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)

We compared the effect of high-dose therapy together with autologous peripheral blood stem cell transplantation (autoPBSCT) in 60 patients with multiple myeloma (MM) with 90 patients who underwent conventional chemotherapy. We scored the prognostic factors according to our reported classification system that includes measurements of serum albumin, serum beta-2-microglobulin, and morphology of myeloma cells selected by multivariate analysis. We separated the patients into three risk groups at stratification level I (low, intermediate and high) and into two risk groups at stratification level II (low and high). AutoPBSCT tended to be as effective for high, as for low-risk patients in level I, and was obviously as helpful for high, as for low-risk patients in stratification II. In conclusion, high-risk patients with MM should be treated with high-dose therapy accompanied with autoPBSCT like low-risk patients.
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PMID:High-dose chemotherapy and autologous peripheral blood stem cell transplantation in high-risk multiple myeloma. 1528 13

To determine the clinical significance of the T helper 1(Th1)/T helper 2 (Th2) ratio in multiple myeloma, the intracellular IFN-gamma and IL-4 were analyzed by flow cytometry in 56 patients with multiple myeloma. The mean Th1/Th2 ratio of cases in the initial diagnosis phase and the refractory phase were higher than that of the control group. The mean serum beta-2-microglobulin in the high Th1/Th2 subgroup was significantly higher than that in the normal Th1/Th2 subgroup (P < 0.05). In conclusion, the Th1/Th2 ratio was closely related to the disease status of multiple myeloma.
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PMID:High Th1/Th2 ratio in patients with multiple myeloma. 1560 60

Solitary plasmacytoma is plasma cell neoplasm. It is a localized bone disease and for this reason it is different from multiple myeloma (systemic plasma cell neoplasm). Sometimes, solitary plasmacytoma precedes a following multiple myeloma. Clinical findings of solitary plasmacytoma are related to the univocal localization on damaged bone, while laboratory findings could be similar to multiple myeloma (i.e. M component, kidney dysfunction, blood calcium alterations, increased beta-2-microglobulin). However, during a solitary plasmacytoma, laboratory findings could not be present contemporaneously such clinical complications (i.e. kidney failure, immunological disorders with a trend toward infectious disease and/or autoimmunity, neurological disorders, haematological disorders, amyloidosis, POEMS syndrome). These raise the reason because solitary plasmacytoma has better prognosis compared to multiple myeloma.
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PMID:Up-date on solitary plasmacytoma and its main differences with multiple myeloma. 1581 50

Morphological changes of plasma cells (PC) are common in multiple myeloma (MM). Loss of round or oval nuclear shape has been related to cell malignancy in human, and we looked for the occurrence of such morphological change on PC from bone marrow (BM) smears in a retrospective series of 169 MM patients at diagnosis. Nuclear shape changes of PC differed according to the patients (notch, dumb-bell, folded or monocytoid appearance), even in the same patient; all subtypes were pooled and defined as PC with irregular nuclear shape (PCIN). A significant number of PCIN (>/=5% of all BMPC) was found at diagnosis in 20.7%. Median survival was of 22 months for patients with >/=5% PCIN, and 41 months for others (p=0.0001). Significant relationship was observed with prognostic parameters related intrinsic malignancy of the tumour process but not with beta-2-microglobulin (b2m). A clear-cut relationship was found also between PCIN and hypodiploidy (p=0.0001), but not with deletion of chromosome 13. This study emphasises the relationship between PCIN, an easy-to-ascertain marker of intrinsic malignancy of the tumour process, and adverse prognosis.
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PMID:Irregular nuclear shape of bone marrow plasma cells defines a multiple myeloma subgroup related to hypodiploidy and to short survival. 1586 7

In all, 451 myeloma patients, 51% previously untreated, underwent elective single autotransplantation after 200 mg/m(2) melphalan between 1985 and 2001 at the Royal Marsden Hospital. The therapy sequence was: Induction (vincristine, doxorubicin, methylprednisolone+/-cyclophosphamide), marrow or filgrastim-mobilized blood stem cell harvest, autograft, and interferon-alpha2b maintenance. A total of 27 (6%) died of transplant-related toxicity, all within 3 months. Complete or near-complete remission was seen in 59% with an overall response rate of 91%. Subsequent disease progression was seen in 285, and 17 died of unrelated causes. In all, 206 patients were alive at the last follow-up, 6 months to 17.7 years post-transplant (median 65 months); 122 without disease progression at 6 months to 17.7 years (median 58 months). The median overall (OS) and event-free (EFS) survivals were 5.9 and 2.4 years, with 10-year OS and EFS probabilities of 31.4 and 16.5%, respectively. In Cox analysis, it was seen that significantly longer OS occurred for patients who had beta-2-microglobulin <3.5 mg/l (P<0.0001), age <60 years (P=0.001) and albumin > or =35 g/l (P=0.009). EFS was also longer if beta-2-microglobulin was <3.5 mg/l (P=0.0056) and patients were <60 years of age (P=0.033). We conclude that with a single planned autograft, patients with myeloma have an excellent outcome.
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PMID:An elective single autograft with high-dose melphalan: single-center study of 451 patients. 1589 15

In the present study the immunohistochemical expression of Bcl-xl, a downstream target of the IL-6-controlled signal transducer and activator of transcription-3 (Stat3) was studied in 40 multiple myeloma (MM) cases before treatment and 11 MM patients at relapse. Correlation analysis was performed between Bcl-xl expression, C-reactive protein (CRP) level, beta-2-microglobulin (beta2m), microvessel density (MVD), and clinical outcome. Before treatment 28 (70%) patients demonstrated a Bcl-xl expression similar to normal plasma cells ("normal pattern"), while 12 (30%) patients demonstrated an elevated expression in a subgroup of the malignant plasma cells. At relapse, no change in Bcl-xl expression was observed as compared to pretreatment sample. No correlation was observed between the Bcl-xl expression and the level of CRP and b2m. In addition, no significant correlation was observed between the Bcl-xl expression and the MVD, but MVD was significantly increased as compared to normal bone marrow biopsy specimens (p=0.02). Patients with an elevated or normal Bcl-xl expression showed no statistically significant difference in overall and event-free survival. In summary, these data indicate that Bcl-xl is elevated in a subgroup of MM patients that so far did not correlate with CRP, b2m, MVD, and clinical outcome.
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PMID:Bcl-xl expression in multiple myeloma. 1596 82

To delineate multiple myeloma (MM) subgroups and their clonal evolution, we analyzed 81 newly diagnosed patients by interphase fluorescence in situ hybridization using a comprehensive probe set for 10 chromosomes and two IGH rearrangements. A median of 5 probes per patient displayed aberrant signal numbers (range, 1-10). Additional copies most frequently found were for 15q22, 19q13, 9q34, 11q23, and 1q21. Losses commonly observed were of 13q14.3, 17p13, and 22q11. Predominance of gain or loss was quantified by a copy number score (CS) for each patient. Two peaks (CS = +3 and CS = 0) were found by plotting patient copy number scores over CS values corresponding to hyperdiploid and nonhyperdiploid MM. Cluster analysis revealed four major branches: (i) gain of 9q, 15q, 19q, and/or 11q; (ii) deletion of 13q and t(4;14); (iii) t(11;14); and (iv) gain of 1q. Statistical modeling of an oncogenetic tree indicated that early independent events were gain of 15q/9q and/or 11q, t(11;14); deletion of 13q followed by t(4;14); and gain of 1q. Aberrations of 17p13, 22q11, 8p12, and 6q21 were found as subsequent events. MM with gain of 1q was delineated as a subentity with significantly higher beta-2-microglobulin and lower hemoglobin levels, indicating a poor prognosis. From our results, we propose a model of MM for clonal evolution.
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PMID:Delineation of distinct subgroups of multiple myeloma and a model for clonal evolution based on interphase cytogenetics. 1600 33

Aberrant methylation of tumor suppressor genes (TSG) has been studied in multiple myeloma (MM). We determined the methylation status of the FHIT (fragile histidine triad) gene, a putative TSG, in 48 patients with MM. Clinical association with its methylation status was then analyzed. The FHIT gene methylation was observed in 21 of the 48 patients (44%). No association between FHIT gene methylation and clinical variables such as age, gender and clinical stage was found. However, the estimated 50% survival time of the methylated group was significantly shorter than that of the unmethylated group (18.2 vs. 45.1 months, P < 0.05). Univariate analysis revealed adverse prognostic factors: FHIT gene methylation (P = 0.028), poor performance status (I to IV, P = 0.002), anemia (< or =8.5 g/dL, P = 0.007), hypoalbuminemia (< or =3.5 g/dL, P < 0.002), high serum C-reactive protein levels (>0.5 mg/dL, P = 0.002), elevated beta-2-microglobulin serum levels (>6.5 mg/L, P < 0.001), and treatments not including autologous peripheral blood stem cell transplantation (auto-PBSCT) (P = 0.007). Multivariate analysis identified FHIT gene methylation [hazard ratio (HR) 1.722, 95% confidence interval (CI) 1.150-2.603, P = 0.009], elevated beta-2-microglobulin serum levels (>6.5 mg/L, HR 2.005, 95% CI 1.035-3.937, P = 0.004), and treatments not including auto-PBSCT are independent predictive variables. These findings indicate that aberrant methylation of the FHIT gene is an independent adverse prognostic factor in MM.
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PMID:Methylation status of fragile histidine triad (FHIT) gene and its clinical impact on prognosis of patients with multiple myeloma. 1631 63

The value of intensive therapy, including autologous stem cell transplantation, in newly diagnosed myeloma patients >60 years is not clear. We evaluated the impact of age (<60 years vs. 60-64 years) on survival in a prospective, population-based setting and compared survival with conventionally treated historic controls. The prospective population comprised 452 patients registered between 1998 and 2000. Of these, 414 received intensive therapy. The historic population, derived from our most recent population-based study on conventional therapy, comprised 281 patients. Of these, 243 fulfilled our eligibility criteria for intensive therapy. For patients undergoing intensive therapy it was found that two factors, beta-2-microglobulin and age <60 years vs. 60-64 years, had independent prognostic impact on survival. However, compared with the historic controls a survival advantage was found both for patients <60 (median 66 months vs. 43 months, P < 0.001) and 60-64 years (median 50 months vs. 27 months; P = 0.001). We conclude that in a population-based setting higher age adversely influences outcome after intensive therapy. Our results indicate that intensive therapy prolongs survival also at age 60-64 years but with less superiority than in younger patients.
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PMID:Impact of age on survival after intensive therapy for multiple myeloma: a population-based study by the Nordic Myeloma Study Group. 1664 45

Serum-free light chain (SFLC) levels are useful for diagnosing nonsecretory myeloma and monitoring response in light-chain-only disease, especially in the presence of renal failure. As part of a tandem autotransplantation trial for newly diagnosed multiple myeloma, SFLC levels were measured at baseline, within 7 days of starting the first cycle, and before both the second induction cycle and the first transplantation. SFLC baseline levels higher than 75 mg/dL (top tertile) identified 33% of 301 patients with higher near-complete response rate (n-CR) to induction therapy (37% vs 20%, P = .002) yet inferior 24-month overall survival (OS: 76% vs 91%, P < .001) and event-free survival (EFS: 73% vs 90%, P < .001), retaining independent prognostic significance for both EFS (HR = 2.40, P = .008) and OS (HR = 2.43, P = .016). Baseline SFLC higher than 75 mg/dL was associated with light-chain-only secretion (P < .001), creatinine level 176.8 microM (2 mg/dL) or higher (P < .001), beta-2-microglobulin 297.5 nM/L (3.5 mg/L) or higher (P < .001), lactate dehydrogenase 190 U/L or higher (P < .001), and bone marrow plasmacytosis higher than 30% (P = .003). Additional independent adverse implications were conferred by top-tertile SFLC reductions before cycle 2 (OS: HR = 2.97, P = .003; EFS: HR = 2.56, P = .003) and before transplantation (OS: HR = 3.31, P = .001; EFS: HR = 2.65, P = .003). Unlike baseline and follow-up analyses of serum and urine M-proteins, high SFLC levels at baseline-reflecting more aggressive disease-and steeper reductions after therapy identified patients with inferior survival.
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PMID:High serum-free light chain levels and their rapid reduction in response to therapy define an aggressive multiple myeloma subtype with poor prognosis. 1826 91


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