| 1. |
- Beksac, Meral, et al.
(författare)
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Does Low-Molecular-Weight Heparin Influence the Antimyeloma Effects of Thalidomide? A Retrospective Analysis of Data from the GIMEMA, Nordic and Turkish Myeloma Study Groups
- 2015
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Ingår i: Acta Haematologica. - : S. Karger AG. - 1421-9662 .- 0001-5792. ; 133:4, s. 372-380
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Tidskriftsartikel (refereegranskat)abstract
- Background/Aim: Low-molecular-weight heparin (LMWH) has been shown to prolong survival among patients with solid tumors, but its role among myeloma patients is unknown. Patients: Data from the GIMEMA (Gruppo Italiano Malattie Ematologiche dell'Adulto), Nordic and Turkish myeloma study groups comparing melphalan and prednisolone with (MPT, n: 404) or without thalidomide (MP, n: 393) are analyzed for effects of LMWH. Forty percent (159/394) of the patients on MPT and 7.4% (29/390) in the MP arm received LMWH. Results: Thalidomide improved response and progression-free survival (PFS). Regardless of thalidomide treatment, response rate was higher among those receiving LMWH vs. none vs. other anticoagulants (58.1 vs. 44.9 vs. 50.4%, p = 0.01). PFS was significantly longer (median 32 vs. 21 and 17 vs. 17 months, p = 0.004) only among international scoring system (ISS) I patients receiving MPT +/- LMWH vs. MP +/- LMWH. The group of MPT patients who also received LMWH had a better OS compared to those who did not [45 months, 95% confidence interval (CI) 27.7-62.3, vs. 32 months, 95% CI 26.1-37.9; p = 0.034]. When multivariate analysis was repeated in subgroups, thalidomide was no longer a significant factor (response, PFS) among those receiving LMWH. Conclusion: Addition of LMWH to MPT, in particular in patients with low ISS, suggests additive effects, but the results are limited by the retrospective design of our study. (C) 2015 S. Karger AG, Basel
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| 2. |
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| 3. |
- Björkholm, Magnus, et al.
(författare)
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Success Story of Targeted Therapy in Chronic Myeloid Leukemia : A Population-Based Study of Patients Diagnosed in Sweden From 1973 to 2008
- 2011
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Ingår i: Journal of Clinical Oncology. - 0732-183X .- 1527-7755. ; 29:18, s. 2514-2520
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Tidskriftsartikel (refereegranskat)abstract
- Purpose Chronic myeloid leukemia (CML) management changed dramatically with the development of imatinib mesylate (IM), the first tyrosine kinase inhibitor targeting the BCR-ABL1 oncoprotein. In Sweden, the drug was approved in November 2001. We report relative survival (RS) of patients with CML diagnosed during a 36-year period. Patients and Methods Using data from the population-based Swedish Cancer Registry and population life tables, we estimated RS for all patients diagnosed with CML from 1973 to 2008 (n = 3,173; 1,796 males and 1,377 females; median age, 62 years). Patients were categorized into five age groups and five calendar periods, the last being 2001 to 2008. Information on use of upfront IM was collected from the Swedish CML registry. Results Relative survival improved with each calendar period, with the greatest improvement between 1994-2000 and 2001-2008. Five-year cumulative relative survival ratios (95% CIs) were 0.21 (0.17 to 0.24) for patients diagnosed 1973-1979, 0.54 (0.50 to 0.58) for 1994-2000, and 0.80 (0.75 to 0.83) for 2001-2008. This improvement was confined to patients younger than 79 years of age. Five-year RSRs for patients diagnosed from 2001 to 2008 were 0.91 (95% CI, 0.85 to 0.94) and 0.25 (95% CI, 0.10 to 0.47) for patients younger than 50 and older than 79 years, respectively. Men had inferior outcome. Upfront overall use of IM increased from 40% (2002) to 84% (2006). Only 18% of patients older than 80 years of age received IM as first-line therapy. Conclusion This large population-based study shows a major improvement in outcome of patients with CML up to 79 years of age diagnosed from 2001 to 2008, mainly caused by an increasing use of IM. The elderly still have poorer outcome, partly because of a limited use of IM.
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| 4. |
- Blimark, Cecilie, et al.
(författare)
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Multiple myeloma and infections: a population-based study on 9253 multiple myeloma patients.
- 2015
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Ingår i: Haematologica. - : Ferrata Storti Foundation (Haematologica). - 1592-8721 .- 0390-6078. ; 100:1, s. 107-13
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Tidskriftsartikel (refereegranskat)abstract
- Infections are a major cause of morbidity and mortality in patients with multiple myeloma. To estimate the risk of bacterial and viral infections in multiple myeloma patients, we used population-based data from Sweden to identify all multiple myeloma patients (n=9253) diagnosed from 1988 to 2004 with follow up to 2007 and 34,931 matched controls. Cox proportional hazard models were used to estimate the risk of infections. Overall, multiple myeloma patients had a 7-fold (hazard ratio =7.1; 95% confidence interval = 6.8-7.4) risk of developing any infection compared to matched controls. The increased risk of developing a bacterial infection was 7-fold (7.1; 6.8-7.4), and for viral infections 10-fold (10.0; 8.9-11.4). Multiple myeloma patients diagnosed in the more recent calendar periods had significantly higher risk of infections compared to controls (P<0.001). At one year of follow up, infection was the underlying cause in 22% of deaths in multiple myeloma patients. Mortality due to infections remained constant during the study period. Our findings confirm that infections represent a major threat to multiple myeloma patients. The effect on infectious complications due to novel drugs introduced in the treatment of multiple myeloma needs to be established and trials on prophylactic measures are needed.
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| 5. |
- Goldin, Lynn R., et al.
(författare)
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Elevated risk of chronic lymphocytic leukemia and other indolent non-Hodgkin's lymphomas among relatives of patients with chronic lymphocytic leukemia
- 2009
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Ingår i: Haematologica. - : Ferrata Storti Foundation (Haematologica). - 1592-8721 .- 0390-6078. ; 94:5, s. 647-653
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Tidskriftsartikel (refereegranskat)abstract
- Background Previous Studies have shown increased familial risk for chronic lymphocytic leukemia. In the most comprehensive study to date, we evaluated risk of chronic lymphocytic leukemia and lymphoproliferative disorders among First-degree relatives of chronic lymphocytic leukemia cases compared to first-degree relatives of controls. Design and Methods Population-based registry data from Sweden were used to evaluate outcomes in 26,947 first-degree relatives of 9,717 chronic lymphocytic leukemia patients (diagnosed 19583 8,159 matched controls. Using a 2004) compared with 107,223 first-degree relatives of 1 as marginal survival model, we calculated relative risks (RR) and 95% confidence intervals measures of Familial aggregation. Results Compared to relatives of controls, relatives of chronic lymphocytic leukemia patients had an increased risk for chronic lymphocytic leukemia (RR=8.5, 6.1-11.7) and other non-Hodkin's lymphomas (NHLs) (RR=1.9, 1.5-2.3). Evaluating NHL subtypes, we found a striking excess of indolent B-cell NHL specifically lymphoplasmacytic lymphoma/Waldenstrom macroglobulinemia and hairy cell leukemia. No excesses of aggressive B-cell or T-cell lymphomas were found. There was no statistical excess of Hodgkin's lymphoma, multiple myeloma, or the precursor condition, monoclonal gammopathy of undetermined significance, among chronic lymphocytic leukemia relatives. Conclusions These familial aggregations are striking and provide novel clues to research designed to uncover early pathogenetic mechanisms in chronic lymphocytic leukemia including studies to identify germ line susceptibility genes. However, clinicians should counsel their chronic lymphocytic leukemia patients emphasizing that because the baseline population risks are low, the absolute risk for a first-degree relative to develop chronic lymphocytic leukemia or another indolent lymphoma is low. At this time, an increased medical surveillance of first-degree relatives of chronic lymphocytic leukemia patients has no role Outside research studies.
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| 6. |
- Goldin, Lynn R., et al.
(författare)
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Highly increased familial risks for specific lymphoma subtypes
- 2009
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Ingår i: British Journal of Haematology. - : Wiley. - 0007-1048 .- 1365-2141. ; 146:1, s. 91-94
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Tidskriftsartikel (refereegranskat)abstract
- P>Studies have shown that familial risk contributes to aetiology of lymphomas. Using large population registries from Sweden, we evaluated risk of lymphoma subtypes among first-degree relatives of 2668 follicular lymphoma (FL) patients, 2517 diffuse large B-cell lymphoma (DLBCL) patients, and 6963 Hodgkin lymphoma (HL) patients compared to first-degree relatives of controls. Relatives were at the highest risk for developing the same lymphoma subtype as the case. DLBCL was increased 10-fold among relatives of DLBCL patients, FL was increased fourfold among relatives of FL patients and HL was increased fourfold among relatives of HL patients. These results imply that germline susceptibility genes are specific to lymphoma subtype.
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| 7. |
- Jonsdottir, Gudbjorg, et al.
(författare)
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Cumulative exposure to melphalan chemotherapy and subsequent risk of developing acute myeloid leukemia and myelodysplastic syndromes in patients with multiple myeloma
- 2021
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Ingår i: European Journal of Haematology. - : Wiley. - 0902-4441 .- 1600-0609. ; 107:2, s. 275-282
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: The aim of this study was to determine risk factors for development of acute myeloid leukemia/myelodysplastic syndromes (AML/MDS) in patients with multiple myeloma (MM). Methods: We identified all patients diagnosed with MM in Sweden from January 1st, 1958 to December 31, 2011. A total of 26 627 patients were diagnosed with MM with during the study period. Of these, 124 patients (0.5%) developed subsequent AML/MDS. For each patient with MM and a subsequent AML/MDS diagnosis, we randomly selected a matched (age, sex, and date of MM diagnosis) MM patient without a subsequent second malignancy diagnosis. Results: The cumulative melphalan exposure was significantly higher (OR = 2.8, 95% CI 1.7-5.2; P <.001) among cases (median 988 mg; IQR 644-1640) compared with controls (median 578 mg; IQR 360-967). Median time to AML/MDS development was 3.8 years (IQR 2.8-5.8). Risk of AML/MDS was not statistically altered by M protein isotype, anemia, renal failure, hypercalcemia, lytic bone lesions, or radiation therapy. Conclusion: In this nationwide population-based study, we show that increased cumulative doses of alkylating therapy with melphalan increases the subsequent risk of developing AML/MDS in patients with MM. Given improved survival in MM patients over the last decade future studies will be important to better define long-term risks.
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| 8. |
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| 9. |
- Knudsen, Jenny Dahl, et al.
(författare)
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Selection of Resistant Streptococcus pneumoniae during Penicillin Treatment In Vitro and in Three Animal Models.
- 2003
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Ingår i: Antimicrobial Agents and Chemotherapy. - 1098-6596. ; 47:8, s. 2499-2506
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Tidskriftsartikel (refereegranskat)abstract
- Pharmacokinetic (PK) and pharmacodynamic (PD) properties for the selection of resistant pneumococci were studied by using three strains of the same serotype (6B) for mixed-culture infection in time-kill experiments in vitro and in three different animal models, the mouse peritonitis, the mouse thigh, and the rabbit tissue cage models. Treatment regimens with penicillin were designed to give a wide range of T>MICs, the amounts of time for which the drug concentrations in serum were above the MIC. The mixed culture of the three pneumococcal strains, 107 CFU of strain A (MIC of penicillin, 0.016 µg/ml; erythromycin resistant)/ml, 106 CFU of strain B (MIC of penicillin, 0.25 µg/ml)/ml, and 105 CFU of strain C (MIC of penicillin, 4 µg/ml)/ml, was used in the two mouse models, and a mixture of 105 CFU of strain A/ml, 104 CFU of strain B/ml, and 103 CFU of strain C/ml was used in the rabbit tissue cage model. During the different treatment regimens, the differences in numbers of CFU between treated and control animals were calculated to measure the efficacies of the regimens. Selective media with erythromycin or different penicillin concentrations were used to quantify the strains separately. The efficacies of penicillin in vitro were similar when individual strains or mixed cultures were studied. The eradication of the bacteria, independent of the susceptibility of the strain or strains or the presence of the strains in a mixture or on their own, followed the well-known PK and PD rules for treatment with ß-lactams: a maximum efficacy was seen when the T>MIC was >40 to 50% of the observation time and the ratio of the maximum concentration of the drug in serum to the MIC was >10. It was possible in all three models to select for the less-susceptible strains by using insufficient treatments. In the rabbit tissue cage model, a regrowth of pneumococci was observed; in the mouse thigh model, the ratio between the different strains changed in favor of the less-susceptible strains; and in the mouse peritonitis model, the susceptible strain disappeared and was overgrown by the less-susceptible strains. These findings with the experimental infection models confirm the importance of eradicating all the bacteria taking part in the infectious process in order to avoid selection of resistant clones.
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| 10. |
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| 11. |
- 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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| 12. |
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| 13. |
- Kristinsson, Sigurdur Y., et al.
(författare)
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Autoimmunity and risk for Hodgkin's lymphoma by subtype
- 2009
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Ingår i: Haematologica. - : Ferrata Storti Foundation (Haematologica). - 1592-8721 .- 0390-6078. ; 94:10, s. 1468-1469
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 14. |
- 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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| 15. |
- Kristinsson, Sigurdur Y., et al.
(författare)
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Familial Aggregation of Lymphoplasmacytic Lymphoma/Waldenstrom Macroglobulinemia with Solid Tumors and Myeloid Malignancies
- 2012
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Ingår i: Acta Haematologica. - : S. Karger AG. - 1421-9662 .- 0001-5792. ; 127:3, s. 173-177
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Forskningsöversikt (refereegranskat)abstract
- Lymphoplasmacytic lymphoma (LPL)/Waldenstrom macroglobulinemia (WM) is a B-cell disorder resulting from the accumulation, predominantly in the bone marrow, of clonally related lymphoplasmacytic cells. LPL/WM is a very rare disease, with an incidence rate of 3-4 cases per million people per year. Currently, the causes of LPL/WM are poorly understood; however, there are emerging data to support a role for immune-related factors in the pathogenesis of LPL/WM. In addition, data show that genetic factors are of importance in the etiology of LPL/WM. In this paper, we will review the current knowledge about familiality of LPL/WM and provide novel data on solid tumors and myeloid malignancies in first-degree relatives of LPL/WM patients. Copyright (C) 2012 S. Karger AG, Basel
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| 16. |
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| 17. |
- Kristinsson, Sigurdur Y., et al.
(författare)
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Genetic and immune-related factors in the pathogenesis of lymphoproliferative and plasma cell malignancies
- 2009
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Ingår i: Haematologica. - : Ferrata Storti Foundation (Haematologica). - 1592-8721 .- 0390-6078. ; 94:11, s. 1581-1589
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Forskningsöversikt (refereegranskat)abstract
- There are data to support a role for genetic and immune-related factors in the pathogenesis of lymphomas and plasma cell diseases. In this paper, we review our published large population-based studies and other relevant studies in Hodgkin's and non-Hodgkin's lymphomas, multiple myeloma, and the precursor condition monoclonal gammopathy of undetermined significance. We discuss the overlap in risk factors between related malignancies and explore the underlying mechanisms. Based on these studies, we provide clinical implications and discuss the relevance of these data for patient counseling and clinical follow-up. Finally, we suggest future directions for new studies designed to increase our current knowledge and to define underlying biological mechanisms of our findings.
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| 18. |
- Kristinsson, Sigurdur Y., et al.
(författare)
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Genetics- and Immune-Related Factors in the Pathogenesis of Lymphoplasmacytic Lymphoma/Waldenstrom's Macroglobulinemia
- 2009
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Ingår i: Clinical Lymphoma & Myeloma. - 1557-9190. ; 9:1, s. 23-26
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Konferensbidrag (refereegranskat)abstract
- There are emerging data to support a role for genetic and immune-related factors in the pathogenesis of lymphoplasmacytic lymphoma/Waldenstrom's macroglobulinemia. In this article, we review our recently published, large, population-based studies using data from Sweden and from United States veterans and propose mechanisms and pathways underlying our observations. We also discuss future directions for new studies designed to increase our current knowledge and to define underlying biologic mechanisms of our findings. Finally, based on novel insights on this topic, we discuss clinical implications and provide perspective on the relevance of these data for patient counseling and clinical follow-up.
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| 19. |
- Kristinsson, Sigurdur Y, et al.
(författare)
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Immune-Related and Inflammatory Conditions and Risk of Lymphoplasmacytic Lymphoma or Waldenstrom Macroglobulinemia.
- 2010
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Ingår i: Journal of the National Cancer Institute. - : Oxford University Press (OUP). - 1460-2105 .- 0027-8874. ; 102, s. 557-567
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Tidskriftsartikel (refereegranskat)abstract
- Background Chronic immune stimulation appears to be associated with lymphoplasmacytic lymphoma (LPL)-Waldenström macroglobulinemia (WM); however, available information is sparse. We conducted, to our knowledge, the most comprehensive study to date to evaluate associations between a personal or family history of many immune-related and/or inflammatory disorders and the subsequent risk of LPL-WM. Methods We used Swedish population-based registries to identify 2470 case patients with LPL-WM, 9698 matched control subjects, and almost 30 000 first-degree relatives of either case patients or control subjects. We evaluated a wide range of autoimmune, infectious, allergic, and inflammatory conditions. We calculated odds ratios (ORs) and 95% confidence intervals (CIs) for each condition by use of logistic regression. Results An increased risk of LPL-WM was associated with a personal history of the following autoimmune diseases: systemic sclerosis (OR = 4.7, 95% CI = 1.4 to 15.3), Sjögren syndrome (OR = 12.1, 95% CI = 3.3 to 45.0), autoimmune hemolytic anemia (OR = 24.2, 95% CI = 5.4 to 108.2), polymyalgia rheumatica (OR = 2.9, 95% CI = 1.6 to 5.2), and giant cell arteritis (OR = 8.3, 95% CI = 2.1 to 33.1). An increased risk of LPL-WM was associated with a personal history of the following infectious diseases: pneumonia (OR = 1.4, 95% CI = 1.1 to 1.7), septicemia (OR = 2.4, 95% CI = 1.2 to 4.3), pyelonephritis (OR = 1.7, 95% CI = 1.1 to 2.5), sinusitis (OR = 2.7, 95% CI = 1.4 to 4.9), herpes zoster (OR = 3.4, 95% CI = 2.0 to 5.6), and influenza (OR = 2.9, 95% CI = 1.7 to 5.0). An increased risk of LPL-WM was associated with a family history of the following autoimmune or infectious diseases: Sjögren syndrome (OR = 5.0, 95% CI = 2.1 to 12.0), autoimmune hemolytic anemia (OR = 3.8, 95% CI = 1.1 to 13.2), Guillain-Barré syndrome (OR = 4.1, 95% CI = 1.8 to 9.4), cytomegalovirus (OR = 2.7, 95% CI = 1.4 to 5.3), gingivitis and periodontitis (OR = 1.9, 95% CI = 1.3 to 2.7), and chronic prostatitis (OR = 4.3, 95% CI = 1.7 to 11.1). Conclusions Personal history of certain immune-related and/or infectious conditions was strongly associated with increased risk of LPL-WM. The association of both personal and family history of Sjögren syndrome and autoimmune hemolytic anemia with risk of LPL-WM indicates the potential for shared susceptibility for these conditions.
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| 20. |
- 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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| 21. |
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| 22. |
- 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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| 23. |
- 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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| 24. |
- 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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| 25. |
- Kristinsson, Sigurdur Y., et al.
(författare)
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Patterns of survival in lymphoplasmacytic lymphoma/waldenstrom macroglobulinemia: A population-based study of 1,555 patients diagnosed in Sweden from 1980 to 2005
- 2013
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Ingår i: American Journal of Hematology. - : Wiley. - 0361-8609 .- 1096-8652. ; 88:1, s. 60-65
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Tidskriftsartikel (refereegranskat)abstract
- Clinical management of lymphoplasmacytic lymphoma (LPL)/Waldenstrom macroglobulinemia (WM) has changed considerably over recent years, reflected in the use of new therapeutic agents (purine analogs, monoclonal antibodies, thalidomide- and bortezomib-based therapies). No population-based studies and few randomized trials have been performed to assess survival in newly diagnosed LPL/WM. We performed a large population-based study in Sweden including 1,555 LPL/WM patients diagnosed from 1980 to 2005. Relative survival ratios (RSRs) and excess mortality rate ratios (EMRR) were computed as measures of survival. Survival of LPL/WM patients has improved significantly (P = 0.007) over time with 5-year RSR = 0.57 (95% confidence interval [CI] 0.460.68), 0.65 (0.570.73), 0.74 (0.680.80), 0.72 (0.660.77), and 0.78 (0.710.85) for patients diagnosed during the calendar periods 19801985, 19861990, 19911995, 19962000, and 20012005, respectively. Improvement in 1- and 5-year relative survival was found in all age groups and for LPL and WM separately. Patients with WM had lower excess mortality compared to LPL (EMRR = 0.38; 95% CI 0.300.48). Older age at diagnosis was associated with a poorer survival (P < 0.001). Taken together, we found a significant improvement in survival in LPL/WM over time. Despite this progress, new effective agents with a more favourable toxicity profile are needed to further improve survival in LPL/WM, especially in the elderly. Am. J. Hematol. 2013. (c) 2012 Wiley Periodicals, Inc.
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