| 1. |
- Goldin, Lynn R., et al.
(författare)
-
Elevated risk of chronic lymphocytic leukemia and other indolent non-Hodgkin's lymphomas among relatives of patients with chronic lymphocytic leukemia
- 2009
-
Ingår i: Haematologica. - : Ferrata Storti Foundation (Haematologica). - 1592-8721 .- 0390-6078. ; 94:5, s. 647-653
-
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.
|
|
| 2. |
- Goldin, Lynn R., et al.
(författare)
-
Highly increased familial risks for specific lymphoma subtypes
- 2009
-
Ingår i: British Journal of Haematology. - : Wiley. - 0007-1048 .- 1365-2141. ; 146:1, s. 91-94
-
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.
|
|
| 3. |
|
|
| 4. |
- Kristinsson, Sigurdur Y., et al.
(författare)
-
Autoimmunity and risk for Hodgkin's lymphoma by subtype
- 2009
-
Ingår i: Haematologica. - : Ferrata Storti Foundation (Haematologica). - 1592-8721 .- 0390-6078. ; 94:10, s. 1468-1469
-
Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
|
|
| 5. |
- Kristinsson, Sigurdur Y., et al.
(författare)
-
Deep vein thrombosis after monoclonal gammopathy of undetermined significance and multiple myeloma
- 2008
-
Ingår i: Blood. - : American Society of Hematology. - 1528-0020 .- 0006-4971. ; 112:9, s. 3582-3586
-
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)
|
|
| 6. |
|
|
| 7. |
- Kristinsson, Sigurdur Y., et al.
(författare)
-
Genetic and immune-related factors in the pathogenesis of lymphoproliferative and plasma cell malignancies
- 2009
-
Ingår i: Haematologica. - : Ferrata Storti Foundation (Haematologica). - 1592-8721 .- 0390-6078. ; 94:11, s. 1581-1589
-
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.
|
|
| 8. |
- Kristinsson, Sigurdur Y., et al.
(författare)
-
Genetics- and Immune-Related Factors in the Pathogenesis of Lymphoplasmacytic Lymphoma/Waldenstrom's Macroglobulinemia
- 2009
-
Ingår i: Clinical Lymphoma & Myeloma. - 1557-9190. ; 9:1, s. 23-26
-
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.
|
|
| 9. |
- Kristinsson, Sigurdur Y, et al.
(författare)
-
Patterns of hematologic malignancies and solid tumors among 37,838 first-degree relatives of 13,896 patients with multiple myeloma in Sweden.
- 2009
-
Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 125:9, s. 2147-2150
-
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.
|
|
| 10. |
- Kristinsson, Sigurdur Y, et al.
(författare)
-
Patterns of survival and causes of death following a diagnosis of monoclonal gammopathy of undetermined significance. A population-based study.
- 2009
-
Ingår i: Haematologica. - : Ferrata Storti Foundation. - 0390-6078 .- 1592-8721. ; 94:12, s. 1714-1720
-
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.
|
|
| 11. |
- Kristinsson, Sigurdur Y., et al.
(författare)
-
Risk of lymphoproliferative disorders among first-degree relatives of lymphoplasmacytic lymphoma/Waldenstrom macroglobulinemia patients: a population-based study in Sweden
- 2008
-
Ingår i: Blood. - : American Society of Hematology. - 1528-0020 .- 0006-4971. ; 112:8, s. 3052-3056
-
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.
|
|
| 12. |
|
|
| 13. |
|
|
| 14. |
- Landgren, Ola, et al.
(författare)
-
Risk of plasma cell and lymphoproliferative disorders among 14621 first-degree relatives of 4458 patients with monoclonal gammopathy of undetermined significance in Sweden.
- 2009
-
Ingår i: Blood. - : American Society of Hematology. - 0006-4971 .- 1528-0020. ; 114:4, s. 791-795
-
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.
|
|
| 15. |
- McMaster, Mary L., et al.
(författare)
-
Novel Aspects Pertaining to the Relationship of Waldenstrom's Macroglobulinemia, IgM Monoclonal Gammopathy of Undetermined Significance, Polyclonal Gammopathy, and Hypoglobulinemia
- 2009
-
Ingår i: Clinical Lymphoma & Myeloma. - 1557-9190. ; 9:1, s. 19-22
-
Konferensbidrag (refereegranskat)abstract
- Waldenstrom's macroglobulinemia (WM) is associated with a precursor condition, monoclonal gammopathy of undetermined significance (MGUS) of immunoglobulin-M (IgM) type. The etiology of these conditions is unknown. Recent studies at the population level have provided new data regarding familial aggregation of these disorders and other B-cell malignancies. Studies of familial clusters of WM have demonstrated an increased frequency of IgM MGUS compared with the general population and have provided new data suggesting that the phenotypic spectrum might also include polyclonal gammopathy and hypoglobulinemia. While the preponderance of immunoglobulin abnormalities in relatives of WM cases involves IgM, other immunoglobulin types (IgG and IgA) might also be affected. Large collaborative studies are needed to confirm these findings, which present an opportunity to define the earliest lesion(s) in the WM oncogenic pathway.
|
|
| 16. |
- Turesson, Ingemar, et al.
(författare)
-
Ascertainment and diagnostic accuracy for hematopoietic lymphoproliferative malignancies in Sweden 1964-2003.
- 2007
-
Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 121:10, s. 2260-2266
-
Tidskriftsartikel (refereegranskat)abstract
- Population-based cancer registries are widely used to provide key information about cancer incidence, survival, determinants of progression and clues about pathogenesis. To substantially expand the limited data on diagnostic accuracy and completeness for lym-phoproliferative (LP) tumors in such databases, we conducted a retrospective investigation of close to 1,000 cases diagnosed during 4 decades in Sweden. We identified and reviewed medical records for 494 LP tumor patients reported to the population-based Swedish Cancer registry and 503 LP tumor patients identified from hospitals in Sweden among patients with LP tumors diagnosed during 1964-2003. The stratified samples were randomly selected from patients according to LP subtype, over 4 equal calendar periods, and among 6 selected hospitals of diverse size and from different geographic regions. We found 97.9% of reported LP tumor cases to fulfill current diagnostic criteria for having an LP tumor and observed 89.7% to have accurate LP tumor subtype. The overall completeness of non-Hodgkin lymphoma, Hodgkin lymphoma and multiple myeloma cases in the Cancer registry was 95-99% but was lower for the more indolent tumors, chronic lymphocytic leukemia (87.9%) and Waldenstrom's macroglobulinemia (68.1%). We observed increased overall under-ascertamment for patients diagnosed above age 80 (27%) and among individuals diagnosed before 1973 (12%). In conclusion the diagnostic accuracy and completeness for classically defined LP tumor entities in the Swedish Cancer registry is high. However, we found under-ascertainment of patients with indolent LP tumors, particularly among patients diagnosed at older ages, with early-stage disease and diagnosed in earlier years.
|
|
