UMLS:C0026764 - FACTA Search

Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Target Concepts:

Query: UMLS:C0026764 (multiple myeloma)
36,148 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In this review, the pathophysiology and treatment of the anemia of multiple myeloma will be examined. While the anemia of cancer has multiple causes, an important component is labeled the "anemia of chronic disease" which is characterized by the combination of a shortened erythrocyte survival with failure of the bone marrow to increase red cell production in compensation. Depressed erythropoiesis is itself related to a combination of factors, including impaired availability of storage iron, inadequate erythropoietin response to anemia, and overproduction of cytokines which are capable of inhibiting erythropoiesis. These cytokines are involved in the retention of iron in the reticuloendothelial system, gastrointestinal tract and hepatocytes, may interfere with erythropoietin production by the kidney, and may exert direct inhibitory effects on erythroid precursors. While overproduction of several such cytokines, including IL-6, IL-1 and TNF-alpha, has been definitely demonstrated in multiple myeloma patients, it is still unclear whether they are directly involved in the pathogenesis of the anemia which develops. Although several mechanisms, such as hemodilution, bleeding, and decreased red cell survival operate, the anemia is mostly caused by defective erythropoietic activity. This in turn is partly explained by inadequate erythropoietin (Epo) production even in some patients without renal impairment. Based on measurements of serum erythropoietin and transferrin receptor, the distinction between marrow unresponsiveness to normal Epo stimulation and deficient Epo production is important for the treatment of the anemia of multiple myeloma with recombinant human Epo. Higher doses would probably be necessary if adequate Epo production is present, whereas only replacement therapy with lower doses may be sufficient when Epo production has been shown to be inappropriate.
...
PMID:Erythropoiesis and erythropoietin in multiple myeloma. 852 47

Previous phase I-II clinical trials have shown that recombinant human erythropoietin (rHuEpo) can ameliorate anemia in a portion of patients with multiple myeloma (MM) and non-Hodgkin's lymphoma (NHL). Therefore, we performed a randomized controlled multicenter study to define the optimal initial dosage and to identify predictors of response to rHuEpo. A total of 146 patients who had hemoglobin (Hb) levels < or = 11 g/dL and who had no need for transfusion at the time of enrollment entered this trial. Patients were randomized to receive 1,000 U (n = 31), 2,000 U (n = 29), 5,000 U (n = 31), or 10,000 U (n = 26) of rHuEpo daily subcutaneously for 8 weeks or to receive no therapy (n = 29). Of the patients, 84 suffered from MM and 62 from low- to intermediate-grade NHL, including chronic lymphocytic leukemia; 116 of 146 (79%) received chemotherapy during the study. The mean baseline Hb level was 9.4 +/- 1.0 g/dL. The median serum Epo level was 32 mU/mL, and endogenous Epo production was found to be defective in 77% of the patients, as judged by a value for the ratio of observed-to-predicted serum Epo levels (O/P ratio) of < or = 0.9. An intention-to-treat analysis was performed to evaluate treatment efficacy. The median average increase in Hb levels per week was 0.04 g/dL in the control group and -0.04 (P = .57), 0.22 (P = .05), 0.43 (P = .01), and 0.58 (P = .0001) g/dL in the 1,000 U, 2,000 U, 5,000 U, and 10,000 U groups, respectively (P values versus control). The probability of response (delta Hb > or = 2 g/dL) increased steadily and, after 8 weeks, reached 31% (2,000 U), 61% (5,000 U), and 62% (10,000 U), respectively. Regression analysis using Cox's proportional hazard model and classification and regression tree analysis showed that serum Epo levels and the O/P ratio were the most important factors predicting response in patients receiving 5,000 or 10,000 U. Approximately three quarters of patients presenting with Epo levels inappropriately low for the degree of anemia responded to rHuEpo, whereas only one quarter of those with adequate Epo levels did so. Classification and regression tree analysis also showed that doses of 2,000 U daily were effective in patients with an average platelet count greater than 150 x 10(9)/L. About 50% of these patients are expected to respond to rHuEpo. Thus, rHuEpo was safe and effective in ameliorating the anemia of MM and NHL patients who showed defective endogenous Epo production. From a practical point of view, we conclude that the decision to use rHuEpo in an individual anemic patient with MM or NHL should be based on serum Epo levels, whereas the choice of the initial dosage should be based on residual marrow function.
...
PMID:Recombinant human erythropoietin in the anemia associated with multiple myeloma or non-Hodgkin's lymphoma: dose finding and identification of predictors of response. 854 33

Multiple myeloma is very frequently associated with anaemia which has the character of hypo-proliferative anaemia of chronic diseases. In this type of anaemia the erythropoietin formation is frequently inadequate. According to data in the literature pharmacological doses of erythropoietin lead to an increase of the haemoglobin concentration in blood. Erythropoietin (Eprex Cilag) was administered to 11 patients whose haemoglobin concentration was lower than 100 g/l. The results from 10 patients were finally evaluated. During the first month all patients were given erythropoietin - 150 U/kg three times per week. Unless during the first month of treatment the haemoglobin concentration increased by 10 g/l, the dose was doubled to 300 U/kg. In patients where the haemoglobin value had risen above 120 g/l, the authors assessed an individual maintenance dose. In case three-month erythropoietin treatment did not lead to an increase of haemoglobin by 20 g/l as compared with the baseline value, erythropoietin administration was discontinued. The haemoglobin concentration increased by 20 g/l in a total of 8 (80%) of 10 evaluated patients. In all five patients where the haemoglobin concentration increased by 20 g/l during the first month, the endogenous erythropoietin concentration was less than 60 U/l. In another three patients the mentioned therapeutic response was recorded only during the 2nd or 3rd month of treatment after the erythropoietin dose had been increased. These three patients had higher baseline concentrations of endogenous erythropoietin, 100 to 350 U/l. During treatment no undesirable effects of erythropoietin were observed. Erythropoietin is a useful drug for anaemic patients with the diagnosis of multiple myeloma. According to the results of the authors work and data in the literature it is obvious that in patients with endogenous serum erythropoietin below 100 U/l a rapid riae of haemoglobin can be observed already during the first month. Patients with a higher baseline concentration of endogenous erythropoietin (100 to 500 U/l) respond less frequently to treatment and larger doses of erythropoietin must be administered. In patients with an erythropoietin value above 500 U/l there is a minimal probability that a response will be produced.
...
PMID:[Evaluation of treatment of anemia with erythropoietin in patients with multiple myeloma]. 855 96

6 patients with anaemia associated with myeloma multiplex were treated with human recombinant erythropoietin (rHuEPO, Exprex*) at a dose of 150 units/kg s.c. three times a week for 12 weeks. A good response, defined as an increase of hemoglobin > 20 milligrams above the pretreatment level, was achieved in 4 patients. The erythropoietin serum concentration was measured four times in each patient: twice before commencing and twice after completing the treatment. In patients who responded to rHuEPO therapy the Epo serum concentration decreased whereas in non-responders increased.
...
PMID:[The level of erythropoietin in patients with anemia and myeloma multiplex treated with erythropoietin]. 859 50

One hundred twenty-one anemic, transfusion-dependent patients with multiple myeloma (MM) or low-grade non-Hodgkin's lymphoma (NHL) were randomly allocated to receive (a) recombinant human erythropoietin (rhEPO) 10,000 U/d subcutaneously 7 days a week (fixed dose group) (n = 38), or (b) rhEPO 2,000 U/d subcutaneously for 8 weeks followed by step-wise escalation of the rhEPO dose (titration group) (n = 44), or (c) no rhEPO therapy (control group) (n = 39). The total treatment period was 24 weeks. There were no differences between the three groups with regard to baseline clinical, demographic, or health status measures. The cumulative response frequency, defined as elimination of the transfusion need in combination with an increase in the hemoglobin concentration by >20 g/L, was 60% in both rhEPO treatment groups and 24% in the control group (P = .01 and .02, respectively, log rank test). For patients in the titration group the response rate on the first dose level (2,000 U/d) was only 14%. Cox's univariate regression analysis revealed that an inadequately low endogenous erythropoietin concentration in relation to the degree of anemia and a baseline platelet concentration > or = 100 x 10(9)/L were significant predictors for response to rhEPO therapy (P < .01). Multivariate regression analysis showed that relative erythropoietin concentration was the most important factor and the platelet count had no additional influence on response. Treatment with rhEPO was well tolerated. We conclude that treatment with rhEPO may be indicated in anemic MM and NHL patients with a relative erythropoietin deficiency. An initial dose of 5,000 U/d subcutaneously may be recommended.
...
PMID:Recombinant human erythropoietin in transfusion-dependent anemic patients with multiple myeloma and non-Hodgkin's lymphoma--a randomized multicenter study. The European Study Group of Erythropoietin (Epoetin Beta) Treatment in Multiple Myeloma and Non-Hodgkin's Lymphoma. 863 83

The Norwegian Society of Haematology has worked out guidelines for the use of granulocyte-colony stimulating factor and granulocyte-monocyte colony stimulating factor and interferon alpha in clinical haematological practice. We recommend not using growth factors as a routine to prevent or to treat fever in patients with granulocytopenia induced by cytostatics, or patients with myelodysplastic syndromes. At present such treatment should be restricted to clinical trials. The same conclusion was reached in regard to use of erythropoietin in the case of myelodysplastic syndromes. Harvesting of stem cells from peripheral blood is a well documented indication for administration of growth factors. Interferon alpha as maintenance treatment for cases of multiple myeloma and low grade malignant lymphoma delays progression of the disease but does not improve chance of survival. There is no documentation of improved quality of life. Use of interferon alpha is not justified as a routine treatment for multiple myeloma. In chronic myelogenous leukemia, interferon alpha seems to be equal to or better than hydroxyurea, and may be considered for patients who cannot undergo allogeneic bone marrow transplantation.
...
PMID:[Treatment with growth factors and cytokines in hematologic diseases]. 880 16

The pathogenesis of the anemia of cancer involves the combination of a shortened erythrocyte survival in circulation with the failure of bone marrow to increase red cell production in compensation. Inappropriate red cell production is itself related to a conjunction of factors, including impaired availability of reticuloendothelial storage iron, inadequate erythropoietin (Epo) response to anemia, and overproduction of cytokines which are capable of inhibiting erythropoiesis. Many of these cytokines may interfere with erythropoietin production by the kidney. Consequently inadequate serum erythropoietin levels are often encountered in cancer patients, though more frequently in those with solid tumors or multiple myeloma than in those with other hematologic malignancies. There is little evidence supporting a negative impact of chemotherapy, including cisplatin, on erythropoietin production. Rather, chemotherapy usually causes a transient elevation of serum Epo. Red cell transfusions are often administered to cancer patients, possibly resulting, among other deleterious effects, in enhancement of tumor growth. Recombinant human erythropoietin (rHuEpo) has thus been proposed as an alternative. RHuEpo has been shown to be safe and effective in correcting the anemia of cancer and reducing the need for transfusions. The response rate is as good in hematologic malignancies as in solid tumors, but it is extremely poor in those with myelodysplastic syndromes. The effect of rHuEpo does not differ among patients receiving or not receiving chemotherapy, including cisplatin. The probability of response is also similar in patients with adequate or inappropriate erythropoietin production before therapy, although the doses used are usually 2 to 3 times higher than in renal failure patients.
...
PMID:Erythropoietin and the anemia of cancer. 866 61

Recombinant erythropoietin (r-HuEPO) was the first growth factor introduced into clinical practice. The main indication for its therapeutic use remains treatment of anaemias during chronic renal failure. In Czech Republic it is at present administered to 55% of patients included in a regular haemodialyzation program and in the pre-dialyzation stage of the disease, consistent with European practice. In addition to a marked improvement of the quality of life, during r-HuEPO treatment also the prevalence of some cardiovascular complications is reduced and immune functions improve. The list of diseases where r-HuEPO therapy is indicated has been, however, extended nowadays. A very favourable effect was recorded in some haematological malignicies and solid tumours. The best results were observed so far in the treatment of anaemia associated with multiple myeloma and chronic lymphatic leukaemia, and also in malignant lymphomas, carcinoma of the breast and ovary. It is used also in the treatment of suppressed erythropoiesis resulting from cytoreducing therapy. Other indications include anaemia after transplantations of bone marrow, preparation before autologous transfusions and some cases of myelodysplastic syndrome. The authors mention also other contemporary possibilities of r-HuEPO use.
...
PMID:[Erythropoietin in the treatment of anemias]. 868 10

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.
...
PMID:[Erythropoietin in oncology. II. Evaluation of the effectiveness of erythropoietin in hematologic and oncologic diseases]. 876 96

The diurnal rhythm in the circulating serum levels of erythropoietin (EPO) were determined in a group of 20 adult clinically-healthy subjects, in a group of 10 patients with myeloma without renal impairment and 10 patients with myeloma and renal failure. Venous blood samples were drawn during the span of a whole day and every 4 hr, starting from midnight, for the measurement of serum EPO levels by radioimmunoassay (RIA). Statistical analysis was carried out by means of the "cosinor" method. Results show that the controls and the myeloma patients without renal insufficiency present significant (P < 0.05) circadian rhythms in serum EPO levels; no rhythm (P < 0.05) was detected in patients with myeloma and renal failure. Patients with myeloma and renal failure have significant (P < 0.05) lower mean daily levels and diurnal fluctuations of EPO than the other groups, whereas the patients with myeloma without renal involvement present higher (P < 0.05) mean daily levels and lower (P < 0.05) diurnal variations of EPO than controls; no differences (P > 0.05) exist between the groups regarding peaks of rhythms. These data confirm the existence of a physiological circadian rhythm in serum EPO concentrations, with maximum in the afternoon, and they suggest that renal failure is an important cause of anemia and loss of EPO circadian rhythm in patients with myeloma.
...
PMID:Circadian rhythm of serum erythropoietin in multiple myeloma. 881 96

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