scholarly journals Proteomic Landscape of Extracellular Vesicles for Diffuse Large B-Cell Lymphoma Subtyping

2021 ◽  
Vol 22 (20) ◽  
pp. 11004
Author(s):  
Ana Sofia Carvalho ◽  
Henrique Baeta ◽  
Andreia F. A. Henriques ◽  
Mostafa Ejtehadifar ◽  
Erin M. Tranfield ◽  
...  
Keyword(s):  
B Cell ◽  
Extracellular Vesicles ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Preclinical Model ◽  
P Value ◽  
Whole Cell ◽  
Large B Cell Lymphoma ◽  
Cell Proteome ◽  
Large B Cell

The role of extracellular vesicles (EVs) proteome in diffuse large B-cell lymphoma (DLBCL) pathology, subclassification, and patient screening is unexplored. We analyzed by state-of-the-art mass spectrometry the whole cell and secreted extracellular vesicles (EVs) proteomes of different molecular subtypes of DLBCL, germinal center B cell (GCB subtype), and activated B cell (ABC subtype). After quality control assessment, we compared whole-cell and secreted EVs proteomes of the two cell-of-origin (COO) categories, GCB and ABC subtypes, resulting in 288/1115 significantly differential expressed proteins from the whole-cell proteome and 228/608 proteins from EVs (adjust p-value < 0.05/p-value < 0.05). In our preclinical model system, we demonstrated that the EV proteome and the whole-cell proteome possess the capacity to separate cell lines into ABC and GCB subtypes. KEGG functional analysis and GO enrichment analysis for cellular component, molecular function, and biological process of differential expressed proteins (DEP) between ABC and GCB EVs showed a significant enrichment of pathways involved in immune response function. Other enriched functional categories for DEPs constitute cellular signaling and intracellular trafficking such as B-cell receptor (BCR), Fc_gamma R-mediated phagocytosis, ErbB signaling, and endocytosis. Our results suggest EVs can be explored as a tool for patient diagnosis, follow-up, and disease monitoring. Finally, this study proposes novel drug targets based on highly expressed proteins, for which antitumor drugs are available suggesting potential combinatorial therapies for aggressive forms of DLBCL. Data are available via ProteomeXchange with identifier PXD028267.

Outcome of Diffuse Large B Cell Lymphoma in the VA System: The Rituximab Era.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 4729-4729
Author(s):  
Rami S. Komrokji ◽  
Sanjay Maraboyina ◽  
Rami Y. Haddad ◽  
Zeina A. Nahleh ◽  
Malek M. Safa
Keyword(s):  
Overall Survival ◽  
B Cell ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Population Based ◽  
Wilcoxon Test ◽  
P Value ◽  
Medical Centers ◽  
Large B Cell Lymphoma ◽  
Large B Cell

Abstract Background: Addition of rituximab to chemotherapy in patients with diffuse large B cell Lymphoma (DLBCL) has been shown to improve survival in several recent clinical studies. A study from British Columbia confirmed those results in a population-based cohort. No similar population based studies were conducted in the USA. Our study aims to address outcome of DLBCL in the era of rituximab in the VA health system. Methods: This was a retrospective analysis. The VA Central Cancer Registry (VACCR) database was used to identify patients with DLBCL diagnosed between 1995 and 2005. There are approximately 120 VA medical centers diagnosing and/or treating patients with cancer. The VACCR aggregates the data collected by the medical centers’ cancer registries. Data were extrapolated and analyzed using bio-statistical software SPSS. Variables included age, sex, stage of disease, histology subtype, date of diagnosis, date of last contact, date of relapse, vital status, whether patients received chemotherapy and or radiation. Use of rituximab was not specifically recorded in the registry. Due to that we divided the patients into two groups, patients diagnosed with DLBCL before 2001 (pre rituximab era group) and patients diagnosed after 2001 (rituximab era group). The initial results of rituximab in DLBCL were presented in 2000 and published in January 2002. Independent t test was used for comparing continuous variables and chi square test for categorical variables. Wilcoxon test was used to compare survival among the two groups. Results: There were 2792 patients with DLBCL at the VACCR between 1995 and 2005, 1772 patients in pre rituximab era and 1020 patients in the rituximab era. The mean age at diagnosis was to 64 in pre rituximab group and 66 in rituximab group (P-value 0.015). Race distribution was similar between the two groups. More patients were diagnosed at advanced stage (stage III and IV) 61 % in rituximab group compared to 57% in pre rituximab group (P-value &lt;0.005), IPI score data were not available. More patients in pre rituximab era did not receive multi-agent chemotherapy 28% versus 22% (P-value &lt; 0.005). More patients received radiation 21 % in pre rituximab group compared to 16% in rituximab era group (P-value &lt; 0.005). The 5-year overall survival was 26% in pre rituximab era and 36% after rituximab (P-value 0.0025). Using Cox regression multivariable analysis age, use of mutli-agent chemotherapy, radiation and whether patients were diagnosed and treated before or after 2001 were statistically significant independent variables affecting survival. Conclusions: Overall survival of DLBCL in VA patients had improved in the rituximab era. The magnitude of improvement observed in this study is similar to what was described in previous studies. Other factors contributing to improvement in outcomes such as supportive care could not be differentiated in this study. This is a population-based study suggesting improvement in survival in DLBCL in the rituximab era.

scholarly journals Outcomes of Cardiac Diffuse Large B-Cell Lymphoma in the Rituximab Era

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 9-10
Author(s):  
Taha Al-Juhaishi ◽  
Ghaith Abu Zeinah ◽  
Sadeer Al-Kindi
Keyword(s):  
B Cell ◽  
Survival Data ◽  
Conflicts Of Interest ◽  
Cell Lymphoma ◽  
Univariate Analysis ◽  
B Cell Lymphoma ◽  
Disease Stage ◽  
P Value ◽  
Large B Cell Lymphoma ◽  
Large B Cell

Introduction: Cardiac lymphomas are very rare with diffuse large B-cell lymphoma (DLBCL) considered to be the most common histology. These lymphomas can be either local "primary cardiac" disease, or part of dissemination by systemic lymphoma. There is limited data regarding outcomes of patients with this disease. We sought to evaluate the outcomes of cardiac DLBCL in both pre- and rituximab eras using a large retrospective database. Methods: The public Surveillance, Epidemiology and End Results (SEER) database was used to identify all patients diagnosed with DLBCL and heart as the primary disease site. Data cutoff in the database was in 2016. Patients with missing date of diagnosis or survival data were excluded. Patients were divided into two groups based on diagnosis year, with rituximab cohort included all DLBCLs diagnosed in 2006 and later (2006 was FDA approval year of rituximab in untreated DLBCL). Treatment effect (surgery, radiation, chemotherapy) was analyzed when available. survival was estimated using the Kaplan-Meier method, and compared using Log-Rank test. Cox proportional hazards models were used for adjusted survival analyses. Results: Total of 106 patients were included in the final analysis, baseline characteristics are summarized in table 1. Median age at diagnosis was 69.5 years with only about 10% of patients being 50 years or younger. Most patients were white 71 (67%), had local stage I/II disease 68 (64.2%), and belonged to the rituximab era group 71 (67%). Most patients had chemotherapy 82 (77.4%), while only 25 (23.6%) had surgery, and 16 (15.1%) had radiotherapy. Median overall survival (OS) for the entire cohort was 22 months (0-292). Median OS was 16 months (95% CI, 0.55 -31) for the pre-rituximab group, and was 26 months (95% CI, 7.5 - 45) for the rituximab group which were not statistically different (p-value =0.340). Median lymphoma-specific survival (LCS) was 30 months (95% CI, 8.0 -52) for the pre-rituximab group, and was 36 months (95% CI, 16 - 158) for the rituximab group which were not statistically different (p-value =0.295). OS and LCS were also not different between the two era groups when stratified by chemotherapy (figure 1). On univariate analysis, Chemotherapy was associated with better OS [HR = 0.472, 95% CI (0.277-0.806); p-value = 0.006] but not LCS [HR = 0.690, 95% CI (0.341-1.396); p-value = 0.302]. Using a multivariate analysis model, both OS and LCS were associated with lymphoma stage, insurance status and age but not with diagnosis era or chemotherapy (table 2). Conclusion: Cardiac DLBCLs are rare and affecting mostly the elderly. No significant improvement in outcomes were noted in the current rituximab era. Age, disease stage, and having health insurance were associated with better outcomes. The role of chemotherapy needs further evaluation in larger studies. Disclosures No relevant conflicts of interest to declare.

Disparities In Receipt Of Radiotherapy and Survival By Age, Sex and Ethnicity Among Patients With Localized Diffuse Large B-Cell Lymphoma

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 558-558
Author(s):  
Binay K. Shah ◽  
Amir Bista
Keyword(s):  
B Cell ◽  
Cell Lymphoma ◽  
Survival Rates ◽  
Relative Survival ◽  
B Cell Lymphoma ◽  
Population Based ◽  
P Value ◽  
Large B Cell Lymphoma ◽  
To Receive ◽  
Large B Cell

Abstract Background Combination therapy with 3 cycles of chemotherapy followed by involved field radiotherapy has been a standard of care for treatment of localized diffuse large B-cell lymphoma (Miller TP NEJM 1998). This population based study evaluated ethnic disparities in receipt of radiotherapy (RT) and its effect on survival in patients with localized diffuse large B cell lymphoma (DLBCL) in the United States. Methods The Surveillance, Epidemiology, and End Results database was reviewed to identify patients with stage I DLBCL diagnosed between 1998 and 2008. We used unadjusted and adjusted odds ratio (OR) to analyze association of receipt of radiotherapy with age (<60 and 60+ years), sex and ethnicity (White, Black and Others). We calculated relative survival rates for different cohorts using SEER*Stat software. We used cox’s proportional hazard model to investigate the impact of age, sex and ethnicity on survival rates. Results A total of 11763 patients with localized DLBCL as the only primary malignancy were included in the study. Of the cohort, 38.2% received radiotherapy. Receipt of radiotherapy varied significantly by patient ethnicity - whites were more likely to receive RT compared to blacks and others. Similarly, age <60 years and females were more likely to receive radiotherapy compared with older patients and males (Table – 1). The 1- and 5- year relative survival rates for patients receiving RT were higher compared to those who did not receive RT: 88.3±0.5% vs 73.4±0.6%, p-value <0.0001 at 1-year and 77.8±0.8% vs 62.5±0.7%, p-value <0.0001 at 5-years. Among patients who received RT, 1- and 5- year relative survival rates were significantly higher in whites compared to black or other- race patients. Conclusions This population based study showed that only 38.2% of patients with localized DLBCL received radiotherapy. White patients were more likely to receive RT compared to blacks and others. Survival rates are significantly higher for patients who received RT. Disclosures: No relevant conflicts of interest to declare.

scholarly journals The Addition of Rituximab to Chemotherapy Decreased Rates of Primary Surgery for Gastric Diffuse Large B-Cell Lymphoma without Increasing Early Mortality

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 4475-4475
Author(s):  
Eric Wiedower ◽  
Smith Giri ◽  
Andrew Fintel ◽  
Philip Prouet ◽  
Elena Paulus ◽  
...  
Keyword(s):  
Mortality Rate ◽  
B Cell ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Mortality Rates ◽  
Early Mortality ◽  
P Value ◽  
Stage At Diagnosis ◽  
Large B Cell Lymphoma ◽  
Large B Cell

Abstract Introduction: Rituximab (R) has improved outcomes in diffuse large B-cell lymphoma (DLBCL) but early complications, such as gastric perforation, have been reported (median time to event 6 days). As the role of surgery for gastric diffuse large B cell lymphoma (gDLBCL) has evolved from the primary management of the disease to the management of its complications, we sought to further define surgical trends and to explore whether the introduction of R and the decreasing rates of primary surgery influenced early mortality in patients with gDLBCL. Methods: The authors utilized the Surveillance Epidemiology and End Results (SEER) 18 database (November 2014 submission) to extract relevant data on patients with gDLBCL diagnosed between 1983-2012 using the case listing session. Eligible cases of gDLBCL were identified from the SEER 13 database using a combination of International Classifications of Diseases for Oncology, 3rd edition (ICD-O-3) code for DLBCL (9680/3) and site codes for stomach (C60.x). Primary site-specific cancer directed surgery using SEER site-specific surgical codes and annual trends in the receipt of surgery among patients with gDLBCL using Joinpoint regression program were evaluated. Unadjusted percentages along with 95% confidence intervals (computed using Bootstrapping methods) were computed for each year. Changes in the trend of surgical rates were evaluated by Monte Carlo Permutation method. We compared the impact of the introduction of R on early mortality rates in our study population. Using the year 2006, date of FDA approval for R as first-line therapy, as a cutoff, we studied the 30 and 60-day mortality rates. Multivariate logistic regression was used to study the impact of year of diagnosis (before and after 2006) on early mortality rates adjusting for age, sex, race and stage at diagnosis. The level of significance chosen was 0.05. All p-values were two sided. Results: 5814 patients (pts) with gDLBCL were identified. There were 4124 pts diagnosed prior to 2006 and 1690 patients with gDLBCL diagnosed after 2006. Median age was 71 years (range 1 to 105 years), of which 55.5% (n=3224) were males and 80.7% (n=4694) were white. The majority of patients were Stage I (43.7%; n =2539) or Stage II (19.7%; n= 1145) at diagnosis. 16% (n=932) received any form of radiation therapy. 1088 (18.7%) received primary cancer directed surgery. Patients receiving surgery for gDLBCL declined from 63% in 1983 (34 out of 54 patients) to 8% (19 out of 250) in 2012. Joinpoint trend analysis revealed that the sharpest decline was seen between the years 2000-2010 (annual percentage change, APC -12.31; 95% confidence interval -16.8 to -7.6; p value <0.01). The adjusted rates of surgery computed using poisson regression (adjusted for age, sex, race and stage at diagnosis) declined from 54.4% in 1983 to 6.9% in 2012 with an APC of -8.9% (95% CI -9.7% to -8.3%; p value <0.01). The 30-day mortality rate prior to 2006 was 9.7% as compared to 10.3% among patients diagnosed after 2006 (p value 0.48). The 60-day mortality rate was similar in the two groups as well (16.3% versus 15.2%; p value 0.29). Multivariate logistic regression showed that the patients before and after 2006 were similar in terms of the 30-day mortality rate (OR 0.97; 95% CI 0.79-1.18; p value 0.79) and the 60-day mortality rate (OR 0.94; 95% CI 0.80-1.11; p value 0.48) after adjusting for age, gender, race and stage at diagnosis. Conclusions: The period after the introduction of R was associated with the sharpest decline in primary cancer directed surgery for gDLBCL. While R is associated with perforation risk, no significant increase in 30 or 60-day mortality was seen in those treated after R was approved for first-line therapy. While R appears to have significantly changed how surgery is utilized in gastric DLBCL, early mortality was unchanged. Figure 1. Trend of surgical rates Figure 1. Trend of surgical rates Disclosures No relevant conflicts of interest to declare.

Unstaged Diffuse Large B Cell Lymphoma in the United States: Predictors and Patient Outcomes

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 2109-2109
Author(s):  
Binay K. Shah ◽  
Amir Bista ◽  
Sandhya Sharma
Keyword(s):  
United States ◽  
B Cell ◽  
Household Income ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
The United States ◽  
P Value ◽  
Factors Associated ◽  
Large B Cell Lymphoma ◽  
Large B Cell

Abstract Background: Treatment and prognosis of diffuse large B cell lymphoma (DLBCL) depends on the stage of lymphoma. We conducted this study to examine unstaged DLBCL in the United States. Methods and methodology: We used Surveillance Epidemiology and End Result (SEER) 18 registries to select patients with DLBCL diagnosed during January 2000 to December 2012. We used LRD Summary stage 2000 was used to determine stage of the disease - localized, regional, distant or unstaged. We used Logistic regression to investigate factors associated with unstaged DLBCL. We used Cox Proportional Hazard model to compare survival outcomes. Results: Among 67765 patients, 3194 (4.71%) were unstaged. Age (60+years), "Others" and Caucasian races, single or single/divorced/widow marital status, metropolitan residence, median household income> $50,000, lymph node as the primary site and cased with other primaries before diagnosis of DLBCL were the factors associated with unstaged cases (Table 1). The 5- year relative survival rate for unstaged patients was inferior to those with localized and regional disease, and superior to those with distant disease (HRs of 0.58, 0.66 and 1.24 for localized, regional and distant respectively when compared to unstaged cases). Conclusion: In this large population-based study, 4.71% patients with DLBCL had unstaged disease. Patients with unstaged DLBC had significantly inferior survival rates compared to patients with localized and regional stage. Table 1. Factors associated with unstaged DLBCL cases Parameters Unadjusted OR (95% CI) P value Adjusted OR (95% CI) P value Age (60+ Vs. <60 years) 1.478 (1.363 - 1.602) <0.001 1.458 (1.335 - 1.592) <0.001 Sex (Female Vs. Male) 1.063 (0.990 - 1.141) 0.093 0.983 (0.911 - 1.059) 0.646 Race Caucasians Reference Reference African American 0.804 (0.691 - 0.935) 0.005 0.835 (0.715 - 0.974) 0.022 Others 1.109 (0.976 - 1.261) 0.112 1.257 (1.104 - 1.431) 0.001 Marital Status Married Reference Reference Single 1.026 (0.927 - 1.135) 0.662 1.208 (1.086 - 1.345) 0.001 Single/divorced/widow 1.249 (1.152 - 1.355) <0.001 1.185 (1.087 - 1.291) <0.001 Rural/Urban Rural Reference Reference Urban 0.878 (0.651 - 1.183) 0.393 0.896 (0.661 - 1.214) 0.479 Metropolitan 0.882 (0.667 - 1.165) 0.882 1.028 (0.767 - 1.379) 0.852 Median annual household income Upto 25,000 Reference Reference >25,000-50,000 01.009 (0.753 - 1.354) 0.951 0.927 (0.675 - 1.271) 0.636 >50,000 0.758 (0.563 - 1.021) 0.068 0.673 (0.486 - 0.933) 0.017 Sequence (Not first or only primary vs. first or only primary) 1.261 (1.156 - 1.377) <0.001 1.219 (1.115 - 1.334) <0.001 Site of primary Lymph nodes Reference Reference Extra-lymphatic 0.760 (0.704 - 0.821) <0.001 0.748 (0.693 - 0.808) <0.001 Unknown primary 6.295 (4.569 - 8.672) <0.001 6.727 (4.865 - 9.300) <0.001 Disclosures No relevant conflicts of interest to declare.

scholarly journals SPECT-CT Imaging of Dog Spontaneous Diffuse Large B-Cell Lymphoma Targeting CD22 for the Implementation of a Relevant Preclinical Model for Human

2020 ◽  
Vol 10 ◽  
Author(s):  
Floriane Etienne ◽  
Maxime Berthaud ◽  
Frédérique Nguyen ◽  
Karine Bernardeau ◽  
Catherine Maurel ◽  
...  
Keyword(s):  
B Cell ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Ct Imaging ◽  
Preclinical Model ◽  
Large B Cell Lymphoma ◽  
Large B Cell
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