| 61. |
- Landgren, Ola, et al.
(författare)
-
Association of Immune Marker Changes with Progression of Monoclonal Gammopathy of Undetermined Significance to Multiple Myeloma
- 2019
-
Ingår i: JAMA Oncology. - : American Medical Association (AMA). - 2374-2437 .- 2374-2445.
-
Tidskriftsartikel (refereegranskat)abstract
- Importance: Multiple myeloma is consistently preceded by monoclonal gammopathy of undetermined significance (MGUS). Risk models that estimate the risk of progression from MGUS to multiple myeloma use data from a single time point, usually the initial workup. Objective: To longitudinally investigate the alterations of serum immune markers with stable vs progressive MGUS. Design, Setting, and Participants: This prospective cross-sectional cohort study included 77469 adult participants aged 55 to 74 years in the screening arm of the National Cancer Institute Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial who had a diagnosis of progressing MGUS (n = 187) or stable MGUS (n = 498), including light-chain subtype, from November 1993, through December 2011. For each participant, all available serially stored prediagnostic serum samples (N = 3266) were obtained. Data analysis was performed from April 2018, to December 2018. Main Outcomes and Measures: Serum protein and monoclonal immunoglobulin levels, serum free light chains, and serum light chains within each immunoglobulin class were measured. Results: Of 685 individuals included in the study, 461 (67.3%) were men; the mean (SD) age was 69.1 (5.6) years. In cross-sectional modeling, risk factors associated with progressive MGUS were IgA isotype (adjusted odds ratio [OR], 1.80; 95% CI, 1.03-3.13; P =.04), 15 g/L or more monoclonal spike (adjusted OR, 23.5; 95% CI, 8.9-61.9; P <.001), skewed (<0.1 or >10) serum free light chains ratio (adjusted OR, 46.4; 95% CI, 18.4-117.0; P <.001), and severe immunoparesis (≥2 suppressed uninvolved immunoglobulins) (adjusted OR, 19.1; 95% Cl, 7.5-48.3; P <.001). Risk factors associated with progressive light-chain MGUS were skewed serum free light chains ratio (adjusted OR, 44.0; 95% CI, 14.2-136.3; P <.001) and severe immunoparesis (adjusted OR, 48.6; 95% CI, 9.5-248.2; P <.001). In longitudinal analysis of participants with serial samples prior to progression, 23 of 43 participants (53%) had high-risk MGUS before progression; 16 of these 23 (70%) experienced conversion from low-risk or intermediate-risk MGUS within 5 years. Similar results were found for light-chain MGUS. Conclusions and Relevance: The findings of evolving risk patterns support annual blood testing and risk assessment for patients with MGUS or light-chain MGUS.
|
|
| 62. |
|
|
| 63. |
- Landgren, Ola, et al.
(författare)
-
Risk of malignant disease among 1525 adult male US veterans with gaucher disease
- 2007
-
Ingår i: Archives of Internal Medicine. - 0003-9926. ; 167:11, s. 1189-1194
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Some, but not all, reports suggest that patients with Gaucher disease are at increased risk of developing malignancies, particularly hematopoietic tumors. The aim of this study was to assess the pattern of Gaucher disease and subsequent malignancies among male veterans admitted to US Veterans Affairs hospitals. Methods: Among 832 294 African American and 3 668 983 white male veterans with at least 1 hospital admission in US Veterans Affairs hospitals and up to 27 years of follow-up, we identified a total of 1525 patients with Gaucher disease; 11.7% were African Americans. We used Poisson regression methods for cohort data to estimate relative risks ( RRs) and 95% confidence intervals ( CIs) after adjusting for attained age and calendar year, race, number of hospital visits, and latency. Results: When patients with Gaucher disease were compared with patients without Gaucher disease, the RR of any cancer was 0.91 ( 95% CI, 0.76-1.08 [ n = 137]). When we stratified our analyses by race, risks were similar for whites ( RR, 0.89; 95% CI, 0.74-1.07 [ n = 120]) and African Americans ( RR, 1.00; 95% CI, 0.61-1.64 [ n = 17]). Patients with Gaucher disease had an elevated risk for non-Hodgkin lymphoma ( RR, 2.54; 95% CI, 1.32-4.88 [ n = 9]), malignant melanoma ( RR, 3.07; 95% CI, 1.28-7.38 [ n = 5]), and pancreatic cancer ( RR, 2.37; 95% CI, 1.13-4.98 [ n = 7]). Among the remaining 19 cases involving defined solid tumors and 7 other hematologic malignancies, we found no statistical association with Gaucher disease. Conclusion: We found 2- to 3-fold risks of non-Hodgkin lymphoma, malignant melanoma, and pancreatic cancer in patients with Gaucher disease, but no significant association between Gaucher disease and cancer in general or with other specific malignancies such as multiple myeloma.
|
|
| 64. |
- Landgren, O, et al.
(författare)
-
Risk of monoclonal gammopathy of undetermined significance (MGUS) and subsequent multiple myeloma among African American and white veterans in the United States
- 2006
-
Ingår i: Blood. - : American Society of Hematology. - 1528-0020 .- 0006-4971. ; 107:3, s. 904-906
-
Tidskriftsartikel (refereegranskat)abstract
- The age-adjusted incidence of multiple myeloma (MM) is 2-fold higher in African Americans than in whites. A few small studies have reported a higher prevalence of monoclonal gammopathy of undetermined significance (MGUS) in African Americans versus whites. Etiologic factors for MGUS and determinants for transformation of MGUS to MM are unknown. We quantified the prevalence of MGUS and subsequent risk of MM among 4 million African American and white male veterans admitted to Veterans Affairs (VA) hospitals. The age-adjusted prevalence ratio of MGUS in African Americans compared with whites was 3.0 (2.7-3.3 95% confidence interval). Among 2046 MGUS cases, the estimated cumulative risk of MM during the first 10 years of follow-up was similar (P = .37) for African Americans (17%) and whites (15%). In the largest study to date, we suggest that the excess risk of MM in African Americans results from an increase in risk of MGUS rather than an increased risk of progression from MGUS to MM.
|
|
| 65. |
- 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.
|
|
| 66. |
|
|
| 67. |
|
|
| 68. |
|
|
| 69. |
- Lenhoff, Stig, et al.
(författare)
-
Intensive therapy for multiple myeloma in patients younger than 60 years. Long-term results focusing on the effect of the degree of response on survival and relapse pattern after transplantation
- 2006
-
Ingår i: Haematologica. - 0390-6078 .- 1592-8721. ; 91:9, s. 1228-1233
-
Tidskriftsartikel (refereegranskat)abstract
- Background and Objectives. From 1994 to 1997 we conducted a population-based, prospective study on intensive therapy in newly diagnosed symptomatic myeloma patients younger than 60 years, comparing their survival to that of a conventionally treated historic population. Long-term results are presented, including the impact of the degree of response on survival and relapse pattern after transplantation. Design and Methods. The prospective population was formed of 397 patients and the historic population of 313 patients. Both populations were calculated to comprise more than 75% of the expected number of new cases. Results. After a median follow-up of 7 years survival was longer in the prospective population than in the historic one (median 60 versus 39 months; p=0.0002). When comparing only patients eligible for intensive therapy the median survival was 63 versus 44 months (p < 0.0001). Attaining a complete response was associated with prolonged event-free survival but not overall survival. The pattern of relapse after transplantation was heterogeneous but could be divided into four major groups; insidious, classical, plasmacytoma form and transformed disease. The median survival after relapse was 29 months. The relapse pattern and time to relapse predicted outcome. Patients relapsing with an insidious or classical form of disease with skeletal events only, or after a long lasting first response were likely to respond well to conventional salvage therapy. In contrast, relapse with multiple symptoms, transformed disease or a short duration of first response implied bad prognosis. Interpretation and conclusions. The relapse pattern after autologous transplantation is heterogeneous and response to salvage therapy is variable. The degree of response and event-free survival after transplantation are not reliable surrogate markers for survival.
|
|
| 70. |
- Lindqvist, Ebba K., et al.
(författare)
-
Personal and family history of immune-related conditions increase the risk of plasma cell disorders : a population-based study
- 2011
-
Ingår i: Blood. - : American Society of Hematology. - 0006-4971 .- 1528-0020. ; 118:24, s. 6284-6291
-
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)
|
|
