Addition of Rituximab to CHOP Regimen Improves Clinical Outcome in Non-Germinal Center Type Diffuse Large B-Cell Lymphoma.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 4725-4725
Author(s):  
Masahiro Yokoyama ◽  
Daisuke Ennishi ◽  
Kyoko Ueda ◽  
Makoto Kodaira ◽  
Shuhei Yamada ◽  
...  
Keyword(s):  
Clinical Outcome ◽  
B Cell ◽  
Germinal Center ◽  
Cell Lymphoma ◽  
Expression Patterns ◽  
B Cell Lymphoma ◽  
Chop Regimen ◽  
Large B Cell Lymphoma ◽  
Type 3 ◽  
Large B Cell

Abstract Background: In recent years, diffuse large B-cell lymphoma (DLBCL) has been classified into the germinal center B-cell (GC) type, the activated B-cell (ABC) type, and the type 3 using global gene expression profiling or immunohistochemical staining. It has been reported that the GC type DLBCL showed significantly longer survival than the non-GC (ABC and the type 3) type DLBCL treated with CHOP or CHOP like regimen not using rituximab. Methods: We analyzed retrospectively the prognosis between the GC and non-GC types of DLBCL treated with R-CHOP regimen. All 50 patients with DLBCL, diagnosed between July 2003 and July 2005 were included in this study. The pathology was reviewed by hematopathologist and confirmed to be de novo DLBCL according to the WHO classification. Patients with primary CNS- and post-transplant lymphomas were excluded. GC type or non-GC type DLBCL was determined by immunohistochemistry such as the expression patterns of CD10, BCL-6, and IRF-4 (MUM1). All patients were initially treated with six cycles of R-CHOP regimen consisting of rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone. If we evaluated partial response after six cycles of R-CHOP, the patients have added radiation therapy. Results: The patients consisted of 30 GC type and 20 non-GC type DLBCL with a median age of 61.0 yr (range 31–83 yr). The median follow up of surviving patients was 24 months. CR rate between GC and non-GC types were 57.0% vs. 75.0%, p=0.186, and overall response rate were 87.0% vs. 90.0%, p=0.929, respectively. The median of progression free survival was 17.3 months vs. 19.6 months, p=0.80. There is no statistical significance difference between two groups. Conclusion: These results suggest that addition of rituximab to CHOP regimen improves clinical outcome of non-GC type DLBCL as well as GC type DLBCL.

Distinct Expression Patterns of microRNAs in Activated B Cell (ABC) and Germinal Center B (GC) Subtypes of Diffuse Large B Cell Lymphoma (DLBLC).

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 562-562
Author(s):  
Jean-Noel Bastie ◽  
Jean-Philippe Jais ◽  
Thierry Molina ◽  
Emmanuelle Come ◽  
Bertrand Coiffier ◽  
...  
Keyword(s):  
B Cell ◽  
Mirna Expression ◽  
Germinal Center ◽  
Cell Lymphoma ◽  
Expression Patterns ◽  
B Cell Lymphoma ◽  
Rt Pcr ◽  
Large B Cell Lymphoma ◽  
Micro Rnas ◽  
Large B Cell

Abstract The Micro RNAs (miRNAs) are small non-coding, single-stranded RNAs that regulate the expression of genes by hybridizing the mRNA target with complementary sequences that are followed by translational repression, mRNa cleavage or destabilization. There is evidence that miRNA play an important role in carcinogenesis. Aberrant miRNA expression has been found in a variety of human malignancies including B-cell leukemias and lymphomas. The purpose of this study is to determine the miRNA expression patterns in DLBCL and their relationship with clinical characteristics and outcome. We used high throughput quantitative RT-PCR technology (Taqman Low density Arrays) to analyze the expression profile of 365 different mature miRNA in 12 Diffuse Large B-Cell Lymphoma (DLBCL) samples which had been previously characterized at the transcriptional level with Affymetrix HU133A micro-arrays. MiR-155 expression was significantly lower in the 6 samples with a Germinal Center (GC) mRNA profile than in the 6 samples with an Activated B-Cell (ABC) profile. Expression of miR-155 and of different miRNA involved in lymphoid differentiation (miR-181a, miR127) or tumour pathogenesis (cluster miR 17–92) were further evaluated in a series of 64 patients with DLBCL treated with Rituximab associated with chemotherapy (R-CHOP). 28 patients had been enrolled in the LNH98.5 GELA trial between February 1998 and February 2000 and 36 were treated with R-CHOP in GELA centers after the closure of the LNH98-5 trial, between November 2000 and June 2004. The median follow up of these patients is 69 months. Patients median age at diagnosis was 69 years (range 59–82) and 28 patients presented with an International Prognostic Index (IPI) score of more than 3. Mature miRNA expression was determined by quantitative RT-PCR with Applied Biosystems specific miRNA primer and probe sets and normalized to U6 small nuclear RNA expression. MiR-155 expression was significantly higher in patients with a lymphoma of the ABC subtype, defined on the basis of the transcriptional profile (mean delta Ct = − 3.9 in the 41 ABC samples, mean delta Ct = − 1.67 in the 23 GC samples, p<0.00001) and significantly higher in patients with a high (4 or 5) IPI score (p=0.02). A high miR-155 expression was associated with a trend towards a poorer overall survival. The expression of miR-127, miR-181a and the cluster 17–92 were not correlated with clinical outcome. These analyses are currently being extended to a larger series of patients in order to determine whether other miRNA can be used to classify DLBCL samples into ABC and GC subtypes and whether some miRNA have prognostic significance in the era of treatments combining Rituximab and chemotherapy.

Fas and Fas ligand expression on germinal center type-diffuse large B-cell lymphoma is associated with the clinical outcome

2006 ◽  
Vol 76 (6) ◽  
pp. 465-472 ◽  
Author(s):  
Yasushi Kojima ◽  
Hisashi Tsurumi ◽  
Naoe Goto ◽  
Masahito Shimizu ◽  
Senji Kasahara ◽  
...  
Keyword(s):  
Clinical Outcome ◽  
B Cell ◽  
Germinal Center ◽  
Fas Ligand ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Large B Cell Lymphoma ◽  
Ligand Expression ◽  
Large B Cell

Fas or Fas Ligand Expression Can Determine the Clinical Outcome of Germinal Center Type in Diffuse Large B Cell Lymphoma.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 3267-3267
Author(s):  
Yasushi Kojima ◽  
Hisashi Tsurumi ◽  
Naoe Goto ◽  
Michio Sawada ◽  
Toshiki Yamada ◽  
...  
Keyword(s):  
Overall Survival ◽  
B Cell ◽  
Germinal Center ◽  
Fas Ligand ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Large B Cell Lymphoma ◽  
Significant Difference ◽  
Type 3 ◽  
Large B Cell

Abstract In recent years, diffuse large B cell lymphoma (DLBCL) has been classified by a cDNA microarray, an oligonucreotide microarray, or a tissue microarray. From the prognostic point of view, DLBCL consists of germinal center B-cell-like (GC) type, activated B-cell-like (ABC) type and type 3. ABC type and type 3 can be collectively categorized as non-GC (NGC) type. GC type has favorable prognosis compared with NGC type. Escape from apoptosis is considered to be an important mechanism for the progression of lymphoma. Fas is the major protein which leads to apoptosis by binding with Fas-ligand (FasL). We evaluated the prognostic significance of such markers as CD10, Bcl-6, MUM1, Fas and FasL, as well as GC or NGC type with paraffin embedded sections from 69 DLBCL patients immunohistochemicaly. The patients were 40 men and 29 women with median age of 67 years old (range, 20–82 years old). The median follow-up of surviving patients was 43 months. The 3-year OS for the entire group was 56%. There was no significant difference in sex, age, clinical stage, lactate dehydrogenase, or International Prognostic Index between GC and NGC type. Expression of CD10 was seen in 29% (20 of 69 of the patients), Bcl-6 in 27% (19 of 69), MUM1 in 27% (19 of 69), Fas in 51% (36 of 69), and FasL in 50% (35 of 69). We divided 69 DLBCLs to 26 GC type (CD10 positive or Bcl-6 positive and MUM1 negative) and 43 NGC type (the other). Positive CD10 was the best marker to indicate favorable overall survival (p=0.0156). GC type had tendency to have better overall survival than NGC type, though it was not significant (p=0.0723). Although Fas or FasL expression was not significant for overall survival in all DLBCL, it predicted significantly a longer over all survival (Fas; p=0.0021, FasL; p=0.0165) in GC type. These results may suggest that the presence of a subtype of DLBCL in which Fas/FasL system works effectively. This group is approximately 20% of DLBCL and mainly belongs to the GC type. Fas expression in GC type of DLBCL may predict the prognosis and be useful to choose the appropriate therapy. Furthermore, CD10 was more significant than GC type and, thus, we may need to build the strict consensus for GC type.

scholarly journals Increased Expression of EZH2 Is Associated with Inferior Survival in Primary Central Nervous System Diffuse Large B-Cell Lymphoma

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 4216-4216
Author(s):  
Briana Gibson ◽  
Rahul Matnani ◽  
Zheng Ping ◽  
Balabhadrapatruni VSK Chakravarthi ◽  
Yang Yang ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Clinical Outcome ◽  
Protein Expression ◽  
B Cell ◽  
Germinal Center ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Large B Cell Lymphoma ◽  
Large B Cell

Abstract Introduction: Primary central nervous system lymphomas (PCNSL) are rare and aggressive diseases with a poorly understood biology. Due to clinical heterogeneity and lack of prognostic biomarkers, effective and less toxic therapies are yet to be discovered. Enhancer of zeste homolog 2 (EZH2), a histone methyltransferase, was demonstrated to regulate cancer cell fate in response to DNA damage. EZH2 has been shown to be frequently overexpressed in various human cancers including lymphoma and is associated with inhibition of apoptosis through trimethylation of histone H3 lysine 27 (H3K27me3). The runt-related transcription factor 3 (RUNX3) is a downstream effector of the transforming growth factor-β (TGF-β) signaling pathway, and is critical for promoting cell death and apoptosis. Various studies have shown RUNX3 downregulation as a result of EZH2 upregulation. We investigated the EZH2 and RUNX3 protein expression and its impact on clinical outcome in PCNSL. Methods: A retrospective clinicopathologic chart review was conducted and 33 cases with diagnosis of PCNSL at our institution were included. Cases of secondary CNS involvement by diffuse large B-cell lymphoma (DLBCL) and HIV-related PCNSL were excluded. A tissue microarray (TMA) was constructed using archived formalin-fixed-paraffin-embedded tissue from 33 PCNSL cases. EZH2 and RUNX3 protein expression was assessed using immunohistochemistry and the staining was specifically classified based on percentage of the cells staining: 0 (<10%), 1+ (10-30%), 2+ (30-75%) and 3+ (>75%) and staining intensity: negative, weak positive and strong positive. Overall survival (OS) was calculated using the Kaplan-Meier method and log-rank test. Chi-square test was used to determine relationships between immunophenotypic subtype and protein expressions. Results: EZH2 and RUNX3 protein expression results were obtained in 25 out of 33 cases. The median age was 65 years (range 51-86 years) with a male:female ratio of 4:1. The majority of the cases were non-germinal center subtype (n=16, 64%) while the remaining 16% were germinal center subtype (n=9). Median OS was 11 months (range 2-120 months). Six out of 25 cases showed 3+ and strong staining for EZH2 while five cases were 2+, two were 1+ and the remaining was negative. The staining profile and number of cases for RUNX3 are as follows; 3+: seven, 2+: four, 1+: four, 0: 10. Strong and diffuse (3+) expression of EZH2 strongly correlated with inferior outcome (P=0.0045), independent of immunophenotypic subtype, while there was no significant correlation between OS and 0-2+ EZH2 expression. RUNX3 staining did not correlate with clinical outcome (P=0.67). Conclusions: Our data suggests a role of EZH2 overexpression in the pathogenesis of PCNSL. Overexpression of EZH2 appears to be an adverse prognostic factor and a potential target in PCNSL. Larger scale studies are warranted to elucidate the biology and prognostic utility of EZH2 in PCNSL. Disclosures No relevant conflicts of interest to declare.

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