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)

Erythroid cell stimulating factor (ESF) is present in mouse serum and has been reported to function in concert with erythropoietin (EPO) in the formation of erythroid cells in in vitro culture systems. We report here the generation and characterization of a monoclonal antibody (MAb) directed against ESF, with potent anti-ESF-neutralizing activity. A hybridoma-producing MAb to ESF was selected following enzyme-linked immunosorbent assay (ELISA)-based screening of 270 colonies obtained from a fusion of immunized mouse splenocytes with NS1 myeloma cells. Western blot analyses of mouse serum using this antibody specifically detected a single protein (approximate molecular weight of 60 kDa and 120 kDa, under reducing and nonreducing conditions, respectively) corresponding to ESF, with no reactivity to EPO. Furthermore, this MAb demonstrated reactivity to a protein similar in molecular mass, across species, showing reactivity in sera obtained from human, horse, goat, guinea pig, rabbit, and rat. Immuno-chemical characterization demonstrated this antibody to be of IgG3 isotype, bearing kappa light chains. Injection of this monoclonal anti-ESF antibody to exhypoxic polycythemic mice at 6 and 24 h after EPO injection significantly reduced 59Fe incorporation into red blood cells, demonstrating its ability to neutralize in vivo erythropoiesis in our mouse model system. Thus, this novel erythroid cell-specific MAb will be an invaluable tool for further delineating the physiological role of ESF in in vivo erythropoiesis.
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PMID:Generation and characterization of a neutralizing monoclonal antibody against erythroid cell stimulating factor. 1112 24

Anaemia, manifesting as fatigue, dizziness, dyspnoea and anorexia, is common among patients with cancer. A host of factors, such as neoplastic bone marrow infiltration, impaired haematopoiesis, autoimmune haemolysis, impaired endogenous erthropoietin production and treatment with cytotoxic agents contribute to the underlying pathology. Traditionally, blood transfusions have formed the mainstay of therapy for the treatment of cancer-related anaemia. Numerous clinical trials have subsequently confirmed the safety and therapeutic utility of recombinant human erythropoietin (rHuEPO) in anaemic cancer patients, including those with haematological malignancies, such as multiple myeloma and non-Hodgkin's lymphoma. Indeed, well over 50% of unselected patients treated with rHuEPO can be expected to respond with increases in haemoglobin level and/or elimination of transfusion need. In addition, a low baseline serum erythropoietin level can identify those patients with haematological malignancies having a very high likelihood of responding to rHuEPO therapy. These findings, in combination with the possibility of titrating to a lower, maintenance dose, have improved the cost-benefit relationship and thus support the use of rHuEPO as an appropriate alternative to blood transfusions for the management of anaemic patients with lymphoma and myeloma.
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PMID:The role of recombinant human erythropoietin in the management of anaemic cancer patients: focus on haematological malignancies. 1118 81

Recombinant human erythropoietin (rHuEpo) has been used successfully in the treatment of cancer-related anemia. Clinical observations with several patients with multiple-myeloma treated with rHuEpo has shown, in addition to the improved quality of life, a longer survival than expected, considering the poor prognostic features of these patients. Based on these observations, we evaluated the potential biological effects of rHuEpo on the course of tumor progression by using murine myeloma models (MOPC-315-IgAlambda(2) and 5T33 MM-IgG(2b)). Here we report that daily treatment of MOPC-315 tumor-bearing mice with rHuEpo for several weeks induced complete tumor regression in 30-60% of mice. All regressors that were rechallenged with tumor cells rejected tumor growth, and this resistance was tumor specific. The Epo-triggered therapeutic effect was shown to be attributed to a T cell-mediated mechanism. Serum Ig analysis indicated a reduction in MOPC-315 lambda light chain in regressor mice. Intradermal inoculation of 5T33 MM tumor cells followed by Epo treatment induced tumor regression in 60% of mice. The common clinical manifestation of myeloma bone disease in patients with multiple-myeloma was established in these myeloma models. Epo administration to these tumor-bearing mice markedly prolonged their survival and reduced mortality. Therefore, erythropoietin seems to act as an antitumor therapeutic agent in addition to its red blood cell-stimulating activity.
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PMID:Erythropoietin induces tumor regression and antitumor immune responses in murine myeloma models. 1130 90

In the diagnosis of multiple myeloma (MM), the clinician must exclude other disorders in which a plasma cell reaction may occur such as rheumatoid arthritis and connective tissue disorders, or metastatic carcinoma where the patient may have osteolytic lesions associated with bone metastases. Patients with smoldering multiple myeloma (SMM) or monoclonal gammopathy of undetermined significance (MGUS) have none of the complicating features of MM and do not require treatment with potentially toxic agents. The plasma cell labeling index can help make a differential diagnosis of MM from SMM. Patients with a high labeling index have a high risk of complications and should be monitored carefully. However, the labeling index can be low in active MM. In addition, SMM or MGUS patients have few or no circulating plasma cells. High-dose chemotherapy and stem cell support prolong overall survival in contrast to conventional therapy. If stem cell transplantation is considered, it is important to harvest the cells before using alkylating agents to obtain a sufficient number of cells. Supportive treatment consists of the occasional use of erythropoietin to maintain adequate hemoglobin levels and adequate hydration to protect renal function. Vaccination against pneumococcal infections and the prophylactic use of antibiotic therapy during the first 2 months of treatment can be beneficial. Recognizing the symptoms of spinal cord compression and initiating dexamethasone therapy promptly to prevent paraplegia are critical.
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PMID:Multiple Myeloma. Diagnostic challenges and standard therapy. 1130 3

Patients with malignant diseases frequently develop anemia. An alternative to blood transfusions is the application of recombinant human erythropoietin. Several nonrandomized and prospective, placebo-controlled studies have demonstrated the effect and safety of erythropoietin in patients with hematological malignancies, particularly in patients with multiple myeloma and low- to intermediate-grade non-Hodgkin's lymphoma. However, in patients with myelodysplastic syndromes, the rather low response rate of erythropoietin is overcome by the combination of erythropoietin with granulocyte colony-stimulating factor. A significant acceleration of the reconstitution of erythropoiesis has been reported in allogeneic, but not in autologous bone marrow transplantation. Especially in large open-label, multicenter studies, a statistically and clinically significant improvement in quality of life independent from chemotherapeutic response or tumor type has been demonstrated. A number of simple algorithms have been proposed using the pretreatment serum erythropoietin level, transfusion requirements, and early changes in hematological parameters.
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PMID:Recombinant human erythropoietin in the treatment of anemic patients with hematological malignancies. 1147 44

This review discusses the evolution of novel diagnostic and treatment strategies for multiple myeloma based upon increased understanding of basic disease pathogenesis. Although myeloma has remained an incurable illness to date, these new developments will derive treatments to improve outcome and achieve eventual cure. In Section I, Dr. Kyle reviews the results of current therapy for multiple myeloma, including high dose therapy and stem cell transplantation which have proven to achieve improved response rates, event-free, and overall survival. Supportive therapy, such as erythropoietin to treat disease-related anemia, and methods of prophylaxis against infection, which both lessen toxicities of treatment and improve quality of life for patients, are also addressed. In Section II, Dr. Dalton with Drs. Landowski, Shain, Jove and Hazlehurst discusses mechanisms of drug resistance in myeloma, with emphasis on novel treatment approaches to prevent development of drug resistance and to overcome drug resistance. Laboratory studies delineating mechanisms whereby myeloma cells resist drug-induced apoptosis provide the framework for related treatment protocols for patients with refractory disease. In Section III, Dr. Berenson reviews the management of complications in bone, which occur in the majority of patients with myeloma and are the major cause of decreased quality of life. New insights into the mediators of bone resorption and new bone formation in the marrow milieu have already derived effective bisphosphonate therapy. These drugs not only reduce bone complications and related pain, thereby improving quality of life, but also may have intrinsic anti-tumor activity by virtue of inducing tumor cell adherence to marrow, reducing interleukin-6 secretion, inducing tumor cell apoptosis, or inhibiting angiogenesis. In the last section, Dr. Anderson explores the potential for future therapies which offer great promise to improve patient outcomes. First, drugs which alter the marrow microenvironment include thalidomide and its derivative immunomodulatory drugs, which act directly on tumor cells to induce apoptosis or G1 growth arrest, alter tumor cell adhesion to marrow stroma, inhibit angiogenesis, and trigger a cellular anti-tumor response. The proteasome inhibitors both act directly on tumor cells and also inhibit the transcription factor NFkappaB-dependent upregulation of IL-6 secretion triggered by tumor cell adhesion. Second, delineation of both growth and apoptotic pathways has derived novel treatment strategies. Third, the preclinical basis and early clinical trial results using vaccination and adoptive immunotherapy to harness autoimmune and alloimmune anti-myeloma responses are presented. This review sets the stage for an evolving new biologically based treatment paradigm in myeloma targeting both the tumor and its microenvironment to improve outcome and achieve eventual cure.
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PMID:Multiple Myeloma: New Insights and Therapeutic Approaches. 1170 40

Patients with cancer frequently develop anaemia. Various factors, including the type of malignancy and the intensity of chemotherapy influence the prevalence of anaemia and need of transfusions. Among the numerous causes of its development, the most frequent type is cancer anaemia, the so-called "anaemia of chronic disorders". Anaemia of chronic disorders is diagnosed when neoplastic disease is accompanied by an otherwise unexplained microcytic anaemia with compromised iron utilisation and decreased erythropoietin secretion. In 50-70% of patients with solid tumors or hematological malignancies, mainly with multiple myeloma and malignant lymphomas, transfusion can be avoided, or significantly decreased by the use of recombinant erythropoietin. This review provides tools to decide the best candidates for this treatment and a guideline to monitor its efficacy.
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PMID:[Etiology and treatment of malignancy-associated anaemia] 1205 Jun 93

Of patients presenting with multiple myeloma, 5% to 15% satisfy criteria for the diagnosis of multiple myeloma but have no or minimal symptoms and do not require chemotherapy (NRC). These patients are classified as having smoldering, asymptomatic stage 1, or indolent multiple myeloma in order of their increasing risk of progression. We avoid chemotherapy, especially with alkylating agents in such patients, and we either closely monitor them or use a nonchemotherapeutic intervention. If significant bone lesions, renal failure, or hypercalcemia occur, chemotherapy or transplant is recommended. Patients with mild anemia or with small or isolated bone lesions who are asymptomatic or minimally symptomatic because of anemia may be monitored and are classified as having indolent multiple myeloma. Unnecessary treatment with melphalan or cyclophosphamide probably has no benefit in multiple myeloma NRC and can cause significant risk. In long-term follow up, 25% of patients receiving alkylating agents develop myelodysplastic syndrome or acute leukemia. Patients who do not receive chemotherapy must be monitored closely to avoid complications of overt multiple myeloma, including anemia, bone lesions, renal failure, and hypercalcemia. We and others have begun to take a more active approach with the use of nonchemotherapeutic agents in selected patients. We use bisphosphonates in patients with bone lesions or osteoporosis or when there is a progressive rise in M-protein. We use dexamethasone alone in NRC multiple myeloma to reduce tumor burden in selected patients who do not yet have overt multiple myeloma or who are not candidates for chemotherapy. We use bisphosphonates to prevent osteoporosis in such patients. We use erythropoietin to correct anemia, and dexamethasone and erythropoietin together in patients with higher tumor burden (eg, indolent multiple myeloma). Future progress in treating multiple myeloma NRC depends on better identification of new therapeutic targets that control progression from the stable asymptomatic to the progressive symptomatic phase of multiple myeloma. We need to better understand the biologic target of new agents like thalidomide to design more effective treatment for this early phase of multiple myeloma. Although these approaches may delay chemotherapy, it is not known whether survival is prolonged. Nonchemotherapeutic approaches must be systematically studied in clinical trials in order to be put to better use.
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PMID:Smoldering, asymptomatic stage 1, and indolent myeloma. 1205 49

Anemia is a common complication in patients with hematologic malignancies, and is caused by a variety of mechanisms, including neoplastic cell infiltration into the bone marrow, hemolysis, nutritional deficiencies, and defects in erythropoiesis as a result of the disease itself or cytotoxic therapy. The anemia associated with multiple myeloma is caused by inadequate erythropoietin levels consequent to renal impairment and the effect of inflammatory cytokines. The degree of anemia can have prognostic importance, as is the case with multiple myeloma, or be a significant indicator of disease stage, as noted with chronic lymphocytic leukemia. Anemia results in fatigue, exhaustion, dizziness, headache, dyspnea, and decreased motivation, seriously affecting a patient's quality of life. Since anemia is so prevalent in hematologic malignancy patients, its treatment must be an integral part of disease management, to improve quality of life and to possibly increase potential survival. Clinical studies have shown that effectively treating anemia and increasing hemoglobin levels using recombinant human erythropoietin (rHuEPO, epoetin alfa) has a significant effect on transfusion requirements and quality of life.
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PMID:The effects of anemia in hematologic malignancies: more than a symptom. 1208 53

Multiple myeloma (MM) and chronic lymphocytic leukemia (CLL) patients often develop anemia due to the disease process and effects from disease therapy. Blood transfusion, the established treatment, has an immediate effect in improving patients' hemoglobin levels. However, this effect is transient and transfusion is associated with several risks, including infections and mild to life-threatening immunologic reactions. A newer option is recombinant human erythropoietin (epoetin); a biological treatment that leads to increased hemoglobin levels over an extended time without the risks of blood transfusion. Extensive evidence has shown that epoetin is effective in the treatment of cancer-associated anemia. An international expert panel met to develop treatment recommendations for the use of epoetin in MM and CLL patients. Based on the available data, it is recommended that treatment be initiated only after other possible causes of anemia are eliminated. Epoetin should be administered to any patient with hemoglobin < or=10 g/dl. Patients with hemoglobin 10-12 g/dl should receive epoetin if they suffer from significant symptoms of anemia and/or have progressively decreasing hemoglobin values. Dosage should be initiated at 10 000 IU three times/week or 40 000 IU once/week and be titrated to maintain hemoglobin at 12 g/dl. Nonresponsive patients (<1 g/dl increase over four weeks) may have their dose increased to 20 000 IU three times/week or 60 000 IU once/week, respectively. Epoetin treatment should be discontinued if there is no response to the increased dosage, or hemoglobin >14 g/dl. Treatment should resume for patients who exceed 14 g/dl, at a reduced dosage, if their hemoglobin falls below 12 g/dl.
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PMID:Management of disease-related anemia in patients with multiple myeloma or chronic lymphocytic leukemia: epoetin treatment recommendations. 1269 28


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