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

A site-specific monoclonal antibody to human erythropoietin has been developed. It is secreted by a hybridoma cell line derived from the fusion of murine myeloma cells with the splenocytes of a mouse that had been immunized with a 26-residue synthetic peptide antigen homologous to the amino-terminal sequence of the hormone. The antibody binds specifically to peptide, 125I-erythropoietin, and biologically active erythropoietin. The equilibrium dissociation constants of the antibody-erythropoietin and the antibody-peptide interactions are identical, Kd = 6.7 X 10(-9) M, suggesting strong conformational similarity or identity of the epitope as expressed on the peptide and the hormone. Immune complexes formed between the antibody and either human or rat erythropoietin exhibit full biologic activity. However, the antibody does not recognize the baboon, sheep, or canine hormones, indicating antigenic differences or structural variation among these erythropoietins. These results indicate that the amino-terminal region of erythropoietin is not involved in receptor binding. Furthermore, they form a basis for the study of the structure and function of the hormone using anti-peptide antibodies.
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PMID:Isolation and characterization of an anti-peptide monoclonal antibody to human erythropoietin. 405 99

Twenty-four untreated patients with myelomatosis were studied in order to characterize their anaemia, using standard haematological and ferrokinetic techniques, together with measurements of circulating erythropoietin, erythropoietin sensitivity of marrow cultures and in vitro measurements of haem synthesis. There is a reduction in total erythroid output by the marrow, together with a minor degree of plasma expansion. In patients with normal renal function there is an appropriate increase in erythropoietin in response to anaemia, but in a few cases there may be reduced response of CFU-E to the hormone in vitro. No abnormality of iron status or haem synthesis was found. One case of folate deficiency was discovered.
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PMID:Anaemia in patients with myelomatosis. 709 23

Recombinant human erythropoietin (rHuEPO) was used to treat the anaemia in a hemodialyzed 60 year old man with multiple myeloma requiring chemotherapy; the type of serum M component was IgA kappa. During the 5 months before rHuEPO treatment the patient was given multiple blood transfusions. rHuEPO was started 125 U/kg/week subcutaneously in divided doses after dialysis. After introduction of rHuEPO, blood transfusions were no longer required and haemoglobin concentration increased from 5.2 mmol/l to 6.9 mmol/l after 8 weeks of treatment. We conclude that rHuEPO treatment in haemodialysed patients with multiple myeloma may be safe, well tolerated and clinically effective.
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PMID:[Treatment of multiple myeloma associated anemia with human recombinant erythropoietin in a hemodialysis patient]. 747 22

A patient with advanced multiple myeloma (MM) and renal failure presented a severe chronic anemia requiring frequent blood transfusions. Treatment with recombinant human erythropoietin (rHuEPO) led to a rapid improvement of anemia, and further blood transfusions were not required. Pathophysiological studies about the erythropoiesis in patients with MM and trials with rHuEPO in myeloma-associated anemia are commented.
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PMID:[Recombinant human erythropoietin in the treatment of the anemia of multiple myeloma with kidney failure]. 762 64

Recombinant human erythropoietin (rHu-EPO) is an effective growth factor for erythroid progenitor cells in anemia provoked by several conditions, including bone marrow tumors such as multiple myeloma (MM). We studied a group of 54 patients with MM undergoing second-induction chemotherapy. Thirty of them were randomly assigned to receive rHu-EPO at an initial dosage of 150 units/kg body weight three times a week, increased to 300 units/kg from the sixth week to the end of the 24-week study. Hemoglobin (Hb) levels increased in 77.7% of these patients by the eighth week. In addition, five transfusion-dependent patients in treatment with the VMCP protocol completed the trial without requiring blood supplement after the third month, whereas seven control patients required frequent supplements. Monthly assessment of hematologic parameters demonstrated the ability of rHu-EPO to increase reticulocyte counts, whereas five patients became resistant to the second-induction chemotherapy in apparent concurrence with their rHu-EPO therapy. The response to rHu-EPO in four of the five MM patients receiving cytotoxic protocols combined with alpha-interferon (alpha-IFN) included an increase of serum IgM after the third month. This effect was not demonstrable in any other group, including three rHu-EPO-untreated patients undergoing alpha-IFN + VMCP combined therapy, as well as rHu-EPO-treated patients not receiving alpha-IFN. Our data suggest that alpha-IFN plus rHu-EPO treatment in MM patients is effective in restoring normal B cell function. These results may reflect in vivo the modulation of normal human B cells and lymphoblasts by rHu-EPO observed in vitro.
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PMID:Long-term therapy with recombinant human erythropoietin (rHu-EPO) in progressing multiple myeloma. 763 11

The most common cause of limited response to recombinant human erythropoietin (r-HuEPO) is unrecognized, mild-to-moderate iron deficiency, either at the start of treatment or secondary to enhanced iron utilization by newly formed erythrocytes. Iron stores in patients with chronic renal failure (CRF) are often depleted through gastrointestinal bleeding, blood loss during haemodialysis, and blood sampling. Mobilization of iron stores may be inadequate, especially during rapid haemoglobin regeneration. Aluminium overload may also interfere with gastrointestinal and cellular iron uptake. Overt or unrecognized infection or inflammation is another common cause of hyporesponsiveness, and is a consequence of increased blood concentrations of cytokines such as tumour necrosis factor (TNF), interleukin-1 (IL-1), and interferon-gamma (IFN-gamma), which suppress erythrocyte stem-cell proliferation. Less common causes include severe secondary hyperparathyroidism and myeloma (during chemotherapy). Response to r-HuEPO can be best predicted by baseline fibrinogen (a marker of subclinical inflammation); baseline transferrin receptor (sTfR) concentrations (a marker of functional iron deficiency); and sTfR increment after 2 weeks (a marker of early change in erythropoietic activity).
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PMID:R-HuEPO hyporesponsiveness--who and why? 764 9

T and B lymphocyte functions were investigated in the course of a long-term trial of recombinant human erythropoietin in patients with progressing multiple myeloma. Peripheral mononuclear cell as well as T and B lymphocyte cultures were established at the 1st, 13th, and last week of the 24-week protocol from 16 treated and 15 untreated patients. Control cultures from healthy individuals were also obtained. A suppression of phytohemagglutinin-induced proliferation of T cells was noted in all 1st-week cultures, whereas a variable increase of 3H-thymidine uptake was noted at the end of the trial in the cultures from erythropoietin-treated patients. A significant increase was observed, however, in cultures from 5 erythropoietin-treated patients who also received alpha-interferon when their cells were grown in the presence of the hormone. In contrast, the pokeweed mitogen-driven in vitro synthesis of immunoglobulins was not significantly influenced by the duration of erythropoietin treatment, nor by addition of the hormone. IgG secretion by Epstein-Barr virus-transformed B cells in cultures from 9 erythropoietin-treated and 6 untreated patients was enhanced in the presence of both recombinant human erythropoietin and alpha-interferon. These data suggest that synergy between the two cytokines may variably modulate certain immune functions in vitro. This effect might account for the increase of serum IgM levels noted in some patients who received alpha-interferon.
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PMID:Immunomodulation of T and B cell functions in multiple myeloma patients treated with combined erythropoietin and alpha-interferon therapy. 766 9

Anemia and bleeding are commonly observed in patients with multiple myeloma (MM). Anemia in MM is multifactorial in origin. Three common causes are marrow replacement by the malignant cells, thereby reducing the available number of BFU-E, chronic renal failure and shortening of the half life of erythrocytes. Some patients with anemia but without renal failure show a good response to erythropoietin (Epo) with full correction of anemia. This indicates that human Epo is a promising therapeutic tool or treating myeloma-associated anemia. The incidence of severe bleeding complications is low, despite the diversity of abnormal hemostatic tests in patients with MM. These patients frequently show abnormal coagulation tests, including thrombin time, fibrin degeneration products, platelet aggregation tests and bleeding time. The most effective therapeutic approach to bleeding is to treat the underlying malignancy. Supplemental to this, plasma exchange is useful.
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PMID:[Anemia and hemostatic abnormalities associated with multiple myeloma]. 769 6

Novel compounds based upon the thiol N-(carboxy)-beta-alanyl-cysteamine (vitaletheine) have strikingly potent and seemingly diverse biological activities. Concentrations of vitaletheine modulators from 1 femtograms/ml to 100 picograms/ml medium regulate RBC production from progenitors initially deprived of erythropoietin. Similarly, as little as attograms/ml concentrations of the disulfide vitalethine stimulate immunological responses of murine splenocytes toward sheep RBC in a hemolytic plaque assay. Because dosages of vitalethine as low as femtograms/kg substantially diminish tumor size and incidence and increase survival to 80% in mice inoculated with a uniformly fatal melanoma (Cloudman S-91), activities of these compounds have in vivo significance. A preliminary probe of the benzyl derivative of vitalethine in a myeloma model (NS-1) suggests efficacy (100% survival) as well. The high potencies of the vitaletheine modulators, both in cell culture and in vivo, indicate that these or similar regulatory components, if constitutively present, probably occur endogenously at vanishingly small concentrations and may be prone to deficiency resulting from metabolic imbalances, irradiation, aging, diet, pathogenic or parasitic infections, or exposure to environmental pollutants. Pathways for the biosynthesis of vitaletheine are proposed and chemical syntheses of the vitaletheine modulators are described. Possible molecular mechanisms of action, including interactions with peptidyl hormones, other endogenous effectors, and xenobiotic and pharmaceutical compounds, are explored. Indications for the treatment of other diseases are identified.
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PMID:Vitalethine modulates erythropoiesis and neoplasia. 792 8

Nowadays, maintenance dialysis can be proposed to patients suffering from myeloma with end-stage chronic renal failure. We report here data from eight patients dialysed either by hemo- (6) or peritoneal dialysis (2), together with chemotherapy in half of them. Six patients died; the longest survival has been about 6 years. The main cause of morbidity was sepsis, especially in peritoneal dialysis patients; therefore we now favour hemodialysis in patients exposed to aggressive chemotherapy. We think dialysis justified in all cases, including those with high tumor mass, in order to expect the effect of chemotherapy; then, provided good response to drugs, further survival can be consistently improved. Once on maintenance dialysis, main drawbacks for these patients are cardiovascular complications (AL amyloidosis) and above all anemia; the latter however can be markedly improved, thanks to erythropoietin therapy which provides these patients with much better quality of life.
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PMID:[End-stage chronic renal failure in myeloma: results of dialysis]. 819 Oct 93


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