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(searched for: doi:10.3816/clml.2011.n.003)
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, P. Desbordes, A. Banjar, , P. Vera, P. Ruminy, F. Jardin, H. Tilly, S. Becker
European Journal of Pediatrics, Volume 45, pp 680-688; doi:10.1007/s00259-017-3907-x

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O. Balagué,
Annals of Oncology, Volume 28, pp 918-920; doi:10.1093/annonc/mdx133

Abstract:
Efforts to understand the heterogeneous group of diffuse large B-cell lymphomas (DLBCL) have led to the identification of two major molecular subtypes based on the gene expression profile (GEP) related to different cells of origin (COO) either in germinal center (GCB) or activated B-cells (ABC) [1, 2]. In addition to the GEP, these two molecular subtypes differ in the activation of different molecular pathways, profile of chromosomal alterations and somatic mutations. GCB tumors rely preferentially on the activation of the PI3K pathway and BCL6 overexpression whereas ABC tumors have a constitutive activation of the NFkB through different mechanisms including the activation of the BCR signaling pathway [3–7]. These biological differences translate into different patient outcomes, with most of the...
Ashley D Staton, Jean L Koff, Qiushi Chen, Turgay Ayer, Christopher R Flowers
Published: 1 September 2015
Future Oncology, Volume 11, pp 2443-2457; doi:10.2217/fon.15.144

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John S. Hall, Suzanne Usher, , Rebekah C. Higgins, Danish Memon, John A. Radford,
The Journal of Molecular Diagnostics, Volume 17, pp 402-411; doi:10.1016/j.jmoldx.2015.03.010

Abstract:
Emerging therapies targeting the molecularly distinct GCB and non-GCB/ABC subtypes of diffuse large B-cell lymphoma (DLBCL) have created the need to develop an accurate subtyping assay for routine use. We investigated the potential of QuantiGene Plex (QGP)-branched DNA signal amplification assay-for DLBCL subtyping. We performed in silico analysis of public DLBCL datasets to develop and validate a naïve Bayes classifier, and migrated the resulting 21-gene classifier to QGP and real-time quantitative PCR (qPCR) assays. Forty DLBCL formalin-fixed, paraffin-embedded tumors of known subtype (20 per subtype by gene expression profiling of paired fresh-frozen tissues) were reclassified, and results for QGP (on 38/40 for 21/21 targets) and qPCR (on 40/40 samples for 19/21 targets) compared for recapitulation of microarray data and classification accuracy. The 21-gene bayesian classifier achieved mean area under the curve values >0.9 on independent validation. QGP showed a higher correlation with microarray data (mean R(2) = 0.66 ± 0.05 versus 0.34 ± 0.07; P < 0.0001) and classification accuracy (92.1% versus 78.9%). The proportion of validated targets was also higher for QGP (85.7% versus 47.4%). The QGP protocol was rapid and simple to perform, at a cost similar to qPCR. These promising preliminary results strongly support ongoing work to develop a QGP companion diagnostic assay for DLBCL subtyping.
Yan Chen, Xiao-Fei Sun, Zi-Jun Zhen, Juan Wang, Jia Zhu, Su-Ying Lu, Fei-Fei Sun, Fei Zhang, Peng-Fei Li, Rui-Qing Cai
Chinese Journal of Cancer, Volume 32, pp 561-566; doi:10.5732/cjc.012.10198

Abstract:
Pediatric diffuse large B-cell lymphoma (DLBCL) is a highly aggressive disease with unique clinical characteristics. This study analyzed the germinal-center type B-cell (GCB) classification and clinical characteristics of Chinese pediatric DLBCL. A total of 76 patients with DLBCL newly diagnosed in Sun Yat-sen University Cancer Center between February 2000 and May 2011, with an age younger than 18 years, were included in the analysis. The male/female ratio was 3.47:1. The median age was 12 years (range, 2 to 18 years), and 47 (61.8%) patients were at least 10 years old. Of the 76 patients, 48 (63.2%) had stage III/IV disease, 9 (11.8%) had bone marrow involvement, 1 (1.3%) had central nervous system (CNS) involvement, and 5 (6.6%) had bone involvement. The GCB classification was assessed in 45 patients: 26 (57.8%) were classified as GCB subtype, and 19 (42.2%) were classified as non-GCB subtype. The modified B-NHL-BFM-90/95 regimen was administered to 50 patients, and the 4-year event-free survival (EFS) rate was 85.8%. Among these 50 patients, 31 were assessed for the GCB classification: 17 (54.8%) were classified as GCB subtype, with a 4-year EFS rate of 88.2%; 14 (45.2%) were classified as non-GCB subtype, with a 4-year EFS rate of 92.9%. Our data indicate that bone marrow involvement and stage III/IV disease are common in Chinese pediatric DLBCL patients, whereas the percentage of patients with the GCB subtype is similar to that of patients with the non-GCB subtype. The modified B-NHL-BFM-90/95 protocol is an active and effective treatment protocol for Chinese pediatric patients with DLBCL.
Murat Ozbalak, , Nukhet Tuzuner, Ayse Salihoglu, A. Emre Eskazan, Seniz Ongoren Aydin, Zafer Baslar, Teoman Soysal, Yildiz Aydin, Anil Barak Dolgun, et al.
Published: 30 July 2013
ISRN Hematology, Volume 2013, pp 1-9; doi:10.1155/2013/908191

Abstract:
The aim of this single-center, retrospective study was to investigate the impact of rituximab, reconsider the validity of International Prognostic Index (IPI), and evaluate the prognostic role of the cell of origin (CoO) in a relatively young cohort. Three hundred twelve diffuse large B cell lymphoma patients (median age: 52) were included. Rituximab significantly improved the 3- and 5-year progression free survival (PFS) (70% versus 65% and 41% versus 36%, resp.; P<0.001) but led only to a slight, insignificant increase in 3- and 5-year overall survival (OS) (71% versus 77.3% and %67 versus 74.5%, resp.; P=0.264). In the young, low risk patient subgroup (aaIPI = 0&1; n=129), rituximab improved 3- and 5-year PFS and OS rates (P<0.001 and P=0.048, resp.). The efficacy of rituximab in young high risk patients was comparable to the literature. CoO data were available in 190 patients. The OS at 3 years was 79% for GC and 64% for non-GC subgroups (P=0.014). To the best of our knowledge, this is the first study which investigated the impact of R-CHOP in the context of CoO and IPI in a relatively young cohort. CoO was not an independent risk factor for prognosis in the multivariate analysis although patients with GC showed a significant survival advantage in the univariate analysis. CoO was also found to be a significant determinant of response in refractory/relapsed patients. Our results confirm the efficacy of rituximab in low and high risk, young patients outside of a randomized clinical trial setting.
Fabrice Jardin,
Lymphoma pp 177-202; doi:10.1007/978-1-62703-408-1_11

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Hee Sang Hwang, Dok Hyun Yoon, Cheolwon Suh, Chan-Sik Park,
Published: 1 January 2013
Blood Research, Volume 48, pp 266-273; doi:10.5045/br.2013.48.4.266

Abstract:
Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous clinicopathological entity, and its molecular classification into germinal center B cell-like (GCB) and activated B cell-like (ABC) subtypes using gene expression profile analysis has been shown to have prognostic significance. Recent attempts have been made to find an association between immunohistochemical findings and molecular subgroup, although the clinical utility of immunohistochemical classification remains uncertain. The clinicopathological features and follow-up data of 68 cases of surgically resected gastrointestinal DLBCL were analyzed. Using the immunohistochemical findings on tissue microarray, the cases were categorized into GCB and non-GCB subtypes according to the algorithms proposed by Hans, Muris, Choi, and Tally. The median patient age was 56 years (range, 26-77 years). Of the 68 cases included, 39.7% (27/68) involved the stomach, and 60.3% (41/68) involved the intestines. The GCB and non-GCB groups sorted according to Hans, Choi, and Tally algorithms, but not the Muris algorithm, were closely concordant (Hans vs. Choi, κ=0.775, P<0.001; Hans vs. Tally, κ=0.724, P<0.001; Choi vs. Tally, κ=0.528, P<0.001). However, there was no prognostic difference between the GCB and non-GCB subtypes, regardless of the algorithm used. On univariate survival analyses, international prognostic index risk group and depth of tumor invasion both had prognostic significance. The Hans, Choi, and Tally algorithms might represent identical DLBCL subgroups, but this grouping did not correlate with prognosis. Further studies may delineate the association between immunohistochemical subgroups and prognosis.
Brian T. Hill, John Sweetenham
Published: 5 January 2012
Leukemia & Lymphoma, Volume 53, pp 763-769; doi:10.3109/10428194.2011.626882

The publisher has not yet granted permission to display this abstract.
, Sin-Ho Jung, Pierluigi Porcu, David Hurd, Jeffrey Johnson, S. Eric Martin, Myron Czuczman, Raymond Lai, Jonathan Said, Amy Chadburn, et al.
Haematologica, Volume 97, pp 758-765; doi:10.3324/haematol.2011.056531

Abstract:
Background A phase II trial of dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin and rituximab (DA-EPOCH-R) from the National Cancer Institute showed promising activity in untreated diffuse large B-cell lymphoma. The Cancer and Leukemia Group B conducted a study to determine if these results could be reproduced in a multi-institutional setting. Design and Methods The study included 69 patients with untreated diffuse large B-cell lymphoma at least 18 years of age and at least stage II. Radiaton therapy was not permitted on study. Median age was 58 years (range 23–83) and 40% had high-intermediate or high International Prognostic Index risk. Immunohistochemical biomarkers for cell of origin and proliferation were performed. Results With a median follow up of 62 months, time to progression and overall survival were 81% and 84%, respectively, and time to progression was 87%, 92% and 54% for low/low-intermediate, high-intermediate and high International Prognostic Index risk groups, respectively, at 5-years and beyond. The time to progression and event-free survival of germinal center B-cell lymphoma were 100% and 94%, respectively, and non-germinal center B-cell GCB diffuse large B-cell lymphoma were 67% and 58%, respectively, at 62 months (germinal center vs. non-germinal center B cell P=0.008). DA-EPOCH-R was tolerated without significant grade 4 non-hematologic toxicities. Conclusions These results provide the first confirmation by a multi-institutional group that DA-EPOCH-R provides high durable remissions in diffuse large B-cell lymphoma and is effective in both germinal center and non-germinal center B-cell subtypes. The trial was registered at ClinicalTrials.Gov (NCT00032019).
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