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- Kristinsson, Sigurdur Y, et al.
(författare)
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Arterial and venous thrombosis in monoclonal gammopathy of undetermined significance and multiple myeloma : a population-based study
- 2010
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Ingår i: Blood. - : American Society of Hematology. - 0006-4971 .- 1528-0020. ; 115:24, s. 4991-4998
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Tidskriftsartikel (refereegranskat)abstract
- Patients with multiple myeloma (MM) have an increased risk of venous thrombosis. Interestingly, excess risk of venous thromboembolism has been observed among patients with monoclonal gammopathy of undetermined significance (MGUS). Using population-based data from Sweden, we assessed the risks of venous and arterial thrombosis in 18,627 MM and 5326 MGUS patients diagnosed from 1958 to 2006, compared with 70,991 and 20,161 matched controls, respectively. At 1, 5, and 10 years after MM diagnosis, there was an increased risk of venous thrombosis: hazard ratios (95% confidence intervals) were 7.5 (6.4-8.9), 4.6 (4.1-5.1), and 4.1 (3.8-4.5), respectively. The corresponding results for arterial thrombosis were 1.9 (1.8-2.1), 1.5 (1.4-1.6), and 1.5 (1.4-1.5). At 1, 5, and 10 years after MGUS diagnosis, hazard ratios were 3.4 (2.5-4.6), 2.1 (1.7-2.5), and 2.1 (1.8-2.4) for venous thrombosis. The corresponding risks for arterial thrombosis were 1.7 (1.5-1.9), 1.3 (1.2-1.4), and 1.3 (1.3-1.4). IgG/IgA (but not IgM) MGUS patients had increased risks for venous and arterial thrombosis. Risks for thrombosis did not vary by M-protein concentration (> 10.0 g/L or < 10.0 g/L) at diagnosis. MGUS patients with (vs without) thrombosis had no excess risk of MM or Waldenström macroglobulinemia. Our findings are of relevance for future studies and for improvement of thrombosis prophylaxis strategies.
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- Kristinsson, Sigurdur Y., et al.
(författare)
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Deep vein thrombosis after monoclonal gammopathy of undetermined significance and multiple myeloma
- 2008
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Ingår i: Blood. - : American Society of Hematology. - 1528-0020 .- 0006-4971. ; 112:9, s. 3582-3586
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Tidskriftsartikel (refereegranskat)abstract
- Patients with multiple myeloma ( MM) have an increased risk of deep venous thrombosis (DVT), particularly when treated with immunomodulatory drugs. Recently, 2 small hospital-based studies observed persons with the MM precursor condition, monoclonal gammopathy of undetermined significance (MGUS), to be at increased risk of developing DVT. Among 4 196 197 veterans hospitalized at least once at US Veterans Affairs hospitals, we identified a total of 2374 cases of MGUS, and 39 272 persons were diagnosed with DVT ( crude incidence 0.9 per 1000 person-years). A total of 31 and 151 DVTs occurred among MGUS and MM patients, respectively ( crude incidence 3.1 and 8.7 per 1000 person-years, respectively; P <.01). Compared with the entire study population, the relative risk (RR) of DVT after a diagnosis of MGUS and MM was 3.3 (95% confidence interval [CI], 2.3-4.7) and 9.2 ( 95% CI, 7.9-10.8), respectively. The most prominent excess risk of DVT was found during the first year after diagnosis of MGUS ( RR = 8.4; 95% CI, 5.7-12.2) and MM ( RR = 11.6; 95% CI, 9.2-14.5). Among 229 MGUS cases (9.5%) that progressed to MM, only one person had a DVT diagnosis before transformation. Our findings suggest the operation of shared underlying mechanisms causing coagulation abnormalities among patients with MGUS and MM. (Blood. 2008; 112: 3582-3586)
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- Kristinsson, Sigurdur Y, et al.
(författare)
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Monoclonal gammopathy of undetermined significance and risk of skeletal fractures : a population-based study
- 2010
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Ingår i: Blood. - : American Society of Hematology. - 0006-4971 .- 1528-0020. ; 116:15, s. 2651-2655
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Tidskriftsartikel (refereegranskat)abstract
- Patients with multiple myeloma (MM) have an increased risk of fractures. On the basis of small numbers, patients with monoclonal gammopathy of undetermined significance (MGUS) have been reported to have an increased fracture risk. Using population-based data from Sweden, we assessed the risks of fractures in 5326 MGUS patients diagnosed from 1958 to 2006, compared with 20 161 matched controls. MGUS patients had an increased risk of any fracture at 5 (hazard ratio [HR] = 1.74; 95% confidence interval [CI], 1.58-1.92) and 10 (HR = 1.61; 95% CI, 1.49-1.74) years. The risk was significantly higher for axial (skull, vertebral/pelvis, and sternum/costae) compared with distal (arm and leg) fractures (P < .001). On the basis of 10 years of follow-up, there was an increased risk of vertebral/pelvic (HR = 2.37; 95% CI, 2.02-2.78), sternal/costae (HR = 1.93; 95% CI, 1.5-2.48), arm (HR = 1.23; 95% CI, 1.06-1.43), leg (HR = 1.40; 95% CI, 1.26-1.56), and other/multiple fractures (HR = 4.25; 95% CI, 3.29-5.51). Risks for fractures did not differ by isotype or M protein concentration at diagnosis. MGUS patients with (versus without) fractures had no excess risk of MM or Waldenström macroglobulinemia. Our results suggest that bone alterations are present in early myelomagenesis. Our findings may have implications for the development of better prophylaxis for bone disease in MGUS, and they provide novel clues on pathogenesis of MM bone disease.
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- Kristinsson, Sigurdur Y., et al.
(författare)
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Risk of lymphoproliferative disorders among first-degree relatives of lymphoplasmacytic lymphoma/Waldenstrom macroglobulinemia patients: a population-based study in Sweden
- 2008
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Ingår i: Blood. - : American Society of Hematology. - 1528-0020 .- 0006-4971. ; 112:8, s. 3052-3056
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Tidskriftsartikel (refereegranskat)abstract
- A role for genetic factors in the etiology of lymphoplasmacytic lymphoma/Waldenstrom macroglobulinemia (LPL/WM) is implicated based on prior findings from multiply affected families and small case-control and cohort studies. We identified 2144 LPL/WM patients (1539 WM [72%] and 605 LPL [28%]) diagnosed in Sweden, 8279 population-based matched controls, and linkable first-degree relatives of patients (n = 6177) and controls (n = 24 609). Using a marginal survival model, we calculated relative risks and 95% confidence intervals as measures of familial aggregation. We found first-degree relatives of LPL/WM patients to have 20-fold (4.1-98.4), 3.0-fold (2.0-4.4), 3.4-fold (1.7-6.6), and 5.0-fold (1.3-18.9) increased risks of developing LPL/WM, non-Hodgkin lymphoma (NHL), chronic lymphocytic leukemia (CLL), and monoclonal gammopathy of undetermined significance (MGUS), respectively. However, there was no evidence of an increased risk of developing multiple myeloma or Hodgkin lymphoma. In analyses stratified by type of first-degree relative (parent, sibling, offspring), age at diagnosis of the probands (greater or less than 70 years), and sex of the first-degree relative, we did not observe the risk estimates to be significantly different compared with the overall analyses. Our findings of highly increased risks of developing LPL/WM, NHL, CLL, and MGUS support the operation of shared susceptibility genes that predispose to LPL/WM and other lymphoproliferative disorders.
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- Landgren, Ola, et al.
(författare)
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Risk of plasma cell and lymphoproliferative disorders among 14621 first-degree relatives of 4458 patients with monoclonal gammopathy of undetermined significance in Sweden.
- 2009
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Ingår i: Blood. - : American Society of Hematology. - 0006-4971 .- 1528-0020. ; 114:4, s. 791-795
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Tidskriftsartikel (refereegranskat)abstract
- Familial clustering of the precursor condition, monoclonal gammopathy of undetermined significance (MGUS) has been observed in case reports and in smaller studies. Using population-based data from Sweden, we identified 4458 MGUS patients, 17505 population-based controls, and first-degree relatives of patients (n = 14621) and controls (n = 58387) with the aim to assess risk of MGUS and lymphoproliferative malignancies among first-degree relatives of MGUS patients. Compared with relatives of controls, relatives of MGUS patients had increased risk of MGUS (relative risk [RR] = 2.8; 1.4-5.6), multiple myeloma (MM; RR = 2.9; 1.9-4.3), lymphoplasmacytic lymphoma/Waldenström macroglobulinemia (LPL/WM; RR = 4.0; 1.5-11), and chronic lymphocytic leukemia (CLL; RR = 2.0; 1.2-2.3). Relatives of patients with IgG/IgA MGUS had a 4.0-fold (1.7-9.2), 2.9-fold (1.7-4.9), and 20-fold (2.3-170) elevated risk of developing MGUS, MM, and LPL/WM, respectively. Relatives of IgM MGUS patients had 5.0-fold (1.1-23) increased CLL risk and nonsignificant excess MM and LPL/WM risks. The results were very similar when we assessed risk by type of first-degree relative, age at MGUS (above/below 65 years), or sex. Risk of non-Hodgkin lymphoma or Hodgkin lymphoma was not increased among MGUS relatives. Among first-degree relatives of a nationwide MGUS cohort, we found elevated risks of MGUS, MM, LPL/WM, and CLL, supporting a role for germline susceptibility genes, shared environmental influences, or an interaction between both.
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