多发性骨髓瘤并发髓外浸润的临床分析

目的:了解多发性骨髓瘤(MM)髓外浸润的发生率及临床特点.方法:回顾分析357例MM患者中并发髓外浸润患者的临床表现、实验室检查、疗效及预后.结果:共有43例患者在初诊或治疗过程中出现髓外浸润,发生率为12.04%.Logistic回归分析,发现仅M蛋白类型与是否浸润相关(P<0.05).最常见的发病部位为软组织(19...     

Clinicopathological and prognostic characteristics of CD33-positive multiple myeloma

There have been few reports about the CD33 expression on multiple myeloma (MM) cells so far, showing that only a few patients expressed CD33 homogenously on their MM cells. However, in these reports, neither detailed clinical information nor its prognostic significance was described. Therefore, we analyzed the CD33 expression on MM cells from 63 newly diagnosed patients by flow cytometry and the correlation with other clinical parameters to determine the clinicopathological significance of this molecule. Fourteen (22%) patients were positive for CD33. Of the 14 patients with CD33+ MM, >80% of MM cells were positive in six (9.5%). The CD33+ patients had higher beta 2 microglobulin and lactate dehydrogenase levels and higher incidence of anemia and thrombocytopenia than did CD33- patients. The estimated 3-yr overall survival in CD33+ patients was significantly lower than in the CD33- ones (31% and 50%, respectively, P = 0.042). Especially, mortality within a year from diagnosis in the CD33+patients was higher than that in CD33- patients (43% and 10%, respectively, P = 0.005). Serial evaluation of CD33 expression showed that the amount of CD33 significantly increased after a variety of treatment including melphalan and steroid in individual patients. These results suggest that the CD33 expression might be associated with drug resistance to these conventional agents, and CD33 might be a useful target for the development of new therapeutic agents in MM.     

Substratification of patients with newly diagnosed standard-risk multiple myeloma

Despite the absence of high-risk cytogenetics and lower International Staging System (ISS) stages, a subset of patients with multiple myeloma (MM) experience poor overall survival (OS). We studied 1461 patients with newly diagnosed MM to identify patient and disease characteristics that predict a high-risk phenotype among standard-risk patients. Fifty-six percent of all patients presented with standard-risk disease. Among them, advanced age, extremes of body mass index, non-hyperdiploid karyotype and abnormal lymphocyte counts were associated with worse OS. Standard-risk patients with 0–1 of these adverse factors (hazard ratio [HR] 0·32, 95% confidence interval [CI] 0·24–0·43, P < 0·001) and 2 adverse factors (HR 0·54, 95% CI 0·41–0·72, P < 0·001) experienced better OS than high-risk patients. Two or more adverse factors were present in 17% of standard-risk patients and were associated with OS comparable to high-risk patients (HR 0·91, 95% CI 0·67–1·24, P = 0·548). Predictive power among standard-risk patients was improved using score groups compared to ISS stages. Patients with standard-risk MM are a heterogeneous group with one in six patients experiencing OS comparable to high-risk disease. Patients at risk can be identified using readily available patient and disease characteristics. These findings emphasize the importance of accurate risk stratification and help explain part of the heterogeneity observed in clinical practice.     

Comparative genomic hybridisation identifies two variants of smoldering multiple myeloma

Two variants of smoldering multiple myeloma (SMM) have been recognised: (i) an evolving type, characterised by a progressive increase in the M-protein size and short time to progression to overt multiple myeloma (MM) and (ii) a non-evolving type, with a long-lasting, stable M-protein and longer time to progression. Comparative genomic hybridisation (CGH) analyses in both subtypes of SMM (seven evolving and eight non-evolving SMM) were performed. Evolving SMM showed cytogenetic changes consistent with those found in de novo symptomatic MM (1q gains, chromosome 13 deletions) while the non-evolving variant showed no 1q gains and deletions were uncommon.     

Methylation status of fragile histidine triad (FHIT) gene and its clinical impact on prognosis of patients with multiple myeloma

Abstract:  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 (≤8.5 g/dL, P  = 0.007), hypoalbuminemia (≤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.     

Renal failure in multiple myeloma: reversibility and impact on the prognosis. Nordic Myeloma Study Group

The purpose of the present study was to analyse the importance and prognostic value of renal failure in multiple myeloma patients. The frequency and reversibility of renal failure in 775 multiple myeloma patients diagnosed between 1984-86 and 1990-92 in the Nordic countries were studied. Renal failure, defined as plasma creatinine > 130 micromol/l, was observed in 29% of the cases at the time of diagnosis. During the first year after diagnosis 58% achieved normalisation of p-creatinine, and this was achieved mainly during the first 3 months. Reversibility of renal failure was more frequently observed in patients with moderate renal failure, hypercalcaemia and low Bence-Jones protein excretion. In a multivariate analysis renal failure, high age, stage III disease and hypercalcaemia were independent prognostic factors for survival. Patients who needed dialysis had a poor prognosis, with a median survival of 3.5 months. A 12-months landmark analysis showed that reversibility of renal failure was a more important prognostic factor than response to chemotherapy. It is concluded that renal failure in multiple myeloma is reversible in about half the cases, and reversibility of renal failure improves long-term survival.     

Bortezomib in multiple myeloma

Multiple myeloma (MM) remains an incurable disease, and novel agents are therefore needed to improve outcome. Bortezomib is the first proteasome inhibitor to be approved by the US Food and Drug Administration and the European Agency for the Evaluation of Medicinal Products for the treatment of refractory/relapsed MM. Bortezomib has demonstrated significant anti-myeloma activity as a single agent in refractory/relapsed MM. When used in combination with other agents, responses have suggested the possibility of chemosensitization and synergy. All these facts have been the rationale for the use of bortezomib-based regimens as upfront treatment in young and elderly newly diagnosed MM patients. Furthermore, bortezomib does not appear to have an adverse effect on subsequent stem-cell collection. Bortezomib is well tolerated; most side-effects are only mild to moderate and manageable. Practical management of these side-effects is given so that they can be recognized and minimized by dose modification or concomitant therapy.     

Prognostic features of multiple myeloma

The outcome of myeloma patients is highly heterogeneous, with survival ranging from a few months to more than 10 years. Accordingly, investigation of prognostic factors may contribute to identification of risk categories and to provision of more accurate information about individual disease outcome. For many years prognostic factors have relied on clinical parameters such as age, hemoglobin level and renal function. Subsequently, biological parameters such as the proliferative activity of plasma cells and beta2-microglobulin have been added to the prognostic arsenal. More recently, cytogenetic and molecular markers with significant influence on disease outcome have been identified. Here we will review the most relevant prognostic factors reported in the literature in patients treated with both conventional chemotherapy and high-dose therapy followed by autologous stem-cell support, as well as in asymptomatic MM and MGUS patients.     

Genetic variations in multiple myeloma I: effect on risk of multiple myeloma

Few risk factors have been established for the plasma cell disorder multiple myeloma, but some of these like African American ethnicity and a family history of B-cell lymphoproliferative diseases suggest a genetic component for the disease. Genetic variation represents the genetic basis of variability in a population. The complex interplay between environment and genes for the development of cancer may therefore be influenced by genetic variations. A genetic variation may change the function of the gene, and if the genetic variation is associated with the risk of disease, that particular gene may be involved in the pathogenesis of disease. Genes of interest are genes involved in the normal development and function of the plasma cell and genes that protect us against exposures from the environment, for example, genes involved in the metabolism of xenobiotics, metabolism of folate and methionine, as well as genes involved in inflammation and DNA repair. Identification of genes with potential influence on cancer risk may help us to establish relevant laboratory studies on exposure and dose-response assessment and may help us to test the hypothesis in epidemiological studies. Knowledge of individual at high risk of cancer may offer promising insight for the prevention of cancer.     

Thalidomide in multiple myeloma: lack of response of soft-tissue plasmacytomas

Thalidomide is active in patients with refractory myeloma. Seventeen patients (nine men/eight women, median age 73 years) with multiple myeloma (MM) were treated with thalidomide. Fifteen patients had refractory disease and two untested relapse. The median dose of thalidomide was 500 mg (range, 200-800 mg). Nine of the 17 patients (53%) responded. The response rate was significantly higher in patients with no extramedullary disease than in those with soft tissue masses (75% CI: 43-95% versus 0%; P = 0.01)). Of note, no decrease in the size of soft tissue plasmacytomas was observed in all the five patients who had extramedullary involvement. This data suggests that the mechanism of action and effectiveness of thalidomide might depend on the site of the tumour cells.     

Telomere length is a critical determinant for survival in multiple myeloma

The variable clinical outcomes of Multiple Myeloma (MM) patients are incompletely defined by current prognostication tools. We examined the clinical utility of high‐resolution telomere length analysis as a prognostic marker in MM. Cohort stratification, using a previously determined length threshold for telomere dysfunction, revealed that patients with short telomeres had a significantly shorter overall survival (P < 0·0001; HR = 3·4). Multivariate modelling using forward selection identified International Staging System (ISS) stage as the most important prognostic factor, followed by age and telomere length. Importantly, each ISS prognostic subset could be further risk‐stratified according to telomere length, supporting the inclusion of this parameter as a refinement of the ISS.     

多发性骨髓瘤患者血清OPG检测及临床意义

目的：探讨OPG在多发性骨髓瘤（MM）患者血清中的表达水平及与骨病、预后的关系,初步探索其在MM骨病和预后判断中的作用。方法：采用双抗体夹心酶联免疫吸附试验（ELISA）技术分别检测28例MM患者和28例对照组的血清中OPG的水平。结果：MM患者的血清OPG水平为（222．4&#177;114．8）pg／ml,与对照组相比明显降低（P〈0．01）。0～1个骨损组血清OPG水平为（312．4&#177;129．6）pg／ml,而2～3个骨损组为（179．0&#177;59．4）pg／ml,0～1个骨损组明显高于2～3个骨损组（P〈0．01）。MM患者血清OPG水平与β2-微球蛋白相关（P〈0．01）,与球蛋白相关（P〈0．01）,与白蛋白无关（P〉0．05）,与临床分期、免疫学分型、血红蛋白、血钙未发现有相关性。结论：MM患者血清OPG水平明显低于正常对照,且其降低程度与骨损害的严重程度密切相关;同时,OPG水平与β2-微球蛋白呈负相关,提示血清OPG水平可能对MM的预后具有重要意义。     

Recent advances in cytogenetic characterization of multiple myeloma

The detection of cytogenetic abnormalities in multiple myeloma (MM) has received more importance over last years for risk stratification and the new risk‐adapted treatment strategies. Conventional G‐banding analysis should be included in a routine procedure for the initial diagnostic workup for patients suspected of MM. However, the detection of chromosomal abnormalities in MM by conventional cytogenetics is limited owing to the low proliferative activity of malignant plasma cells as well as the low number of plasma cells in bone marrow specimens. Fluorescence in situ hybridization (FISH) or microarray‐based technologies can overcome some of those drawbacks and detect specific target arrangements as well as chromosomal copy number changes. In this review, we will discuss different cytogenetic approaches and compare their strength and weakness to provide genetic information for risk stratification and prediction of outcome in MM patients.     

Prognostic value of serum free light chain ratio at diagnosis in multiple myeloma

The prognostic value of baseline serum free light chain ratio (sFLCR) was investigated in 94 multiple myeloma (MM) patients. sFLCR was calculated as kappa/lambda or lambda/kappa, depending on the patients' dominating monoclonal light chain. Median baseline sFLCR was 3.57 in kappa-MM patients, 45.09 in lambda-MM. 'High' sFLCR (> or = the observed median value for kappa- and lambda-MM respectively) correlated with elevated serum creatinine and lactate dehydrogenase, extensive marrow infiltration and light chain type MM. The 5-year disease-specific survival was 82% and 30% in patients with sFLCR lower than and equal or greater than the median, respectively (P = 0.0001). sFLCR was an independent prognostic factor.