Prognostic Significance of BCL6 Translocation in Diffuse Large B-Cell Lymphoma Patients Treated with R-CHOP

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 3782-3782
Author(s):  
Jesse Shustik ◽  
Christian Steidl ◽  
Laurie Sehn ◽  
Randy D Gascoyne
Keyword(s):  
Overall Survival ◽  
B Cell ◽  
Prognostic Value ◽  
Cell Lymphoma ◽  
Prognostic Significance ◽  
B Cell Lymphoma ◽  
Immunohistochemical Analysis ◽  
Prognostic Impact ◽  
Large B Cell Lymphoma ◽  
Large B Cell

Abstract Translocation of the BCL6 oncogene is the most commonly-detected chromosomal abnormality in diffuse large B-cell lymphoma (DLBCL), but its prognostic significance remains uncertain. BCL6 translocation has been associated with variable outcomes in prior clinical series, and its clinical impact has not been reevaluated since the introduction of rituximab (R). The objective of this study was to determine the prognostic value of BCL6 translocation in DLBCL patients treated with both CHOP and R-CHOP immunochemotherapy. Methods We included 163 DLBCL patients treated with CHOP (n=72) or R-CHOP (n=73) at the British Columbia Cancer Agency between the years 1999–2002. Formalin-fixed paraffin-embedded diagnostic lymph node specimens were analyzed for BCL6 translocation on tissue microarray (TMA) by fluorescence in situ hybridization (FISH), using commercially available dual-color break-apart probes (Abbott Molecular, IL, USA). Immunohistochemical analysis was performed for BCL6, CD10, and MUM1 expression, and cases were categorized as germinal centre B-cell-like (GCB) or non-GCB using a standard algorithm (Hans, Blood 2004). Results BCL6 translocation status was evaluable in 145 cases, and was positive (BCL6+) in 26% (37/145). Median age (65 vs. 59 years, p=0.03) and overall IPI score (p=0.03) were higher in the BCL6+ than in the BCL6− subgroup. Presence of BCL6 translocation correlated with non-GCB phenotype by immunohistochemical analysis (p=0.03), and showed no significant association with BCL6 protein expression (p=0.32). Median follow-up duration was 4.8 years (range, 0.1–8.4). BCL6 translocation was associated with a trend toward decreased overall survival (OS) among patients treated with R-CHOP (5-year OS 46.7% vs. 68%, p=0.098), though not among CHOP-treated patients (5-year OS 36.4% vs.49.5%, p=0.393). Kaplan-Meier analysis limited to the BCL6+ subgroup showed no overall survival difference between patients treated with CHOP and R-CHOP (p=0.67). Conclusions BCL6 translocations are found in approximately 25% of patients with de novo DLBCL. Presence of BCL6 translocation appears to predict unfavorable outcome in DLBCL patients treated with R-CHOP. However, the adverse prognostic impact of BCL6 translocation is confounded by an association with high IPI score and with non-GCB phenotype. Prospective analysis within large clinical trials would help to determine the independent prognostic value of this marker in the rituximab era.

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.

Tumor-collagen digital proximity signature to indicate prognosis in diffuse large B-cell lymphoma.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e19073-e19073
Author(s):  
Talha Qaiser ◽  
Matthew Pugh ◽  
Sandra Margielewska ◽  
Robert Hollows ◽  
Paul Murray ◽  
...  
Keyword(s):  
Overall Survival ◽  
Tumor Cell ◽  
B Cell ◽  
Tumor Cells ◽  
Cell Lymphoma ◽  
Prognostic Significance ◽  
B Cell Lymphoma ◽  
Automated Image Analysis ◽  
Large B Cell Lymphoma ◽  
Large B Cell

e19073 Background: Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous tumor that originates from normal B-cells. Despite the use of combination chemotherapy, around 40% of DLBCL patients die (de Jonge, et al. European Journal of Cancer, 2016). Limited studies have investigated the role of collagen in the acellular tumor microenvironment. In this study, we present a novel digital signature of the proximity of tumor cells and collagen-VI (COL6) that can predict overall survival (OS) in DLBCL patients. To the best of our knowledge, this is the first study of its kind to employ automated image analysis. Methods: The proposed digital proximity signature (DPS) aggregates summary-level statistics from the entire whole slide image (WSI) and serves as a marker of regions, categorizing weak, moderate, significant, and strong tumor-collagen proximity and can be described as a surrogate for signaling. To accomplish this, we developed a novel artificial intelligence (AI) based multi-task model for simultaneous detection and classification of tumor cells and another bespoke method for automatically identifying COL6 fiber. The tumor-collagen proximity analysis was then performed by aggregating tumor cell statistics within the vicinity of COL6 fibres. Finally, the prognostic significance of DPS for OS in DLBCL was investigated with Kaplan-Meier analysis, stratifying patients into two groups based on the median of the DPS values. Results: We took WSIs of DLBCL tissue slides for 32 cases immunohistochemically stained with COL6 and Hematoxylin counterstain. The AI model for tumor cell identification achieved a high F1-score of 0.84, outperforming recent single-task learning models. Our results show that strong proximity of COL6 and tumor cells is linked to better OS in DLBCL patients ( p = 0.03). Conclusions: Our novel digitally computed COL6-tumor proximity signature shows prognostic significance for overall survival on a pilot dataset of 32 DLBCL patients. We are further validating the utility of this novel signature as a prognostic biomarker in larger cohorts of DLBCL patients.

scholarly journals 5-Hydroxymethylcytosines of Circulating Cell-Free DNA and Prognosis in Diffuse Large B-Cell Lymphoma

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 2985-2985
Author(s):  
Brian C.-H. Chiu ◽  
Zhou Zhang ◽  
Qiancheng You ◽  
Elizabeth Stepniak ◽  
Paige Bracci ◽  
...  
Keyword(s):  
Overall Survival ◽  
B Cell ◽  
Cell Lymphoma ◽  
Prognostic Significance ◽  
B Cell Lymphoma ◽  
Cell Free Dna ◽  
Free Dna ◽  
Large B Cell Lymphoma ◽  
Large B Cell ◽  
Circulating Cell Free Dna

Abstract Background: Elevated levels of circulating cell-free DNA (cfDNA) have been associated with poor prognosis and relapse in patients with diffuse large B-cell lymphoma (DLBCL). However, the tumor-specific molecular targets in cfDNA that have prognostic significance remain unclear. We investigated the association between 5-hydroxymethylcytosine (5hmC), a mark of active demethylation and gene activation, in cfDNA from plasma and prognosis in DLBCL. Methods: We used the 5hmC-Seal, a highly sensitive chemical labeling technique integrated with next-generation sequencing (NGS), to profile 5hmC in plasma cfDNA samples from Caucasian patients at the University of Chicago who were newly diagnosed with DLBCL (n=43) or follicular lymphoma (FL, n=28), the two most common histological subtypes of non-Hodgkin lymphoma (NHL), in 2011-13. Baseline clinical, laboratory, and vital status data were abstracted from medical records. Patients were followed through December 31, 2017 and those who relapsed after completion of treatment, lost to follow-up, or died were censored. We profiled 5hmC with 1-2 ng of cfDNA extracted from ~2 ml of plasma for library construction and the NGS. We obtained ~25 million reads per sample, providing a depth of coverage ~600X in terms of gene bodies. We normalized read counts and identified differential 5hmC markers using DESeq2. Cox proportional hazards model were used to estimate the association between 5hmC markers and overall survival. Results: We found that in cfDNA from DLBCL patients, 5hmC markers were enriched within gene bodies and depleted in CpG islands. The cfDNA-based 5hmC profiles at diagnosis differed between DLBCL and FL, and in DLBCL, the 5hmC profiles differed between Ann Arbor stage (stage 1/2 vs stage 3/4), lactate dehydrogenase (LDH) level (normal vs elevated), and cell-of-origin (germinal center B-like and activated B-cell-like DLBCL). In addition, genome-wide 5hmC distribution patterns in cfDNA samples are highly correlated with those found in cfDNA-paired tumor tissues, supporting the tumor relevance of cfDNA in a patient. Next, we evaluated the prognostic significance of cfDNA-based 5hmC in DLBCL using a two-step approach. In the discovery phase (7 DLBCL patients with relapse and 12 age- and sex-matched patients without relapse within two years following treatment), a substantial number of 5hmC markers were associated with relapse (449 gene bodies at 5% false discovery rate [FDR]). These relapse-associated 5hmC signatures showed high sensitivity, specificity, and overall accuracy (area under curve [AUC]=0.91) in predicting relapse in the independent validation set (relapse=5, no relapse=13). Finally, we identified a panel of 128 5hmC markers (fold change >20% and p-value <0.05) that were associated with 4-year overall survival. Conclusion: These findings suggest that 5hmC signatures in cfDNA at the time of DLBCL diagnosis correlate with standard clinical prognostic indices and hold promise as non-invasive markers for prognosis and survival. Disclosures Smith: BMS: Consultancy; Portola: Honoraria.

BCL2 Expression Is a Prognostic Marker for the Activated B-Cell–Like Type of Diffuse Large B-Cell Lymphoma

2006 ◽  
Vol 24 (6) ◽  
pp. 961-968 ◽  
Author(s):  
Javeed Iqbal ◽  
Vishala T. Neppalli ◽  
George Wright ◽  
Bhavana J. Dave ◽  
Douglas E. Horsman ◽  
...  
Keyword(s):  
Overall Survival ◽  
B Cell ◽  
Cell Lymphoma ◽  
Mrna Level ◽  
Prognostic Significance ◽  
B Cell Lymphoma ◽  
Large B Cell Lymphoma ◽  
The Difference ◽  
Large B Cell ◽  
Bcl2 Expression

Background The role of BCL2 as a predictor of survival in diffuse large B-cell lymphoma (DLBCL) is controversial. DLBCL is heterogeneous, and the expression of BCL2 is variable within the two major subgroups of DLBCL, germinal center B-cell–like (GCB) and activated B-cell–like (ABC) DLBCL, as well as primary mediastinal DLBCL. Patients and Methods In this study, we investigated the correlation of BCL2 expression with survival in the two major subgroups of DLBCL, as well as the mechanisms of BCL2 expression. Results There was no significant correlation between BCL2 protein expression and overall survival within the GCB subgroup, but BCL2 expression had a significant adverse effect on overall survival within the ABC subgroup (P = .008). This correlation was also observed at the mRNA level (P < .04). The difference remained significant when the analyses were performed at different cutoff values. The t(14;18) was frequently observed in the GCB subgroup and was highly associated with BCL2 expression. Patients with ABC DLBCL did not exhibit t(14;18) but had a markedly higher frequency of chromosome 18q21 amplification, on which BCL2 resides. Thus, alternative mechanisms such as 18q21 amplification or activation of the nuclear factor-kappa B pathway, as reported previously, seem to be mainly responsible for the upregulation of BCL2 expression in the ABC subgroup. Conclusion Treating all DLBCL as a single entity ignores the mechanistic differences in BCL2 upregulation and obscures the prognostic significance of BCL2 expression. Hence, the significance of BCL2 and other biomarkers should be assessed in the context of DLBCL subgroups in future studies.

scholarly journals Clinical Features and Prognostic Significance of NOTCH1 Mutations in Diffuse Large B-Cell Lymphoma

2021 ◽  
Vol 11 ◽  
Author(s):  
Zhongqi Li ◽  
Fang Yu ◽  
Wenle Ye ◽  
Liping Mao ◽  
Jiansong Huang ◽  
...  
Keyword(s):  
B Cell ◽  
Clinical Features ◽  
Cell Lymphoma ◽  
International Prognostic Index ◽  
Prognostic Significance ◽  
Prognostic Index ◽  
B Cell Lymphoma ◽  
Prognostic Impact ◽  
Large B Cell Lymphoma ◽  
Large B Cell

Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous group of large lymphoid B cell malignancy with distinct clinical and genetic features. Recently, NOTCH1 mutations were identified in DLBCL cases by Next-generation sequencing (NGS), but the clinical features and prognostic impact were not systematically studied. Here, NOTCH1 genes in 161 DLBCL samples were sequenced by NGS. The prognostic value of NOTCH1 mutations was assessed in the context of clinical and laboratory factors, such as international prognostic index (IPI), cell-of-origin classification, double expression of BCL2 and c-MYC. The combined data from three Western cohorts were used to validate these results. As a result, NOTCH1 mutations were found in 17(10.6%) patients, and three patients had a hotspot mutation of c.7541_7542delCT. The presence of NOTCH1 mutations was significantly associated with poor complete response and progression free survival(PFS), which was independent of established clinical and laboratory parameters. In addition, 30 (1.92%) of 1562 patients treated with R-CHOP regimen in those combined Western cohorts had NOTCH1 mutations. Meta-analysis of the Western cohorts confirmed that NOTCH1 mutations were also associated with poor PFS and OS. In conclusion, DLBCL patients with the NOTCH1 mutations have worse PFS and OS, and the NOTCH1 mutations can be used as an independent predictor for patients with DLBCL.

scholarly journals Bcl-2 protein frequency in patients with high-risk diffuse large B-cell lymphoma

2010 ◽  
Vol 128 (1) ◽  
pp. 14-17 ◽  
Author(s):  
Abrahão Elias Hallack Neto ◽  
Sheila Aparecida Coelho Siqueira ◽  
Frederico Luiz Dulley ◽  
Alfredo Chauobah ◽  
Marcelo Belesso ◽  
...  
Keyword(s):  
Overall Survival ◽  
High Risk ◽  
B Cell ◽  
Cell Lymphoma ◽  
Survival Rates ◽  
Disease Free Survival ◽  
B Cell Lymphoma ◽  
Prognostic Impact ◽  
Large B Cell Lymphoma ◽  
Large B Cell

CONTEXT AND OBJECTIVE: Gene expression and immunohistochemical profiling of diffuse large B-cell lymphoma (DLBCL) have revealed important prognostic subgroups: germinal center B-cell-like (GCB-like) DLBCL and activated B cell-like (ABC-like) DLBCL. Although few reports on high-risk DLBCL are available, the prognosis for the GCB-like subgroup has been shown to be better than that of the ABC-like subgroup. The role of Bcl-2 as a predictor of survival in DLBCL cases is unclear and its expression varies between the two subgroups of DLBCL. In this study, we analyzed the frequency and prognostic impact of Bcl-2 protein expression in high-risk DLBCL cases. DESIGN AND SETTING: Retrospective cohort study among DLBCL patients treated at Hospital das Clínicas, Faculdade de Medicina da Universidade de São Paulo (HC-FMUSP). METHODS: The prognostic impact of the expression of the proteins CD10, Bcl-6, MUM1 (multiple myeloma oncogene-1) and Bcl-2 on high-risk DLBCL cases was evaluated by means of immunohistochemistry. Seventy-three patients aged 18-60 years were evaluated for all these markers. RESULTS: Twenty-four cases (32.9%) were GCB-like and 49 (67.1%) were ABC-like, with no difference regarding complete remission, disease-free survival or overall survival rates. Twenty-seven patients (37%) showed Bcl-2 expression, which was the only independent factor predicting a worse prognosis for overall survival according to multivariate analysis. CONCLUSION: Bcl-2 protein was expressed in 37% of the high-risk DLBCL patients, without any difference between the ABC-like DLBCL and GCB-like DLBCL cases.

Prognostic Impact of Tumor Infiltrating FOXP3 Positive Regulatory T Cells in Diffuse Large B-Cell Lymphoma at Diagnosis.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 1565-1565
Author(s):  
Jae-Yong Kwak ◽  
Na-Ri Lee ◽  
Eun-Kee Song ◽  
Kyu Yun Jang ◽  
Ha Na Choi ◽  
...  
Keyword(s):  
T Cells ◽  
Regulatory T Cells ◽  
B Cell ◽  
Cell Lymphoma ◽  
International Prognostic Index ◽  
Prognostic Significance ◽  
B Cell Lymphoma ◽  
Prognostic Impact ◽  
Large B Cell Lymphoma ◽  
Large B Cell

Abstract Tumor infiltrating immune cells play an important role in host immune reactions against diffuse large B-cell lymphoma (DLBCL). In the present study, we have identified a subset of tumor infiltrating FOXP3-positive regulatory T cells (Tregs) in the initial DLBCL biopsy specimens and evaluated its prognostic significance. Ninety-six patients with DLBCL were retrospectively evaluated. Expression pattern of FOXP3 protein was examined using standard immunohistochemistry in paraffin-embedded tissue samples. The median overall survival (OS) was 28 months. Compared to the others, the patients with higher percentage of FOXP3-positive Tregs in the initial tumor biopsy, showed a significantly longer OS (p=0.003). When prognostic factors were evaluated in a multivariate model, the international prognostic index and the percentage of infiltrating FOXP3-positive Tregs in the initial biopsy were shown to be independent predictors of OS. In conclusion, the presence of increased percentage of FOXP3-positive Tregs in DLBCL predicts a better prognosis. Figure Figure

Prognostic impact of immunohistochemically defined germinal center B-cell and nongerminal center B-cell subtypes of diffuse large B-cell lymphoma in rituximab era.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e18517-e18517
Author(s):  
Yabing Cao ◽  
Ying Huang ◽  
Sheng Ye ◽  
Tongyu Lin
Keyword(s):  
B Cell ◽  
Germinal Center ◽  
Survival Data ◽  
Prognostic Value ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Prognostic Impact ◽  
Large B Cell Lymphoma ◽  
Germinal Center B Cell ◽  
Large B Cell

e18517 Background: Diffuse large B-cell lymphoma (DLBCL) can be molecularly subtyped as either germinal center B-cell (GCB) or non-GCB. The role of rituximab(R) in these two groups remains unclear. Methods: We studied 204 patients with de novo DLBCL (107 treated with CHOP; 97 treated with R-CHOP); patients being stratified into GCB and non-GCB on the basis of BCL-6, CD10 and MUM1 protein expression. The relationships between clinical characteristics, survival data and immunophenotype were studied. Results: The median follow-up was 51months for CHOP group and 56 months for R-CHOP group. The 5-year overall survival (OS) in the CHOP and R-CHOP group was 50.4% and 66.6% (p=0.031), respectively. GCB patients had a better 5-year OS than non-GCB patients whether treated with CHOP (65.0% vs. 40.9%; p=0.011). In contrast, there’s no difference in the 5-year OS for the GCB and non-GCB with R-CHOP (76.5% vs. 61.3%; p=0.141). In non-GCB subtype, additional rituximab improved survival than CHOP (61.3% vs. 40.9%; p=0.0303). Conclusions: These results indicated that addition of rituximab to standard chemotherapy eliminate the prognostic value of immunohistochemically defined GCB and non-GCB phenotypes in DLBCL by improving the prognostic value of non-GCB subtype of DLBCL

scholarly journals Prognostic Value of Baseline PET/CT Imaging in Diffuse Large B-Cell Lymphoma: Does the Largest Distance between Two Lesions Play a Role in Prognosis?

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 4577-4577
Author(s):  
Carolina Afonso ◽  
Sara Duarte ◽  
Bárbara Almeida Marques ◽  
Carla Barros Lima ◽  
Dulcelena Neves ◽  
...  
Keyword(s):  
Overall Survival ◽  
B Cell ◽  
Lymphocyte Count ◽  
Prognostic Value ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Cns Involvement ◽  
Large B Cell Lymphoma ◽  
Pet Ct ◽  
Large B Cell

Abstract Background: 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG-PET/CT) has become the international standard for diffuse large B-cell lymphoma (DLBCL) staging and is widely used for response assessment. In the past few years, the prognostic value of a variety of imaging-derived quantitative parameters has been investigated. One of these parameters is the distance between the 2 lesions that are farthest apart (Dmax). Dmax is a simple feature that captures lymphoma dissemination and has been reported to be a strong prognosticator of shorter progression-free survival (PFS) and overall survival (OS) in DLBCL patients (pts). Methods: Retrospective analysis of 146 pts with newly diagnosed Ann Arbor stage III-IV DLBCL, NOS, treated with R-CHOP(-like) regimens, between January 2010 and December 2019 in a tertiary center. Dmax was normalized with the body surface area [standardized Dmax (SDmax)]. The receiver operating characteristic curve (ROC) method was applied in resetting the optimal cut-off point for predicting prognosis and treatment outcome. The Kaplan-Meier method was used to describe time-to-event end points. A p-value of 0,05 was used as cut-off for significance. Results: Dmax was available for 40 pts. The median age at diagnosis was 63 years (24-78); 58% of pts were male. Most pts (69%) presented lactate dehydrogenase (LDH) above the upper limit of normal (ULN); 40% presented lymphopenia (lymphocyte count below 1000/μL), and 26% had albumin levels below 3.2 g/dL. Bone marrow (BM) infiltration occurred in 41% of pts, and 5% had central nervous system (CNS) involvement at diagnosis. According to the international prognostic index (IPI), 74% of pts were high-intermediate (HI) and high (H) risk; according to National Comprehensive Cancer Network (NCCN)-IPI, 68% of pts were HI and H risk. According to the cell of origin (COO) 63% of pts presented non-germinal center DLBCL. A complete metabolic response (CMR) on interim PET/CT was observed in 65% of pts, and 71% presented a CMR on end-of-treatment (EOT) PET/CT. At EOT the overall response rate was 80%. Seven percent of pts presented CNS relapse. The 5-year PFS was 58.5% and the 5-year overall survival (OS) was 69.4%. Higher SDmax was significantly associated with BM and CNS involvement at diagnosis (p=0.034 and p=0.049, respectively), as well as with CNS relapse (p=0.048). No statistically significant association was found between SDmax and the following features: lymphocyte count of &lt; 1000/μL (p=0.505), albumin levels &lt; 3.2 g/dL (p=0.140), LDH &gt; ULN (p=0.501), IPI risk ≥ HI risk (p=0.719), NCCN-IPI ≥ HI risk (p=0.239) and COO (p=0.493). There was a tendency, although not significant, towards a lower rate of CMR on interim and EOT PET/CT in pts with higher SDmax (p=0.072 and p=0.077, respectively). A higher SDmax had no statistically significant impact on either PFS (HR 0.456; p=0.500) or OS (HR 0.339; p=0.561). The combination of NCCN-IPI and SDmax allowed to identify a subgroup of pts with low (L) risk and low-intermediate (LI) risk NCCN-IPI and higher (≥ 4.1cm) SDmax with inferior 5-year OS (87.5% vs 50%; HR 4.64; p=0.031) and with a trend towards an inferior 5-year PFS (75% vs 50%; HR 1.92; p=0.166). Conclusions: In our cohort, a higher SDmax was associated with some high-risk features, as well as with a trend towards an inferior response to treatment. Additionally, the combination of SDmax and NCCN-IPI allowed to identify a subgroup of L risk and LI risk pts with inferior OS and a trend towards an inferior PFS. Interpretation of these results may be limited by the small sample size. The role of Dmax in DLBCL prognostication may therefore require further validation before widespread clinical use. Disclosures Gomes: Takeda: Consultancy; Gilead: Consultancy; Janssen: Consultancy.

LMO2 and Bcl-6 Expression in Diffuse Large B-Cell Lymphoma Predict Overall Survival in R-CHOP Treated Patients

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 5304-5304
Author(s):  
Heather D. Brooks ◽  
Robert M. Graham ◽  
Randall L. Woodford ◽  
Audrey K. Bennett ◽  
Xin Qun Wang ◽  
...  
Keyword(s):  
Overall Survival ◽  
B Cell ◽  
Germinal Center ◽  
Cell Lymphoma ◽  
Prognostic Significance ◽  
Previous History ◽  
B Cell Lymphoma ◽  
Large B Cell Lymphoma ◽  
Significant Difference ◽  
Large B Cell

Abstract LMO2, a germinal center marker and transcription factor with an important role in angiogenesis and erythropoiesis, was found to confer improved prognosis in diffuse large B-cell lymphoma (DLBCL) when expressed in tissue microarray (TMA) samples (Natkunam et al J Clin Oncol2008,26:447). Bcl-6, a transcriptional repressor controlling germinal center formation, has been associated with favorable outcomes in DLBCL patients treated with CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) but was found to have no prognostic significance in DLBCL patients older than 60 treated with rituximab (R) + CHOP (Winter et al Blood2006,107:4207). Hans previously described an algorithm to subclassify DLBCL into germinal center B-cell like (GCB) and activated B-cell like (ABC) using immunohistochemical staining for CD10, bcl-6 and MUM1 with GCB exhibiting improved survival (Hans et al Blood2004,103:275). The aim of this study was to evaluate the prognostic value of LMO2, CD10, bcl-6, bcl-2 and MUM1 expression in DLBCL patients treated with R-CHOP. We also applied the Hans classification to our cohort and incorporated LMO2 into the algorithm. Adults (&gt;18 years) with DLBCL who were diagnosed and treated at the University of Virginia between 2000 and 2007 were retrospectively evaluated. Patients were selected based on adequate tissue, treatment with at least 3 cycles of R-CHOP and if a minimum of 6 months of follow-up data was available at the time of data analysis. Forty-one cases were included of which 26 were de novo DLBCL, 12 were DLBCL with concurrent follicular lymphoma (FL) and 3 cases were new diagnoses of DLBCL with a previous history of FL. H&E-stained sections from paraffin-embedded, formalin-fixed blocks were used to define diagnostic areas, and 3 representative 1.0-mm cores were obtained from each case. TMA sections were then stained with antibodies to CD10, bcl-6, bcl-2, MUM1 and LMO2. Cases were assigned to GCB-like and ABC-like subgroups based on the Hans algorithm. The LMO2 stain was incorporated into the Hans algorithm to create modified-Hans (m-Hans) subgroups; the sample received an m-GCB designation if LMO2 positive but the normal Hans classification was applied if the sample was LMO2 negative. For 41 complete patient samples, a nonparametric Kaplan-Meier estimator was used to estimate overall survival (OS) probability for each group (m-GCB, m-ABC). A log-rank test demonstrated that there was a significant difference in OS probability between m-ABC and m-GCB groups (p = 0.047). Six month and 3 year survival for m-ABC and m-GCB were 71% and 88%, and 44% and 68% respectively. A semi-parametric Cox proportional hazard model was used to assess association between OS and each individual stain (CD10, bcl-2, bcl-6, MUM1 and LMO2), and a hazards ratio was used to quantify the effect of each stain. Bcl-6 and LMO2 expression were highly correlated, with bcl-6 expression significantly associated with OS (p=0.011). Patients without bcl-6 expression had more than four-fold risk than those expressing bcl-6 in OS (Hazard Ratio = 4.29, 95% CI: 1.4–13.1). Also, LMO2 expression showed a marginal association with OS (p=0.065). In conclusion, LMO2 incorporated into the Hans classification and bcl-6 expression are both significant predictors of OS in DLBCL patients treated with R-CHOP. Figure Figure

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