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.

scholarly journals Clinical and prognostic significance of aberrant T-cell marker expression in 225 cases of de novo diffuse large B-cell lymphoma and 276 cases of other B-cell lymphomas

Oncotarget ◽  
2017 ◽  
Vol 8 (20) ◽  
pp. 33487-33500 ◽  
Author(s):  
Naoko Tsuyama ◽  
Daisuke Ennishi ◽  
Masahiro Yokoyama ◽  
Satoko Baba ◽  
Reimi Asaka ◽  
...  
Keyword(s):  
T Cell ◽  
B Cell ◽  
De Novo ◽  
Cell Lymphoma ◽  
Prognostic Significance ◽  
B Cell Lymphoma ◽  
Cell Marker ◽  
Large B Cell Lymphoma ◽  
Marker Expression ◽  
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.

CD30 Immunohistochemical Expression In Diffuse Large B-Cell Lymphoma Is Associated With Decreased Overall Survival and The Non-Germinal Center Molecular Subtype

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 4318-4318 ◽  
Author(s):  
Angela M. B. Collie ◽  
Brian T. Hill ◽  
Elena A. Manilich ◽  
Mitchell R Smith ◽  
Eric D. Hsi
Keyword(s):  
Overall Survival ◽  
B Cell ◽  
Poor Prognosis ◽  
De Novo ◽  
Cell Lymphoma ◽  
Molecular Subtype ◽  
B Cell Lymphoma ◽  
Cell Of Origin ◽  
Immunohistochemical Expression ◽  
Large B Cell Lymphoma

Abstract Background Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous disease entity with multiple potential prognostic biomarkers. Cell of origin (COO) molecular subtype classification using gene expression profiling with microarrays and immunohistochemical expression of CD30 have been examined as potential prognostic markers, often with conflicting results. A recent study demonstrated that patients with CD30-positive DLBCL had better prognosis compared to patients with CD30-negative DLBCL and had a distinct gene expression profile (Hu S et al. Blood. 121(14): 2715-24, 2013). In addition, due to the development of targeted therapies such as an anti-CD30 monoclonal antibody drug conjugate, the identification and prognostic relevance of this biomarker has potential therapeutic impact. We evaluated CD30 expression, determined by immunohistochemistry, in a cohort of de novo DLBCL cases at our institution and examined cell of origin molecular subtype in the CD30-positive and CD30-negative groups. Design 94 adult patients with de novo DLBCL uniformly treated with rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP) as first line therapy were identified at The Cleveland Clinic. Clinical data was collected for these patients. A tissue microarray was created and stained with antibodies to CD10, CD20, CD30, BCL-6, and MUM-1. COO subtype was determined for the Hans algorithm in all cases. CD30 was considered positive when expression was seen in ≥ 20% of tumor cells. Results There were no significant differences in sex, age, IPI score, or stage between patients in the CD30-positive and CD30-negative groups. The median age of the DLBCL cohort was 63 years (range 17-91 years) with a male : female ratio of 1:1.1. 54% of patients had stage III or IV disease. Median follow-up was 58 months. 9 of 94 DLBCL samples (9.6%) were positive for CD30 by immunohistochemistry. By Kaplan-Meier analysis, the CD30-positive cases showed a decreased overall survival compared to the CD30-negative cases (Figure 1, p=0.044). Multivariate analysis using a Cox proportional hazard model confirmed that CD30 expression was independent of IPI and a significant factor for overall survival (hazard ratio = 3.05; 95% confidence interval = 1.12-8.30; p = 0.0291). All 9 of the CD30-positive DLBCL samples were of the non-germinal center B-cell-like (NGC) subtype using the Hans immunohistochemical algorithm, which was significantly more than the CD30-negative samples (42/85) (p = 0.003). Conclusion CD30 expression was associated with poor prognosis in our cohort, in contrast to recent studies. However, CD30 expression was highly associated with the NGC subtype of DLBCL and might contribute to the pathogenesis of these lymphomas through NF-κB activation. Given the poor prognosis of NGC DLBCLs, targeting CD30 in DLBCL should be explored. Disclosures: No relevant conflicts of interest to declare.

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.

Prognostic Significance of Cell of Origin Subclassification in Diffuse Large B Cell Lymphoma

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 5081-5081
Author(s):  
Muath Dawod ◽  
Juan Gomez-Gelvez ◽  
Ahmad Mattour ◽  
Kedar V. Inamdar ◽  
Nalini Janakiraman
Keyword(s):  
Overall Survival ◽  
B Cell ◽  
Cell Lymphoma ◽  
Statistical Significance ◽  
Prognostic Significance ◽  
Progression Free Survival ◽  
B Cell Lymphoma ◽  
Cell Of Origin ◽  
Free Survival ◽  
Large B Cell Lymphoma

Abstract Abstract 5081 Background: Diffuse large B cell lymphoma (DLBCL) is a heterogeneous disease that has been divided into three different prognostic subgroups: Germinal Center B cell-like (GC), Activated B cell-like (ABC) and type 3 according to gene expression profile using cDNA. Immunohistochemistry (IHC) has been used as surrogate to identify these cell-of-origin subgroups. Data about the prognostic value of IHC has been conflicting. Patients and methods: In this retrospective study, we reviewed the charts of 252 patients diagnosed with DLBCL at Henry Ford Hospital from 1999 to 2012. We excluded patients with HIV, transformed lymphomas and unavailable samples. Data was collected on a total of 157 patients. The following data was gathered: age, sex, race, IPI score, disease stage, hemoglobin, white blood and platelet counts, best response achieved and dates of treatment start, relapse, death or last follow up. Tissue microarray slides with the following IHC stains (CD10, MUM1, Bcl6) were prepared and reviewed when needed. Using Hans Algorithm, samples were divided into two major groups (GC-like and non-GC-like). 3-year progression free and overall survivals were compared between all subgroups using a log-rank test. Continuous variables were reported as median and range, and compared using Wilcoxon rank-sum tests. Categorical variables were reported as median and range, and compared using Chi-square tests. Statistical significance was set at p<0. 05. Results: Eighty patients (51%) were classified as GC-like, and 77 patients (49%) as non-GC-like. GC-like subgroup had a significantly longer 3-year progression free survival (90% vs 74%, P=0. 024), as compared with the non-GC-like subgroup. There was a trend toward longer overall survival but it didn't reach statistical significance (74% vs 67%, P=0. 161). For all patients, IPI stands as a strong prognostic index with 3-year overall survival of (85% and 46%, P=<. 001) in patients with low IPI (0 to 2) and high IPI (3 to 5) respectively. Interestingly, in patients with low IPI, cell of origin stands as a prognostic factor with 3-year progression free survival of (96% and 81%, P=0. 032) in GC-like and non-GC-like groups respectively. While in patients with high IPI, there was no significant difference in progression free survival in cell-of-origin subgroups. Conclusion: Cell of origin subclassification as determined by IHC surrogate markers predict for better progression free survival in GC-like subgroup but not for overall survival. While this prognostic value was maintained in patients with low IPI, there was no prognostic significance in patients with high IPI. IPI is still a valuable prognostic tool in patients with DLBCL. Disclosures: No relevant conflicts of interest to declare.

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 Immunohistochemical Methods for Predicting Cell of Origin and Survival in Patients With Diffuse Large B-Cell Lymphoma Treated With Rituximab

2011 ◽  
Vol 29 (2) ◽  
pp. 200-207 ◽  
Author(s):  
Paul N. Meyer ◽  
Kai Fu ◽  
Timothy C. Greiner ◽  
Lynette M. Smith ◽  
Jan Delabie ◽  
...  
Keyword(s):  
B Cell ◽  
Cell Lymphoma ◽  
Prognostic Significance ◽  
B Cell Lymphoma ◽  
Ease Of Use ◽  
Survival Prediction ◽  
Cell Of Origin ◽  
Large B Cell Lymphoma ◽  
High Concordance ◽  
Large B Cell

Purpose Patients with diffuse large B-cell lymphoma (DLBCL) can be divided into prognostic groups based on the cell of origin of the tumor as determined by microarray analysis. Various immunohistochemical algorithms have been developed to replicate these microarray results and/or stratify patients according to survival. This study compares some of those algorithms and also proposes some modifications. Patients and Methods Two-hundred and sixty-two cases of de novo DLBCL treated with rituximab and cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) or CHOP-like therapy were examined. Results The Choi algorithm and Hans algorithm had high concordance with the microarray results. Modifications of the Choi and Hans algorithms for ease of use still retained high concordance with the microarray results. Although the Nyman and Muris algorithms had high concordance with the microarray results, each had a low value for either sensitivity or specificity. The use of LMO2 alone showed the lowest concordance with the microarray results. A new algorithm (Tally) using a combination of antibodies, but without regard to the order of examination, showed the greatest concordance with microarray results. All of the algorithms divided patients into groups with significantly different overall and event-free survivals, but with different hazard ratios. With the exception of the Nyman algorithm, this survival prediction was independent of the International Prognostic Index. Although the Muris algorithm had prognostic significance, it misclassified a large number of cases with activated B-cell type DLBCL. Conclusion The Tally algorithm showed the best concordance with the microarray data while maintaining prognostic significance and ease of use.

scholarly journals Cell-of-origin classification using the Hans and Lymph2Cx algorithms in primary cutaneous large B-cell lymphomas

2022 ◽  
Author(s):  
Anne M. R. Schrader ◽  
Ruben A. L. de Groen ◽  
Rein Willemze ◽  
Patty M. Jansen ◽  
Koen D. Quint ◽  
...  
Keyword(s):  
B Cell ◽  
Cell Lymphoma ◽  
Prognostic Significance ◽  
B Cell Lymphoma ◽  
Large Cell ◽  
Cell Of Origin ◽  
B Cell Lymphomas ◽  
Large B Cell Lymphoma ◽  
And Behavior ◽  
Large B Cell

Abstract Primary cutaneous diffuse large B-cell lymphoma, leg type (PCDLBCL-LT) and primary cutaneous follicle center lymphoma with a diffuse population of large cells (PCFCL-LC) are both primary cutaneous B-cell lymphomas with large-cell morphology (CLBCL) but with different clinical characteristics and behavior. In systemic diffuse large B-cell lymphoma, not otherwise specified (DLBCL-NOS), gene-expression profiling (GEP) revealed two molecular subgroups based on their cell-of-origin (COO) with prognostic significance: the germinal center B-cell-like (GCB) subtype and the activated B-cell-like (ABC) subtype. This study investigated whether COO classification is a useful tool for classification of CLBCL. For this retrospective study, 51 patients with PCDLBCL-LT and 15 patients with PCFCL-LC were analyzed for their COO according to the immunohistochemistry-based Hans algorithm and the NanoString GEP-based Lymph2Cx algorithm. In PCFCL-LC, all cases (100%) classified as GCB by both Hans and Lymph2Cx. In contrast, COO classification in PCDLBCL-LT was heterogeneous. Using Hans, 75% of the PCDLBCL-LT patients classified as non-GCB and 25% as GCB, while Lymph2Cx classified only 18% as ABC, 43% as unclassified/intermediate, and 39% as GCB. These COO subgroups did not differ in the expression of BCL2 and IgM, mutations in MYD88 and/or CD79B, loss of CDKN2A, or survival. In conclusion, PCFCL-LC uniformly classified as GCB, while PCDLBCL-LT classified along the COO spectrum of DLBCL-NOS using the Hans and Lymph2Cx algorithms. In contrast to DLBCL-NOS, the clinical relevance of COO classification in CLBCL using these algorithms has limitations and cannot be used as an alternative for the current multiparameter approach in differentiation of PCDLBCL-LT and PCFCL-LC.

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