Central nervous system (CNS) relapse is a devastating complication that occurs in about 5% of diffuse large B-cell lymphoma (DLBCL) patients. Currently, there are no predictive biological markers. We ...wanted to study potential biomarkers of CNS tropism that play a role in adhesion, migration and/or in the regulation of inflammatory responses. The expression levels of ITGA10, CD44, PTEN, cadherin-11, CDH12, N-cadherin, P-cadherin, lactoferrin and E-cadherin were studied with IHC and IEM. GEP was performed to see whether found expressional changes are regulated at DNA/RNA level. IHC included 96 samples of primary CNS lymphoma (PCNSL), secondary CNS lymphoma (sCNSL) and systemic DLBCL (sDLBCL). IEM included two PCNSL, one sCNSL, one sDLBCL and one reactive lymph node samples. GEP was performed on two DLBCL samples, one with and one without CNS relapse. CNS disease was associated with enhanced expression of cytoplasmic and membranous ITGA10 and nuclear PTEN (P < 0.0005, P = 0.002, P = 0.024, respectively). sCNSL presented decreased membranous CD44 and nuclear and cytoplasmic cadherin-11 expressions (P = 0.001, P = 0.006, P = 0.048, respectively). In PCNSL lactoferrin expression was upregulated (P < 0.0005). IEM results were mainly supportive of the IHC results. In GEP CD44, cadherin-11, lactoferrin and E-cadherin were under-expressed in CNS disease. Our results are in line with previous studies, where gene expressions in extracellular matrix and adhesion-related pathways are altered in CNS lymphoma. This study gives new information on the DLBCL CNS tropism. If further verified, these markers might become useful in predicting CNS relapses.
Purpose - We wanted to examine the potential of the Scandinavian Sarcoma Group (SSG) Central Register, and evaluate referral and treatment practice for soft-tissue sarcomas in the extremities and ...trunk wall (STS) in the Nordic countries.
Background - Based on incidence rates from the literature, 8,150 (7,000-9,300) cases of STS of the extremity and trunk wall should have been diagnosed in Norway, Finland, Iceland, and Sweden from 1987 through 2011. The SSG Register has 6,027 cases registered from this period, with 5,837 having complete registration of key variables. 10 centers have been reporting to the Register. The 5 centers that consistently report treat approximately 90% of the cases in their respective regions. The remaining centers have reported all the patients who were treated during certain time periods, but not for the entire 25-year period.
Results - 59% of patients were referred to a sarcoma center untouched, i.e. before any attempt at open biopsy. There was an improvement from 52% during the first 5 years to 70% during the last 5 years. 50% had wide or better margins at surgery. Wide margins are now achieved less often than 20 years ago, in parallel with an increase in the use of radiotherapy. For the centers that consistently report, 97% of surviving patients are followed for more than 4 years. Metastasis-free survival (MFS) increased from 67% to 73% during the 25-year period.
Interpretation - The Register is considered to be representative of extremity and trunk wall sarcoma disease in the population of Scandinavia, treated at the reporting centers. There were no clinically significant differences in treatment results at these centers.
We performed a large nested case-control study within the Finnish and Icelandic maternity cohorts to verify/falsify the association of maternal EBV infection with an increased risk of acute ...lymphoblastic leukemia (ALL) in the offspring found in previous studies. All hematologic malignancies diagnosed among children born during 1983 to 2006 in Finland and 1997 to 2005 in Iceland were identified through national cancer registries. For each index mother of a leukemia case, three matched control mothers with cancer-free offspring were identified. First trimester sera from 561 ALL and 144 non-ALL index mothers and from 2,105 control mothers were analyzed for antibodies to EBV viral capsid antigen (IgG and IgM), early antigen (IgG) and ZEBRA protein (IgG). Conditional logistic regression-based estimates of odds ratios and 95% confidence intervals adjusted for birth order and sib-ship size were calculated. Overall, there was no evidence of increased risk of ALL associated to EBV viral capsid antigen IgM (odds ratio, 0.9; 95% confidence interval, 0.5-1.8). The early antigen and ZEBRA antibodies (EBV reactivation markers) were also not associated with risk. The data argue against a role of EBV in ALL.
The role of rituximab in combination with different CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone)-like chemotherapy regimens in young patients with good-prognosis diffuse ...large-B-cell lymphoma remains to be defined. We aimed to compare CHOP-like chemotherapy and rituximab with CHOP-like chemotherapy alone in these patients.
824 patients who were from 18 countries; aged 18–60 years; and who had no risk factors or one risk factor according to age-adjusted International Prognostic Index (IPI), stage II–IV disease, or stage I disease with bulk were enrolled. These patients were randomly assigned to six cycles of CHOP-like chemotherapy and rituximab (n=413) or to six cycles of CHOP-like chemotherapy alone (n=411). Bulky and extranodal sites received additional radiotherapy. The primary endpoint was event-free survival; secondary endpoints were response, progression under therapy, progression-free survival, overall survival, and frequency of toxic effects. Analyses were done by intention to treat and per protocol. This trial is registered at
http://www.clinicaltrials.gov, NCT 00064116.
After a median follow-up of 34 months (range 0·03–61), patients assigned chemotherapy and rituximab had increased 3-year event-free survival compared with those assigned chemotherapy alone (79% 95% CI 75–83
vs 59% 54–64; difference between groups 20% 13–27, log-rank p<0·0001), and had increased 3-year overall survival (93% 90–95
vs 84% 80–88; difference between groups 9% 3–13, log-rank p=0·0001). Event-free survival was affected by treatment group, presence of bulky disease, and age-adjusted IPI: after chemotherapy and rituximab, a favourable subgroup (ie, IPI=0, no bulk) could be defined from a less-favourable subgroup (ie, IPI=1 or bulk, or both). Groups did not differ in the frequency of adverse events.
Rituximab added to six cycles of CHOP is an effective treatment for young patients with good-prognosis diffuse large-B-cell lymphoma. The definition of two prognostic subgroups allows for a more refined therapeutic approach for these patients.
Nodular lymphocyte predominant Hodgkin lymphoma (NLPHL) usually presents in middle aged men and shows an indolent clinical behavior. However, up to 30% of the patients present a secondary ...transformation into aggressive diffuse large B cell lymphoma (DLBCL). The aim of the present study was to characterize morphology and immunophenotype of this kind of DLBCL in detail and compare it with conventional DLBCL.
Morphology and immunophenotype of 33 cases of NLPHL with simultaneous or sequential transformation into DLBCL were investigated. These cases were compared with 41 de novo DLBCL in Finnish men.
The majority of cases exhibited different immunophenotypes in the NLPHL and the DLBCL components. The immunophenotype of the DLBCL secondary to NLPHL was heterogeneous. However, BCL6, EMA, CD75 and J-chain were usually expressed in both components (≥73% positive). Overall, the NLPHL component was more frequently positive for EMA, CD75 and J-chain than the DLBCL component. In contrast, B cell markers, CD10 and BCL2, were more frequently expressed and were expressed at higher levels in the DLBCL component than in the NLPHL component. In the independent series of de novo DLBCL 4 cases could be identified with a growth pattern and immunophenotype that suggested that they had arisen secondarily from NLPHL.
The morphology and immunophenotype of DLBCL arisen from NLPHL is heterogeneous. Further characterization of the particular molecular features of this subgroup is warranted to be able to better identify these cases among conventional DLBCL.
T cells influence outcome in follicular lymphoma, but their contributions seem to be modified by therapy. Their impact in patients receiving rituximab without chemotherapy is unknown.
Using flow ...cytometry, we evaluated the T cells in tumors and/or blood in a total of 250 follicular lymphoma patients included in two Nordic Lymphoma Group randomized trials that compared single rituximab with IFN-α2a-rituximab combinations.
In univariate analysis, higher levels of CD3(+), CD4(+), and CD8(+) T cells in both tumors and blood correlated with superior treatment responses, and in multivariate analysis, tumor-CD3(+) (P = 0.011) and blood-CD4(+) (P = 0.029) cells were independent. CD4(+) cells were favorable regardless of treatment arm, but CD8(+) cells were favorable only in patients treated with single rituximab, because IFN-α2a improved responses especially in patients with low CD8(+) cell levels. Higher levels of blood-CD3(+) (P = 0.003) and blood-CD4(+) (P = 0.046) cells predicted longer overall survival, and higher levels of blood-CD8(+) cells longer times to next treatment (P = 0.046).
We conclude that therapeutic effects of rituximab are augmented by tumor-associated T cells for rapid responses and by systemic T cells for sustained responses. CD4(+) and CD8(+) cells are both favorable in patients treated with rituximab. IFN-α2a abrogates the negative impact of few CD8(+) cells.
Abstract
Background. Primary central nervous system lymphoma (PCNSL) is a rare brain tumour with a dismal prognosis. Several phase II studies with high-dose methotrexate-based regimens have shown ...promising early results, but in all hospital-based data published so far, the disease outcome is poor.
Material and methods. We performed a hospital-based retrospective analysis to evaluate the long-term results of the Nordic type of Bonn chemotherapy regimen in PCNSL patients. The study included 54 patients with newly diagnosed PCNSL who received chemotherapy with curative intent as their first-line treatment.
Results. We found promising response rates, 76% of the patients achieving CR and 22% patients achieving PR, with corresponding two-year EFS 53% and OS 76%. However, with longer follow-up a constant pattern of relapses was observed with only one patient remaining in primary remission after 60 months.
Discussion. The finding suggests that basic biological differences exist between PCNSL and systemic diffuse large B-cell lymphoma and there is a need for consolidation or maintenance therapy after achieving a remission in patients with PCNSL.
Lynch syndrome (LS) is an autosomal dominant cancer syndrome including increased life-long risk for colorectal (CRC) and endometrial (EC) cancer, but also for cancers of other types. The risk for CRC ...is up to 70–80 % and for EC up to 50–60 %. Due to screening and early diagnosing the mortality related to CRC and EC seems to be low. In spite of many studies on surveillance of mutation carriers, there is no comprehensive evaluation on causes of death in LS families. The disease history and cause of death of all the deceased, tested mutation carriers and their mutation negative relatives in the Finnish LS families (N = 179) was examined utilizing hospital records and relevant national registries. Out of 1069 mutation carriers 151 had succumbed; 97 (64 %) from cancer. Out of 1146 mutation-negative family 44 members had died; 11 (25 %) of them from cancer. In 12 (7.7 %) of the deceased mutation carriers no cancer had been diagnosed. The mean age of death from cancer was 63.2 years vs. 68.8 years from non-cancer causes. Only 7.9 % of the patients with CRC had died from CRC and 5 % of those with EC, respectively. 61 % of the cancer deaths were related to extra-colonic, extra-endometrial cancers. The cumulative overall and cancer specific death rates were significantly increased in Mut+ compared to Mut− family members. Even surveillance yields decrease in the life-long risk and mortality of the most common cancers CRC and EC in LS, almost all mutation carriers will contract with cancer, and two thirds of the deceased have died from cancer. This should be taken in account in genetic counseling. Mutation carriers should be encouraged to seek help for abnormal symptoms.
Abstract Background Few studies have evaluated the role of the ubiquitous Epstein–Barr virus (EBV) infection, together with levels of the immunomodulator, vitamin D, in different breast cancer ...entities. We studied, prospectively, the association of EBV and vitamin D status with the risk of pregnancy-associated breast cancer (PABC), breast cancer diagnosed during pregnancy or 1 year post-partum, using a nested case–control study. Methods Serum vitamin D and antibodies to EBV were measured for 108 PABC cases of the Finnish Maternity Cohort, and 208 controls matched for date of birth, date of sampling and parity. The joint effect of vitamin D and EBV on the risk of PABC was evaluated. Results EBV seropositivity was generally not associated with the risk of PABC. Among individuals with sufficient (⩾75 nmol/l) levels of vitamin D, we, however, found similar increased risk estimates for PABC associated with serum immunoglobulin G (IgG) antibodies to EBV early antigens odds ratio (OR) = 7.7, 95% (confidence interval) CI 1.4–42.3 and the viral reactivator protein, ZEBRA (OR = 7.8, 95% CI 1.1–61.2). Conclusion Immunological markers of EBV reactivation status among individuals with sufficient vitamin D levels were consistently associated with increased risk of the disease. This suggests that EBV reactivation may be an indicator of the progression of breast cancer occurring soon after pregnancy, while the virus probably is not the aetiological agent.
Atopy and Risk of Non-Hodgkin Lymphoma Melbye, Mads; Smedby, Karin Ekström; Lehtinen, Tuula ...
JNCI : Journal of the National Cancer Institute,
01/2007, Letnik:
99, Številka:
2
Journal Article
Recenzirano
Odprti dostop
Background A possible connection between allergy and cancer has been suspected, but allergy-related conditions or atopy have been inconsistently associated with reduced risks of non-Hodgkin lymphoma. ...We investigated this association in a population-based case–control study and in a prospective study with prediagnostic blood specimens. Methods We carried out a population-based study of 3055 case patients with non-Hodgkin lymphoma and 3187 control subjects in Denmark and Sweden, including questionnaire information on allergy and blood specimens, and a nested case–control study within a prospective cohort of more than 400 000 Finnish women. In the second study, serum specimens from the 198 case patients who developed non-Hodgkin lymphoma within a median of 8.9 years after the blood was drawn were matched with serum specimens from 594 control subjects. In both studies, laboratory-based evidence of allergy (atopy) was determined in serum on the basis of specific IgE reactivity to common inhalant allergens. Dissemination of disease was classified by the Ann Arbor system. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated by logistic regression. Results In the first study, ever having hay fever, but not other allergic conditions, was associated with a reduced risk of non-Hodgkin lymphoma. In particular, subjects with specific IgE reactivity in serum had a 32% (95% CI = 20% to 42%) lower risk of overall non-Hodgkin lymphoma than those without such reactivity. However, among case patients, dissemination of the disease was strongly inversely associated with specific IgE reactivity. In the second (i.e., prospective) study, no association was found between non-Hodgkin lymphoma and specific IgE reactivity, except possibly immediately before a diagnosis of non-Hodgkin lymphoma (≥10 years before diagnosis, OR = 1.00, 95% CI = 0.48 to 2.09; 5–9 years before, OR = 0.95, 95% CI = 0.50 to 1.84; 1–4 years before, OR = 0.33, 95% CI = 0.11 to 1.02; and <1 year before, OR = 0.27, 95% CI = 0.03 to 2.31). Conclusion Allergy may not be causally associated with the risk of non-Hodgkin lymphoma. The inverse association observed in some case–control studies may arise because non-Hodgkin lymphoma suppresses the immunologic response to allergens.
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