Comparison Between CD20-Negative and CD20-Positive Diffuse Large B Cell Lymphoma; Characteristics and Clinical Outcome

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 4891-4891
Author(s):  
Jungmin Jo ◽  
Changhoon Yoo ◽  
Yongchel Ahn ◽  
Seong Joon Park ◽  
Shin Kim ◽  
...  
Keyword(s):  
Clinical Outcome ◽  
B Cell ◽  
Conflicts Of Interest ◽  
Cell Lymphoma ◽  
Risk Group ◽  
International Prognostic Index ◽  
B Cell Lymphoma ◽  
Large B Cell Lymphoma ◽  
Significant Difference ◽  
Large B Cell

Abstract Abstract 4891 Background CD20 is a non-glycosylated phosphoprotein expressed on the surface of all mature B-cells. CD20 is expressed on all stages of B cell development except the first and last. However, complete lack of CD20 expression occurred in a few cases without previous rituximab (R-) treatment. The immunohistochemostry (IHC) studies which we used were not perfect for confirmation of expression. However, we intended to investigate characteristics and clinical outcome of CD20-negative diffuse large B-cell lymphoma (DLBCL), not detected with usual method, and to compare with CD20-positive. Methods The records of Non-Hodgkin's Lymphoma patient registry were reviewed in Asan Medical Center. Between September 2003 and February 2009, a total of 407 patients were diagnosed DLBCL and 16 patients (3.9%) out of 407 confirmed CD20-negative DLBCL by IHC. The rest of patients (n=391) were CD20-positive and unconfirmed cases were excluded. Retrospective analysis of complete response (CR), disease-free survival (DFS), and overall survival (OS) was performed. Results The median age was 60.5 years old (range 31–81) in CD20-negative patients. Ten patients were males. The Ann Arbor stage was I in 3 patients, II in 3 patients, and III or IV in 10. Six patients were low risk group, 7 patients in intermediate, and 3 in high risk group according to international prognostic index (IPI). Most of patients (62.5%) received cyclophosphamide, doxorubicin, vincristin, and prednisone (CHOP) chemotherapy in CD20-negative and 295 patients (75.4%) with R-CHOP in CD20-positive DLBCL. The Baseline characteristics was not different in both groups except Hans classifier (p=0.02). With a median follow-up time of 32.3 months (range 0.5–83.4), the CR rate was 73.5%, the 3-year OS was 69.5%, and 3-year DFS 74.2% in all patients. CD20-positive and CD20 negative groups had a CR rate of 73.7%, 68.8% (p=0.146), respectively, a 3-year OS of 70.7%, 40.0% (p=0.003), a 3-year DFS of 75.4%, 44.6% (p< 0.001), respectively. The 3-year OS and DFS also had significant difference with adjusted IPI (p<0.001, respectively). Conclusions CD20-negaive DLBLC was not infrequently with usual IHC method (around 4%). The survival outcome was poor compared with CD20-positive DLBLC because of high relapse rate. It was caused without rituximab treatment in CD20-negative. Development of novel target agents like rituximab should be explored to improve outcome and maintain the CR status of CD20-negative DLBCL. Disclosures: No relevant conflicts of interest to declare.

Prediction of Survival In Diffuse Large B-Cell Lymphoma Based On the Expression of Two Genes Reflecting Tumor and Microenvironment

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 2006-2006
Author(s):  
Ash A. Alizadeh ◽  
Andrew J. Gentles ◽  
Alvaro J. Alencar ◽  
Holbrook E Kohrt ◽  
Roch Houot ◽  
...  
Keyword(s):  
B Cell ◽  
Tumor Cells ◽  
Conflicts Of Interest ◽  
Cell Lymphoma ◽  
Single Gene ◽  
International Prognostic Index ◽  
Prognostic Index ◽  
B Cell Lymphoma ◽  
Large B Cell Lymphoma ◽  
Large B Cell

Abstract Abstract 2006 Background: Several gene expression signatures predict survival in diffuse large B cell lymphoma (DLBCL), but the lack of practical methods for genome scale analysis has limited translation to clinical practice. Methods: We examined the power of individual genes to predict survival across different therapeutic eras. In studying 787 patients with DLBCL, we built and validated a simple model employing one gene expressed by tumor cells and another expressed by host immune cells, assessing added prognostic value to the clinical International Prognostic Index (IPI). We validated models in an independent cohort using diagnostic formalin-fixed specimens. Results: We verified expression of LMO2 as an independent predictor of survival and ‘Germinal Center B-cell’ subtype. We identified expression of TNFRSF9 from the tumor microenvironment, as the best in bivariate combination with LMO2. We studied distribution of TNFRSF9 tissue expression in 95 patients. A model integrating these two genes (TGS) was independent of ‘cell of origin’ classification, ‘stromal signatures’, IPI, and added to the predictive power of the IPI. This bivariate model and a composite score integrating the IPI (TGS-IPI) performed well in three independent cohorts of 545 previously described patients. Both models robustly stratified outcomes in a simple assay of routine specimens from 147 newly diagnosed patients as depicted. Conclusion: Measurement of a single gene expressed by tumor cells (LMO2) and a single gene expressed by the immune microenvironment (TNFRSF9) powerfully predicts overall survival in patients with DLBCL. A simple test integrating these two genes with the IPI can readily be used to select patients of different risk groups for clinical trials. Disclosures: No relevant conflicts of interest to declare.

scholarly journals The clinical features and prognosis of 31 HIV-infected diffuse large B-cell lymphoma cases

2021 ◽  
Vol 104 (2) ◽  
pp. 003685042110225
Author(s):  
Yun Lian ◽  
Jiayu Huang ◽  
Huihui Zhao
Keyword(s):  
High Risk ◽  
B Cell ◽  
Cell Lymphoma ◽  
Risk Group ◽  
International Prognostic Index ◽  
Prognostic Index ◽  
B Cell Lymphoma ◽  
Standard Chemotherapy ◽  
Large B Cell Lymphoma ◽  
Large B Cell

This retrospective study was designed to describe the clinical characteristics and prognosis of human immunodeficiency virus (HIV)-infected diffuse large B-cell lymphoma (DLBCL) patients. We retrospectively enrolled 31 patients newly diagnosed with HIV-infected DLBCL from 2009 to 2019 in our institution. The median age of patients was 47 years, and most patients were male ( n = 27, 87.1%). Baseline mean CD4+ count was 150.72 ± 146.57/μl. Eighteen (58.1%) patients had B symptoms. Categorized by international prognostic index (IPI) score, 7 cases (22.6%) were in low-risk group (IPI 0-1) and 24 cases (77.4%) were in medium-high risk group (IPI 2-5). Twenty-five (80.6%) patients received highly active antiretroviral therapy (HAART) and 16 (51.6%) underwent standard chemotherapy. The mortality rate was 58.1% (18/31). Univariate survival analysis revealed that HCV infection ( p = 0.032), standard chemotherapy treatments ( p = 0.038) were associated with overall survival (OS). Our results showed that HIV-infected DLBCL patients had high-risk stratification and high mortality. HCV-coinfection might be associated with poor OS. Early diagnosis and standardized treatments might be beneficial for promoting the survival of HIV-infected DLBCL patients.

scholarly journals NCCN-IPI Is Superior to aaIPI and IPI in Predicting Survival of DLBCL in the Rituximab Era

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 1872-1872 ◽  
Author(s):  
Yongqiang Wei ◽  
Yuankun Zhang ◽  
Xiaoxiao Hao ◽  
Xiaolei Wei ◽  
Weimin Huang ◽  
...  
Keyword(s):  
B Cell ◽  
Conflicts Of Interest ◽  
Cell Lymphoma ◽  
International Prognostic Index ◽  
B Cell Lymphoma ◽  
Risk Groups ◽  
Chinese Patients ◽  
Intermediate Risk ◽  
Large B Cell Lymphoma ◽  
Large B Cell

Abstract Objective International prognostic index (IPI) has been widely used for predicting outcome in diffuse large B cell lymphoma. Although the introduction of rituximab to chemotherapy has dramatically improved the outcome of DLBCL, it also changed the prognostic value of IPI. The National Comprehensive Cancer Network IPI (NCCN-IPI) and age-adjusted IPI (aaIPI) were used to evaluate the prognosis for DLBCL in the rituximab era. However which one of them is more powerful in predicting survival remains unknown in Chinese patients. Patients and Methods A total of 334 patients with de novo diffuse large B-cell lymphoma diagnosed from 2003 to 2012 were included. All patients were treated with CHOP with or without rituximab. They were divided into CHOP and R-CHOP groups. IPI, NCCN-IPI and aaIPI score were recorded. Survival was performed according to the Kaplan-Meier (K-M) curves using the log-rank test. The predictive abilities of PI, NCCN-IPI and aaIPI were investigated by Harrell's C-statistics. Result Compared with the IPI, the NCCN-IPI and the aaIPI had better discrimination in different scores in all patients treated with or without rituximab. Both the NCCN-IPI and aaIPI had power in discriminating low, low-intermediate and high-intermediate risk groups. In comparison, the NCCN-IPI discriminated low-intermediate and high-intermediate risk groups (5-year overall survival [OS]: 74% vs 50%) better than the aaIPI (5-year OS: 80% vs 62%) in all patients and in the R-CHOP group with the NCCN-IPI 5-year OS: 85% vs 67% while the aaIPI: 87% vs 77%. In the CHOP group, the aaIPI discriminated low-intermediate and high-intermediate risk groups better (5-year OS: 70% vs 25%) than the NCCN-IPI (5-year OS: 60% vs 24%). According to the Harrel C statistic, the NCCN-IPI showed higher discrimination of the different scores (C_index: 0.669 ) than the aaIPI (C_index: 0.663 ) in all the patients (C_index: 0.669 vs. 0.663), especially in the R-CHOP group (C_index: 0.681 vs. 0.636). In the CHOP group, the aaIPI had stronger power (C_index: 0.711 ) than the NCCN-IPI (C_index: 0.683 ) in discriminating different scores. Conclusion The NCCN-IPI is more powerful than the IPI for predicting survival in the rituximab era. In patients aged 60 or younger and treated with CHOP without rituximab, aaIPI is a preferable tool for evaluating prognosis. Disclosures No relevant conflicts of interest to declare.

Quantitative Defects Of Cellular Immune Responses In Patients With Newly-Diagnosed Diffuse Large B-Cell Lymphoma

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 4733-4733
Author(s):  
Pairaya Rujirojindakul
Keyword(s):  
B Cell ◽  
Conflicts Of Interest ◽  
Cell Lymphoma ◽  
Conditional Logistic Regression ◽  
International Prognostic Index ◽  
B Cell Lymphoma ◽  
Newly Diagnosed ◽  
Color Flow ◽  
Large B Cell Lymphoma ◽  
Large B Cell

Altered immune status in non-Hodgkin lymphoma is characterized by undesired autoimmune phenomena and frequent occurrence of infections. The immune defects may be responsible for the initiation, maintenance and progression of malignant clone. We therefore evaluated immune effector cells between 35 patients with newly diagnosed diffuse large B-cell lymphoma (DLBCL) and 34 age- and sex- matched healthy controls using three-color flow cytometry. For patients with DLBCL, there were 19 males and 16 females with a mean age of 59.9 ± 15.6 years. There were 6, 17 and 13 patients with ECOG > 2, stage III-IV and high intermediate to high International Prognostic Index, respectively. We found significant decreases in CD3+CD4+, CD4/CD8 ratio, CD4 central memory (CD4+CD45RO++CD27+) and B cells (Figure 1). From conditional logistic regression, only CD4/CD8 ratio showed significant association with being cases with the odds ratio of 0.29 (95% CI 0.12, 0.68). Disclosures: No relevant conflicts of interest to declare.

Pro-Angiogenic Mir-296 Is Frequently Overexpressed and Is Associated with Advanced Stage Disease in Diffuse Large B-Cell Lymphoma

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 1570-1570
Author(s):  
Natália Morais Borges ◽  
Marina Lourenço de Conti ◽  
Tathiana Azevedo de Andrade ◽  
Marina Petaccia Macedo ◽  
Maria Dirlei Ferreira de Souza Begnami ◽  
...  
Keyword(s):  
B Cell ◽  
De Novo ◽  
Cell Lymphoma ◽  
International Prognostic Index ◽  
B Cell Lymphoma ◽  
Advanced Stage ◽  
Large B Cell Lymphoma ◽  
Stage Disease ◽  
Significant Difference ◽  
Large B Cell

Abstract Abstract 1570 Introduction: MicroRNAs (miRNAs) are a class of endogenous short non-coding RNAs that control gene expression by acting on target mRNAs for promoting either their degradation or translational repression. Some of them have involvement in regulating various aspects of angiogenesis, including proliferation, migration and morphogenesis of endothelial cells, which are important in regulating cardiovascular development and cancer. The term “angiomiR” is used to define the miRNAs that control angiogenesis. They are classified into pro-angiomiRs, those that promote angiogenesis, and anti-angiomiRs, those that inhibit angiogenesis. The identification of angiomiRs as the key to regulating angiogenesis has opened new paths in the treatment of vascular and oncology diseases. Aims: This study aims to analyze the expression angiomiRs in diffuse large B-cell lymphoma (DLBCL) and to correlate them with clinical and histological features to identify possible biomarkers and prognostic factors. Patients and Methods: We studied 93 samples of de novo DLBCL diagnosed between 2000 and 2010. All the cases were HIV-negative. MicroRNAs were obtained from paraffin embedded tumor samples using RecoverAll™ Total Nucleic Acid Isolation Kit for FFPE Tissues (Applied Biosystems). Four angiomiRs (miR-378, miR-296, miR-210 and miR-126) were analyzed. RNU44 and U18 were used as endogenous controls for quantitative PCR (TaqMan®Small RNA Assays). We set a threshold of a 1.5-fold difference in angiomiRs expression compared to controls (palatine tonsil). Results: miR-378, miR-296, miR-210 and miR-126 overexpression were observed in 43%, 47%, 22% and 5%, respectively. Considering that miR-378 and miR-296 were frequently overexpressed in DLBCL, we further analyzed the following variables: age (<=60 versus >60 years), Ann Arbor Staging System (I-II versus III-IV), International Prognostic Index (0–2 versus 3–5), DLBCL classification (NOS versus subtypes), tumor origin according to Hans (2004) algorithm (GCB versus non-GCB). We observed higher median miR-296 expression in DLBCL classified as stage III-IV (p = 0.0415, Mann-Whitney). For the other variables, were did not find any statistically significant difference between groups. Conclusions: miR-296, that directly decreased the levels of hepatocyte-growth factor regulated tyrosine kinase substrate (HGS) and indirectly upregulate VEGFR2 and PDGFRβ, was overexpressed in almost 50% of de novo DLBCL and was associated with advanced stage disease. Our study brings new information about the role of microRNA importance in DLBCL development and can be explored as prognostic and therapeutic target for patients suffering from this prevalent malignancy (Supported by FAPESP 2010/17668-6). Disclosures: No relevant conflicts of interest to declare.

scholarly journals OCT1 gene Expression Is an Independent Prognostic Factor in Diffuse Large B Cell Lymphoma

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 5185-5185
Author(s):  
Gisele Rodrigues Gouveia ◽  
Suzete Cleusa Ferreira ◽  
Sheila Siqueira ◽  
Juliana Pereira
Keyword(s):  
Gene Expression ◽  
B Cell ◽  
Cell Lymphoma ◽  
International Prognostic Index ◽  
B Cell Lymphoma ◽  
Prognostic Impact ◽  
Large B Cell Lymphoma ◽  
Significant Difference ◽  
The Impact ◽  
Large B Cell

Abstract Background: Transcription factors associated with the POU domain modulate the expression of several genes of B lymphoid differentiation, including the IgH. The study of these factors allowed to better understand the pathogenesis of lymphomas and to establish the lineage and the differentiation stage of the malignant cell. The silencing of OCT1 in tumor cell lines reduced its malignant transformation, but its ectopic expression enhanced the tumorigenesis ability. However, few studies has been evaluated the role of the OCT1 gene expression in lymphoma. In this study we assessed the impact of the OCT1 gene expression in the survival of patients with Diffuse Large B Cell Lymphoma (DLBCL). Methods: From January 2006 to January 2011 were evaluated 77 patients with DLBCL treated with R-CHOP at Clinical Hospital and Cancer Institute of Sao Paulo University. The RNA was extracted from the paraffin block at lymphoma diagnosis and gene expression analysis was performed by relative quantification method by Real-Time PCR (qRT-PCR). After the data normalization using two different reference genes, the median expression of OCT1 was obtained. The overall survival (OS) and progression-free survival (PFS) were estimated by the Kaplan-Meier method. The relative risks were obtained by Cox regression bivariate intervals with 95% of confidence. The significance level of 5% was accepted and the IBM SPSS Statistics software version 20.0 was used. Results: Patients showing OCT1 expression < the median presented higher OS (p = 0.010) and PFS (p = 0.016) than patients with OCT1 expression ≥ median with a hazard rate (HR) for OS and PFS of 2.45 and 1.14, respectively. In multivariate analysis the PFS was also higher in patients with OCT1 expression < the median (p = 0.035). The stratification by the international prognostic index (IPI) and age showed that the expression of OCT1 < median showed a statistically significant difference in the OS (p = 0.048) in IPI intermediate-high (HI) and high (HR) patients (p = 0.048), with a HR of 2.32 in HI plus HR group. The PFS (p = 0.025) and OS (p = 0.025) were lower in patients ≥ 60 years and OCT1 expression ≥ the median. Conclusion: Our data suggest that the expression of OCT1 showed a predictive prognostic impact in DLBCL independently of IPI. Patients with lower expression of OCT1 presented a better OS and PFS. Figure 1 SG curve for the OCT1 gene expression. Figure 1. SG curve for the OCT1 gene expression. Figure 2 SLP curve for the OCT1 gene expression. Figure 2. SLP curve for the OCT1 gene expression. Figure 3 SG curve for to expression of OCT1 gene for subgroup IPI intermediate-high and high. Figure 3. SG curve for to expression of OCT1 gene for subgroup IPI intermediate-high and high. Disclosures No relevant conflicts of interest to declare.

Clinical impact of the differentiation profile assessed by immunophenotyping in patients with diffuse large B-cell lymphoma

Blood ◽  
2003 ◽  
Vol 101 (1) ◽  
pp. 78-84 ◽  
Author(s):  
Lluı́s Colomo ◽  
Armando López-Guillermo ◽  
Marı́a Perales ◽  
Susana Rives ◽  
Antonio Martı́nez ◽  
...  
Keyword(s):  
B Cell ◽  
Germinal Center ◽  
Cell Lymphoma ◽  
International Prognostic Index ◽  
B Cell Lymphoma ◽  
Clinicopathological Features ◽  
Ki 67 ◽  
Large B Cell Lymphoma ◽  
Significant Difference ◽  
Large B Cell

Abstract To analyze the relationship between immunophenotyping profile and main clinicopathological features and outcome in diffuse large B-cell lymphoma (DLBCL), we studied 128 patients (59 men, 69 women; median age 65 years) consecutively diagnosed with de novo DLBCL in a single institution. Cells from each patient were immunostained with CD20, CD79a, CD5, CD10, bcl-6, MUM1, CD138, bcl-2, p53, p27, and Ki-67 antibodies. Four immunophenotyping profiles were distinguished according to the pattern of differentiation: germinal center–CD10+ (GC-CD10+; CD10+/Bcl-6+/MUM1−/CD138−), germinal center–CD10− (GC-CD10−; CD10−/Bcl-6+/ MUM1−/CD138−), post–germinal center (pGC; CD10−/bcl-6±/ MUM1+/CD138−), and plasmablastic (CD10−/bcl-6−/MUM1+/CD138+). Rearrangement of bcl-2 was studied by polymerase chain reaction (PCR) in 57 patients. Single-antigen expression was as follows: CD5, 2%; CD10, 21%; bcl-6, 72%; MUM1, 54%; CD138, 2%; bcl-2, 59%; p53, 28%; p27, 40%. Distribution according to differentiation profiles was as follows: GC-CD10+, 24 patients, GC-CD10-, 30 patients; pGC, 60 patients; plasmablastic, 2 patients; other patterns, 12 patients. The pGC profile was associated with primary nodal presentation and immunoblastic morphology, whereas GC-CD10+ tumors showed disseminated disease, centroblastic morphology, bcl-2 rearrangement, and lower Ki-67 proliferative index. GC-CD10− patients more often presented with primary extranodal origin, early stage, normal lactic acid dehydrogenase (LDH) levels, and low or low/intermediate International Prognostic Index (IPI) scores than the others. However, no significant difference was found in terms of response or overall survival (OS) according to these profiles. Expression of bcl-2 was associated with advanced stage, high or high-intermediate IPI, and poor OS. Expression of bcl-2 maintained predictive value in multivariate analysis, with stage and LDH. In conclusion, differentiation profile was associated with particular clinicopathological features but was not essential to predicting outcome in DLBCL patients.

scholarly journals Circulating long non-coding RNAs HOTAIR, Linc-p21, GAS5 and XIST expression profiles in diffuse large B-cell lymphoma: association with R-CHOP responsiveness

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Mahmoud A. Senousy ◽  
Aya M. El-Abd ◽  
Raafat R. Abdel-Malek ◽  
Sherine M. Rizk
Keyword(s):  
B Cell ◽  
Cell Lymphoma ◽  
Expression Profiles ◽  
International Prognostic Index ◽  
Prognostic Index ◽  
B Cell Lymphoma ◽  
Diagnostic Tools ◽  
Large B Cell Lymphoma ◽  
Non Coding Rnas ◽  
Large B Cell

AbstractThe reliable identification of diffuse large B-cell lymphoma (DLBCL)-specific targets owns huge implications for its diagnosis and treatment. Long non-coding RNAs (lncRNAs) are implicated in DLBCL pathogenesis; however, circulating DLBCL-related lncRNAs are barely investigated. We investigated plasma lncRNAs; HOTAIR, Linc-p21, GAS5 and XIST as biomarkers for DLBCL diagnosis and responsiveness to R-CHOP therapy. Eighty-four DLBCL patients and thirty-three healthy controls were included. Only plasma HOTAIR, XIST and GAS5 were differentially expressed in DLBCL patients compared to controls. Pretreatment plasma HOTAIR was higher, whereas GAS5 was lower in non-responders than responders to R-CHOP. Plasma GAS5 demonstrated superior diagnostic accuracy (AUC = 0.97) whereas a panel of HOTAIR + GAS5 superiorly discriminated responders from non-responders by ROC analysis. In multivariate analysis, HOTAIR was an independent predictor of non-response. Among patients, plasma HOTAIR, Linc-p21 and XIST were correlated. Plasma GAS5 negatively correlated with International Prognostic Index, whereas HOTAIR positively correlated with performance status, denoting their prognostic potential. We constructed the lncRNAs-related protein–protein interaction networks linked to drug response via bioinformatics analysis. In conclusion, we introduce plasma HOTAIR, GAS5 and XIST as potential non-invasive diagnostic tools for DLBCL, and pretreatment HOTAIR and GAS5 as candidates for evaluating therapy response, with HOTAIR as a predictor of R-CHOP failure. We provide novel surrogates for future predictive studies in personalized medicine.

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