scholarly journals Cell of origin in diffuse large B-cell lymphoma in systemic lupus erythematosus: molecular and clinical factors associated with survival

2019 ◽  
Vol 6 (1) ◽  
pp. e000324 ◽  
Author(s):  
Basile Tessier-Cloutier ◽  
David DW Twa ◽  
Eva Baecklund ◽  
Randy Gascoyne ◽  
Nathalie A Johnson ◽  
...  
Keyword(s):  
Overall Survival ◽  
General Population ◽  
B Cell ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Cell Of Origin ◽  
Large B Cell Lymphoma ◽  
Extranodal Disease ◽  
Bcl2 Protein ◽  
Large B Cell

BackgroundSLE is associated with increased risk of diffuse large B-cell lymphoma (DLBCL). DLBCL is routinely classified by cell of origin (COO), with germinal centre B-cell (GCB) being more common and indicating better prognosis in the general population. We studied COO subtyping in patients with SLE diagnosed with DLBCL and their survival.Patients and methodsWe evaluated 20 cases of SLE with DLBCL. Immunohistochemistry analysis was performed (BCL2, MYC, BCL6, CD10, CD20, FOXP1, GCET1, MUM1) in tissue microarrays. We examined associations between molecular and clinical features, including overall survival.ResultsOf the 20 DLBCL SLE cases, 12/20 cases (60%) were classified as non-GCB using Hans or Choi algorithms. MYC and BCL2 protein expression was positive in 6/20 (30%) and 8/20 (40%) SLE cases, respectively, with 2/20 (10%) co-expressing both markers. Seven (7/20) had only extranodal involvement at DLBCL diagnosis. As expected, non-GCB cases had worse survival. Cases presenting exclusively with extranodal disease were associated with shorter SLE duration and better survival despite higher BCL2 protein expression.ConclusionsWe present novel data characterising DLBCL in SLE. Sixty per cent of the DLBCL in patients with SLE were non-GCB. The nodal and extranodal distribution in SLE was similar to what is known in the general population, but extranodal disease occurred more often with short SLE duration and was associated with longer overall survival. More research on cancer in SLE is the key to further understanding the complex interplay between cancer and the immune system.

scholarly journals Impact of Genetic Polymorphism of Myeloid Differentiation Primary Response Gene 88, Enhancer of Zeste Homolog 2, and B-cell Lymphoma 2 like 11 in Patients with Diffuse Large B Cell Lymphoma Treated with Rituximab, Cyclophosphamide, Doxorubicin, Vincristin

2021 ◽  
Vol 9 (A) ◽  
pp. 98-105
Author(s):  
Hussam Zawam ◽  
Noha E. Ibrahim ◽  
Rasha Salama ◽  
Mai Samir ◽  
Walaa Abdelfattah ◽  
...  
Keyword(s):  
B Cell ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Poor Response ◽  
Cell Of Origin ◽  
Bulky Disease ◽  
Large B Cell Lymphoma ◽  
Younger Age ◽  
Extranodal Disease ◽  
Large B Cell

BACKGROUND: Despite the growing landscape of genetic drivers in Diffuse Large B-cell Lymphoma, yet their clinical implication is still unclear and R-CHOP regimen remains a “one size fits all” therapy. We aimed in this study to examine the prevalence of EZH2, BCL211 and MYD 88 genetic polymorphisms in DLBCL patients and correlate the results with various clinical and survival outcomes. METHODS: Genotyping of MYD88 (rs387907272 T/C), EZH2 (rs3757441 C/T), and BCL2L11 (rs3789068 A/G) polymorphisms were conducted using real time polymerase chain reaction analysis in a total of 75 DLBCL patients. RESULTS: Most of our cases carried the wild TT genotype of MYD88 gene (64%), the mutant TT genotype of EZH2 gene (52%) and the wild AA genotype of BCL2L11 gene (48%). Regarding cell of origin, Germinal Centre (GC) phenotype was present in 56% of cases while 44% expressed the Post-GC (PGC) phenotype. Poor response outcome to first line R-CHOP was significantly correlated with the mutated CC genotype of MYD 88 (p=0.02), while better response to R-CHOP was significantly associated with younger age <50 years (p <0.0001), good PS (p=0.046), normal LDH level (p=0.003), earlier stage (p <0.0001), good IPI score (p=0.009), absence of extranodal disease (p <0.0001) and absence of bulky disease (p=0.004). The median PFS and the 2 year OS were significantly higher in younger age, earlier stage, good IPI score, absence of extranodal disease, absence of bulky disease and in GC phenotype. CONCLUSIONS: Our results emphasized that the mutated genotype of MYD 88 gene polymorphism is significantly associated with poor response to R-CHOP therapy.

Effect of addition of rituximab to CHOP on survival of patients in both the GCB and non-GCB subgroups of diffuse large B-cell lymphoma

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 8040-8040 ◽  
Author(s):  
K. Fu ◽  
K. D. Perry ◽  
L. M. Smith ◽  
C. P. Hans ◽  
T. C. Greiner ◽  
...  
Keyword(s):  
Overall Survival ◽  
B Cell ◽  
De Novo ◽  
Cell Lymphoma ◽  
Prognostic Significance ◽  
B Cell Lymphoma ◽  
Rank Test ◽  
Cell Of Origin ◽  
Large B Cell Lymphoma ◽  
Large B Cell

8040 Background: Diffuse large B-cell lymphoma (DLBCL) includes at least two prognostically important subgroups, i.e. germinal center B-cell (GCB) and activated B-cell (ABC) DLBCL, which were initially characterized by gene expression profiling and subsequently validated by immunostaining. Bcl-2 has also been identified as a prognostic indicator in the ABC subgroup. However, with the addition of rituximab (R) to standard chemotherapy, the prognostic significance of this subclassification of DLBCL is unclear. Methods: We studied 119 cases of de novo DLBCL including 70 cases treated with R-CHOP and 49 cases treated with CHOP. The cases were assigned to either the GCB or non-GCB subgroups using the methodology described by Hans et al (Blood 2004; 103:275). Characteristics of the patients were compared using the Chi-square test. Overall survival (OS) and event-free survival (EFS) were estimated using the Kaplan Meier method and compared with the log-rank test. Results: The median age of the 119 patients was 67 years, ranging from 20 to 90 years, and there were 62 males and 57 females. The clinical characteristics of patients treated with CHOP versus R-CHOP, including the IPI, were comparable. R-CHOP was more effective than CHOP with improved 5-year EFS (63% vs 41%, p=0.013) and OS (78% vs 47%, p<0.001). In both patient groups treated with R-CHOP or CHOP, the GCB subgroup had a significantly better 5-year EFS and OS compared to the non-GCB subgroup (OS: 91% vs 64% for R-CHOP, p=0.0073; 67% vs 31% for CHOP, p=0.034, respectively). Additionally, both the GCB and non-GCB subgroups treated with R-CHOP had a significantly improved OS compared to their respective subgroups receiving CHOP alone (GCB, p=0.015; non-GCB, p=0.019). Bcl-2 expression was not a significant predictor in either the GCB or non-GCB subgroups treated with R-CHOP (OS, GCB: p=0.32; non-GCB: p=0.43). Conclusions: In this retrospective study, we demonstrate that subclassification based on the cell of origin continues to have prognostic significance in patients with DLBCL treated with R-CHOP. Addition of rituximab to CHOP improves the overall survival of patients with DLBCL in both the GCB and non-GCB subgroups. No significant financial relationships to disclose.

scholarly journals Primary Cutaneous Diffuse Large B Cell Lymphoma -Leg Type in United States: Epidemiology and Survival Outcome

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 2202-2202
Author(s):  
Lubina Arjyal ◽  
Megha Giri ◽  
Dipesh Uprety ◽  
Yazhini Vallatharasu ◽  
Swapna Talluri ◽  
...  
Keyword(s):  
Overall Survival ◽  
General Population ◽  
B Cell ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Survival Outcome ◽  
Younger Patients ◽  
Large B Cell Lymphoma ◽  
Large B Cell ◽  
Cutaneous B Cell Lymphoma

Background: Primary cutaneous diffuse large B cell lymphoma-leg type (DLBCL-LT) is relatively uncommon lymphoma accounting for about 1 to 3 % of all cutaneous lymphoma and about 10-20% of primary cutaneous B cell lymphomas. There is data for survival outcomes in primary cutaneous B cell lymphoma in general population after introduction of rituximab but little is known about outcomes in DLBCL-LT patients in general population. The available data on survival in DLBCL-LT are from small case series and single institution studies. We conducted this study to evaluate the survival outcome in patients with PCDLBCL-LT after introduction of rituximab. Methods: We utilized SEER 18 database to select adult (18+ years) patients diagnosed from 2004 to 2014 with ICD-3-0 code of 9680/3 (diffuse large B cell lymphoma, not otherwise specified)with localized stage by summary stage 2000 with skin as the primary site of disease to identify patient with DLBCL-LT. Patients were divided into various cohorts based on age (<65 versus 65+ years), sex, race (Caucasians, African American and Others) and median household income of county of residence (< $50,00 versus ≥ $50,000). We utilized SEER*stat to calculate age adjusted incidence rate using 2000 US standard population. Kaplan Meyer curve was utilized to calculate 5-year overall survival. Cox proportional hazard model was used for multivariate analysis of factor associated with survival. Result: A total of 485 patients were identified with DLBCL-LT as the only or first primary cancer case. The median age at diagnosis was 70 years. Its incidence was found to be about 0.09 case per 100,000 population with incidence in males being about 1.6 times that of females. Majority of patient included in our study were males (52 %), older (59.4%), and Caucasians (85.6%). 5-year overall survival was found to be 59%. Older patients were found to have significantly worse 5-year overall survival compared to younger patients with HR of 7.9 with 95% CI of 4.9 to 12.7. There was no disparity in cancer outcome based on race, sex or median income of the county of residence. When we compared the outcome of patients diagnosed in earlier 5 years to later 6 years of the study period, the survival curves almost overlapped suggesting that there has been little if any improvement in outcome in recent years. Conclusion: Our study showed that about 60% of patients with DLBCL-LT live for 5 years in real world setting which is comparable to the outcome reported by other studies on outcome in primary cutaneous B cell lymphoma. Even though this is disease of elderly, as the median age at diagnosis is 70 years, the outcome in older population was found to be significantly worse compared to younger patients. Given this is relatively uncommon disease, we recommend large registry-based studies to try to improve outcome in these patient population. Disclosures No relevant conflicts of interest to declare.

Ten-Year Follow-up Data of Diffuse Large B-Cell Lymphoma Patients: Single Center Experience

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 5223-5223
Author(s):  
Murat Ozbalak ◽  
M. Cem Ar ◽  
Ayse Salihoglu ◽  
Emine Gulturk ◽  
Ahmet Emre Eskazan ◽  
...  
Keyword(s):  
Overall Survival ◽  
B Cell ◽  
Cell Lymphoma ◽  
Survival Curve ◽  
B Cell Lymphoma ◽  
Common Type ◽  
Large B Cell Lymphoma ◽  
Extranodal Disease ◽  
And Performance ◽  
Large B Cell

Abstract Abstract 5223 Background Non-Hodgkin's Lymphoma (NHL) is the most common type of hematopoietic cancers and it constitutes 4% of all cancers. It is the seventh most common type of all cancers in Turkey. The NHL is 1.5 times more common among males and the median age of most subtypes is equal to or more than 50. About 85% of NHL has B cell origin and 5-year overall survival is around 60%. Tumor volume, histology, patient's age and performance, serum lactate dehydrogenase (LDH) and beta-2 microglobulin levels, stage of disease and presence of extranodal disease are related to prognosis of NHL. International Prognostic Index (IPI) includes five of these factors to predict prognosis: patient's age and performance, stage of the disease, serum LDH level, extranodal disease. Methods The aim of this study is to evaluate the responses to actual treatments applied and survival periods of our Diffuse Large B Cell Lymphoma (DLBCL) patients. Non-Burkitt's, aggressive non-Hodgkin's lymphoma records obtained from our hematology department, which belong to the period between January 2000 and May 2011 were retrospectively analyzed. 278 patients diagnosed morphologically/immune-histochemically as CD20 positive DLBCL were included in this study. 153 of 278 paraffin blocks of diagnostic tissue were accessible and two subgroups of DLBCL were determined as Germinal Center B cell (GC) and Activated B cell (AB). From the remaining 125 cases, paraffin blocks of diagnostic tissue could not be accessed 115 cases, so any subgroup could not be determined (ND) and Mediastinal Large Cell Lymphoma (MLCL) were assessed in 10 cases. The subgroups were compared in order to evaluate the survival and also the responses to treatment. In the non-parametric comparison process, we used Mann-Whitney-U test. Results Patient characteristics according to the subgroups are detailed in Table 1. Complete remission was achieved with the first line treatment in 75% of patients and from those, 20% were relapsed at the median of 9 months. Overall Survival (OS) was significantly longer in GC than in AB patients (median OS: 27 vs 24 months, p=0.006). The Time to Relapse (TTR) is two times longer in GC group than in AB group, however this data is not statistically significant (median TTR: 12 vs 5.5 months, p=0.221). Survival curve of ND patients is not significantly different from GC curve (p= 0.436). Nevertheless, AB subgroup survival curve is significantly worse than ND group (p= 0.024, Figure 1). Regarding all patients, IPI predicts the survival of DLBCL independent from subgroups and treatment modalities (p<0.001, Figure 2). The longest survival time is in MLCL patients, nonetheless statistical analysis could not be made because of the small number of patients. Conclusion The data should be analyzed carefully because all data could not be accessed in some patients as this is a retrospective analysis. However, our data is valuable at the point that it reflects “real-life” patient data. Disclosure This study was supported by Istanbul University Research Fund. Disclosures: No relevant conflicts of interest to declare.

Survival and Clinicopathological Characteristics of EBV-Positive Diffuse Large B-Cell Lymphoma

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 1588-1588
Author(s):  
Brady E Beltran ◽  
Erick Cotacallapa ◽  
Jorge J Castillo
Keyword(s):  
Overall Survival ◽  
Prognostic Factor ◽  
B Cell ◽  
Lymphocyte Count ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Conventional Chemotherapy ◽  
Large B Cell Lymphoma ◽  
Extranodal Disease ◽  
Large B Cell

Abstract Abstract 1588 Background: EBV-positive diffuse large B-cell lymphoma (EBV+ DLBCL) of the elderly is a provisional entity included in the 2008 WHO Classification of Lymphomas. Diagnostic criteria include age >50 years, DLBCL morphology and EBV expression in lymphomatous cells. However, these criteria are evolving as several patients are <50 years and a specific cut-off for the percentage of EBV expression has not been defined. The goal of this retrospective study is to evaluate clinical and pathological characteristics of EBV+ DLBCL from Peruvian patients. Methods: Between January 2002 and January 2012, all patients meeting criteria for EBV+ DLBCL were included in the analysis. Patients with evidence of immunosuppression were excluded. All cases re positive for the presence of EBV-encoded RNA (EBER) by in situ hybridization, and CD20 and/or PAX-5 expression by immuno-histochemistry. Clinical data were reviewed retrospectively and patient's biopsies were analyzed for the expression of BCL6, CD10, CD30 and MUM-1/IRF4 using a tissue microarray (TMA) technique. The overall survival (OS) curves were calculated using the Kaplan-Meier method, and compared using the log-rank test. Results: A total of 43 EBV+ DLBCL patients are included in this study. The median age was 73 years (range 25–95 years). Four patients (9% ) were <50 years. The male:female ratio was 2.2:1. B symptoms occurred in 59%, ECOG >21 in 60%, advanced stage (III/IV) in 58%, elevated LDH levels in 44%, and lymphocyte count <1000/uL in 35%. The International Prognostic Index (IPI) score was 0–2 in 39% and 3–5 in 61% of the patients. Extranodal disease occurred in 20 patients (46%): stomach (n=3), tonsil (n=3), pleura (n=2), palate (n=2), cecum (n=2), bone marrow (n=2), ileum (n=1), bone (n=1), skin (n=1), lung (n=1), meninges (n=1), breast (n=1) and peritoneum (n=1). Three patients had central nervous system involvement (7%), one at presentation and two at relapse. Based on the Hans classification, 76% had non-germinal center profile. Ki67 expression was >80% in 53% of the patients. Eleven evaluated patients had a c-myc-negative status. Chemotherapy was received in 75% of the cases due to poor performance status. The overall response rate with conventional chemotherapy was 46%, with complete response in 39%, partial response in 7%, and no response in 54%. The median survival was 7.5 months. The Oyama score was: 0 factors (13%), 1 factor (47%), and 2 factors (40%) with median OS of 41, 11 and 1.5 months respectively (p=0.07). A lymphocyte count <1000/uL was a prognostic factor for OS (p=0.001). Conclusions: Based on our study, which is the largest cohort in Latin-America, EBV+ DLBCL is an aggressive entity with frequent extranodal disease and poor response to conventional chemotherapy. The overall survival remains poor. Lymphopenia, as defined as lymphocyte count <1000/uL, appears as a prognostic factor for OS. Disclosures: No relevant conflicts of interest to declare.

Prediction of Survival in Diffuse Large B-Cell Lymphoma Based On the Expression of Two Genes: Integration of Tumor and Microenvironment Contributions.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 622-622 ◽  
Author(s):  
Ash A Alizadeh ◽  
Andrew J Gentles ◽  
Alvaro J. Alencar ◽  
Holbrook E Kohrt ◽  
Roch Houot ◽  
...  
Keyword(s):  
Gene Expression ◽  
Overall Survival ◽  
B Cell ◽  
Tumor Cells ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Cell Of Origin ◽  
Bivariate Model ◽  
Large B Cell Lymphoma ◽  
Large B Cell

Abstract Abstract 622 Background: Several gene-expression signatures are predictive of prognosis in diffuse large-B-cell lymphoma (DLBCL), but the lack of practical methods for a genome-scale analysis has restricted their routine clinical applicability. Methods: We studied genes whose expression had been reported to predict survival in DLBCL, attempting to validate genes and prognostic models with robust survival associations that are amenable to rapid diagnostic testing. Results: Among a previously described set of 6-genes shown to predict survival independent of measurement platform or therapy era (Lossos, et al. 2004 NEJM 350:1828), we identified LMO2 as the single gene with strongest independent prognostic value in 3 independent cohorts of patients with DLBCL. To assess the independent contribution of other genes in predicting survival, using existing microarray gene expression data (Lenz, et al. 2008 NEJM 359:2313), we evaluated all pairwise models that included LMO2 toward construction of a robust bivariate survival predictor. Among 54674 possible models, one combining expression of LMO2 with TNFRSF9 (encoding 4-1BB, also known as CD137) emerged as among the best in cross-validation when assessed in training (n=233) and test (n=181) cohorts. This bivariate predictor remained prognostic in both CHOP (p=1.7e-6) and R-CHOP (p=6.5e-8) therapy eras, was highly independent of the International Prognostic Index, Cell-of-Origin classification, 6-gene predictive model, ‘stromal' model, and added significantly to their prognostic power. While LMO2 expression was highly restricted to tumor cells and was linked to Cell-of-Origin (GCB, p=2.2e-16), TNFRSF9 expression was highest in non-tumor cells (P=0.02), particularly in an activated subset of infiltrating CD8 T-cells. To validate this bivariate model and devise a practical diagnostic assay, we used quantitative real-time polymerase-chain-reaction to measure the expression of LMO2 and TNFRSF9 as well as other components of the 6-gene model (BCL2, BCL6, FN1, CCL3, and CCND2) in diagnostic formalin fixed and paraffin-embedded samples of lymphoma from an independent set of 147 patients with de novo DLBCL treated with R-CHOP. The IPI distribution for these patients was: 0-1 factor (n=70), 2 factors (n=40), 3 factors (n=26), ≥4 factors (n=11). In univariate and multivariate analyses of this independent cohort, LMO2 and TNFRSF9 expression remained individually prognostic of both progression free and overall survival. The bivariate model combining LMO2/TNFRSF9 could be used to stratify distinct risk groups for overall survival (p=0.004), and remained independent of IPI. Conclusion: Measurement of the expression of two genes integrating contributions of tumor cells and the tumor microenvironment is sufficient to predict overall survival in patients with DLBCL treated with R-CHOP. Disclosures: Advani: Seattle Genetics, Inc.: Research Funding.

scholarly journals Event-Free Survival at 24 Months Is a Robust End Point for Disease-Related Outcome in Diffuse Large B-Cell Lymphoma Treated With Immunochemotherapy

2014 ◽  
Vol 32 (10) ◽  
pp. 1066-1073 ◽  
Author(s):  
Matthew J. Maurer ◽  
Hervé Ghesquières ◽  
Jean-Philippe Jais ◽  
Thomas E. Witzig ◽  
Corinne Haioun ◽  
...  
Keyword(s):  
Overall Survival ◽  
General Population ◽  
B Cell ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Population Data ◽  
Newly Diagnosed ◽  
Large B Cell Lymphoma ◽  
Large B Cell ◽  
Age And Sex

Purpose Studies of diffuse large B-cell lymphoma (DLBCL) are typically evaluated by using a time-to-event approach with relapse, re-treatment, and death commonly used as the events. We evaluated the timing and type of events in newly diagnosed DLBCL and compared patient outcome with reference population data. Patients and Methods Patients with newly diagnosed DLBCL treated with immunochemotherapy were prospectively enrolled onto the University of Iowa/Mayo Clinic Specialized Program of Research Excellence Molecular Epidemiology Resource (MER) and the North Central Cancer Treatment Group NCCTG-N0489 clinical trial from 2002 to 2009. Patient outcomes were evaluated at diagnosis and in the subsets of patients achieving event-free status at 12 months (EFS12) and 24 months (EFS24) from diagnosis. Overall survival was compared with age- and sex-matched population data. Results were replicated in an external validation cohort from the Groupe d'Etude des Lymphomes de l'Adulte (GELA) Lymphome Non Hodgkinien 2003 (LNH2003) program and a registry based in Lyon, France. Results In all, 767 patients with newly diagnosed DLBCL who had a median age of 63 years were enrolled onto the MER and NCCTG studies. At a median follow-up of 60 months (range, 8 to 116 months), 299 patients had an event and 210 patients had died. Patients achieving EFS24 had an overall survival equivalent to that of the age- and sex-matched general population (standardized mortality ratio [SMR], 1.18; P = .25). This result was confirmed in 820 patients from the GELA study and registry in Lyon (SMR, 1.09; P = .71). Simulation studies showed that EFS24 has comparable power to continuous EFS when evaluating clinical trials in DLBCL. Conclusion Patients with DLBCL who achieve EFS24 have a subsequent overall survival equivalent to that of the age- and sex-matched general population. EFS24 will be useful in patient counseling and should be considered as an end point for future studies of newly diagnosed DLBCL.

DIFFUSE LARGE B-CELL LYMPHOMA SURVIVAL PROGNOSTICATION, A COMPARATIVE ANALYSIS OF CELL OF ORIGIN VS. MYC/BCL2 EXPRESSION

2019 ◽  
Vol 37 ◽  
pp. 353-353
Author(s):  
M. Rodriguez ◽  
I. Fernandez-Miranda ◽  
R. Mondejar ◽  
J. Capote ◽  
S. Rodriguez-Pinilla ◽  
...  
Keyword(s):  
Comparative Analysis ◽  
B Cell ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Cell Of Origin ◽  
Large B Cell Lymphoma ◽  
Large B Cell ◽  
Bcl2 Expression
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