Marked improvement of overall survival in mantle cell lymphoma: a population based study from the Swedish Lymphoma Registry.

Abstract In recent years, more intensive chemotherapy regimens for mantle cell lymphoma (MCL) have been associated with prolongation of survival. In this study, our aim was to investigate prognostic factors and evaluate improvement in survival in MCL on a population level. The cohort included all patients diagnosed with MCL from 1 January 2000 to 31 March 2010 in the Swedish Lymphoma Registry. At total of 785 patients with MCL were identified. Age, performance status, and B-symptoms were significant prognostic factors for overall survival (OS) in multivariate analysis. In addition, OS was markedly improved (hazard ratio 0.8, 95% confidence interval 0.7-0.9) for patients diagnosed during the latest time period, 2006-2010, also when corrected for prognostic factors as above. Estimated OS at 3 years was 62%, compared to 47% for patients diagnosed earlier (p < 0.01). The reasons for this dramatic improvement in OS are not yet clear, but may be due to the introduction of specific and more potent therapeutic regimens

Improvement in survival of diffuse large B-cell lymphoma in relation to age, gender, International Prognostic Index and extranodal presentation: a population based Swedish Lymphoma Registry study

Our aim was to describe a large population-based cohort of diffuse large B-cell lymphoma (DLBCL) during the last decade, evaluating possible improvement in survival and to identify subgroups in need of novel treatment strategies. The study population encompassed all patients diagnosed with DLBCL in Sweden from 2000 through 2010. Altogether 5349 patients were identified. There was no increase in incidence for females, but for males there was an estimated yearly increase in incidence by 0.019 per 10 000. When adjusted for age and gender, the improvement in overall survival for the whole group was estimated at 4.5% per year, most prominent in the age group 60-78 years, and in patients with good performance status. In this large dataset, we were able to detect a clear improvement in overall survival in DLBCL, although restricted to specific prognostic subgroups, and to identify specific disease presentations that significantly affect overall survival

Treatment outcome in T-cell lymphoblastic lymphoma in adults - a population-based study from the Swedish Lymphoma Registry

Background. T-cell lymphoblastic lymphoma (T-LBL) is a rare neoplasm of precursor lymphoblast origin, for which there is no standard treatment for adults. Results of current treatment strategies in selected populations do exist but are largely unreported for unselected series. Here, we aimed to investigate treatment outcome in a population-based cohort. Material and methods. Patients were identified through the Swedish Lymphoma Registry and data was retrospectively collected for all adult (>= 18 years) Swedish T-LBL patients diagnosed during 2000-2009. Results. A total of 39 patients with median age 40 years (range 18-78) were identified with females being significantly older than males (median age 66 vs. 37, p = 0.027). The five-year overall survival for all patients was 42%. Female gender was associated with shorter survival also when adjusted for treatment strategy and age [hazard ratio (HR) 4.29; p = 0.002]. Thirty patients received intensive chemotherapy, otherwise used for treatment of acute lymphoblastic leukemia (ALL), which resulted in an overall response rate of 97% and a five-year progression-free survival (PFS) of 49%. In this group only CNS involvement at diagnosis predicted shorter PFS (HR 13.3; p = 0.03). Among patients treated with hyper-CVAD the addition of mediastinal irradiation resulted in prolonged time to progression compared to patients receiving only chemotherapy (p = 0.047). The major reason for treatment failure was relapse and in this series 18-fluoro-deoxyglucose positron emission tomography (PET) did not predict this risk. Conclusion. This population-based study indicates that all fit T-LBL patients should be considered for intensive treatment. Our results also suggest a beneficial effect of mediastinal irradiation in combination with hyper-CVAD treatment. Relapsing patients have a dismal outcome irrespective of salvage treatment

Survival in patients with intermediate or high grade non-Hodgkin's lymphoma: meta-analysis of randomized studies comparing third generation regimens with CHOP

In patients with intermediate or high grade non-Hodgkin lymphoma (NHL), third generation chemotherapy regimens have been introduced to improve survival in comparison with the standard CHOP regimen. However, most studies have found no difference between these two treatments. We conducted a meta-analysis to assess the effectiveness of third generation regimens as compared with CHOP. Our study included the randomized controlled trials published in English from 1970 to 1999. After a Medline search, 5 trials were found to meet our inclusion criteria. A total of 1982 patients, that were enrolled in these trials, were included in the survival meta-analysis. Our methodology retrieved patient-level information from all of these subjects; survival up to 9 years after randomization was compared between the two treatment options. The results of our meta-analysis showed that, in comparison with CHOP, third generation chemotherapy did not prolong survival at levels of statistical significance (chi-square by log-rank test = 1.44, P = 0.23). The relative death risk for third generation regimens vs. CHOP was 0.92 (95%CI: 0.80 to 1.06;P  = 0.26). We conclude that, on the basis of our meta-analysis, third generation regimens do not confer any survival benefit to patients with intermediate or high grade NHL as compared with CHOP. © 2001 Cancer Research Campaign http://www.bjcancer.co

Impact of chemotherapy regimen and rituximab in adult Burkitt lymphoma: a retrospective population-based study from the Nordic Lymphoma Group.

BackgroundStandard treatment of adult Burkitt lymphoma is not defined due to the lack of randomised trials. In this situation, population-based data may represent a useful contribution in order to identify an optimal treatment strategy.Patients and methodsThe aims of this study were to investigate the outcome for adult HIV-negative BL with different chemotherapy regimens, and to assess possible improvement within the time frame of the study. The study population was identified through the Swedish and Danish lymphoma registries 2000-2009.ResultsA total of 258 patients were identified. Since 2000, overall survival (OS) improved significantly only for younger patients (<65 years). Intensive regimens such as the Berlin-Frankfurt-Münster, hyper-fractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone (hyper-CVAD) and cyclophosphamide, vincristine, doxorubicin, methotrexate, ifosfamide, etoposide, and cytarabine (CODOX-M/IVAC) were associated with a favourable 2-year OS of 82%, 83%, and 69%, respectively. The low-intensive CHOP/CHOEP regimens achieved a 2-year OS of 38.8%, confirming their inadequacy for the treatment of BL. In a multivariate analysis, rituximab was not significantly associated with improved OS.ConclusionsIn this population-based retrospective series of adult BL, intensive chemotherapy regimens were associated with favourable outcome. The impact of the addition of rituximab remains uncertain and warrants further investigation

Pharmacologically relevant doses of valproate upregulate CD20 expression in three diffuse large B-cell lymphoma patients in vivo.

Epigenetic code modifications by histone deacetylase inhibitors (HDACi) have been proposed as potential new therapies for lymphoid malignancies. Diffuse large B-cell lymphoma (DLBCL) is the most common type of aggressive lymphoma for which standard first line treatment is the chemotherapy regimen CHOP (cyclophosphamide, doxorubicin, vincristine and prednisone) combined with the monoclonal anti-CD20 antibody rituximab (R-CHOP). The HDACi valproate, which has for long been utilized in anti-convulsive therapy, has been shown to sensitize to chemotherapy in vitro. Valproate upregulates expression of CD20 in lymphoma cell lines; therefore, 48 hour pre-treatment with valproate before first line R-CHOP in DLBCL stages II-IV is evaluated in the phase I clinical trial VALFRID; Valproate as First line therapy in combination with Rituximab and CHOP in Diffuse large B-cell lymphoma

EHA/ESMO Clinical Practice Guidelines for the Management of Malignant Lymphoma: Recommendations for the Second Phase of the COVID-19 Pandemic

No abstract availabl

SOX11 expression correlates to promoter methylation and regulates tumor growth in hematopoietic malignancies

<p>Abstract</p> <p>Background</p> <p>The transcription factor SOX11 plays an important role in embryonic development of the central nervous system (CNS) and is expressed in the adult immature neuron but is normally not expressed in any other adult tissue. It has recently been reported to be implicated in various malignant neoplasms, including several lymphoproliferative diseases, by its specific expression and in some cases correlation to prognosis. SOX11 has been shown to prevent gliomagenesis <it>in vivo </it>but the causes and consequences of aberrant expression of <it>SOX11 </it>outside the CNS remain unexplained.</p> <p>Results</p> <p>We now show the first function of <it>SOX11 </it>in lymphoproliferative diseases, by demonstrating <it>in vitro </it>its direct involvement in growth regulation, as assessed by siRNA-mediated silencing and ectopic overexpression in hematopoietic malignancies. Gene Chip analysis identified cell cycle regulatory pathways, including Rb-E2F, to be associated with SOX11-induced growth reduction. Furthermore, promoter analysis revealed that <it>SOX11 </it>is silenced through DNA methylation in B cell lymphomas, suggesting that its regulation is epigenetically controlled.</p> <p>Conclusions</p> <p>The data show that SOX11 is not a bystander but an active and central regulator of cellular growth, as both siRNA-mediated knock-down and ectopic overexpression of <it>SOX11 </it>resulted in altered proliferation. Thus, these data demonstrate a tumor suppressor function for <it>SOX11 </it>in hematopoietic malignancies and revealed a potential epigenetic regulation of this developmentally involved gene.</p

Chronic hepatitis C in Swedish subjects receiving opiate substitution therapy-Factors associated with advanced fibrosis.

Background: Opiate substitution therapy (OST) reduces the risk of death from directly drug-related causes in heroin users, allowing other chronic health problems to emerge. People who inject drugs (PWID) are exposed to hepatitis C virus (HCV), with an associated risk of chronic liver disease. We investigated HCV prevalence and liver-related morbidity in a cohort of OST recipients, and analyzed factors associated with significant hepatic fibrosis. Methods: All patients registered on 1 April 2008 in 4 clinics providing OST in the 3 largest cities in Sweden were eligible for inclusion. HCV viremic subjects were evaluated for fibrosis stage by liver biopsy, transient elastometry (TE), and/or a biochemical fibrosis index (Göteborg University Cirrhosis Index; GUCI). Factors associated with severity of fibrosis were determined by logistic regression analysis. Results: Out of 524 eligible patients, 277 consented to enrolment. Two hundred and thirty-six subjects (88%) were anti-HCV-positive, and 162 of these were viremic (69%). Significant liver fibrosis (defined as Ishak stages F3-F6, TE value ≥ 8.85 kPa, or GUCI > 0.33) was found in 69 out of 103 (67%) tested viremic patients, and was associated with alcohol intake (p = 0.03), higher body mass index (BMI; p = 0.04), and the presence of anti-HBc antibodies (indicating exposure to hepatitis B virus (HBV); p = 0.02). Conclusions: Significant liver fibrosis was detected in two-thirds of HCV viremic OST recipients in this cohort, and was associated with alcohol use, high BMI, and exposure to HBV. These findings indicate that the management of HCV and associated risk factors should be emphasized in Swedish OST programs