| 1. |
- Berglund, David, et al.
(författare)
-
Expression of Intratumoral Forkhead Box Protein 3 in Posttransplant Lymphoproliferative Disorders : Clinical Features and Survival Outcomes
- 2015
-
Ingår i: Transplantation. - : Lippincott Williams & Wilkins. - 0041-1337 .- 1534-6080. ; 99:5, s. 1036-1042
-
Tidskriftsartikel (refereegranskat)abstract
- Background. The infiltration of regulatory T cells (Tregs) in lymphomas is associated with better prognosis for some types of lymphomas, but knowledge of their role in posttransplant lymphoproliferative disorders (PTLDs) is limited. We therefore investigated the association between the expression of the Treg marker forkhead box protein 3 (FoxP3) in biopsies of PTLDs and survival, PTLD subtype, and clinical characteristics.Methods. Seventy-four cases of PTLD after solid organ transplantation with sufficient material for further analysis were included from a population-based study of PTLDs in Sweden. The PTLD biopsies were reevaluated and stained with the 236A/E7 antibody to detect FoxP3 in lymphoma tissue. Detailed clinical data were collected retrospectively from medical records.Results. Based on a cutoff level of 29 FoxP3+ cells per mm2, most (80%) of the PTLDs were FoxP3-. Forty-seven of 74 PTLDs displayed no FoxP3+ cells at all. The frequency of FoxP3+ cells did not influence median overall survival. The FoxP3- PTLDs were more frequently of T-cell phenotype (P=0.04), located at the graft (P=0.03), occurred earlier after transplantation (P=0.04), were more likely to develop in lung recipients (P=0.04), and in patients that had received anti T-cell globulin as induction therapy (P=0.02). The FoxP3+ PTLDs were associated with hepatitis C seropositivity (P=0.03). In multivariate analysis, B-cell PTLD and hepatitis C infection were independent predictors of FoxP3 positivity.Conclusion. Our findings suggest that intratumoral FoxP3+ Tregs do not influence survival in patients with PTLD. FoxP3+ Tregs are rare in PTLD, possibly because of heavy immunosuppression.
|
|
| 2. |
- Brauner, S., et al.
(författare)
-
Reduced expression of TRIM21/Ro52 predicts poor prognosis in diffuse large B-cell lymphoma patients with and without rheumatic disease
- 2015
-
Ingår i: Journal of Internal Medicine. - : Wiley. - 0954-6820 .- 1365-2796. ; 278:3, s. 323-332
-
Tidskriftsartikel (refereegranskat)abstract
- ObjectiveTRIM21 (also known as Ro52) is an autoantigen in rheumatic disease and is predominantly expressed in leucocytes. Overexpression is associated with decreased proliferation, and the TRIM21 gene maps to a tumour suppressor locus. We therefore investigated the expression of TRIM21 in patients with diffuse large B-cell lymphoma (DLBCL) and its potential usefulness as a prognostic biomarker. Materials and methodsTRIM21 expression levels were assessed by immunohistochemistry in lymphoma biopsies from three cohorts of patients with DLBCL: 42 patients with rheumatic disease treated with a cyclophosphamide, vincristine, doxorubicin and prednisone (CHOP)-like regimen, 76 CHOP-treated and 196 rituximab-CHOP-treated nonrheumatic patients. Expression was correlated with clinical and biomedical parameters. TRIM21 expression was assessed in relation to lymphocyte proliferation by quantitative PCR and correlated with H-3-thymidine incorporation and propidium iodine staining. ResultsTRIM21 expression levels differed in the lymphomas compared to normal lymphoid tissue, with reduced expression correlating with shorter overall survival in all three cohorts. In the two larger cohorts, progression-free survival was assessed and was also found to correlate with TRIM21 expression. The association was independent of commonly used clinical prognostic scores, lymphoma subtype and several previously reported prognostic biomarkers. In agreement with this clinical observation, we noted an inverse correlation between TRIM21 expression and proliferation of leucocytes invitro. ConclusionsWe show that loss of TRIM21 expression is associated with more aggressive lymphoma and increased proliferation, whereas maintenance of TRIM21 expression is associated with better prognosis in patients with DLBCL. Based on our findings, we suggest that TRIM21 should be considered as a novel biomarker for lymphoma characterization and for predicting patient survival.
|
|
| 3. |
- Hellbacher, Erik, et al.
(författare)
-
Malignant lymphoma in granulomatosis with polyangiitis : subtypes, clinical characteristics and prognosis
- 2019
-
Ingår i: Acta Oncologica. - 0284-186X .- 1651-226X. ; 58:11, s. 1655-1659
-
Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Several autoimmune and inflammatory conditions, such as rheumatoid arthritis (RA) and primary Sjögrens’s syndrome (pSS), have repeatedly been linked to an increased risk of malignant lymphoma [1,2]. Certain inflammatory conditions are also associated with the development of specific lymphoma subtypes such as mucosa-associated lymphoid tissue (MALT) lymphoma in pSS and diffuse large B-cell lymphoma (DLBCL) in RA. The underlying mechanisms behind this association remain unclear. The highly increased risk of developing MALT lymphoma of the parotid gland in pSS indicates that local inflammatory processes can promote lymphoma development at the site of chronic inflammation [3]. In RA, an association between disease severity and risk of lymphoma has been shown.Granulomatosis with polyangiitis (GPA), formerly Wegener’s granulomatosis, is a systemic small vessel vasculitis associated with the presence of anti-neutrophil cytoplasmic antibodies (ANCA) and characterized by granulomatous inflammation and necrotizing vasculitis of the airways and kidneys but possibly affecting any organ system. An increased risk of lymphoma in patients with GPA has been reported in several epidemiological studies [4,5]. However, very little is known about risk factors for lymphoma development in this group, possible relation to disease severity, treatment and lymphoma subtypes or the prognosis for the lymphomas. This is the first published study on GPA and lymphoma, giving detailed information on the GPA characteristics and possible risk factors for lymphoma and also lymphoma subtypes treatment and survival.
|
|
| 4. |
- Hellgren, K., et al.
(författare)
-
Rheumatoid Arthritis and Risk of Malignant Lymphoma - Is the risk still increased?
- 2017
-
Ingår i: Arthritis & Rheumatology. - : Wiley. - 2326-5191 .- 2326-5205. ; 69:4, s. 700-708
-
Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Patients with rheumatoid arthritis (RA) are at increased risk of malignant lymphomas with a strong correlation with RA disease severity. Given the changes in RA therapy over recent decades, we aimed at assessing whether lymphoma risk remains increased, and if so, to explore risk predictors and lymphoma subtypes.METHODS: We identified 12,656 incident RA patients from the Swedish Rheumatology Register 1997-2012 including information on therapy and inflammatory activity during the first year following diagnosis. Each patient was matched to 10 population comparator subjects. Through linkage to the Swedish Cancer Register, lymphomas including subtypes were identified. We assessed Hazard ratios (HRs) using Cox regression.RESULTS: Overall, the HR of lymphoma was increased, 1.6, 95% confidence interval [CI] 1.2-2.1. Taking RA duration into account, risks did not appear to have declined over successive calendar years of RA diagnosis. Neither use of methotrexate the 1(st) year following RA diagnosis nor ever use of TNF inhibitors (HR=0.9; 95% CI 0.4-1.9) increased lymphoma risk. Use of oral corticosteroids the 1(st) year following RA diagnosis was associated with a reduced risk (HR=0.6; 95% CI 0.5 -0.9). Inflammatory activity during the 1(st) year following RA diagnosis did not predict future lymphoma risk. Chronic lymphocytic lymphoma occurred less, and Hodgkin lymphoma more frequently than expected compared to the general population.CONCLUSION: The average lymphoma risk in recently diagnosed RA is of similar magnitude as that reported from historical cohorts. Standard anti-rheumatic treatment including TNF inhibitors did not predict future lymphoma risk. Distribution of lymphoma subtypes warrants further investigation.
|
|
| 5. |
- Kinch, Amelie, 1973-, et al.
(författare)
-
Expression of PD-1, PD-L1, and PD-L2 in posttransplant lymphoproliferative disorder after solid organ transplantation
- 2019
-
Ingår i: Leukemia and Lymphoma. - : Informa UK Limited. - 1042-8194 .- 1029-2403. ; 60:2, s. 376-384
-
Tidskriftsartikel (refereegranskat)abstract
- We studied the expression of programed death 1 (PD-1) receptor and its ligands (PD-L1/-L2) by immunohistochemistry and its association with clinicopathological features in 81 posttransplant lymphoproliferative disorders (PTLDs) following solid organ transplantation. Overall, 67% (54/81) of the PTLDs were positive in any of the three immunostainings. PD-1 was detected on tumor-infiltrating cells in 41% (33/81) of the PTLDs. PD-L1 was expressed on ≥5% of the tumor cells in 50% (40/80) and PD-L2 in 32% (23/72) of the PTLDs. All Burkitt lymphomas were PD-L1 negative. Expression of PD-L1 tended to be associated with non-germinal center-type of diffuse large B-cell lymphoma (63% vs. 33% in GC-type, p = .14) and latent membrane protein-1+ PTLD (76% vs. 44% in LPM1-, p = .09). Heart recipients had more frequent PTLDs with PD-1+ microenvironment (p = .01). The frequent expression of PD-1 or -L1/-L2 in PTLD warrants further clinical evaluation of the efficacy and safety of PD-(L)1 inhibitors for refractory PTLD.
|
|
| 6. |
- Vasaitis, Lilian, et al.
(författare)
-
Comparison of patients with and without pre-existing lymphoma at diagnosis of primary Sjögren's syndrome
- 2019
-
Ingår i: Scandinavian Journal of Rheumatology. - : Informa UK Limited. - 0300-9742 .- 1502-7732. ; 48:3, s. 207-212
-
Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: In the 2016 American College of Rheumatology/European League Against Rheumatism classification criteria for primary Sjögren's syndrome (pSS), pre-existing lymphoma is not an exclusion criterion for pSS diagnosis, as in earlier criteria. We aimed to explore whether there are differences between pSS patients with and without pre-existing lymphoma at pSS diagnosis.METHOD: Patients with ICD-7-10 codes for Sjögren's syndrome (SS) and a diagnosis of malignant lymphoma before or after SS diagnosis were identified by linking the Swedish Patient Register 1964-2007 with the Cancer Register 1990-2007 (n = 224). Clinical data were collected from medical records. Lymphoma diagnoses were evaluated by tissue review. Characteristics of pSS patients with and without pre-existing lymphoma were compared.RESULTS: We identified 107 patients with pSS as the reason for an SS diagnosis code and a verified lymphoma. Of these, 18 (17%) had a pre-existing lymphoma at pSS diagnosis, defined as lymphoma diagnosed before or within 6 months of pSS diagnosis. Male gender (39% vs 10%, p = 0.006), enlarged lymph nodes during the pSS disease (61% vs 27%, p = 0.01), mucosa-associated lymphoid tissue (MALT) lymphoma (50% vs 22%, p = 0.02), and salivary gland lymphoma (61% vs 26%, p = 0.006) were more common in patients with a pre-existing lymphoma at pSS diagnosis. Other pSS characteristics were similar.CONCLUSION: In a substantial proportion of patients, particularly in men, pSS remains undiagnosed until after lymphoma diagnosis. The study highlights the importance of pSS investigation in patients with lymphoma, especially MALT lymphoma, in the salivary glands.
|
|
| 7. |
- Vasaitis, Lilian, et al.
(författare)
-
Sporadic occurrence of non-diagnosed IgG4-related disease in lymphoma patients with a previous Sjögren's syndrome diagnosis.
- 2016
-
Ingår i: Acta Oncologica. - 0284-186X .- 1651-226X. ; 55:9-10, s. 1139-1144
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: IgG4-related disease (IgG4-RD) is a recently recognized fibro-inflammatory disorder, which may affect many organs, and often comes to clinical attention due to tumor-like organ swelling or is identified incidentally by specific biopsy findings. Typical histopathology of IgG4-RD is lymphoplasmacytic infiltration rich in IgG4 + plasma cells (PCs), storiform fibrosis, and obliterative phlebitis. Patients with sicca symptoms can be misdiagnosed as primary Sjögren's syndrome (pSS) instead of IgG4-RD because of clinical and histopathological similarities. Moreover, an association with lymphoma development is described in both diseases. This study investigated signs of IgG4-RD in a population-based cohort of patients diagnosed with pSS complicated by lymphoma.METHODS: Patients with pSS and lymphoma diagnoses and available lymphoma specimens were identified by linkage with the Swedish Patient Register 1964-2007 and the Cancer Register 1990-2007 (n = 79). Clinical data and lymphomas were reviewed and the diagnoses evaluated. All lymphoma tissues and available minor salivary gland biopsies (n = 11) were immunostained for IgG4 + PCs and evaluated for other histopathological signs of IgG4-RD. In a case with specific findings of IgG4-RD, other available tissue specimens of the same patient were investigated for IgG4-RD.RESULTS: Only one patient of 79 (1.3%) had >10 IgG4 + PCs/high power field (HPF) in the lymphoma tissue, an unspecified low-grade B-cell lymphoma localized in the submandibular gland. This patient also had other histopathological features of IgG4-RD in the lymphoma and a surgical lung biopsy taken five years before lymphoma diagnosis and, therefore, fulfilled the criteria for IgG4-RD. Occasional IgG4 + PCs (<10/HPF) without signs of IgG4-RD were observed in another six lymphomas. No IgG4 + PCs were identified in the minor salivary gland biopsies.CONCLUSION: Histopathological findings of IgG4-RD may co-exist with low malignant B-cell lymphoma in patients with initially suspected pSS and may be associated with an underlying IgG4-RD.
|
|
| 8. |
- Knight, Ann, et al.
(författare)
-
Leukemia and Myelodysplastic Syndrome in Granulomatosis with Polyangiitis : Subtypes, Clinical Characteristics, and Outcome
- 2015
-
Ingår i: Journal of Rheumatology. - : The Journal of Rheumatology. - 0315-162X .- 1499-2752. ; 42:4, s. 690-694
-
Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Previous studies have shown that patients with granulomatosis with polyangiitis (GPA) have an increased risk of hematological malignancies, especially leukemia. Our aim was to assess clinical characteristics and treatment of patients with GPA complicated by hematological malignancies with focus on leukemia and to describe these malignancies in more detail.METHODS: From the Swedish population-based patient register, all individuals with a diagnosis of GPA from 1964-2012 were identified (n = 3224). Through linkage with the Swedish Cancer Register, we searched for all cases of leukemia [International Classification of Diseases (ICD) 7: 204-207 and corresponding codes ICD 8-10] registered after the first discharge listing GPA. The GPA diagnosis was evaluated using the European Medical Association classification algorithm. To confirm the hematological malignancy, all diagnostic bone marrow samples were reclassified. Clinical data of both the GPA and hematological malignancy were collected from medical files.RESULTS: Twenty-one cases were identified, all of myeloid origin, including 9 with myelodysplastic syndrome developing to acute myeloid leukemia (MDS-AML), 7 AML, 3 MDS, and 2 chronic myeloid leukemia. The median time from GPA diagnosis to hematological malignancy was 8 years (range 5-21). All patients had severe generalized GPA and had received high doses of cyclophosphamide (CYC; median cumulative dose 96.5 g). Cytopenia occurred in 76% of the patients prior to the hematological malignancy.CONCLUSION: The findings emphasize the longterm risk of leukemia and MDS in CYC-treated, severely ill patients with GPA. Cytopenia during the course of GPA may be a warning sign and warrants a liberal attitude toward bone marrow examination.
|
|
