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)

Patients with a monoclonal gammapathy of undetermined significance (MGUS) are usually submitted to a periodical clinical follow-up, but it is not known if this surveillance can ameliorate the prognosis of a plasma cell malignancy that will be eventually detected. We compared the clinical and laboratory characteristics at onset, the response to chemotherapy and the survival, of 21 cases of newly diagnosed multiple myeloma (MM) arising from the malignant transformation of MGUS and 41 cases without a previous history of MGUS, recruited to the same first-line treatments over a 3-years period. The former group showed a significant lower frequency of advanced stages as well as other several prognostic factors of high risk including anemia, renal failure, bone lesions and increase of beta2 microglobulin and C-reactive protein levels. Despite a similar response to treatment of the two groups, MM arising from MGUS showed a significantly longer median survival than MM without prior MGUS. This was particularly true for stage I, while stages II and III behaved similarly. We conclude that the regular clinical monitoring of MGUS patients allowed the identification of earlier malignant transformation, when tumor burden is lower, as indicated by lower beta2 microglobulin levels and marrow plasmacytosis of stage I MM arising from MGUS. Moreover, a slower proliferation rate of myeloma cells, as suggested by lower C-reactive protein levels, may be considered so as to explain the longer survival of these patients.
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PMID:Clinical features and outcome of multiple myeloma arising from the transformation of a monoclonal gammapathy of undetermined significance. 1049 84

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

Serum levels of beta2-microglobulin (beta2m)-free HLA class I heavy chain (FHC) in 94 patients with multiple myeloma (MM) were higher than in 29 patients with monoclonal gammopathy of undetermined significance (MGUS) (P = 0.023) and in 97 sex- and age-matched healthy controls (P < 0.0001). Spearman correlation analysis indicated that in MM, FHC correlated with beta2m (r = 0.31, P = 0. 003) and the percentage of bone marrow plasma cells (BMPC%) (r = 0. 36, P = 0.002), whereas beta2m, in addition to BMPC% (r = 0.43, P = 0.0003), also correlated with creatinine levels (r = 0.63, P < 0.0001), haemoglobin levels (r = -0.35, P = 0.0007) and patient age (r = 0.34, P < 0.0011). Furthermore, MM patients with poor prognosis (beta2m >/= 6 mg/l) displayed higher FHC levels than those with a better prognosis (beta2m < 6mg/l) (P < 0.021). At variance from beta2m, these levels were not influenced by renal failure, as indicated by the lack of Spearman correlation of FHC with creatinine concentration and of statistical significance between the median FHC concentration of MM patients with creatinine < 176.6 micromol/l and those with creatinine >/= 176.6 micromol/l (P = 0.3). Stratification of patients according to disease activity and stage showed that FHC levels were only statistically different (P = 0.04) for disease activity, whereas beta2m and C-reactive protein were not. Taken together, our data indicate that serum FHC may be a useful disease marker in MM.
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PMID:Increased serum levels of beta2m-free HLA class I heavy chain in multiple myeloma. 1052 2

Interleukin-6 (IL-6) is a proinflammatory cytokine that is normally tightly regulated and expressed at low levels, except during infection, trauma, or other stress. Among several factors that down-regulate IL-6 gene expression are estrogen and testosterone. After menopause or andropause, IL-6 levels are elevated, even in the absence of infection, trauma, or stress. IL-6 is a potent mediator of inflammatory processes, and it has been proposed that the age-associated increase in IL-6 accounts for certain of the phenotypic changes of advanced age, particularly those that resemble chronic inflammatory disease [decreased lean body mass, osteopenia, low-grade anemia, decreased serum albumin and cholesterol, and increased inflammatory proteins such as C-reactive protein (CRP) and serum amyloid A]. Furthermore, the age-associated rise in IL-6 has been linked to lymphoproliferative disorders, multiple myeloma, osteoporosis, and Alzheimer's disease. This overview discusses the data relating IL-6 to age-associated diseases and to frailty. Like the syndrome of inappropriate antidiuretic hormone, it is possible that certain clinically important late-life changes are due to an inappropriate presence of IL-6.
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PMID:Age-associated increased interleukin-6 gene expression, late-life diseases, and frailty. 1077 63

High-dose therapy (HDT) has increased complete remission (CR) rates and survival in multiple myeloma (MM). We now report on continuous CR (CCR) and associated prognostic factors in 1000 consecutive patients receiving melphalan-based tandem HDT. Five-year CCR was 52% among 112 CR patients without chromosome 13 (triangle up13) abnormalities and with beta-2-microglobulin </= 2.5 mg/L, C-reactive protein </= 4 mg/L, and pre-HDT standard chemotherapy </= 12 months. Of all 390 CR patients without triangle up13 abnormalities, 35% enjoyed 5-year CCR but none of 54 with triangle up13 abnormalities. triangle up13 abnormalities, present in overall 16%, reduced 5-year event-free survival from 20% to 0% and overall survival from 44% to 16% (both P <.0001). CR and a second HDT cycle applied within 6 months both extended event-free and overall survival significantly, justifying further pursuit of HDT, especially toward curing non-triangle up13 MM. (Blood. 2000;95:4008-4010)
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PMID:Results of high-dose therapy for 1000 patients with multiple myeloma: durable complete remissions and superior survival in the absence of chromosome 13 abnormalities. 1084 42

Approximately 30% of myeloma patients express cyclin D1 RNA and protein. The low incidence of translocation t(11; 14) detected by conventional cytogenetics suggests that the up-regulation of cyclin D1 protein might result from other mechanisms as well as from gene amplification. Therefore, the frequency and the clinical and prognostic implications of cyclin D1 amplification were examined. We highly purified myeloma cells from bone marrow by magnetic cell sorting and analysed 50 myelomas by fluorescence in situ hybridization (FISH) using probes specific for cyclin D1 and 20 samples by immunoblotting to detect cyclin D1 expression. The amplification of cyclin D1 gene was found in 19 of 50 analysed patients and was associated with expression of cyclin D1 protein. The amplification correlated significantly with the bone marrow infiltration, plasma cell morphology and labelling index as well as serum beta2-microglobulin, C-reactive protein (CRP) and creatinine levels. In univariate analysis, the amplification of the cyclin D1 gene was a significantly unfavourable parameter with regard to overall survival (P = 0.0064) and progression-free survival (P = 0. 0005). In multivariate analysis, cyclin D1 amplification and serum beta2-microglobulin were independent and well-suited parameters for predicting survival. The detection of cyclin D1 amplification seems to be of promising prognostic value in multiple myeloma.
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PMID:Amplification of cyclin D1 gene in multiple myeloma: clinical and prognostic relevance. 1084 79

To improve the complete response (CR) rate in advanced multiple myeloma (MM) without increasing the toxicity of high-dose therapy, we have used a new conditioning regimen. A combination of BE-8 [an anti-interleukin 6 (IL-6) murine monoclonal antibody] and dexamethasone followed by high-dose melphalan (220 mg/m2) and autologous stem cell transplantation was used to treat a series of 16 patients with advanced multiple myeloma. A strong inhibition of IL-6 activity evaluated by quantification of C-reactive protein was observed in all patients and was correlated with the high CR rate achieved with this combination therapy.
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PMID:A combination of anti-interleukin 6 murine monoclonal antibody with dexamethasone and high-dose melphalan induces high complete response rates in advanced multiple myeloma. 1088 21

Since high levels of serum IL-6 predict a poor prognosis of patients with multiple myeloma (MM), we investigated if a related cytokine, oncostatin M (OSM), correlates with clinical or biochemical findings or has prognostic significance in patients with MM. Among 82 newly diagnosed MM patients, OSM was detected in the sera in 45 (55%). Serum OSM had a borderline statistical correlation with serum IL-6 (r = 0.198, p = 0.074) and C-reactive protein (r = 0.199, p = 0.074) concentrations. However, OSM did not have prognostic significance alone or in combination with other factors. The median survival of patients with detectable serum OSM concentration was 41 months (range 2-124 months) and of OSM negative patients 35 months (1-75 months). Serum OSM concentration was not associated with clinical factors or severity of bone disease at diagnosis. We conclude that serum OSM concentration is not a prognostic factor in MM patients.
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PMID:Serum oncostatin M in multiple myeloma: impact on disease severity and prognosis. 1091 39

We investigated the serum concentration of the interleukin-10 (IL-10), along with cytokines of interleukin-6 (IL-6) family (IL-6, IL-11 and oncostatin M - OSM), as well as soluble receptor for IL-6 (sIL-6R), in 121 patients with multiple myeloma (MM) and 28 healthy subjects. We studied the interactions between IL-10 and other cytokines, and the receptor. The correlation between IL-10 and some clinical and laboratory parameters associated with the disease activity were also analysed. The IL-10 was detectable in all patients with multiple myeloma and in all controls. The IL-10 concentration was significantly increased in myeloma patients compared with healthy persons (mean - 7.09 and 2.1 pg/ml, respectively) (p = 0.008). The level of IL-10 correlated positively with the advanced stage of disease estimated according to the Salmon and Durie classification (I versus III stage - p = 0.03). Higher values of IL-10 were found in patients with the light chain disease, hypercalcaemia, and correlated with the elevated concentrations of C-reactive protein (CRP). IL-6 was detected in 117 of the 121 patients and in all controls. The concentration of IL-6 was statistically increased in MM patients compared with control group (mean - 16.06 and 4.49 pg/ml, respectively) (p = 0.01). We found a positive correlation between IL-10 and IL-6 serum levels in MM patients. The relationship, expressed as Spearman's rank sum coefficient (rho = 0.249, p = 0.006) was significant. IL-11 was detected in 26 of the 121 MM patients and in 3 of the 28 healthy subjects at the mean concentration of 1.2 and 0.6 pg/ml respectively (p > 0.05). OSM was at detectable levels in 51 of the 121 patients and in only 4 of the 28 controls (mean - 3.84 and 0.1 pg/ml, p = 0. 002). The correlation between IL-10 and IL-11 levels in MM patients was not significant, but there was a strong statistical correlation between IL-10 and OSM concentrations (rho= 0.327, p = 0.0002). The serum concentration of sIL-6R was measurable in all patients and all controls (mean - 66.00 and 39.57 ng/ml respectively), but the difference between these groups was not significant. We found significant, positive correlation between the levels of IL-10 and sIL-6R (rho= 0.233, p = 0.01). In conclusion, we state that the serum concentrations of IL-10, IL-6, OSM and sIL-6R in MM patients may be a useful markers for the evaluation of the disease activity.
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PMID:Relationship between circulating interleukin-10 (IL-10) with interleukin-6 (IL-6) type cytokines (IL-6, interleukin-11 (IL-11), oncostatin M (OSM)) and soluble interleukin-6 (IL-6) receptor (sIL-6R) in patients with multiple myeloma. 1102 30

The importance of neoangiogenesis for the progressive growth and viability of solid tumors is well established. Recently, there has been growing evidence that angiogenesis might also be important in hematological malignancies, but only few data are available. In this report, we have studied the impact of bone marrow microvessel density and survival in patients with multiple myeloma (MM). Immunohistochemical CD34 stained paraffin-embedded bone marrow biopsies of 44 patients with newly diagnosed MM were studied. Microvessels were counted in 400 x magnification and the mean number of vessels per area in each sample was noted as the microvessel density (MVD). The median MVD was 48 vessels/mm2, the range was 0-125 vessels/mm2. Using a cut-off value of the median MVD in the Kaplan-Meier analysis, the median survival was 22.2 months in the group with the higher MVD and was not reached in the group with the lower MVD (P< 0.01). In a multivariate Cox regression analysis, using previously identified prognostic factors beta2-microglobulin, C-reactive protein (CRP), and age, MVD remained significant as a prognostic factor (P< 0.03).
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PMID:Bone marrow microvessel density is a prognostic factor for survival in patients with multiple myeloma. 1110 Jul 49


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