Familial characteristics of autoimmune and hematologic disorders in 8,406 multiple myeloma patients: a population-based case-control study

A population-based case-control study was conducted to evaluate risk of developing multiple myeloma (MM) associated with personal history of autoimmune diseases and occurrence of autoimmune and selected hematologic disorders in first-degree relatives. Data were obtained for all (n = 8,406) MM cases diagnosed in Sweden (1958-1998), with linkable relatives, 16,543 matched controls and first-degree relatives of cases (n = 22,490) and controls (n = 44,436). Odds ratios (ORs) were calculated to quantify the risk of MM in relation to personal/family history of 32 autoimmune disorders. Familial aggregation of malignancies was evaluated in a marginal survival model using relatives as the cohort. The risk for MM was significantly elevated among subjects with a personal history of pernicious anemia (OR = 3.27; 2.22-4.83) and individuals with a family history of systemic lupus erythematosus (OR = 2.66; 1.12-6.32). Compared with controls, relative risk (RR) of MM was significantly increased (RR = 1.67; 1.02-2.73) in relatives of cases, particularly relatives of probands aged > or =65 at diagnosis (RR = 2.50; 1.19-5.27). Risks were nearly 4-fold elevated among female relatives (RR = 3.97; 1.54-10.2) and among relatives of female probands (RR = 3.74; 1.58-8.83). MM cases had more cases of monoclonal gammopathy of undetermined significance (MGUS) among their relatives than controls, but the numbers were too small to be conclusive. There was generally no increase in risk of MM in probands whose relatives had hematologic malignancies other than MM. These findings do not support a strong association between personal/familial autoimmune diseases and MM. However, MM itself shows significant familial aggregation, implicating the etiologic importance of this type of hematological neoplasm and perhaps MGUS in germ line genes.     

Patterns of hematologic malignancies and solid tumors among 37,838 first‐degree relatives of 13,896 patients with multiple myeloma in Sweden

There are emerging data to suggest a role for genetic factors in the pathogenesis of multiple myeloma (MM). Based on small numbers, certain solid tumors have been reported to occur more frequently among blood relatives of patients with MM. Using population‐based data, we assessed risks for hematologic malignancies, monoclonal gammopathy of undetermined significance (MGUS), and solid tumors among first‐degree relatives of patients with MM. We included 13,896 patients with MM and 54,365 matched controls. Also we identified first‐degree relatives of patients with MM (n = 37,838) and controls (n = 151,068). Using a marginal survival model, we estimated relative risks (RRs) and 95% confidence intervals (CIs) for hematologic and solid tumors among family members of patients with MM and controls as measures of familial aggregation. Compared with relatives of controls, relatives of patients with MM had an increased risk of developing MM (RR = 2.1; 95% CI 1.6–2.9), MGUS (2.1; 1.5–3.1), acute lymphoblastic leukemia (ALL) (2.1; 1.0–4.2), any solid tumor (1.1; 1.0–1.1) and bladder cancer (1.3; 1.0–1.5). No significantly increased risk was found for other hematologic or solid malignancies. Our findings support a role for a shared susceptibility (genetic, environmental or both) that predisposes to MM, MGUS, ALL and bladder cancer. © 2009 UICC     

Alcohol consumption and risk of Hodgkin's lymphoma and multiple myeloma: a multicentre case-control study.

BACKGROUND: Few studies have analysed the association between alcohol intake and Hodgkin's lymphoma (HL) or multiple myeloma (MM) risks. MATERIALS AND METHODS: A multicentre population-based case-control study of 363 HL, 270 MM cases, and 1771 controls offered the opportunity to evaluate the relationship between alcohol and HL/MM risks. Unconditional logistic regression was carried out to estimate odds ratios (ORs) and 95% confidence intervals (CIs), associated with alcohol intake (servings per week, grams per day of ethanol intake) or duration of exposure (year). RESULTS: For HL, considering nonsmokers only, ever drinkers had a significantly decreased risk than never drinkers (OR=0.46). Significantly lower risks in all levels of total alcohol intake were also detected, considering servings per week (OR for one to four servings per week=0.51, 95% CI 0.32-0.82; OR for five to nine servings per week=0.39, 95% CI 0.21-0.73; OR for 10-19 servings per week=0.26, 95% CI 0.12-0.54; OR for >or=20 servings per week=0.34, 95% CI 0.15-0.79) and grams per day of ethanol intake (OR for 0.1-9.0 g/day=0.45, 95% CI 0.27-0.74; OR for 9.1-17.9 g/day=0.52, 95% CI 0.30-0.90; OR for 18.0-31.7 g/day=0.27, 95% CI 0.13-0.57; OR for >31.7 g/day=0.35, 95% CI 0.15-0.79). In the analysis for ever-smoking HL cases and controls, ever drinkers had the same risk as never drinkers. For MM, ever drinkers had a non-significantly decreased risk than non-drinkers (OR=0.74), and ORs in almost all consumption levels were not significant (OR for 0.1-9.0 g/day=0.93; OR for 9.1-17.9 g/day=0.82; OR for 18.0-31.7 g/day=0.47; 95% CI 0.28-0.81; OR for >31.7 g/day=0.68). For HL and MM, the beverage type did not affect the risk significantly, and no consistent dose-response relationships were found, considering intensity or duration of alcohol consumption. CONCLUSIONS: Our study indicates a protective effect of alcohol consumption for nonsmoking HL cases.     

Pesticide exposures and multiple myeloma in Iowa men

A population-based case-control study of 173 White men with multiple myeloma (MM) and 650 controls was conducted in Iowa (United States), an area with a large farming population, to evaluate the association between MM, agricultural risk factors, and exposure to individual pesticides. A slight nonsignificantly elevated risk for MM was seen among farmers (odds ratio [OR]=1.2, 95 percent confidence interval [CI]=0.8–1.7). Although slight excesses were observed, there were no significant associations between MM and handling either classes of pesticides or specific pesticides. Thus, this study found little evidence to suggest an association between risk of MM and farming or pesticides.Ms Brown and Dr Blair are with the Epidemiology and Biostatistics Program, National Cancer Institute, Bethesda, MD, USA. Dr Burmoistor is with the Department of Preventive Medicine, University of Iowa, Iowa City, IA, USA. Dr Everett is with the Department of Internal Medicine, Orlando Regional Medical Center, Orlando, FL, USA. Address correspondence to Ms Brown, Epidemiology and Biostatistics Program, National Cancer Institute, Executive Plaza North, Room 415, Bethesda, MD, USA. This project was supported in part by a grant from the National Institute of Environmental Health Sciences (ES 03099).     

Familial Multiple Myeloma: Report on Two Families and Discussion of Screening Options

Multiple myeloma (MM) is a relatively rare haematological malignancy seen in older persons. It has an unknown aetiology and usually occurs incidentally within a family. However, several families have been reported with multiple cases of MM, so that the existence of hereditary MM has been postulated although no causative germline mutations have been detected so far. First-degree relatives of MM patients have been reported to have a relative risk between two and four times higher than normal of developing MM and we presume the risks are higher for relatives in the case of familial MM. Here we report on two families with MM who requested presymptomatic screening of healthy relatives. Although risk estimates for asymptomatic relatives in these types of families are not available, a clinically significant risk of developing MM cannot be excluded. We suggest that, in a research setting, screening for MM could be offered to individuals with more than one first-degree affected relative, or to those with one first-degree and at least one second-degree relative with MM. We propose a screening programme of annual protein electrophoresis of blood and urine, starting at age 40 (or earlier if a family member presented with MM at a younger age).     

Smoking and risk of non-Hodgkin's lymphoma and multiple myeloma

Population-based case-control interview studies of 622 White men with non-Hodgkin's lymphoma and 820 controls from Iowa and Minnesota (United States) and 173 White men with multiple myeloma and 452 controls from Iowa offered the opportunity to investigate the relationship of these cancers with smoking. Risks were significantly elevated for all lymphoma (odds ratio [OR]=1.4), high-grade lymphoma (OR=2.3), and unclassified lymphoma (OR=2.8) for cigarette smokers. Dose-response gradients were not seen with intensity of cigarette use, but risks for these subtypes were greatest for cigarette smokers of longest duration. Similar elevations in risks were seen for tobacco users. The risk of multiple myeloma was not significantly elevated for either tobacco users or cigarette smokers. The findings from this study confirm the lack of an association between smoking and multiple myeloma and provide some support for an association between tobacco use and certain subtypes of non-Hodgkin's lymphoma.Ms Brown and Dr Blair are with the Epidemiology and Biostatistics Program, National Cancer Institute. Dr Everett is with the Department of Internal Medicine, Orlando Regional Medical Center, Orlando, FL, USA. Drs Gibson and Schuman are in the Department of Epidemiology, University of Minnesota, Minneapolis, MN, USA. Dr Burmeister is in the Department of Preventive Medicine, University of Iowa, Iowa City, IA, USA. Address correspondence to Ms Brown, Epidemiology and Biostatistics Program, National Cancer Institute, Executive Plaza North, Room 415C, Bethesda, MD 20892, USA. This work was supported in part by a grant from the National Institute of Environmental Health Sciences (ES 03099).     

Multiple myeloma and diesel and other occupational exposures in swedish construction workers

We examined the relationships between occupational exposures and the risk of multiple myeloma among male construction workers in Sweden. A total of 446 myeloma subjects were identified among 365,424 male workers followed from 1971 to 1999. Occupational exposure was assessed using a semiquantitative job-exposure matrix, based on a survey carried out by the Construction Industry's Organization for Working Environment, Occupational Safety and Health in Sweden. Rate ratios (RRs) in the exposed groups relative to the unexposed groups were estimated by Poisson regression. We found an increased risk (RR = 1.3, 95% CI 1.04-1.71) among construction workers exposed to diesel exhaust. Adjustment for other occupational exposures did not change this estimate (RR = 1.3, 95% CI 1.00-1.77). However, there was no monotonic increase in risk with estimated level of exposure (RR for low = 1.4, moderate = 1.1, high = 1.4). There was no evidence of increased risk associated with the other occupational exposures among these construction workers, including asbestos, asphalt, cement dust, metal dust, mineral wool, organic solvents, stone dust and wood dust. Occupational exposure to diesel exhaust in the Swedish construction industry may present a small risk of multiple myeloma, but lack of an exposure-response trend tempers our ability to draw clear conclusions.     

Healthcare costs of multiple myeloma: an Italian study

KOLEVA D., CORTELAZZO S., TOLDO C. & GARATTINI L. (2011) European Journal of Cancer Care 20 , 330–336
Healthcare costs of multiple myeloma: an Italian study Few economic evaluations are currently available on multiple myeloma (MM) and they address treatment‐related rather than disease‐related costs. We estimated resource utilisation and costs associated with MM in an Italian haematology department. This was a single‐centre observational study which followed retrospectively for 2 years 90 patients with MM stages II–III. To investigate the association between costs and age as a prognostic factor for treatment eligibility, patients were classified in two age groups (under 65 or >65). The annual average cost per patient was very similar in the two subgroups. Drugs and hospitalisations were the largest cost components. Differences between the two age groups were significant only for drugs, hospital admissions and day hospital (DH) days. Autologous stem‐cell transplantation (ASCT) accounted for more than 80% of the non‐pharmacological therapy costs, being nearly double in the younger patients. Cost of elderly patients is comparable with that of younger ones who generally receive expensive procedures such as ASCT. The higher hospital costs of younger patients were counterbalanced by supportive pharmaceutical care and DH days for older patients, mainly in the group treated with new immunomodulatory agents. Further multi‐centre studies on larger samples of patients are needed.     

Familial and second primary pancreatic cancers: a nationwide epidemiologic study from Sweden

Familial risk of pancreatic cancer has been mainly assessed through case-control studies based on reported but not medically verified cancers in family members. We used the nationwide Swedish Family-Cancer Database on 10.2 million individuals and 21,000 pancreatic cancers to calculate standardized incidence ratios (SIRs) and 95% confidence intervals (CIs) for pancreatic cancer in 0- to 66-year-old offspring of parents with pancreatic or other specified tumors. Additionally, SIRs for second primary pancreatic cancers were analyzed after any first neoplasm. SIRs for pancreatic cancer (1.68, 95% CI 1.16-2.35) and pancreatic adenocarcinoma (1.73, 95% CI 1.13-2.54) were increased when a parent presented with pancreatic cancer. The risk was not dependent on diagnostic age of offspring or parents. Pancreatic cancer was associated with parental lung, rectal or endometrial cancer and with melanoma. SIRs for pancreatic cancer were 10.01 and 7.96 among offspring who were diagnosed before age 50 years when parents were diagnosed with squamous cell and adenocarcinoma of the lung, respectively, before age 60 years. The population-attributable proportion of familial pancreatic cancer was 1.1%. Risks for second pancreatic cancers were increased in men and women after small intestinal, colon and bladder cancer. The degree of familial clustering for pancreatic cancer and its population-attributable proportion were lower than the data cited in the literature. Clustering of pancreatic cancer with sites presenting in hereditary nonpolyposis colorectal cancer was noted. The strong association of pancreatic and lung cancers is puzzling, and it remains unclear to what extent this represents familial sharing of smoking habits.     

Plantar melanoma: a case-control study in Paraguay

In Paraguay, the plantar surface of the foot is the most common site for malignant melanoma, as it is in several other populations worldwide, most notably in those of African descent. Here, we report the results of the first case-control study of plantar melanoma, carried out in Paraguay. Sixty incident, histologically confirmed cases of plantar melanoma and 256 hospital controls were recruited in 11 hospitals throughout the country during1988-93. Information was collected on general demographic, social, and lifestyle variables, on external exposures of feet (shoe wear, work activities,injuries),and on some constitutional factors (skin, eye and haircolor,and pigmented lesions of the feet). Few of the factors examined appeared to be associated with the risk of plantar melanoma. Adjusted for possible confounders, the strongest association was found for reported injuries (odds ratio [OR] = 40.9, 95 percent confidence interval [CI] = 14.8-112.7) and for occurrence of naevi on the soles (OR = 5.9, CI = 2.5-14.3). Walking barefoot did not seem to contribute to the risk although an outdoor workplace was associated with an increased melanoma occurrence (OR = 2.3, CI = 1.1-4.8).Future studies should be aware of problems of recall bias with respect to previous injuries, and ensure that evaluation of pigmentation of the sole is carried out blind to case/control status. This revised version was published online in July 2006 with corrections to the Cover Date.     

Smoking and the risk of leukemia, lymphoma, and multiple myeloma (Sweden)

While several epidemiologic studies have indicated a link between smoking and the risk of developing hema-tolymphoproliferative cancers (chiefly leukemias, lymphomas, and multiple myelomas), in particular myeloid leukemia, the role of tobacco in the etiology of these neoplasms remains unclear. To evaluate the potential impact of tobacco use on development of leukemia, lymphoma, and multiple myeloma, we conducted a cohort study of 334,957 Swedish construction workers using prospectively collected exposure-information with complete long-term follow-up. A total of 1,322 incident neoplasms occurred during the study period, 1971-91. We found no significant association between smoking status, number of cigarettes smoked, or duration of smoking and the risk of developing leukemias, lymphomas, or multiple myeloma. There was a suggestion of a positive association between smoking and the risk of developing Hodgkin's disease, although the rate ratios were not significantly elevated, except for young current smokers. No positive dose-risk trends emerged. Our study provides no evidence that smoking bears any major relationship to the occurrence of leukemias, non-Hodgkin's lymphomas, or multiple myeloma.     

Controversies in multiple myeloma: Evidence-based update

The US Food and Drug Administration (FDA) approved 10 new drugs for the treatment of multiple myeloma (MM) over the last two decades. The influx of new anti-myeloma agents with high efficacy and acceptable tolerability add complexity to the clinical decision-making process. First, treatment of smoldering multiple myeloma (SMM) remains investigational to date, although a randomized trial showed a survival gain in high-risk patients receiving lenalidomide. Second, in newly diagnosed MM, the majority of contemporary induction regimens have been studied in single-arm trials or compared to an older regimen, which complicates evidence-based treatment selection. Third, the role of consolidation chemotherapy followed by autologous stem cell transplant (ASCT) needs to be revisited in the context of highly effective agents, as newer regimens— such as carfilzomib, lenalidomide, and dexamethasone—are able to achieve extremely deep responses equivalent to or exceeding those seen after conventional induction and ASCT. Fourth, risks and benefits of maintenance therapy should also be redefined and individualized, as long-term survival and safety data accumulate. Here we selected four clinical settings where controversies exist, reviewed evidences behind conflicting treatment strategies, and asked myeloma experts to discuss evidence-based recommendations.     

多发性骨髓瘤综合治疗现状与进展

多发性骨髓瘤（MM）是浆细胞克隆增生性恶性肿瘤,其治疗效果较差,迄今仍视为不可治愈的疾病。近年来着眼于MM细胞内信号通路、骨髓微环境及二者的相互作用,MM的治疗有了很大进展。该文综述了MM的化学治疗、造血干细胞移植、生物治疗、支持治疗及免疫治疗现状及其进展。     

Prognostic significance of surface markers expressed in multiple myeloma: CD56 and other antigens

Multiple myeloma (MM) is characterized by increased numbers of malignant plasma cells. Plasma cells, that represent the terminal differentiation of B lymphocytes, have considerable heterogeneity of surface markers expressed on them. Some studies showed the prognostic significance of several immunophenotypic molecules on MM cells. Here, we review several surface markers related to their prognostic significance in MM patients. We also report that CD56-negative MM is the unique entity characterized by poor prognosis with high incidence of extramedullary disease, Bence Jones protein, renal insufficiency, thrombocytopenia and plasmablastic morphology.     

Role of platelet-derived growth factor-AB in tumour growth and angiogenesis in relation with other angiogenic cytokines in multiple myeloma

Angiogenesis is a complex process essential for the growth, invasion, and metastasis of various malignant tumours, including multiple myeloma (MM). Various angiogenic cytokines have been implicated in the angiogenic process. Among them, platelet-derived growth factor-AB (PDGF-AB) has been reported to be a potent stimulator of angiogenesis in many solid tumours and haematological malignancies, including MM. The aim of the study was to investigate the relationship between PDGF-AB, microvascular density (MVD), and various angiogenic cytokines, such as basic fibroblast growth factor (b-FGF), angiogenin (ANG), and interleukin-6 (IL-6), in MM patients. Forty-seven MM patients before treatment, 22 of whom were in plateau phase, were studied. We determined the serum levels of the aforementioned cytokines and MVD in bone marrow biopsies before and after treatment. Mean serum values of PDGF-AB, b-FGF, ANG, and MVD were significantly higher in patients compared with controls and with increasing disease stage. Significant positive correlations were observed between serum PDGF-AB, ANG, and IL-6 levels and MVD. Furthermore, we found significant positive correlations between PDGF-AB and b-FGF, IL-6, ANG, and β2 microglobulin. We also found that patients with high MVD had statistically significantly higher serum levels of PDGF-AB when a median MVD value of 7.7 was used as the cutoff point. Furthermore, a significant difference was found in serum levels of PDGF-AB between pre- and post-treatment patients. Finally, survival time was significantly higher in the low MVD group versus the high MVD group (76 vs 51 months). Our results showed that there is a strong positive correlation between PDGF-AB and the studied angiogenic cytokines and MVD. It seems that PDGF-AB plays a role in the complex network of cytokines inducing bone marrow neovascularization in patients with MM.     

Thalidomide: present and future in multiple myeloma

Multiple myeloma continues to be an incurable disease. The understanding of the disease’s pathophysiology has significantly improved over the past few years, partly due to the discovery of the role of immunomodulatory agents and the study of their mechanism of action. Thalidomide, the first of the immunomodulatory family to be used in the management of multiple myeloma, proved not only to be effective in the treatment of multiple myeloma, but also instigated a wide range of in vitro and in vivo studies to define the pathophysiology of the plasma cell dyscrasia. The attention thalidomide has received in the past and recent history has not been without a price. The drug has a side-effect profile that, if managed appropriately, provides the most unique active molecule in the management of the disease, where it maintains the same response rate in newly diagnosed patients as in advanced relapsed/refractory multiple myeloma patients.     

硼替佐米治疗多发性骨髓瘤的临床初步研究

Objective： To explore the outcome and side-effects in patients with multiple myeloma treated with velcade and combined chemotherapy. Methods： 6 patients with multiple myeloma were treated with the combination of velcade and dexamethasone or DVD （V-DVD regimen） chemotherapy. Results： 6 patients responded to treatment. 4 patients achieved complete remission （CR）, 1 achieved partial remission （PR） and 1 achieved micro responded （MR）. Major toxicities consisted of peripheral neuropathy, thrombocytopenia and hepatic impairment. Conclusion： Velcade combined chemotherapy is an effective and safety treatment for patients with multiple myeloma.