| 1. |
- Askling, Johan, et al.
(author)
-
Anti-TNF therapy in RA and risk of malignant lymphomas Relative risks and time-trends in the Swedish Biologics Register
- 2008
-
In: Annals of the Rheumatic Diseases. - : BMJ Publishing Group Ltd. - 0003-4967 .- 1468-2060. ; 68:5, s. 648-653
-
Journal article (peer-reviewed)abstract
- Background: Tumour necrosis factor (TNF) antagonists have proved effective as treatment against rheumatoid arthritis (RA), but the unresolved issue of whether the use of anti-TNF therapy increases the already elevated risk of lymphoma in RA remains a concern.Methods: Using the Swedish Biologics Register (ARTIS), the Swedish Cancer Register, pre-existing RA cohorts and cross-linkage with other national health and census registers, a national RA cohort (n = 67 743) was assembled and patients who started anti-TNF therapy between 1998 and July 2006 (n = 6604) were identified. A general population comparator (n = 471 024) was also assembled and the incidence of lymphomas from 1999 to 31 December 2006 was assessed and compared in these individuals.Results: Among the 6604 anti-TNF-treated RA patients, 26 malignant lymphomas were observed during 26 981 person-years of follow-up, which corresponded to a relative risk (RR) of 1.35 (95% CI 0.82 to 2.11) versus anti-TNF-naive RA patients (336 lymphomas during 365 026 person-years) and 2.72 (95% CI 1.82 to 4.08) versus the general population comparator (1568 lymphomas during 3 355 849 person-years). RA patients starting anti-TNF therapy in 1998–2001 accounted for the entire increase in lymphoma risk versus the two comparators. By contrast, RR did not vary significantly by time since start of first treatment or with the accumulated duration of treatment, nor with the type of anti-TNF agent.Conclusion: Overall and as used in routine care against RA, TNF antagonists are not associated with any major further increase in the already elevated lymphoma occurrence in RA. Changes in the selection of patients for treatment may influence the observed risk.
|
|
| 2. |
- Askling, Johan, et al.
(author)
-
Anti-tumour necrosis factor therapy in rheumatoid arthritis and risk of malignant lymphomas : relative risks and time trends in the Swedish Biologics Register
- 2009
-
In: Annals of the Rheumatic Diseases. - London, UK : BMJ. - 0003-4967 .- 1468-2060. ; 68:5, s. 648-653
-
Journal article (peer-reviewed)abstract
- BACKGROUND:Tumour necrosis factor (TNF) antagonists have proved effective as treatment against rheumatoid arthritis (RA), but the unresolved issue of whether the use of anti-TNF therapy increases the already elevated risk of lymphoma in RA remains a concern.METHODS:Using the Swedish Biologics Register (ARTIS), the Swedish Cancer Register, pre-existing RA cohorts and cross-linkage with other national health and census registers, a national RA cohort (n = 67,743) was assembled and patients who started anti-TNF therapy between 1998 and July 2006 (n = 6604) were identified. A general population comparator (n = 471,024) was also assembled and the incidence of lymphomas from 1999 to 31 December 2006 was assessed and compared in these individuals.RESULTS:Among the 6604 anti-TNF-treated RA patients, 26 malignant lymphomas were observed during 26,981 person-years of follow-up, which corresponded to a relative risk (RR) of 1.35 (95% CI 0.82 to 2.11) versus anti-TNF-naive RA patients (336 lymphomas during 365,026 person-years) and 2.72 (95% CI 1.82 to 4.08) versus the general population comparator (1568 lymphomas during 3,355,849 person-years). RA patients starting anti-TNF therapy in 1998-2001 accounted for the entire increase in lymphoma risk versus the two comparators. By contrast, RR did not vary significantly by time since start of first treatment or with the accumulated duration of treatment, nor with the type of anti-TNF agent.CONCLUSION:Overall and as used in routine care against RA, TNF antagonists are not associated with any major further increase in the already elevated lymphoma occurrence in RA. Changes in the selection of patients for treatment may influence the observed risk.
|
|
| 3. |
- Askling, J, et al.
(author)
-
Haematopoietic malignancies in rheumatoid arthritis : lymphoma risk and characteristics after exposure to tumour necrosis factor antagonists
- 2005
-
In: Annals of the Rheumatic Diseases. - : BMJ. - 0003-4967 .- 1468-2060. ; 64:10, s. 1414-1420
-
Journal article (peer-reviewed)abstract
- BACKGROUND:Patients with rheumatoid arthritis (RA) are at increased risk of malignant lymphomas, and maybe also of leukaemia and multiple myeloma. The effect of tumour necrosis factor (TNF) antagonists on lymphoma risk and characteristics is unclear.OBJECTIVE:To assess expected rates and relative risks of haematopoietic malignancies, especially those associated with TNF antagonists, in large population based cohorts of patients with RA.METHODS:A population based cohort study was performed of patients with RA (one prevalent cohort (n = 53,067), one incident cohort (n = 3703), and one TNF antagonist treated cohort 1999 through 2003 (n = 4160)), who were linked with the Swedish Cancer Register. Additionally, the lymphoma specimens for the 12 lymphomas occurring in patients with RA exposed to TNF antagonists in Sweden 1999 through 2004 were reviewed.RESULTS:Study of almost 500 observed haematopoietic malignancies showed that prevalent and incident patients with RA were at increased risk of lymphoma (SIR = 1.9 and 2.0, respectively) and leukaemia (SIR = 2.1 and 2.2, respectively) but not of myeloma. Patients with RA treated with TNF antagonists had a tripled lymphoma risk (SIR = 2.9) compared with the general population. After adjustment for sex, age, and disease duration, the lymphoma risk after exposure to TNF antagonists was no higher than in the other RA cohorts. Lymphomas associated with TNF antagonists had characteristics similar to those of other RA lymphomas.CONCLUSION:Overall, patients with RA are at equally increased risks for lymphomas and leukaemias. Patients with RA treated with TNF antagonists did not have higher lymphoma risks than other patients with RA. Prolonged observation is needed to determine the long term effects of TNF antagonists on lymphoma risk.
|
|
| 4. |
- Backlin, Carin
(author)
-
Adrenocortical tumors : Diagnosis, growth regulation and treatment
- 1999
-
Doctoral thesis (other academic/artistic)abstract
- Monoclonal antibodies generated by immunization with human adrenocortical cells reacted with the normal adrenal cortex, adrenocortical adenomas and carcinomas, but failed to stain a variety of normal tissues, renal cell carcinoma, and pheocromocytomas. The antibodies can be used to improve histological diagnosis and characterization of human adrenal lesions, and possibly for scintigraphic detection.Insulin-like growth factor I (IGF-I) influences cellular growth, differentiation and secretion. IGF-I and its receptor were demonstrated in normal adrenal cortex, cortical adenomas and carcinomas, with intense and abundant expression in many carcinomas. Tumors causing aldosterone excess were IGF-I receptor negative. Recombinant IGF-I dose-dependently stimulated proliferation in human adrenocortical cancer cells, with reversal of the effect by IGF-I receptor antibodies. IGF-I may be an important stimulus for cell proliferation in adrenocortical tumors lacking discernible aldosterone excess.Adrenal steroid converting enzymes were expressed in functioning and non-functioning adrenocortical adenomas. Cortical carcinomas had deficient enzyme expression, concurrent with abnormal urinary steroid profile and steroid hormone precursor excretion. Immunostaining for cortisol and sex steroids revealed variable expression, especially in the malignant lesions. Cortisol reactivity in aldosteronomas and non-functioning tumors indicates that the patients may be at risk to have suppressed adrenocortical function.Adrenocortical carcinomas are associated with multidrug resistance related to a cell membrane expressed phosphoglycoprotein (Pgp) mediating extrusion of cytostatic drugs. Adrenocortical carcinomas displayed variable Pgp-immunoreactivity but universal cytostatic drug insensitivity in a fluorescent microculture cytotoxic assay (FMCA), substantiating that mechanisms other than Pgp may mediate resistance to cytostatic drugs in these tumors.Fresh, non-cultured tumor-infiltrating lymphocytes (TIL cells) from two of three adrenocortical carcinomas showed significant lysis of autologous tumor cells. For one TIL cell preparation this activity was markedly enhanced by culture with interleukin-2. The TIL cells with cytolytic capacity mainly consisted of CD45RO+ T cells. Freshly isolated TIL cells strongly expressed TCR Vβ6 and Vβ8 genes, and in vitro cultured TIL lines demonstrated high percentage of CD8+ cells with these gene products. The results indicate possibilities to use transferred TIL cell lines in specific immunotherapy for adrenocortical carcinoma.
|
|
| 5. |
- Backlin, Carin, et al.
(author)
-
Immunohistochemical expression of insulin-like growth factor 1 and its receptor in normal and neoplastic human adrenal cortex
- 1995
-
In: Anticancer Research. - 0250-7005 .- 1791-7530. ; 15:6B, s. 2453-2459
-
Journal article (peer-reviewed)abstract
- BACKGROUND:Insulin-like growth factor 1 (IGF-1) may influence cellular growth, differentiation and secretion.MATERIAL AND METHODS:Cryosectioned normal human adrenal glands (n = 6), cortical adenoma (n = 21), and carcinoma (n = 17) were stained immunohistochemically for IGF-1 and its receptor, and human adrenocortical cancer cells expressing the receptor were analysed for influences on proliferation.RESULTS:Normal cortical parenchyma generally displayed faint IGF-1 reactivity and intracellular receptor staining. Similar labelling encompassed the adenomas, but only 6 of them were receptor reactive. IGF-1 expression was conspicuous in 11 carcinomas, and 6 of them displayed cell surface receptor reactivity. All aldosterone producing lesions were receptor antibody unreactive. Recombinant IGF-1 dose-dependently stimulated the cell proliferation, and this effect was reversed by the receptor antibody.CONCLUSION:IGF-1 may interact with function and proliferation of the human adrenal cortex with particular reference to cortical carcinomas lacking discernible aldosterone excess.
|
|
| 6. |
|
|
| 7. |
- Baecklund, Eva, 1956-, et al.
(author)
-
Anti-cyclic citrullinated peptide antibodies, other common autoantibodies, and smoking as risk factors for lymphoma in patients with rheumatoid arthritis
- 2018
-
In: Scandinavian Journal of Rheumatology. - : Informa UK Limited. - 0300-9742 .- 1502-7732. ; 47:4, s. 270-275
-
Journal article (peer-reviewed)abstract
- OBJECTIVES: Patients with rheumatoid arthritis (RA) are at increased risk of lymphoma. There is no biomarker to indicate future lymphoma risk in RA and it is not known whether factors associated with an increased risk of RA also confer an increased risk of lymphoma. We investigated whether anti-cyclic citrullinated peptide (CCP) antibodies, other autoantibodies, and smoking, are associated with lymphoma development in RA.METHOD: subclasses of anti-CCP antibodies and for 15 antinuclear antibody (ANA)-associated specific autoantibodies. Relative risks were estimated as crude and adjusted odds ratios (adjOR) with 95% confidence intervals (CIs) using logistic regression.RESULTS: We found no association between anti-CCP IgG ≥ 25 units/mL (adjOR 1.4, 95% CI 0.7-2.7), anti-CCP IgG ≥ 500 units/mL (adjOR 1.4, 95% CI 0.7-3.0), anti-CCP Ig of other isotypes, other autoantibodies (adjOR any vs none 0.6, 95% CI 0.3-1.2), or cigarette smoking (adjOR ever vs never 1.1, 95% CI 0.5-2.2) and lymphoma risk among patients with RA.CONCLUSION: In this study, neither anti-CCP antibodies (IgG, IgG1–4, IgM, or IgA), nor other common autoantibodies, nor smoking predicted lymphoma risk in RA
|
|
| 8. |
- Baecklund, Eva, et al.
(author)
-
Association of chronic inflammation, not its treatment, with increased lymphoma risk in rheumatoid arthritis
- 2006
-
In: Arthritis and Rheumatism. - : Wiley. - 0004-3591 .- 1529-0131. ; 54:3, s. 692-701
-
Journal article (peer-reviewed)abstract
- OBJECTIVE:Chronic inflammatory conditions such as rheumatoid arthritis (RA) have been associated with malignant lymphomas. This study was undertaken to investigate which patients are at highest risk, and whether antirheumatic treatment is hazardous or protective.METHODS:We performed a matched case-control study of 378 consecutive Swedish RA patients in whom malignant lymphoma occurred between 1964 and 1995 (from a population-based RA cohort of 74,651 RA patients), and 378 controls. Information on disease characteristics and treatment from onset of RA until lymphoma diagnosis was abstracted from medical records. Lymphoma specimens were reclassified and tested for Epstein-Barr virus (EBV). Relative risks (odds ratios [ORs]) for lymphomas (by subtype) associated with deciles of cumulative disease activity were assessed, as were ORs associated with drug treatments.RESULTS:The relative risks of lymphoma were only modestly elevated up to the seventh decile of cumulative disease activity. Thereafter, the relative risk increased dramatically (OR ninth decile 9.4 [95% confidence interval 3.1-28.0], OR tenth decile 61.6 [95% confidence interval 21.0-181.0]). Most lymphomas (48%) were of the diffuse large B cell type, but other lymphoma subtypes also displayed an association with cumulative disease activity. Standard nonbiologic treatments did not increase lymphoma risk. EBV was present in 12% of lymphomas.CONCLUSION:Risk of lymphoma is substantially increased in a subset of patients with RA, those with very severe disease. High inflammatory activity, rather than its treatment, is a major risk determinant.
|
|
| 9. |
- Baecklund, Eva, et al.
(author)
-
Characteristics of diffuse large B cell lymphomas in rheumatoid arthritis
- 2006
-
In: Arthritis and Rheumatism. - : Wiley. - 0004-3591 .- 1529-0131. ; 54:12, s. 3774-3781
-
Journal article (peer-reviewed)abstract
- OBJECTIVE:Patients with rheumatoid arthritis (RA) are at increased risk of malignant lymphomas, with a correlation between RA disease severity and lymphoma risk, most pronounced for diffuse large B cell lymphomas (DLBCLs), which also constitute the majority of RA-associated lymphomas. DLBCLs can be further subdivided into germinal center (GC)-like and non-GC-like subtypes, with different cellular origins and prognoses. This study was undertaken to investigate whether RA displays a specific association with any of the DLBCL subtypes.METHODS:We identified 139 patients with DLBCLs within a population-based case-control study of 378 RA patients with lymphoma. The DLBCLs were examined for CD10, Bcl-6, and interferon regulatory factor 4 expression patterns, subclassified into GC and non-GC subtypes, and then correlated with clinical parameters.RESULTS:We found a statistically significant predominance of the non-GC subtype (97 patients; 70% of all DLBCLs). These patients more often had an advanced stage of lymphoma at diagnosis and had a worse 5-year overall survival rate (16% versus 33%) compared with patients with the GC subtype. There was a strong association with RA disease activity in both subtypes, with >70% of the GC and non-GC cases occurring in RA patients with the highest overall disease activity scores.CONCLUSION: These findings suggest that severe RA is particularly associated with the non-GC subtype of DLBCL, and indicate a critical role of activated peripheral B cells as the cells of origin in these lymphomas.
|
|
| 10. |
|
|
