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)

A 71-year-old woman with multiple myeloma (MM) in remission was admitted for evaluation of recent abdominal distension and was diagnosed as having massive myeloma ascites. The fluid was characterized by a total nucleated cell count of 6,600/mm3 (67% plasma cells), with a plasma cell CD38+ phenotype. Chemical analysis of the fluid showed lactate dehydrogenase of 122 IU/L, total protein of 2.9 g/dL, albumin of 2.4 g/dL, diastase of 38 IU/dL, cholesterol of 46 mg/dL, and C-reactive protein of 3 g/dL. The serum-ascites albumin gradient (SAAG) was low (0.9). Electrophoresis of the ascitic fluid showed a monoclonal spike in the gamma region and immunoelectrophoresis confirmed the presence of lambda light chains similar to those seen in the urine. Further analysis of the ascitic fluid showed markedly elevated levels of beta2 microglobulin (11,161 microg/L) and interleukin-6 (146 pg/ml compared to serum level of 4.3 pg/ml). There was evidence of intraabdominal masses that completely resolved with continuous high-dose cyclophosphamide (750 mg/m2/day for four days) followed by clinical improvement and disappearance of the ascites. We stress the value of complete fluid characterization and intensive chemotherapy to achieve a favorable outcome.
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PMID:Myeloma ascites--a favorable outcome with cyclophosphamide therapy. 992 7

We compared the prognostic value of conventional cytogenetic analysis and established factors such as beta2-microglobulin and plasma cell labeling index in 70 patients undergoing autologous blood cell transplantation for multiple myeloma. Patients underwent transplantation 5 to 88 months (median, 20 months) after the initial diagnosis of myeloma. Factors studied were age, sex, beta2-microglobulin, response to prior therapy, plasma cell labeling index, cytogenetic analysis, bone marrow plasma cell percentage, lactate dehydrogenase and C-reactive protein. Twenty-eight of 65 patients (43%) had abnormal marrow cytogenetics. Overall survival measured from transplantation was significantly better in patients with normal cytogenetics than in those with abnormal cytogenetics (median survival, 25 vs 12 months, P = 0.003). Progression-free survival was better, with median times of 12 vs7 months, respectively (P = 0.005); overall survival measured from the time myeloma was first diagnosed was also longer, with median survivals of 62 and 39 months, respectively (P = 0.001). Median plasma cell labeling index was 1.5% in patients with abnormal cytogenetics and 0. 2% in those with normal cytogenetics (P < 0.001). Abnormal bone marrow cytogenetics predict poor survival after blood cell transplantation for myeloma. There is a significant correlation between abnormal cytogenetics and high plasma cell labeling index, suggesting that certain cytogenetic abnormalities may offer a proliferative advantage to myeloma cells.
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PMID:Abnormal cytogenetics predict poor survival after high-dose therapy and autologous blood cell transplantation in multiple myeloma. 1048 33

Expression of the lung resistance protein (LRP) is associated with resistance to various anticancer drugs including melphalan and, therefore, may affect the clinical outcome in multiple myeloma (MM). To determine the clinical significance of LRP, we have compared LRP expression in bone marrow plasma cells with clinical parameters including response to chemotherapy and survival of previously untreated patients with MM (n = 72). LRP expression immunocytochemically assessed by means of the LRP-56 monoclonal antibody was positive (> or =10% staining plasma cells) in 44 (61%) samples. There was no correlation between LRP expression and age, sex, type of the paraprotein, serum creatinine, stage, beta2-microglobulin, serum lactate dehydrogenase, or C-reactive protein. However, LRP expression was more frequently observed in patients with a p53 deletion than in those without such a deletion (P = 0.01). The overall response rate for all of the patients evaluable for response to induction chemotherapy (n = 58) was 67%. The response rate was 87% for patients without LRP expression but only 54% for patients with LRP expression (P = 0.01). Kaplan-Meier analysis revealed that patients with LRP expression had a shorter overall survival (median, 33 months) than those without LRP expression (median not reached; P = 0.04). These data show that LRP expression is an important marker for clinical drug resistance and predicts a poor outcome in MM.
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PMID:Expression of the lung resistance protein predicts poor outcome in patients with multiple myeloma. 1049 14

Tumour lysis syndrome (TLS), because of its low proliferative activity, is thought to only rarely complicate the treatment of patients with multiple myeloma. However, as more aggressive therapeutic approaches are increasingly used in the management of this disease, it is conceivable that clinicians will encounter this complication more frequently. A retrospective analysis of > 800 patients with multiple myeloma treated at the University of Arkansas identified nine patients who developed a marked tumour lysis syndrome following intermediate- or high-dose chemotherapy. Evaluation of disease characteristics revealed association with high tumour mass, high proliferative activity, increased lactic dehydrogenase levels, plasmablastic morphology, and unfavourable cytogenetic abnormalities. Recognition of multiple myeloma patients at high risk for the development of tumour lysis syndrome and prompt intervention are required especially in the presence of abnormal baseline renal function frequently complicating the clinical course of these patients.
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PMID:Tumour lysis syndrome complicating high-dose treatment in patients with multiple myeloma. 1055 3

Two myeloma patients presented high fever with no signs or data indicating infection at diagnosis or relapse. Both patients had plasmablastic myeloma, and serum levels of lactic dehydrogenase (LDH) and CRP were extremely high. Plasmablastic morphology, high LDH, and CRP were recognized as poor prognostic factors, indicating a fulminant phase of multiple myeloma. Interleukin-6 (IL-6) was only high in measured cytokines. We proposed that IL-6 caused high fever and induced the fulminant phase in these 2 cases.
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PMID:Multiple myeloma presenting high fever and high serum levels of lactic dehydrogenase, CRP, and interleukin-6. 1081 94

We evaluated possible prognostic factors just before salvage therapy with vincristine, doxorubicin, and dexamethasone (VAD) for 36 patients with refractory multiple myeloma. The median duration from diagnosis to the first VAD salvage was 14 months (range 2-76 months). Among parameters that have been shown to be associated with poor survival, a high serum lactate dehydrogenase (LDH) level was the sole significant predictor of survival. The median survival of patients with high LDH levels was 4 months, whereas that of patients with low LDH levels was 20 months. A multivariate analysis identified high LDH and high age as independent prognostic factors. More aggressive therapies might be indicated for high-LDH patients with refractory myeloma.
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PMID:High serum lactate dehydrogenase level predicts short survival after vincristine-doxorubicin-dexamethasone (VAD) salvage for refractory multiple myeloma. 1099 30

We evaluated the effect of eight species of light chains on cultured human kidney proximal tubule cell proliferation. Exposure to light chains for 48 hours caused dose-dependent inhibition in tritium ((3)H)-thymidine incorporation by simian virus 40 immortalized human proximal tubule cells, although the effect was variable among different species of light chains. We studied cytotoxic effects of selected toxic light chains in further detail. Two of these light chains caused significant DNA degradation. A lambda-light chain caused lactate dehydrogenase release from exposed cells at 48 hours, but not at 24 hours. Cytomorphological and electron microscopic examination of cells exposed to light chains for 24 hours showed condensed nuclei, cell detachment, paucity of mitotic activity, and apoptosis, and at 48 hours of exposure, changes consistent with necrosis. Apoptosis assay by terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling method showed a sixfold increase in the number of apoptotic cells exposed to the same lambda-light chain for 24 hours. Rhodamine-phalloidin staining showed variable but significant disruptions in the actin cytoskeleton. These studies show that some myeloma light chains are toxic to cultured human proximal tubule cells and induce cytoskeletal injury and DNA damage consistent with apoptosis followed by secondary necrosis. Direct proximal tubule cell toxicity may be an important mechanism of renal involvement in multiple myeloma.
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PMID:Cytotoxicity of myeloma light chains in cultured human kidney proximal tubule cells. 1100 75

In a group of 85 patients with multiple myeloma (MM) incl. 50 patients examined at the time when the diagnosis was established the relationship of the values of the propidium-iodide index (PI index) of myeloma plasmocytes of the patients were examined by flow cytometry using the double staining method, and selected laboratory parameters of the disease were analyzed. It was revealed that the values of the PI index examined with the aid of different "identification" monoclonal antibodies did not differ significantly. The median and average value of the PI index was in the whole group for PI/CD38 2.3 and 2.3%, for PI "UHKT" 1.8 and 1.8% and for PI/B-B4(CD138) 2.2 and 2.4%. In the group of patients examined at the time when the diagnosis of MM was established before chemotherapy the median and average value of the PI/CD38 index was 2.0 and 2.2%, PI/"UHKT" was 1.5 and 1.6%, PI/B-B4 (CD138) 2.6 and 2.5%. In the two analyzed groups no statistically significant correlations of PI/CD38,/"UHKT" and B-B4(CD138) index were found with the number of granulocytes, thrombocytes, immunochemical type and the value of the serum M-component, and levels of S-beta 2 microglobulin, S-urea, S-creatinine, S-calcium, and S-lactic dehydrogenase. A significant positive correlation was found in both groups with the level of S-thymidine kinase, in the whole group of indexes PI/CD38 and PI/B-B4(CD138) with the severity of anaemia, index PI/CD38 correlated with S-albumin and index PI/B-B4(CD138) with the percentage ratio of plasmocytes in bone marrow. It was revealed that examination of the propidium-iodide index is a suitable and prompt method for evaluation of proliferative properties of the myeloma population.
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PMID:[Importance of determining the propidium-iodide index of plasmacytes in multiple myeloma. I. Relation to selected laboratory indicators of the disease]. 1104 67

We present a unique case of IgD multiple myeloma (MM) preceding the development of extensive extramedullary disease without medullary involvement. A 63-year-old man was diagnosed with IgD-lambda MM when he developed anemia. After 3 months of chemotherapy, he was in complete remission as evidenced by the disappearance of bone marrow (BM) plasmacytosis, monoclonal IgD protein in his serum, and Bence Jones proteinuria. Six months after diagnosis, his disease took an unusual course with the development of plasmacytomas in the skin, without medullary involvement. He then received chemotherapy, resulting in the complete disappearance of the subcutaneous plasmacytomas. Two years after the initial diagnosis, his disease took an aggressive clinical course with retroperitoneal relapse, leading to the patient's death within 1 month. The two separate episodes of extramedullary disease were associated with elevated serum lactic dehydrogenase levels and the absence of plasma cells in the BM. This case provides evidence of two separate transformations of the original malignant MM clone.
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PMID:IgD multiple myeloma preceding the development of extensive extramedullary disease without medullary involvement. 1111 Nov 22

Aggressive multiple myeloma with high serum lactate dehydrogenase (LDH) often has unusual clinical features and is considered to be a distinct clinical entity of multiple myeloma. A myeloma cell line, designated Maska-98, was established from the bone marrow of a patient with aggressive myeloma with extremely high serum LDH that was resistant to conventional chemotherapy. Maska-98 cells had morphological features of immature plasma cells, and immunophenotypic analysis showed that the cells expressed the plasma cell-associated surface antigens including CD38, 49d, and 56, but no T- or B-cell antigens, such as CD2, 3, 4, 8, 19, and 20. Maska-98 cells contained cytoplasmic immunoglobulin (IgG lambda). By utilizing this cell line we demonstrated that the myeloma cells produce and release a large amount of LDH, since (i) abundant LDH was found in the culture supernatant of Maska-98, (ii) immunocytochemical analysis showed that cytoplasm of the cells was strongly stained with anti-LDH monoclonal antibody, and (iii) Maska-98 cells expressed a greater amount of LDH mRNA than the T-cell line TALL-1, as shown by reverse transcription-polymerase chain reaction. As far as we know, there is no report of a myeloma cell line producing excess LDH. Therefore, Maska-98 would provide a novel source for further studies of the pathogenesis of aggressive multiple myeloma with high serum LDH.
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PMID:Lactate dehydrogenase production and release in a newly established human myeloma cell line. 1127 38


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