scholarly journals Patterns of Infectious Morbidity in Patients with Waldenström’s Macroglobulinaemia/Lymphoplasmacytic Lymphoma: A Population-Based Study

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 3350-3350
Author(s):  
Sigrun Helga Lund ◽  
Malin Hultcrantz ◽  
Lynn Goldin ◽  
Ola Landgren ◽  
Magnus Björkholm ◽  
...  
Keyword(s):  
Bacterial Infections ◽  
Viral Infections ◽  
Large Population ◽  
Population Based ◽  
Calendar Period ◽  
Lymphoplasmacytic Lymphoma ◽  
Population Based Study ◽  
Infectious Morbidity ◽  
Prophylactic Measures ◽  
Increased Risk

Abstract Background Infections are a major cause of morbidity and mortality in patients with hematologic malignancies. However, largely due to the rarity of Waldenström’s macroglobulinemia (WM)/lymphoplasmacytic lymphoma (LPL), the literature on infectious morbidity is limited. Using population-based data from Sweden, we estimated the risk of bacterial and viral infections among 2,608 LPL/WM patients compared to 10,433 matched controls. Patients and Methods We identified all WM/LPL patients diagnosed 1980-2005 in the nationwide Swedish Cancer and Patient Registries, as well as a national network database including all major hematology/oncology centers; duplicate records were removed. Follow-up time was up to 2006. For each WM/LPL patient, four population-based controls (matched by age, sex, and county of residence) were identified randomly from the Swedish population database. Information on type of infection and date of infection was obtained from the Patient Registry which captures information on all individual patient-based discharge diagnosis from inpatient (since 1964) and outpatient care (since 2000). Through linkage to the nationwide Cause of Death Registry, we identified dates of death for WM/LPL patients and controls. Cox proportional hazard models were used to estimate the overall risk of infections. Models were adjusted for sex, age, and calendar period. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated for individual infections. Results Overall, WM/LPL patients had a 3.4-fold (95% CI=3.1-3.6) elevated risk of developing any infection than controls (Figure). Compared to controls, the risk of developing bacterial and viral infections was 3.2-fold (95%; CI=2.9-3.5) and 6.0-fold (95% CI=4.9-7.3) higher, respectively. More specifically, WM/LPL patients had an increased risk (p<0.05) of the following types of bacterial infections: septicaemia (HR=9.3; 95% CI 3.7-23.5), endocarditis (HR=5.0; 95% CI 2.5-10.0), pneumonia (HR=3.8; 95% CI 3.4-4.2), meningitis (HR=3.4; 95% CI 1.1-10.3), cellulitis (HR=2.6; 95% CI 2.0-3.4), osteomyelitis (HR=1.9; 95% CI 1.01-3.6), and pyelonephritis (HR=1.6; 95% CI 1.2-2.4). Regarding viral infections, WM/LPL patients had an increased risk of herpes zoster (HR=9.2; 95% CI 6.7-12.6) and influenza (HR=2.3; 95% CI 1.5-3.5). The risk of infections was highest during the first year after diagnosis. Interestingly, WM/LPL patients diagnosed in the more recent calendar periods had significantly higher risk of infections (Figure). Compared to WM/LPL patients diagnosed in 1980-1989, patients diagnosed in 1990-1999 and 2000-2004 had a 1.5-fold (95% CI=1.3-1.6) and 1.8-fold (95% CI=1.6-2.1) increased risk of any infection, respectively. The same patterns were observed when bacterial infections were analyzed separately. In analysis focusing on viral infections; there was only a significant increased risk during the most recent calendar period (p=0.027). Females had a significantly lower risk of infections compared to males (p<0.001). Increasing age was significantly associated with a higher risk of infections (p<0.001). Discussion In this large population-based study including over 2,600 WM/LPL patients and 10,000 matched controls, we found that bacterial and viral infections represent a major threat to WM/LPL patients. This was particularly true during the first years following diagnosis. Importantly, the risk of infections increased in more recent years. The effects on infectious complications due to novel drugs in the treatment of WM/LPL need to be better defined and trials on prophylactic measures are needed. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

Multiple Myeloma and Infections: A Population-Based Study Based On 9,610 Multiple Myeloma Patients

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 945-945
Author(s):  
Cecilie Blimark ◽  
Ulf-Henrik Mellqvist ◽  
Ola Landgren ◽  
Magnus Björkholm ◽  
Malin L Hultcrantz ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Bacterial Infections ◽  
Viral Infections ◽  
Normal Population ◽  
Large Population ◽  
Population Based ◽  
First Year ◽  
Population Based Study ◽  
Prophylactic Measures ◽  
Increased Risk

Abstract Abstract 945 Background Infections are a major cause of morbidity and mortality in patients with multiple myeloma (MM). No large population-based evaluation has been made to assess the risk of infections in MM patients compared to the normal population. Therefore, we performed a large study, using population-based data from Sweden, to estimate the risk of bacterial and viral infections among 9,610 MM patients compared to 37,718 matched controls. Methods We gathered information on all MM patients reported to the nationwide Swedish Cancer Registry from 1988 to 2004, with follow-up to 2007. For each MM patient, four population-based controls (matched by age, sex, and county of residence) were identified randomly from the Swedish population database. Information on occurrence and date of infections was obtained from the centralized Swedish Patient registry that captures information on individual patient-based discharge diagnosis from inpatient (with very high coverage) and outpatient care (since 2000). Cox proportional hazard models were used to estimate the overall, one- and five-year risk of infections. In addition, the effect of gender, age and calendar period of diagnosis was evaluated. Hazard ratios (HRs) and confidence intervals (CIs) were calculated for the occurrence of different infections. Results Overall, MM patients had a 6-fold (HR= 5.9; 95% CI=5.7-6.1) risk of developing any infection compared to matched controls (Figure). The increased risk of developing a bacterial infection was 6-fold (HR=5.9; 95%; CI=5.6-6.1), and for viral infections 9-fold (HR=9.0; 95% CI=8.0-10.1), compared to controls. More specifically, MM patients had an increased risk (p<0.05) of the following bacterial infections: cellulitis (HR=2.6; 95% CI =2.2-3.1), osteomyelitis (HR=3.0; 95% CI 2.0–4.4), endocarditis (HR=4.4; 95% CI 2.9–6.6), meningitis (HR=14.5; 95% CI 9.1–23.0), pneumonia (HR=6.2; 95% CI 5.9–6.5), pyelonephritis (HR=2.5; 95% CI 2.1–3.0), and septicaemia (HR=13.7; 95% CI 12.5–14.9) and for the viral infections influenza (HR=5.4; 95% CI 4.4–6.7) and herpes zoster (HR=12.8; 95% CI 10.5–15.5). The risk of infections was highest during the first year after diagnosis; the risk of bacterial infections was 11-fold (95% CI 10.7–12.9) and the risk of viral infections was 18-fold (95% CI 13.5–24.4) higher compared to controls during the first year after diagnosis. MM patients diagnosed in the more recent calendar periods had significantly higher risk of infections, reflected in a 1.6-fold (95% CI=1.5-1.7) and 2-fold (95% CI=1.9-2.1) increased risk in patients diagnosed during 1994–1999 and 2000–2004, compared to patients diagnosed 1986–1993. Females had a significantly lower risk of infections compared to males (p<0.001). Increasing age was significantly associated with a higher risk of infections (p<0.001). Discussion In this large population-based study including over 9,000 MM patients and 35,000 matched controls, we found that bacterial and viral infections represent a major threat to myeloma patients. We found the risk of specific infections like pneumonia, and septicemia to be over ten times higher in patients than in controls during the first year after MM diagnosis. Importantly, the risk of infections increased in more recent years. The effect on infectious complications due to novel drugs in the treatment of MM needs to be established and trials on prophylactic measures are required. Disclosures: Mellqvist: Janssen, Celgene: Honoraria.

Monoclonal Gammopathy of Undetermined Significance and Risk of Infections: A Population-Based Study

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 4053-4053
Author(s):  
Sigurdur Y. Kristinsson ◽  
Tang Min ◽  
Ruth Pfeiffer ◽  
Magnus Björkholm ◽  
Lynn Goldin ◽  
...  
Keyword(s):  
Monoclonal Gammopathy ◽  
Bacterial Infections ◽  
Viral Infections ◽  
Population Based ◽  
M Protein ◽  
Risk Of Death ◽  
Prophylactic Measures ◽  
Increased Risk ◽  
Undetermined Significance

Abstract Abstract 4053 Background: Based on clinical case reports and small hospital-based patient series, monoclonal gammopathy of undetermined significance (MGUS) has been reported to increase morbidity due to bacterial infections; however, no comprehensive evaluation has been conducted. Patients and methods: Using population-based data from Sweden, we assessed the risks of viral and bacterial infections (reported to the Patient-Registry) in 5,326 MGUS patients diagnosed 1958–2006, compared to 20,161 matched population-based controls. We fit Cox proportional hazard models to estimate hazard ratios (HRs) as measures of risk. Results: At 5 years of follow-up MGUS patients had a 2.1-fold (95% confidence interval (CI) 2.1–2.3) increased risk of developing any infection compared to controls; at 10 years of follow-up, the risk was very similar (HR=2.2; 95% CI 2.0–2.3). MGUS patients had a 2.2-fold (95% CI 2.0–2.4) and 2.1-fold (95% CI 2.0–2.3) increased risk of developing bacterial infections at 5 and 10 years, respectively. A significantly increased risk (P<0.05) was found for pneumonia, osteomyelitis, septicemia, pyelonephritis, cellulitis, endocarditis and meningitis. We also assessed the risk of developing viral infections; compared to controls, MGUS patients had a 2.7-fold (95% CI 2.2–3.3) and 2.9-fold (95% CI 2.3–3.7) increased risk at 5 and 10 years, respectively, with a significantly increased risk for influenza and herpes infections (P<0.05). Risk of infections did not differ by MGUS isotype. MGUS patients with an M-protein >2.5 g/dL at diagnosis had higher risks of infections compared to those <0.5 g/dL. However, compared to controls the risk of infections was also significantly increased among MGUS patients with a concentration <0.5 g/dL. MGUS patients with (versus without) infections had no excess risk of developing multiple myeloma or related malignancies. Summary and Conclusions: Based on over 5,000 MGUS patients, we found a 2-fold higher risk of developing bacterial and viral infections, compared to controls. The risk was highest among MGUS patients with high M-protein concentrations at diagnosis (>2.5 g/dL); however, the risk was still significantly increased among those with a concentration <0.5 g/dL. Infections in patients with MGUS were not associated with an increased risk of malignant transformation. We recently showed that patients with MGUS have a 3-fold risk of death in bacterial infections. Our findings may have clinical implications for treatment strategies and prophylactic measures, as well as surveillance of MGUS patients. Disclosures: No relevant conflicts of interest to declare.

Migrainous Disorder and its Relation to Migraine Without Aura and Migraine with Aura. A Genetic Epidemiological Study

Cephalalgia ◽  
1996 ◽  
Vol 16 (6) ◽  
pp. 431-435 ◽  
Author(s):  
MB Russell ◽  
J Olesen
Keyword(s):  
Migraine With Aura ◽  
Migraine Without Aura ◽  
International Headache Society ◽  
Large Population ◽  
Population Based ◽  
Population Based Study ◽  
Female Ratio ◽  
First Degree Relatives ◽  
Increased Risk ◽  
Male Female Ratio

Migrainous disorder was analysed in a large population-based study of 4000 forty-year-old males and females. All interviews were conducted by one physician and the diagnostic criteria of the International Headache Society were used. Of the 48 people with migrainous disorder, 40 had migrainous disorder without aura and 9 had migrainous disorder with aura One person had co-occurrence of migrainous disorder with and without aura. The lifetime prevalence of migrainous disorder was 2.5% with a male: female ratio of 1:1.2. The first-degree relatives of probands with migrainous disorder were blindly interviewed. Compared with the general population, first-degree relatives of probands with migrainous disorder without aura had a slightly but less increased risk of migraine without aura than first-degree relatives of probands with migraine without aura. First-degree relatives of probands with migrainous disorder with aura had no increased risk of migraine with aura. We conclude that migrainous disorder without aura in some people is a type of migraine without aura and in other people not. Migrainous disorder with aura may be unrelated to migraine with aura. œ

Peripheral Neuropathy in MGUS and Progression to Amyloid Light-Chain Amyloidosis: A Population-Based Study Including 15,351 MGUS Cases

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 5444-5444
Author(s):  
Sæmundur Rögnvaldsson ◽  
Ingemar Turesson ◽  
Magnus Björkholm ◽  
Ola Landgren ◽  
Sigurður Yngvi Kristinsson
Keyword(s):  
Board Of Directors ◽  
Research Funding ◽  
Large Population ◽  
Diagnostic Delay ◽  
Population Based ◽  
Lymphoproliferative Disorders ◽  
First Year ◽  
Advisory Committees ◽  
Population Based Study ◽  
Increased Risk

Introduction Peripheral neuropathy (PN) is a common disorder that can be caused by amyloid light-chain amyloidosis (AL). AL is a rare disorder caused by the deposition of amyloid fibers, originating from malignant plasma cells. Amyloid deposition in peripheral nerves causes PN and is present in 35% of patients with newly diagnosed AL. Diagnosis of AL can be difficult, leading to under-recognition, diagnostic delay, and delayed treatment. Virtually all instances of AL are preceded by monoclonal gammopathy of undetermined significance (MGUS). MGUS is relatively common with a reported prevalence of 4.2% in the general Caucasian population over the age of 50 years. Although MGUS is usually considered asymptomatic, a significant proportion of affected individuals develop PN. However, we are not aware of any studies assessing how PN affects risk of MGUS progression to AL. We were therefore motivated to conduct a large population-based study including 15,351 Swedish individuals with MGUS diagnosed 1986-2013. Methods Participants diagnosed with MGUS between 1986-2013 were recruited from a registry of a nationwide network of hematology- and oncology centers and the Swedish Patient Registry. We then cross-linked data on recorded diagnoses of AL and PN from the Swedish Patient Registry, diagnoses of lymphoproliferative disorders form the Swedish Cancer Registry, and dates of death from the Cause of Death Registry to our study cohort. Individuals with a previous history of other lymphoproliferative disorders were excluded from the study. A multi-state survival model was created. At inclusion, participants started providing person time into the PN or the non-PN states depending on whether they had a previous diagnosis of PN. Those with MGUS who developed PN after inclusion were included into the PN state at the time of PN diagnosis and provided person time in the PN state after that. We then created a Cox proportional hazard regression model with AL as the endpoint. Participants were censored at diagnosis of other lymphoproliferative disorders. We adjusted for sex, age, and year of MGUS diagnosis. Results We included 15,351 participants with MGUS. Of those, 996 participants provided person-time with PN (6.5%). About half of those had PN at MGUS diagnosis (55%). A total of 174 cases of AL were recorded, with AL being more common among those who had PN (2.1% vs 1.0% p=0.002). Those who had PN had a 2.3-fold increased risk of AL as compared to those who did not have PN (hazard ratio (HR): 2.3; 95% confidence interval (95% CI): 1.5-3.7; p<0.001). The results were similar for those who had PN at MGUS diagnosis and those who did not. More than half of AL cases (53%) were diagnosed within one year after MGUS diagnosis. The rate was even higher among those with PN, with 82% of AL cases among those who presented with PN being diagnosed within one year after MGUS diagnosis. In the first year after inclusion, the incidence of AL was 15.2 and 6.1 per 1000 person-years for participants with and without PN respectively (HR: 1.8; 95% CI:1.0-3.4; p=0.04). Participants with PN continued to have an increased risk of progression to AL after the first year with an incidence of AL of 2.6 per 1000 person-years as compared to 1.1 per 1000 person-years among participants who did not have PN (HR:2.4; 95% CI: 1.1-5.0; p=0.02) (Figure). Discussion In this large population-based study, including 15,351 individuals with MGUS, we found that individuals with MGUS who develop PN have an increased risk of progression to AL. In fact, individuals with MGUS who have PN at MGUS diagnosis might already have AL. This risk of AL was highest during the first year after MGUS diagnosis with participants with PN having a higher risk than those who did not have PN. PN continued to be associated with a higher risk of MGUS progression to AL throughout the study period. This is the largest study that we are aware of assessing the association of PN and MGUS progression to AL. Since this is a registry-based study based on recorded diagnoses, some clinical data, including MGUS isotype, is not available. These findings suggest that increased awareness of PN as a feature of MGUS might decrease diagnostic delay and improve outcomes for patients with AL. Figure Disclosures Landgren: Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Sanofi: Membership on an entity's Board of Directors or advisory committees; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Theradex: Other: IDMC; Adaptive: Honoraria, Membership on an entity's Board of Directors or advisory committees; Merck: Other: IDMC; Abbvie: Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Karyopharm: Membership on an entity's Board of Directors or advisory committees; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding.

The risk of debilitating falls in Manitobans living with prostate cancer (pc).

2013 ◽  
Vol 31 (6_suppl) ◽  
pp. 244-244
Author(s):  
Joel Roger Gingerich ◽  
Pascal Lambert ◽  
Malcolm Doupe ◽  
Paul Joseph Daeninck ◽  
Marshall W. Pitz ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
Cumulative Incidence ◽  
Large Population ◽  
Univariate Analysis ◽  
Population Based ◽  
Community Dwelling ◽  
Low Grade ◽  
Population Based Study ◽  
Increased Risk

244 Background: Falls and fall-related injuries are important patient safety problems. Some studies suggest that pc patients have higher fall rates, however the severity of these falls is unknown. We sought to measure if pc patients are at increased risk of a debilitating fall requiring hospitalization. Methods: This is a retrospective population-based study utilizing the Manitoba Cancer Registry and Manitoba Health administrative databases. Our cohort consists of all community-dwelling patients living in Manitoba Canada who were diagnosed with pc between 2004 and 2008. These individuals were matched by age, sex, and time of diagnosis with up to three cancer-free controls. Debilitating falls were defined as falls/fractures requiring hospitalization and were identified using ICD-9 and -10 billing codes. A competing risk model was used to compare debilitating falls between the pc and cancer-free cohorts and expressed as sub-hazard ratios. Follow-up ended December 31, 2009. Results: 2,903 pc patients were identified along with 8,686 matched controls. The mean age was 69.3 and 68.8 respectively. The median follow-up was 3.05 years. Debilitating falls were identified in 109 patients (3.8%) with pc and 345 (4%) matched controls. The cumulative incidence of debilitating falls for those with pc vs cancer-free controls were: 1.08% vs. 1.13% at 1-year and 5.25% vs. 5.96% at five years of follow-up (SHR = 0.95, 95% CI = 0.77 – 1.18, p = 0.65). On univariate analysis, patients with stage IV pc were at higher risk of falls compared to matched controls. This difference was not significant on multivariate analysis though (SHR = 1.19, 95% CI = 0.74 – 1.89, p = 0.48). On multivariate analysis, patients with a Gleason score of ≤6 experienced a reduced risk of debilitating falls compared to matched controls (SHR = 0.44, 95% CI = 0.27 – 0.72, p = 0.001), whereas patients with other Gleason scores did not. The analysis was similar when patients with fractures were excluded. Conclusions: In this large population-based study, the 1- and 5-year cumulative incidence of debilitating falls did not differ significantly for patients with vs without pc. In fact, compared to matched controls, low grade pc patients were less likely to experience a debilitating fall.

Improving Survival in Patients with Chronic Lymphocytic Leukemia - Population Based Study

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 2852-2852
Author(s):  
Marek Trneny ◽  
Petra Obrtlikova ◽  
Jiri Schwarz ◽  
Tomas Pavlik ◽  
Jan Muzik ◽  
...  
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Large Population ◽  
Relative Survival ◽  
Population Based ◽  
Lymphocytic Leukemia ◽  
Calendar Period ◽  
Population Based Study ◽  
Female Ratio ◽  
Number Of Patients ◽  
Full Picture

Abstract Abstract 2852 Background: The chronic lymphocytic leukemia is the most frequent leukemia in the western world predominantly diagnosed in older population. It is still considered to be incurable disease, but the significant proportion of patients do not require any treatment during the course of disease. The outcome is influenced by many factors including leukemia biology, patient's status, complications based on immune dysfunction, treatment choice, supportive care and other factors. Clinical trials are focused on highly selected population in need of treatment. Population based data providing the full picture is extremely rare, especially with the treatment data. The presented population-based study provides the full picture of CLL population including the untreated as well treated cohorts in different age and gender subgroups. Methods: Using data from the nationwide, population-based Czech Cancer Registry (CCR) and Czech population life-tables provided by the Czech Statistical Office to the Human Mortality Database stratified by age, sex, and calendar time we characterized trends in incidence, mortality and prevalence for all pts diagnosed with CLL in Czech Republic 1979–2008 and relative survival for patients diagnosed in five calendar periods (1980–1984, 1985–1989, 1990–1994, 1995–1999, 2000–2003). All computations were performed using Stata 10.1™ software. Results: Altogether 13, 162 pts with CLL diagnosis have been reported to the CCR from 1979 till 2008. Median age 70 years at diagnosis remains unchanged during the whole period, the male/female ratio was 1.5: 1. The CLL incidence increased from 3.3 in 1979 to 5.6 per 100 thousands inhabitants in 2008. The therapy was administered in 54% of all patients, with the significant trend to decrease with calendar period from 60.4% for pts dg in 1980–84 period to 42.3% in 200019403 period. The treatment was administered in 70.2% of pts younger than 60 y compared to 50.1% of older than 60y with the trend to decreased number of treated pts during the time in both cohorts (from 78.5% to 55.3% for younger and from 55.4% to 38.7% for older cohort). The improvement in five years relative survival ratios (RSRs; 95% confidence interval) with calendar period was observed for all patients starting at 0.46 (0.39–0.53), 0.48 (0.42–0.55), 0.52 (0.46–0.59), 0.60 (0.54–0.66) to 0.69 (0.62–0.74). The 5 y RSRs was better for untreated patients compared to treated pts resp. with improvement in both cohorts from 0.53 (0.44–0–62) and 0.34 (0.25–0.45) resp. in 1980–4 period to 0.77 (0.70–0.84) and 0.51 (0.42–0.60) resp. in 2000–3 period. The same trend was observed for young and old, untreated and treated pts. The females have significant better outcome compared to males in all cohorts, young as well old, untreated as well treated. Conclusions: In this large population-based study with more than 13, 000 patients we confirmed the increased CLL incidence together with decreased need of treatment which can be explained by the higher number of patients diagnosed in early stages in the recent time. The patients without need of treatment have siginificantly better 5y RSRs compared to pts with need of treatment, the females have significantly better 5y RSRs compared to males consistently in all subgroups. The patient's survival was improved with calendar period for the whole CLL population as well for the younger and older, females and males, untreated as well treated cohort. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Peripheral Neuropathy Is Associated with an Increased Risk of Fractures in Individuals with Monoclonal Gammopathy of Undetermined Significance: A Population-Based Study Including 15,351 MGUS Cases

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 1914-1914
Author(s):  
Sæmundur Rögnvaldsson ◽  
Sigrun Thorsteinsdottir ◽  
Ingemar Turesson ◽  
Magnus Björkholm ◽  
Ola Landgren ◽  
...  
Keyword(s):  
Peripheral Neuropathy ◽  
Board Of Directors ◽  
Monoclonal Gammopathy ◽  
Research Funding ◽  
Large Population ◽  
Population Based ◽  
Advisory Committees ◽  
Population Based Study ◽  
Increased Risk ◽  
Swedish Patient

Abstract Introduction: Monoclonal gammopathy of undetermined significane (MGUS) is the precursor of multiple myeloma (MM) and related disorders. MGUS is relatively common in the general population with a reported prevalence of 4.2% over the age of 50. Although MGUS is usually considered asymptomatic, affected individuals have been shown to have an increased risk of fractures. This is believed to be related to an early form of MM bone disease characterized by abnormal bone architecture. Peripheral neuropathy (PN) has also been shown to be associated with MGUS. Currently, the prevalence of PN in MGUS is unclear, with reports ranging from 3 to 70%. PN has been associated with an increased risk of falls and fractures, especially in diabetic neuropathy, the most common type of PN. However, we are not aware of any studies assessing how PN affects fracture risk in individuals with MGUS. Therefore, we were motivated to create a large population-based study to assess how PN affects the risk of fractures in MGUS. Methods: We included all MGUS cases diagnosed in Sweden between 1986 and 2013 and recorded in a registry of a nationwide network of hematology- and oncology centers or in the Swedish patient registry. We then cross-linked data from the Swedish Patient Registry, Cancer Registry, and Cause of Death Registry to our study cohort. Individuals with a previous history of other lymphoproliferative disorders were excluded from the study. We created a multi-state survival model. At inclusion participants started providing person time into the PN or the non PN states depending on whether they had a previous diagnosis of PN or not. Those with MGUS who developed PN after inclusion were included into the PN state at the time of PN diagnosis and provided person time into the PN state after that. We then created a Cox proportional hazard regression model with the endpoint defined as the first fracture of any type after inclusion with participants being censored at diagnosis of MM or related disorders. We adjusted for sex, age, year of MGUS diagnosis and previous fracture in the 2 years before inclusion. Results At total of 15,351 individuals with MGUS were enrolled and followed for a median of 3.2 years, providing a total of 76,141 years of person time. Of those, 951 individuals provided a total of 3,497 years of person time with PN, being followed for a median of 2.7 years. A total of 3,121 fractures were observed, 2,970 among those without PN and 151 among those with PN. Results from an adjusted Cox regression model showed that those who had PN had a higher risk of having a first fracture than did those who did not have PN (hazard ratio (HR): 1.21, 95% confidence interval (95%CI): 1.02-1.42, p=0.027). Discussion In this large population-based study including 15,351 individuals with MGUS we found that individuals with MGUS who also have PN have an increased risk of fractures as compared to those who only have MGUS. In a previous study, we have already showed that PN does not affect the risk of MGUS progression. Therefore, it is unlikely that these findings are attributed to fractures caused by active undiagnosed MM. These findings suggest that the increased fracture risk observed in individuals with MGUS can at least partly be attributed to concomitant PN. We are currently validating these results within the iStopMM trial, a large prospective MGUS screening study. Disclosures Landgren: Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Consultancy, Research Funding; Pfizer: Consultancy; Karyopharm: Consultancy; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Amgen: Consultancy, Research Funding; Merck: Membership on an entity's Board of Directors or advisory committees.

scholarly journals Incidence of Venous Thromboembolism and Impact on Mortality in Patients with Primary CNS Lymphoma: A Population Based Study

Blood ◽  
2017 ◽  
Vol 130 (Suppl_1) ◽  
pp. 754-754
Author(s):  
Anjlee Mahajan ◽  
Ann M Brunson ◽  
Theresa H.M. Keegan ◽  
Aaron S. Rosenberg ◽  
Ted Wun
Keyword(s):  
Major Bleeding ◽  
Proportional Hazards ◽  
Large Population ◽  
Steering Committee ◽  
Population Based ◽  
Cox Proportional Hazards ◽  
Population Based Study ◽  
Risk Of Death ◽  
Proportional Hazards Regression ◽  
Increased Risk

Abstract Background: Venous thromboembolism (VTE) is a known complication of cancer, with a high incidence in patients with both gliomas and lymphoma. Recent studies have shown a high risk of intracranial bleeding in glioma patients treated for VTE with anticoagulation. To date, there are no large, population-based studies describing the incidence of VTE in patients with primary central nervous system lymphoma (PCNSL). Methods: Using the California Cancer Registry, we identified patients with a first histologic diagnosis of PCNSL from 2005-2014 and linked these cases to the California hospitalization and emergency department databases. Patients with a VTE within 6 months prior to PCNSL diagnosis were excluded (n=11). We calculated cumulative incidence of VTE and major bleeding and associated 95% confidence intervals (CI), adjusted for the competing risk of death. Multivariable Cox proportional hazards regression models, using the methods of Fine and Gray to adjust for competing risk of death, were used to analyze factors associated with VTE and major bleeding. Models included sex, race/ethnicity, age at diagnosis, neighborhood sociodemographic status, health insurance at diagnosis, Elixhauser comorbidities, HIV status, initial treatment (chemotherapy, radiation, or CNS procedure), and prior VTE (&gt; 6 months prior to diagnosis). The major bleeding model additionally included VTE type as a time dependent covariate. The association of VTE and major bleeding with PCNSL-specific mortality was analyzed using multivariable Cox proportional hazards regression models; VTE and major bleeding were included as time dependent covariates. Results are presented as adjusted hazard ratios (HR) and 95% CI. Results: There were 992 patients with a PCNSL identified. VTE occurred in 143 patients (14.4%). Of the VTE events, 52% were pulmonary emboli [(PE +/- deep vein thrombosis (DVT)], 23% proximal DVT and 22% distal DVT. The 3- and 12-month cumulative incidences of VTE were 10.2% (CI: 8.4-12.2%) and 13.6% (CI: 11.5-15.8%), respectively (Figure 1). Patients who received chemotherapy had over 2-fold increased risk of developing VTE (HR=2.42, CI: 1.33-4.42) compared to those who did not receive chemotherapy, and those who received radiation were also at increased risk of VTE (HR=1.56 CI: 1.07-2.27). Asian/Pacific Islanders had a decreased risk of VTE compared to non-Hispanic Whites (HR=0.37, CI: 0.21-0.66). Major bleeding occurred in 156 patients (15.7%). Of the major bleeding events, 53% were intracranial hemorrhage, 33% were gastrointestinal bleeds, 12% of patients required a transfusion and 3% had unspecified bleeding. The 3- and 12-month cumulative incidences of major bleeding were 9.8% (CI: 8.1-11.8%) and 13.2% (CI: 11.1-15.3%), respectively (Figure 2). PE and proximal DVT were associated with increased risk of major bleeding (HR=4.57, CI: 2.43-8.60 and HR=5.95, CI: 2.47-14.34, respectively). In the PCNSL specific mortality models, PE was associated with increased risk of death (HR=1.81, CI: 1.14-2.87), though DVT (proximal or distal) was not. Patients with major bleeding were at over 2-fold increased risk of PCNSL death compared to those without major bleeding (HR=2.34, CI: 1.71-3.19). Conclusions: The incidence of VTE in this large population-based study of patients with PCNSL was high at 14.4%, with most VTE events occurring within the first 3 months after diagnosis. Risk factors associated with VTE included treatment with either chemotherapy or radiation. PE and proximal DVT were associated with increased risk of major bleeding, suggesting these patients may have received anticoagulation, and as recently shown in glioma patients, are at a high risk of intracranial hemorrhage. In addition, PE and major bleeding were both independently associated with higher PCNSL mortality. Disclosures Wun: Janssen: Other: Study steering committee and research support (site PI); Pfizer: Other: Study steering committee and research support (site PI).

scholarly journals Personal and family history of immune-related conditions increase the risk of plasma cell disorders: a population-based study

Blood ◽  
2011 ◽  
Vol 118 (24) ◽  
pp. 6284-6291 ◽  
Author(s):  
Ebba K. Lindqvist ◽  
Lynn R. Goldin ◽  
Ola Landgren ◽  
Cecilie Blimark ◽  
Ulf-Henrik Mellqvist ◽  
...  
Keyword(s):  
Family History ◽  
Autoimmune Disease ◽  
Large Population ◽  
Population Based ◽  
Personal History ◽  
Population Based Study ◽  
Inflammatory Conditions ◽  
Increased Risk ◽  
Plasma Cell Disorders ◽  
History Of

Abstract The associations between immune-related conditions and multiple myeloma (MM) and monoclonal gammopathy of undetermined significance (MGUS) have previously been investigated with inconsistent results. In a large population-based study, we identified 19 112 patients with MM, 5403 patients with MGUS, 96 617 matched control subjects, and 262 931 first-degree relatives. We calculated odds ratios (ORs) and 95% confidence intervals (CIs) for the association of MM and MGUS with immune-related conditions by use of logistic regression. A personal history of all infections combined was associated with a significantly increased risk of MM (OR = 1.2; 95% CI, 1.1-1.3), and a personal history of all conditions in the categories infections (OR = 1.6; 95% CI, 1.5-1.7), inflammatory conditions (OR = 1.4; 95% CI, 1.2-1.5), and autoimmune diseases (OR = 2.1; 95% CI, 1.9-2.4) was associated with a significantly increased risk of MGUS. Several specific immune-related conditions elevated the risk of MM and/or MGUS. A family history of autoimmune disease was associated with a significantly increased risk of MGUS (OR = 1.1; 95% CI, 1.00-1.2), but not MM. Our findings suggest that immune-related conditions and/or their treatment are of importance in the etiology of MGUS and possibly MM. The association of both personal and family history of autoimmune disease with MGUS indicates the potential for shared susceptibility for these conditions.

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