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

Serum embryonic neural cell adhesion molecule (eNCAM) levels were measured at diagnosis in 92 patients with plasma cell disorders. Significantly elevated levels of serum eNCAM were detected in patients with multiple myeloma when compared to both normal controls and patients with monoclonal gammopathy of uncertain significance (MGUS). Very high levels of serum eNCAM were seen in patients with high tumour burdens. There was a significant correlation between serum eNCAM and beta 2-microglobulin (beta 2m) (r = 0.33; P = 0.002), but not between serum eNCAM and C-reactive protein or serum albumen. There was a trend towards longer survival for patients with low serum NCAM. The median survival of the low serum eNCAM group (eNCAM < 20 U/ml) was 36 months compared to 16 months for the high serum eNCAM group (log rank test chi 2 = 2.42, P = 0.1). Serum eNCAM is a new marker of tumour mass in multiple myeloma and correlates with clinical stage and beta 2m. Patients with low serum eNCAM levels may have a survival advantage. Serum eNCAM warrants further evaluation as a tumour marker and prognostic factor in multiple myeloma.
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PMID:Serum neural cell adhesion molecule in multiple myeloma and other plasma cell disorders. 856 13

Of 496 consecutive patients with multiple myeloma (MM) enrolled in clinical trials of tandem transplants with peripheral blood stem cells support, 470 (95%) completed the first autotransplant with melphalan 200 mg/m2 (MEL 200) and 363 (73%) completed the second transplant with either MEL 200 (40%), MEL 140 mg/m2 (MEL 140) with total-body irradiation (17%), or a combination of alkylating agents (16%), depending on the response status prior to the second transplant; 31 patients up to age 60 years received an allograft as the second transplant. The median interval from first to second transplant was 5 months. Treatment-related mortality during the first year after transplantation was 7%, and complete remission (CR) was obtained in 36%; the median durations of event-free survival (EFS) and overall survival (OS) after transplant were 26 and 41 months, respectively. Low beta 2-microglobulin ([B2M] < or = 2.5 mg/L) and C-reactive protein ([CRP] < or = 0.4 mg/dL) were the most significant standard parameters associated with both prolonged EFS and OS. Median OS exceeded 5.5 years in the one third of patients with both low B2M and CRP. When cytogenetics were included in the analysis, the presence of 11q abnormalities and/or complete or partial deletion of chromosome 13 ("unfavorable karyotype") became a dominant negative feature for both EFS and OS. In addition to these pretransplant parameters, attainment of CR and application of two transplants within 6 months both significantly extended EFS and OS. The group of patients (7%) with high B2M and CRP with either IgA isotype or unfavorable karyotype had the worst prognosis (EFS, < or = 10 months; median OS, < or = 12 months) and will require novel therapy. We conclude that tandem transplants are feasible in the majority of patients up to age 70 years, effecting CR in one third of all patients. Median OS was greater than 5.5 years, regardless of pretransplant features, if the first transplant was applied within 12 months of initial treatment and the second transplant no more than 6 months later.
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PMID:Autotransplants in multiple myeloma: what have we learned? 870 39

The purpose of this study was to quantitate the number and labeling index of monoclonal plasma cells in the blood of patients with newly diagnosed multiple myeloma (MM) to learn if these values were independent prognostic factors for survival. Patients were candidates for this study if they had untreated myeloma requiring therapy, were evaluated at our institution between 1984 and 1993, and had a sample of blood analyzed with a sensitive immunofluorescence technique for monoclonal plasma cells and the blood B-cell labelling index (BLI). The % blood monoclonal plasma cells (%BPC) and the BLI were analyzed along with stage, marrow plasma cell LI, % marrow plasma cells, calcium, creatinine, albumin, beta-2-microglobulin, and C-reactive protein as univariate and multivariate factors for survival. Eighty percent of the 254 patients accrued to this study had monoclonal BPC detected. The median % BPC was 6% and 57% (144 of 254) of patients had a high number (> or = 4%). Patients with > or = 4% BPC had a median survival of 2.4 years vs 4.4 years for those with < 4% BPC (P < .001). The BLI was also prognostic (P = .008). In a multivariate analysis, the % BPC, age, albumin, stage, marrow plasma cell LI, and the BLI were independent factors for survival. The %BPC and the marrow plasma cell LI best separated the group into low, intermediate, and high risk myeloma with median survivals of 52, 35, and 26 months, respectively. Patients with high %BPC were less likely to have lytic bone disease from their MM (P = .002). The %BPC and the BLI are independent prognostic factors for survival and are useful in identifying patients as low, intermediate, and high risk. Clonal cells in the blood should be quantified in future clinical trials for myeloma.
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PMID:Peripheral blood monoclonal plasma cells as a predictor of survival in patients with multiple myeloma. 910 31

The serum concentration of oncostatin M (OSM) was measured in 40 multiple myeloma patients at diagnosis. Serum OSM level exceeded the sensitivity limit of the ELISA assay in eight (20%) of these patients (OSM+ patients). The serum levels of IL-6, another member of the gp180 cytokine family and C-reactive protein (CRP) as a surrogate of IL-6 were significantly higher in OSM+ patients. There was a trend towards higher serum beta 2M concentration in OSM+ patients, whereas there was no difference in the serum sIL-6R level or clinical data (age, gender, myeloma protein or stage) between the two groups. Two human myeloma cell lines secreted OSM and IL-6, but not IL-11 or leukaemia inhibitory factor (LIF), which suggests an important role for OSM and IL-6 in supporting growth of myeloma cells.
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PMID:Serum oncostatin M in multiple myeloma: association with prognostic factors. 901 1

The median of survival among patients with multiple myeloma (MM) is about 30 months from the onset of treatment. Tumour burden and a range of other parameters, such as C-reactive protein levels, the plasma cell labelling index and beta2-microglobulin levels, can be used to assign patients to favourable and unfavourable prognostic groups. Conventional chemotherapy consists of melphalan and prednisone, and is as effective as moderately intensive cytotoxic drug regimens. Although second-line chemotherapy is initially effective, all patients eventually die. Maintenance therapy will interferon-alpha prolongs the plateau phase of the disease, but its effects on overall survival are minimal. One of the promising developments in the treatment of MM has been the introduction of high dosage chemotherapy, which can now be safely administered when stem cells are used for haematological recovery. Autologous bone marrow transplantation has been shown to produce a significant improvement in survival compared with conventional therapy. Several studies are under way that are examining the effects of multiple courses of high dosage chemotherapy together with peripheral stem cell support. Purging of autologous stem cell harvests will be performed in the near future to minimise contamination with myeloma cells. It is now feasible to use high dosage chemotherapy, with the support of granulocyte colony-stimulating factor-stimulated whole blood, in selected elderly patients. Besides the promising development of intensive therapy, a number of other treatment strategies have emerged, including treatment with monoclonal antibodies against interleukin-6 and multidrug resistance-modulating agents. Better supportive care can be provided for some patients by using epoetin (recombinant human erythropoietin), and the sequelae of lytic bone lesions can be ameliorated through the use of bisphosphonates.
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PMID:Treatment of multiple myeloma in elderly patients. New developments. 925 78

Interleukin-6 (IL-6) is a pleiotropic cytokine which shows multiple biological functions. Pathological significance of IL-6 has been elucidated in various diseases including multiple myeloma, Castleman's disease, and rheumatoid arthritis. Thus the blockade of IL-6 signal transduction may be therapeutically effective for these diseases. For this purpose, humanized anti-IL-6 receptor antibody was prepared, and its therapeutic efficacy has been examined. Immediately after administration of humanized anti-IL-y receptor antibody to the patients with multiple myeloma, fever and systemic edema disappeared followed by the stability of M-protein which had been rapidly increased before the treatment. Humaniged anti-IL-6 receptor antibody also improved not only the chronic inflammatory symptoms but also laboratory findings such a hemoglobin, C-reactive protein, erythrocyte sedimentation rate observed both in Castleman's disease and in rheumatoid arthritis. The data suggest that the blockade of IL-6 signal transduction can be a new therapeutic approach based on the pathological significance of IL-6 in these diseases.
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PMID:[Clinical application of interleukin-6 receptor antibody]. 928 Jun 6

A monoclonal antibody, hPM-1, was constructed by grafting the complementarity determining regions to human interleukin-6 (IL-6) receptor, raised in mouse, onto a human antibody backbone (humanized antibody). It is expected to be useful as a therapeutic agent for IL-6-related diseases such as multiple myeloma. To investigate the toxicological and kinetic properties of hPM-1 preliminarily, normal cynomolgus monkeys, which showed cross-reactivity with hPM-1, were intravenously administered with hPM-1 at doses of 0 (vehicle), 4 or 40 mg/kg once a week for 13 weeks. Upon toxicological examination, there were no changes in clinical signs, food consumption, body weights, urinalyses, body temperatures, electrocardiograms, hematological and biochemical parameters including blood platelet counts, serum levels of immunoglobulin G and C-reactive protein, and pathological findings. In a kinetic study, serum concentrations of hPM-1 showed a linearity between doses of 4 and 40 mg/kg. The serum concentrations, even at a dose of 4 mg/kg, were maintained at a high enough level to inhibit the IL-6 functions throughout the period of the study. Concentrations of hPM-1 in bone marrow were almost equal to those in serum. The antibodies against hPM-1 were detected only in one of four monkeys receiving hPM-1. This study suggests that blockage of the IL-6 receptor by hPM-1 does not induce any influence on a healthy living body, and hPM-1 is not toxic under the conditions of this investigation.
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PMID:Safety and kinetic properties of a humanized antibody to human interleukin-6 receptor in healthy non-human primates. 932 16

Interleukin-6 (IL6) is believed to be involved in alterations of thyroid hormone metabolism in acute nonthyroidal illness. To evaluate the effects of IL6 on thyroid hormone metabolism in a chronic IL6-mediated disease, we measured thyroid hormone concentrations in multiple myeloma patients treated with intravenous anti-IL6 chimeric monoclonal antibodies ([cMabs] Kd = 6.25 x 10(-12) mol/L). Twelve patients were studied, receiving at least one complete treatment cycle of 14 days (daily dose: 5 mg, n = 3; 10 mg, n = 3; 20 mg, n = 3; and 40 mg, n = 3). Eight of them also completed a second treatment cycle of 14 days. Thyroid hormone concentrations were measured before, during, and after treatment with the anti-IL6 cMab. Even in the group with the lowest dosage, IL6 activity measured by the B9 bioassay was blocked completely. Compared with the reference ranges, 10 of 12 patients had one or more abnormal pretreatment values for thyroid hormone concentrations. Thyroid autoantibodies were negative in all patients. There was no correlation between thyroid hormone concentrations and IL6 levels, although plasma IL6 levels were increased in all but one subject. Moreover, neutralization of free IL6 by the anti-IL6 cMab did not affect thyroid hormone concentrations, although IL6-dependent C-reactive protein (CRP) levels decreased to undetectable levels in 11 of 12 patients. Two patients developed infectious complications resulting in increased free IL6 and CRP levels and in profound alterations of thyroid hormone levels consistent with an acute euthyroid sick syndrome. We conclude that IL6 is not a major determinant of thyroid hormone abnormalities in a chronic disease like multiple myeloma, but IL6 may be involved in thyroid hormone metabolism in acute diseases (probably in combination with other factors).
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PMID:Modulation of chronic excessive interleukin-6 production in multiple myeloma does not affect thyroid hormone concentrations. 936 97

Serum soluble interleukin-6 receptor (sIL-6R) concentrations were measured in 52 patients with multiple myeloma (MM) and 24 normal controls, using a commercially available immunoenzymatic assay kit. Patients were staged according to the Bataille et al. myeloma staging system based on the levels of patients' serum beta 2-microglobulin and C-reactive protein. Twenty-one patients were at stage A of disease, 19 at stage B and 12 at stage C at the time of serum collection for sIL-6R determination. Serum sIL-6R concentrations ranged from 15 to 176 ng/ml with a mean of 64.8 +/- 35.9 ng/ml and a median of 58 ng/ml in the entire group of patients studied. These values were significantly higher than those of 34.4 +/- 13.4 ng/ml found in the controls (P < or = 0.001). Patients of stage C had higher sIL-6R levels (94.8 + 41.2 ng/ml) than patients of stage B (67.7 +/- 31.0 ng/ml) (P < 0.01), and markedly higher than patients of stage A (45.0 +/- 23.1 ng/ml) (P < 0.001). Serum levels of sIL-6R in patients with stage A disease did not differ statistically from those of the controls. A linear positive correlation was observed between serum levels of the receptor and the stage of MM (r = 0.539, P < 0.001). These data strongly suggest that serum sIL-6R concentrations correlate with the stages of MM and may be used as an indicator of the activity of the disease.
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PMID:Serum soluble IL-6 receptor concentrations correlate with stages of multiple myeloma defined by serum beta 2-microglobulin and C-reactive protein. 940 Dec 83

Recent observations indicate that chromosome aberrations are important prognostic factors in patients with multiple myeloma (MM) treated with high-dose chemotherapy. Nevertheless, the inherent problems of conventional cytogenetics have hampered the systematic evaluation of this parameter in series of patients treated with conventional chemotherapy. Fluorescence in situ hybridization (FISH) analysis is an attractive alternative for evaluation of numerical chromosomal changes. In the present study, we analyze the relationship between aneuploidies of 15 different chromosomes assessed by FISH and prognosis in a series of 63 patients with MM treated with conventional chemotherapy. After a median follow-up of 61 months (range, 6 to 109), 49% of patients are still alive with a median survival of 33 months. The overall incidence of numerical chromosome abnormalities was 70%. This incidence significantly increased when seven or more chromosomes were analyzed (53 patients), reaching 81%. Trisomies of chromosomes 6, 9, and 17 were associated with prolonged survival (P = .033, P = .035, and P = .026, respectively); by contrast, overall survival (OS) was lower in cases with monosomy 13 (as assessed by deletion of Rb gene, P = .0012). From the clinical point of view, loss of Rb gene was associated with a poor performance status; low hemoglobin levels; high creatinine, C-reactive protein, and lactic dehydrogenase serum levels; high percentage of bone marrow plasma cells (BMPC); extensive bone lytic lesions; and advanced clinical stage. Other chromosome abnormalities such as trisomy of chromosome 9 and 17 were associated with good prognostic features including high hemoglobin levels, early clinical stage, beta2microglobulin less than 6 micro/mL, and low percentage of BMPC. A multivariate analysis for OS showed that S-phase PC greater than 3% (P = .010) and beta2microglobulin serum levels greater than 6 micro/mL (P = .024), together with monosomy of chromosome 13 (P = .031) and nontrisomy of chromosome 6 (P = .048) was the best combination of independent parameters for predicting survival in patients with MM. According to these results, chromosomal analysis is of great use in patients with MM at diagnosis to have a correct prognostic evaluation for clinical decision making.
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PMID:Prognostic value of numerical chromosome aberrations in multiple myeloma: A FISH analysis of 15 different chromosomes. 955 94


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