Diffuse Large B-Cell Lymphoma: Relevance of bcl-2 Expression at a National Hospital from Lima Peru 2000–2002.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 4610-4610
Author(s):  
Cecilia M. Egoavil R. ◽  
Victor M. Delgado G. ◽  
Jesus La Serna
Keyword(s):  
B Cell ◽  
Clinical Characteristics ◽  
De Novo ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Response To Treatment ◽  
Clear Trend ◽  
Large B Cell Lymphoma ◽  
Significant Difference ◽  
Large B Cell

Abstract Diffuse large B-cell lymphoma (DLCL) exhibits heterogeneous clinical features and varies in response to treatment and prognosis. Establishment of parameters that can predict outcome could help to identify patients who may benefit from risk-adjusted therapies. Because apoptosis-related proteins may play an important role in predicting the prognosis of DLCL, the current study investigated the significance of bcl-2 expression in relation to clinical characteristics in this patients. We studied 125 patients (74/51 men/women; median age 64.17 years) consecutively diagnosed with de novo DLBCL in a single institution from Peru (HNGAI) during 3-year period (2000–2002).Morphology, and clinical characteristics were analyzed according to the primary site of the lymphoma and edge. Paraffin-embedded specimens from 88 were analyzed immunohistochemically for bcl-2 protein expression. Cases with a positive immunohistological stain in more than 20% of the tumor cells were considered positive expression. Results: Sites of the disease were: lymph node, 78 cases (62.4%); Waldeyer’s ring, 18 (14.4%); and extranodal sites, 45 (36%), including GI tract in 33 cases. 5-year overall survival (OS) was 19.7%. Log-rank analyses of survival showed significant differences between ≥60 years old and younger patients (P=0.003).bcl-2 expression was identified in 34 patients (38.6%), There was no significant difference in the OS (P=0.453) between the bcl-2+ (n=34) and bcl-2− (n=54) groups. In conclusion, bcl-2 expression appeared to be non predictive of a good OS in patients with DLCL, however, there was still a clear trend that the bcl-2+ patients died sooner than the patients with tumors that contained bcl-2− lymphoma cells. The current study show all patients as were staged or confined in a group with high or high intermediate IPI scores and could be candidates for alternative therapeutic approaches.

De novo CD5-positive diffuse large B-cell lymphoma: clinical characteristics and therapeutic outcome

1999 ◽  
Vol 105 (4) ◽  
pp. 1133-1139 ◽  
Author(s):  
Motoko Yamaguchi ◽  
Toshiyuki Ohno ◽  
Kouji Oka ◽  
Masanori Taniguchi ◽  
Motohiro Ito ◽  
...  
Keyword(s):  
B Cell ◽  
Clinical Characteristics ◽  
De Novo ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Therapeutic Outcome ◽  
Large B Cell Lymphoma ◽  
Large B Cell

scholarly journals Prognostic significance of CXCR4 and mTOR expression in diffuse large B-cell lymphoma patients

2019 ◽  
Vol 9 (1) ◽  
pp. 7
Author(s):  
Rasha Haggag ◽  
Naglaa A. Mostafa ◽  
Marwa Nabil ◽  
Hala A. Shokralla ◽  
Neveen F. H. Sidhom
Keyword(s):  
B Cell ◽  
De Novo ◽  
Cell Lymphoma ◽  
Prognostic Significance ◽  
B Cell Lymphoma ◽  
Poor Response ◽  
Cxcr4 Expression ◽  
Response To Treatment ◽  
Large B Cell Lymphoma ◽  
Large B Cell

Background: The aim of this study was to investigate the prognostic role of mammalian target of Rapamycin (mTOR) and C-X-C chemokine receptor type 4 (CXCR4) in diffuse large-B-cell lymphoma (DLBCL) patients.Patients and methods: This retrospective study was collected data from 64 de novo DLBCL patients, who received standardized R-CHOP therapy at two oncology centers. CXCR4 and mTOR expressions were assessed by immunohistochemistry.Results: Out of the 64 DLBCL patients, 40 patients were positive for CXCR4 (62.5%) and 35 patients for mTOR (54.7%) expressions. CXCR4 expression was positively correlated with mTOR expression (r = 0.7; p < .001). While mTOR expression was significantly associated with high lactate dehydrogenase level (p = .03) and number of extranodal sites one or more (p =.02), CXCR4 expression was significantly associated with high IPI score (p < .001) and ECOG PS (p = .005). Furthermore, theexpression levels of mTOR and CXCR4 were significantly associated with older ages and poor response to treatment (p = .04, <.001 and .04, .03, respectively). After a median Follow up of 22 months, mean ± SD overall survival (OS) was 65.391 ± 4.705. Kaplan–Meier analysis showed that patients positive for mTOR and CXCR4 expression had shorter DFS (p = .01 & .02) and OS (p = .02 & .04). Multivariate analysis showed that CXCR4 and mTOR positivity is an independent prognostic factor for significantly poorer DFS (p = .03, and .02 respectively) but not for OS (p = .09 and .08 respectively) in the DLBCL pateints.Conclusion: Our results indicate that the expression of CXCR4 and mTOR may be poor prognostic biomarkers in DLBCL.

A Retrospective Analysis of Gastric Diffuse Large B-Cell Lymphoma with or without MALT Component

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 4856-4856
Author(s):  
Xiaowu Li ◽  
Bing Xia ◽  
Shanqi Guo ◽  
Eduardo M. Sotomayor ◽  
Yong Yu ◽  
...  
Keyword(s):  
Surgical Treatment ◽  
B Cell ◽  
Clinical Characteristics ◽  
De Novo ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Advanced Stage ◽  
Large B Cell Lymphoma ◽  
H Pylori ◽  
Large B Cell

Abstract Abstract 4856 Background: The aim of this study was to evaluate the clinical characteristics, prognostic factors and survival outcomes of patients with gastric diffuse large B-cell lymphoma (DLBCL). Patients and methods: 162 patients with gastric DLBCL were evaluated retrospectively. Comparisons were made between patients of gastric DLBCL with component of mucosa-associated lymphoid tissue lymphoma (DLBCL/MALT) and patients of gastric DLBCL without detectable MALT component (de novo DLBCL). Results: Results according to the distribution of sex, age, stage, performance status, and other clinical characteristics were similar between de novo DLBCL group and DLBCL/MALT group (p>0.05). The ratio of patients with the germinal center B-cell-like (GCB) subtype to non-GCB subtype did not differ significantly between the two groups (1:1.1 versus 1:1.6, p=0.319). However, the proportion of patients with the stage-modified international prognostic index (m-IPI) ≥2 was higher in DLBCL/MALT groups (18%) than taht in de novo DLBCL groups (34%) (p=0.026). In addition, the H. pylori infection rate was 75% in DLBCL/MALT versus 38% in de novo DLBCL (p<0.001). Patients with de novo DLBCL have better 5-year PFS and OS estimates than those DLBCL/MALT patients (p=0.037 and 0.019 for the 5-year PFS and OS estimates, respectively). Surgical treatment did not offer survival benefit when compared with chemotherapy (p=0.405 and 0.065 for the 5-year PFS and OS estimates, respectively). Multivariate analysis revealed that non-GCB classification and m-IPI≥2 were independently associated with shorter OS and advanced stage was independently associated with shorter PFS. Conclusion: Gastric DLBCL is a heterogeneous disease that included de novo DLBCL and DLBCL/MALT lymphoma. Compared with the former, the latter has a higher H. pylori infection rate. And what's more, the proportion of patients with m-IPI≥2 is higher in DLBCL/MALT groups. De novo DLBCL was associated with higher 5-year PFS and OS estimates. Non-surgical treatment should be a primary consideration for gastric DLBCL. Immunophenotype classification and m-IPI were the most reliable factors for OS, and advanced stage was for PFS. Disclosures: No relevant conflicts of interest to declare.

DA-EPOCH-R Has Comparable Outcomes in De Novo and Transformed Diffuse Large B Cell Lymphoma

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 15-16
Author(s):  
Sanjal H Desai ◽  
Mansi Chaturvedi ◽  
Rumaisa Hameed ◽  
Valentina Baez Sosa ◽  
Aarthi Shenoy
Keyword(s):  
B Cell ◽  
De Novo ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Categorical Variables ◽  
Indolent Lymphoma ◽  
Nodal Disease ◽  
Large B Cell Lymphoma ◽  
Significant Difference ◽  
Large B Cell

Introduction It is increasingly recognized that transformed (T) diffuse large B cell lymphoma (DLBCL) is a clinically and biologically distinct entity from de novo DLBCL. Dose escalated etoposide, doxorubicin, vincristine, cyclophosphamide and prednisone with rituximab (DA-EPOCH-R) is effective in aggressive large B cell lymphomas including de novo DLBCL, Burkitt lymphoma, high grade B cell lymphoma with BCL2-Myc rearrangement and primary mediastinal B cell lymphoma. However, outcomes of transformed DLBCL (T-DLBCL) treated with DA-EPOCH-R are not well-studied. Here, we describe our experience with T-DLBCL after treatment with DA-EPOCH-R. Methods All adult patients with DLBCL diagnosed and treated with DA-EPOCH-R at Medstar Washington Hospital Center from January 2000 to November 2018 were included in this retrospective study. Data was collected from review of electronic medical records. All transformations were biopsy-proven. T-DLBCL was defined as either biopsy-confirmed DLBCL with background of indolent lymphoma (concurrently transformed (CT) DLBCL) or sequential development of DLBCL in a case of known indolent lymphoma (sequentially transformed, (ST) DLBCL). Patient characteristics including age, sex, race were recorded. Stage, extranodal disease, international prognostic index (IPI) of DLBCL were recorded. For patients with CT and ST DLBCL, histology and prior treatment of indolent lymphoma were recorded. Study objectives were to assess response rates, progression free survival (PFS) and overall survival (OS) for de novo DLBCL, CT-DLBCL and ST-DLBCL treated with DA-EPOCH-R. Fisher's exact test was used to compare categorical variables between the groups. Kaplan-Meier method was used to calculate survival curves. Log rank test was used to compare survival between de novo DLBCL, CT-DLBCL and ST-DLBCL. Results Of 183 DLBCL patients treated during the study period, 34 had T-DLBCL (17 CT-DLBCL and 17 ST-DLBCL). Total 91 received DA-EPOCH-R (25 transformed, 66 de novo) and were included in our study. Median age was 56 (23-84). Sixty percent patients were males and 42% were white. Out of 25 Tx DLBCL, 11 had CT-DLBCL and 14 had ST-DLBCL. Patients with T-DLBCL (CT and ST) had higher odds of being white, having advanced stage, extra-nodal disease and high IPI. [OR: 2.6 (CI951.7-6), 4.1 (CI951.6-10), 2.8 (CI95 2.8 (1.8-7) and 2.7 (CI951.2-6), respectively. P &lt;0.001]. Cell of origin, BCL2 and BCL6 expression was not available for all DLBCL patients. Follicular lymphoma was the most common underlying indolent lymphoma (13), followed by chronic lymphocytic leukemia (5), marginal zone lymphoma (3), low grade non-Hodgkin lymphoma not otherwise specified (3) and lymphoplasmacytic lymphoma (1). Seven of T-DLBCL had received prior rituximab and 2 had received prior anthracycline. For ST-DLBCL patients, median time to transformation was 2.25 years (0.3-15). There was no significant difference in ORR (85%, 86%, 91%) and CR (82%, 84%, 89%) of DA-EPOCH-R treated CT, ST and de novo DLBCL, respectively. Median follow up was 5 years. Median PFS and OS for CT and de novo DLBCL were not reached. ST DLBCL had median PFS and OS of 21 years and 37 years, respectively. There was no significant difference between 2-year PFS and OS of CT, ST and de novo DLBCL treated with DA-R-EPOCH. (Table 1). Conclusion T-DLBCL is more likely to have aggressive features such as advance stage, extra nodal disease and high IPI. Despite this, DA-EPOCH-R treated T-DLBCL has outcomes comparable to de novo DLBCL. Large, prospective studies are needed to examine efficacy of DA-EPOCH-R in T-DLBCL. Figure. 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.

De novo CD5+ diffuse large B-cell lymphoma, NOS: clinical characteristics and outcomes in rituximab era

2019 ◽  
Vol 61 (2) ◽  
pp. 328-336
Author(s):  
Bei Hu ◽  
Loretta J. Nastoupil ◽  
Sanam Loghavi ◽  
Jason R. Westin ◽  
Beenu Thakral ◽  
...  
Keyword(s):  
B Cell ◽  
Clinical Characteristics ◽  
De Novo ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Large B Cell Lymphoma ◽  
Large B Cell

scholarly journals Prognostic impact of BCL2, BCL6 and MYC status in de novo diffuse large B-cell lymphoma: a regional study of 43 patients

2019 ◽  
Vol 7 (5) ◽  
pp. 1720
Author(s):  
Dudu Solakoglu Kahraman ◽  
Gulden Diniz ◽  
Cengiz Ceylan ◽  
Faruk Recep Ozalp ◽  
Yetkin Koca ◽  
...  
Keyword(s):  
B Cell ◽  
De Novo ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Prognostic Impact ◽  
Regional Study ◽  
Molecular Features ◽  
Large B Cell Lymphoma ◽  
Significant Difference ◽  
Large B Cell

Background: Diffuse large B-cell lymphoma (DLBCL) is an aggressive non-Hodgkin lymphoma with marked biologic heterogeneity. We aimed to evaluate the status of MYC, BCL2, BCL6 in patients with DLBCL.Methods: Herein, we have investigated the prognostic relevance of MYC, BCL2 and BCL6 from 43 de novo DLBCL patients.Results: In this study, protein overexpression of BCL2 and BCL6 was encountered in 46.5% (n=20) and 27.9% (n=12) of the tumors, respectively.  Rearrangements in MYC, BCL6, and BCL2 were detected in 9.3% (n=4), 25.6% (n=11), and 4.7% (n=2) of the cases, respectively. Any statistically significant difference could not be found between Bcl-2, Bcl-6 expression, C-MYC rearrangement and the survival.Conclusions: We concluded that C-MYC and BCL2 may contribute to aggressive transformation, so more mechanism-based therapy should be explored. A larger study is warranted to better understand the immunophenotypic and molecular features of DLBCL and their respective impact on patient survival.

scholarly journals Bone Marrow Molecular Markers Associated with Relapsed/Refractory Activated B-Cell-Like Diffuse Large B-Cell Lymphoma

2018 ◽  
Vol 2018 ◽  
pp. 1-7 ◽  
Author(s):  
Di Wang ◽  
Peng Liu ◽  
Yue Zhang ◽  
Hui-Ying Liu ◽  
Di Shen ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Molecular Markers ◽  
B Cell ◽  
Bone Marrow Aspirate ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Significant Finding ◽  
Large B Cell Lymphoma ◽  
Significant Difference ◽  
Large B Cell

Activated B-cell-like diffuse large B-cell lymphoma (ABC-DLBCL) is a common subtype of non-Hodgkin’s lymphoma and is very likely to infiltrate the bone marrow. Over 30% of patients are converted to relapsed/refractory DLBCL after first-line rituximab combined with cyclophosphamide, doxorubicin, vincristine, and prednisone therapy, with a poor prognosis. Our aim was to identify molecular markers that might be utilized to predict relapsed/refractory ABC-DLBCL patients. Hence, we collected bone marrow aspirate smears from 202 patients with ABC-DLBCL and detected expression of bone marrow molecular marker proteins by immunocytochemistry. Signal transducer and activator of transcription (Stat)3, nuclear factor (NF)-κB p65, Syk, Bruton’s tyrosine kinase (BTK), and Bcl2 proteins were strongly expressed in bone marrow aspirate smears of ABC-DLBCL patients. The same smear could present positive expression of multiple proteins simultaneously. Positive combinations of protein expression were associated with resistance. The most significant finding was that the Stat3+NF-κB+ group developed resistance, which was significantly higher than that of the Stat3-NF-κB-group (80 vs. 14%). There was a significant difference in two-year relapse-free survival between protein-positive and protein-negative combinations of Stat3-NF-κB (P = 0.005), Bcl2-Stat3 (P = 0.009), Bcl2-Pax5 (P = 0.003), and BTK-Syk (P < 0.001). Thus, we detected key molecules in multiple signaling pathways in bone marrow aspirate smears. At the same time, the results provide further clinical evidence of ABC-DLBCL drug-resistant molecules and provide a theoretical basis for rational second-line treatment after drug resistance.

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