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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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| 4. |
- Kristinsson, Sigurdur Y., et al.
(författare)
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Monoclonal gammopathy of undetermined significance and risk of infections: a population-based study
- 2012
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Ingår i: Haematologica. - : Ferrata Storti Foundation (Haematologica). - 1592-8721 .- 0390-6078. ; 97:6, s. 854-858
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Tidskriftsartikel (refereegranskat)abstract
- No comprehensive evaluation has been made to assess the risk of viral and bacterial infections among patients with monoclonal gammopathy of undetermined significance. Using population-based data from Sweden, we estimated risk of infections among 5,326 monoclonal gammopathy of undetermined significance patients compared to 20,161 matched controls. Patients with monoclonal gammopathy of undetermined significance had a 2-fold increased risk (P < 0.05) of developing any infection at 5- and 10-year follow up. More specifically, patients with monoclonal gammopathy of undetermined significance had an increased risk (P < 0.05) of bacterial (pneumonia, osteomyelitis, septicemia, pyelonephritis, cellulitis, endocarditis, and meningitis), and viral (influenza and herpes zoster) infections. Patients with monoclonal gammopathy of undetermined significance with M-protein concentrations over 2.5 g/dL at diagnosis had highest risks of infections. However, the risk was also increased (P < 0.05) among those with concentrations below 0.5 g/dL. Patients with monoclonal gammopathy of undetermined significance who developed infections had no excess risk of developing multiple myeloma, Waldenstrom macroglobulinemia or related malignancy. Our findings provide novel insights into the mechanisms behind infections in patients with plasma cell dyscrasias, and may have clinical implications.
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| 6. |
- 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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| 7. |
- Kristinsson, Sigurdur Y, et al.
(författare)
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Patterns of hematologic malignancies and solid tumors among 37,838 first-degree relatives of 13,896 patients with multiple myeloma in Sweden.
- 2009
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Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 125:9, s. 2147-2150
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 8. |
- Kristinsson, Sigurdur Y, et al.
(författare)
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Patterns of survival and causes of death following a diagnosis of monoclonal gammopathy of undetermined significance. A population-based study.
- 2009
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Ingår i: Haematologica. - : Ferrata Storti Foundation. - 0390-6078 .- 1592-8721. ; 94:12, s. 1714-1720
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: There are limited data on survival patterns among patients with monoclonal gammopathy of undetermined significance. DESIGN AND METHODS: We compared the survival of 4,259 patients with monoclonal gammopathy of undetermined significance, collected from hematology outpatient units in Sweden, with the survival of the general population by computing relative survival ratios. We also compared causes of death in these patients with those in 16,151 matched controls. RESULTS: One-, 5-, 10-, and 15-year relative survival ratios were 0.98 (95% CI 0.97-0.99), 0.93 (0.91-0.95), 0.82 (0.79-0.84), and 0.70 (0.64-0.76), respectively. Younger age at diagnosis of the gammopathy was associated with a significantly lower excess mortality compared to that in older patients (p<0.001). The excess mortality among patients with gammopathy increased with longer follow-up (p<0.0001). IgM (versus IgG/A) gammopathy was associated with a superior survival (p=0.038). Patients with monoclonal gammopathy of undetermined significance had an increased risk of dying from multiple myeloma (hazards ratio (HR)=553; 95% CI 77-3946), Waldenström's macroglobulinemia (HR=infinity), other lymphoproliferative malignancies (6.5; 2.8-15.1), other hematologic malignancies (22.9; 8.9-58.7), amyloidosis (HR=infinity), bacterial infections (3.4; 1.7-6.7), ischemic heart disease (1.3; 1.1-1.4), other heart disorders (1.5; 1.2-1.8), other hematologic conditions (6.9; 2.7-18), liver (2.1; 1.1-4.2), and renal diseases (3.2; 2.0-4.9). CONCLUSIONS: Our finding of decreased life expectancy in patients with monoclonal gammopathy of undetermined significance, which was most pronounced in the elderly and explained by both malignant transformation and non-malignant causes, is of importance in the understanding and clinical management of this disease. The underlying mechanisms may be causally related to the gammopathy, but may also be explained by underlying disease that led to the detection of the hematologic disease. Our results are of importance since they give a true estimation of survival in patients with monoclonal gammopathy of undetermined significance diagnosed in clinical practice.
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| 9. |
- 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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| 10. |
- Lindqvist, Ebba K., et al.
(författare)
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Personal and family history of immune-related conditions increase the risk of plasma cell disorders : a population-based study
- 2011
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Ingår i: Blood. - : American Society of Hematology. - 0006-4971 .- 1528-0020. ; 118:24, s. 6284-6291
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Tidskriftsartikel (refereegranskat)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. (Blood. 2011; 118(24): 6284-6291)
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