemotherapy may respond faster than those receiving non-platinum regimens. Complications such as infections, bleeding or nutritional deficiencies may have a major negative impact on outcome. An important response-limiting factor is functional iron deficiency, i.e. an imbalance between iron needs in the erythropoietic marrow and iron supply, which depends on the level of iron stores and its rate of mobilisation. Therefore, oral or preferably intravenous iron supplements should be given when serum ferritin is below 40-100 micrograms/l, reflecting the absence of iron stores, or when the percentage of hypochromic red cells rises above 10%, indicating functional iron deficiency even in the presence of adequate storage iron. Because up to 40% of the patients will not respond to rHuEpo, it is of utmost importance to develop models that could help predict response to rHuEpo and thus select the most appropriate cancer patients for this therapy. Most studies of patients with myeloma or lymphoma have indicated that patients with a low baseline serum Epo level will respond better, but this is not true of patients with solid tumors. Also of considerable interest are early changes of erythropoietic parameters after 2 to 4 weeks of treatment, including increments of serum transferrin receptor (sTfR), reticulocytes and haemoglobin, as well as the persistence of elevated ferritin or Epo levels. Combination of baseline serum Epo and the 2-week increment of sTfR or haemoglobin may provide the best prediction of response.
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PMID:Prediction of response to treatment with recombinant human erythropoietin in anaemia associated with cancer. 978 36

Many patients with solid tumours or haematological malignancies develop anaemia, and the use of chemotherapy aggravates this condition. Red blood cell transfusions are often necessary but are associated with many risks, including immunosuppressive effects that may increase the risk of tumour recurrence. Many clinical studies have shown that epoetin (recombinant human erythropoietin) therapy can ameliorate, or even prevent, the anaemia associated with chemotherapy and cancer (including solid tumours as well as multiple myeloma or lymphoma). Response, defined as a significant (>50%) reduction in the rate of transfusions and/or a significant (>2 g/dl) elevation of haemoglobin levels, is usually observed in about 60% of the patients, irrespective of the type of standard chemotherapy given. The decrease in transfusion requirements is the major objective of epoetin therapy, because they are costly, inconvenient and are associated with potential adverse effects. Epoetin therapy also brings about substantial improvements in various indices of quality of life that are proportional to changes in haemoglobin level. However, large dosages of epoetin are generally required and about 40% of patients do not respond even to very high dosages. A number of adverse effects of epoetin therapy have been observed in patients with renal failure. The most prominent include hypertension, headaches, seizures and thrombotic events. These complications can also occur in patients with renal failure who are not receiving epoetin. Their exact incidence has been assessed in placebo-controlled studies, which have demonstrated that there is no increased risk of thrombosis or seizure with epoetin. However, it is now generally accepted that 10 to 20% of haemodialysis patients will experience an elevation of blood pressure because of epoetin and there is no doubt that a rapid elevation of blood pressure may cause generalised seizures. In other settings, including anaemia associated with cancer, very few adverse effects have been attributed to epoetin. However, close monitoring of blood pressure should be implemented in patients with hypertension. There is no evidence that epoetin stimulates tumour growth. With the dosages of epoetin currently used, there is no evidence of stem cell competition, resulting in thrombocytopenia or neutropenia, or of stem cell exhaustion, producing secondary anaemia when treatment is stopped. Epoetin is a remarkably well tolerated drug that offers significant benefits in patients with cancer.
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PMID:A risk-benefit assessment of epoetin in the management of anaemia associated with cancer. 980 42

We describe two patients admitted to our hospital because of renal failure. We diagnosed multiple myeloma in both. One patient had high peripheral blood eosinophilia, that normalized during therapy. The patients were treated with melphalan and prednisone, hemodialysis and one patient with recombinant human erythropoietin. Both patients responded to that treatment: after 7 months the number of plasma cell in bone marrow decreased from 65 to 10% in the first patient, and from 38 to 4% in the second patient. They returned to work and were on maintenance hemodialysis 2 times weekly. The patients have been observed for 21 months.
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PMID:[Multiple myeloma nephropathy as a cause of renal failure--diagnostic difficulties and prospects for treatment]. 1033 31

Anemia, a decreased oxygen-carrying capacity of the blood, develops frequently in patients with end-stage renal disease (ESRD) or cancer. Given the wide variation in clinical response to erythropoietin in the treatment of anemia associated with these diseases, 2 meta-analyses of its effectiveness were undertaken. Databases (MEDLINE and International Pharmaceutical Abstracts) were searched to identify relevant articles. Search terms included erythropoietin, anemia, end-stage renal disease, cancer, multiple myeloma, and myelodysplastic syndrome. Searches were limited to human subjects and the English language. Reference lists of identified articles were reviewed for further articles of interest. The primary author (W.A.M.) selected the articles, and 2 researchers, working independently, extracted the necessary data. Articles had to meet the following criteria to be included in the meta-analyses: (1) Articles must have dealt with treatment of subjects with documented anemia. (2) Studies must have been original research with sample size > or =10. (3) Abstracts could be included if the full research manuscript was unavailable. (4) Patients could not be concurrently receiving other growth factors. (5) The quality of the selected articles must have been assessed by 2 independent researchers. A clinical response to erythropoietin was defined as a 0.06 increase in hematocrit or a 20 g/L increase in hemoglobin. Thirty-nine of the 76 identified articles were included in the meta-analyses. The effectiveness of erythropoietin was calculated at 87% for ESRD, 79% for multiple myeloma, 40% for solid tumor cancer, and 13% for myelodysplastic syndrome. Both subgroup and sensitivity analyses were performed.
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PMID:Meta-analyses of the effectiveness of erythropoietin for end-stage renal disease and cancer. 1050 43

Despite considerable progress in recent years in the understanding of the biology of multiple myeloma (MM), this disease remains incurable, although many new therapeutic approaches are under evaluation. The rapid development of recombinant technologies has permitted the production of large amounts of cytokines and growth factors, favoring the use of biotherapies also in this disease. Among these products, the interferons have been the most extensively used in clinical trials, giving the most promising results especially in the setting of minimal residual disease, as maintenance therapy after response to conventional therapies, or to high dose chemotherapies followed by bone marrow (BM) or peripheral blood stem cell (PBSC) transplantation. However, more recently, a large number of cytokines and growth factors have been introduced in the clinical practice. Data of the use of erythropoietin have consistently demonstrated the role of this growth factor in ameliorating the grade of anemia as well as the quality of life of those MM patients whose disease is complicated by the presence of a severe or moderate anemia. Using hematopoietic growth factor in the mobilization of PBSC, the quantity of progenitor cells in the peripheral blood increased and the hematological toxicity of chemotherapy could be reduced. Despite the large amount of experimental data indicating a role for interleukins, as IL-2 and IL-6, in controlling tumor growth, there are only few clinical studies dealing with their use in MM. Results show that they arrest tumor progression rather than aid tumor regression, for this reason it appears that IL-2 and anti IL-6 antibodies should be investigated as maintenance therapy, in MM patients responding to chemotherapy. In the future it will be necessary to clarify for MM patients the role of other cytokines such as IL-1 beta and TNF alpha. A possible strategy to improve the clinical outcome of MM patients is to prevent the regrowth of residual tumor cells by establishing adoptive immunity at the stages of minimal residual disease previous obtained using chemotherapy. To this end a possible strategy is to induce an immune response against residual tumor cells by passive (using monoclonal antibodies) or active (using the idiotype expressed by malignant cells) immunotherapy.
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PMID:[The role of biotherapy in multiple myeloma]. 1107 35


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