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Sample records for b-cell lymphoma dlbcl

  1. Role of Immunohistochemistry in Staging Diffuse Large B-cell Lymphoma (DLBCL)

    Science.gov (United States)

    Talaulikar, Dipti; Dahlstrom, Jane Esther; Shadbolt, Bruce; Broomfield, Amy; McDonald, Anne

    2008-01-01

    The use of immunohistochemistry (IHC) in staging bone marrow in non-Hodgkin's lymphoma (NHL) is largely limited to ambiguous cases, particularly those with lymphoid aggregates. Its role in routine clinical practice remains unestablished. This study aimed to determine whether the routine use of IHC in diffuse large B-cell lymphoma (DLBCL) would improve the detection of lymphomatous involvement in the bone marrow. It also sought to determine the impact of IHC on predicting survival compared with routine histological diagnosis using hematoxylin and eosin (H&E), Giemsa, and reticulin staining. The bone marrow trephines of 156 histologically proven DLBCL cases were assessed on routine histology, and IHC using two T-cell markers (CD45RO and CD3), two B-cell markers (CD20 and CD79a), and κ and λ light chains. IHC detected lymphomatous involvement on an additional 11% cases compared with histology alone. Although both routine histology and IHC were good predictors of survival, IHC was better at predicting survival on stepwise multivariate Cox regression analysis. IHC performed routinely on bone marrow trephines has the ability to improve detection of occult lymphoma in experienced hands. Furthermore, it is a better predictor of survival compared with routine histological examination alone. (J Histochem Cytochem 56:893–900, 2008) PMID:18574254

  2. CGCI Investigators Reveal Comprehensive Landscape of Diffuse Large B-Cell Lymphoma (DLBCL) Genomes | Office of Cancer Genomics

    Science.gov (United States)

    Researchers from British Columbia Cancer Agency used whole genome sequencing to analyze 40 DLBCL cases and 13 cell lines in order to fill in the gaps of the complex landscape of DLBCL genomes. Their analysis, “Mutational and structural analysis of diffuse large B-cell lymphoma using whole genome sequencing,” was published online in Blood on May 22. The authors are Ryan Morin, Marco Marra, and colleagues.  

  3. Prevalence and clinical implications of cyclin D1 expression in diffuse large B-cell lymphoma (DLBCL) treated with immunochemotherapy

    DEFF Research Database (Denmark)

    Ok, Chi Young; Xu-Monette, Zijun Y; Tzankov, Alexandar;

    2014-01-01

    BACKGROUND: Cyclin D1 expression has been reported in a subset of patients with diffuse large B-cell leukemia (DLBCL), but studies have been few and generally small, and they have demonstrated no obvious clinical implications attributable to cyclin D1 expression. METHODS: The authors reviewed 1435......1-positive according to immunohistochemistry were also assessed for rearrangements of the cyclin D1 gene (CCND1) using fluorescence in situ hybridization. Gene expression profiling was performed to compare patients who had DLBCL with and without cyclin D1 expression. RESULTS: In total, 30 patients...... patients expressed cyclin D2. Gene expression profiling indicated that 17 tumors were of the germinal center type, and 13 were of the activated B-cell type. Genetic aberrations of B-cell leukemia/lymphoma 2 (BCL2), BCL6, v-myc avian myelocytomatosis viral oncogene homolog (MYC), mouse double minute 2...

  4. Racial differences in treatment and survival in older patients with diffuse large B-cell lymphoma (DLBCL)

    International Nuclear Information System (INIS)

    Diffuse large B-cell lymphoma (DLBCL) comprises 31% of lymphomas in the United States. Although it is an aggressive type of lymphoma, 40% to 50% of patients are cured with treatment. The study objectives were to identify patient factors associated with treatment and survival in DLBCL. Using Surveillance, Epidemiology, and End Results (SEER) registry data linked to Medicare claims, we identified 7,048 patients diagnosed with DLBCL between January 1, 2001 and December 31, 2005. Patients were followed from diagnosis until the end of their claims history (maximum December 31, 2007) or death. Medicare claims were used to characterize the first infused chemo-immunotherapy (C-I therapy) regimen and to identify radiation. Multivariate analyses were performed to identify patient demographic, socioeconomic, and clinical factors associated with treatment and with survival. Outcomes variables in the survival analysis were all-cause mortality, non-Hodgkin's lymphoma (NHL) mortality, and other/unknown cause mortality. Overall, 84% (n = 5,887) received C-I therapy or radiation treatment during the observation period: both, 26%; C-I therapy alone, 53%; and radiation alone, 5%. Median age at diagnosis was 77 years, 54% were female, 88% were white, and 43% had Stage III or IV disease at diagnosis. The median time to first treatment was 42 days, and 92% of these patients had received their first treatment by day 180 following diagnosis. In multivariate analysis, the treatment rate was significantly lower among patients ≥ 80 years old, blacks versus whites, those living in a census tract with ≥ 12% poverty, and extra-nodal disease. Blacks had a lower treatment rate overall (Hazard Ratio [HR] 0.77; P < 0.001), and were less likely to receive treatment within 180 days of diagnosis (Odds Ratio [OR] 0.63; P = 0.002) than whites. In multivariate survival analysis, black race was associated with higher all-cause mortality (HR 1.24; P = 0.01) and other/unknown cause mortality (HR 1

  5. Evaluation of BCL6 and MUM1 Expression in Patients with Diffuse Large B Cell Lymphoma (DLBCL and Their Correlation with Staging and Prognosis of the Disease

    Directory of Open Access Journals (Sweden)

    Hossein Rahimi

    2015-01-01

    Patients with DLBCL have a rapidly growing mass that is located in the neck or abdominal region. Multiple Myeloma Oncogene (MUM1 has an important role in lymphoid cell differentiation. MUM1/IRF4 is as oncogene related to myeloma and translocation (p25; q32, t (6; 14 and leads to a change in the heavy chain of Immunoglobulin (IGH. BCL6 exists in approximately (100% of follicular cell cancer cases, (100% of Burkitt lymphoma, (80% of large B-cell lymphoma, and in more than (80% of nodular lymphocytic Hodgkin lymphoma cases. BCL6 is related to cancers with a high proliferation cell index. In some studies BCL6 is expressed as a prognostic factor in LBCL patients

  6. Mutational profile and prognostic significance of TP53 in diffuse large B-cell lymphoma patients treated with R-CHOP: report from an International DLBCL Rituximab-CHOP Consortium Program Study

    NARCIS (Netherlands)

    Xu-Monette, Z.Y.; Wu, L.; Visco, C.; Tai, Y.C.; Tzankov, A.; Liu, W.M.; Montes-Moreno, S.; Dybkaer, K.; Chiu, A.; Orazi, A.; Zu, Y.; Bhagat, G.; Richards, K.L.; Hsi, E.D.; Zhao, X.F.; Choi, W.W.; Zhao, X.; Krieken, J.H. van; Huang, Q.; Huh, J.; Ai, W.; Ponzoni, M.; Ferreri, A.J.; Zhou, F.; Kahl, B.S.; Winter, J.N.; Xu, W.; Li, J.; Go, R.S.; Li, Y.; Piris, M.A.; Moller, M.B.; Miranda, R.N.; Abruzzo, L.V.; Medeiros, L.J.; Young, K.H.

    2012-01-01

    TP53 mutation is an independent marker of poor prognosis in patients with diffuse large B-cell lymphoma (DLBCL) treated with cyclophosphamide, hydroxydaunorubicin, vincristine, and prednisone (CHOP) therapy. However, its prognostic value in the rituximab immunochemotherapy era remains undefined. In

  7. Clinical Impact of TP53 Gene Mutations in Diffuse Large B-Cell Lymphoma (DLBCL)

    DEFF Research Database (Denmark)

    Young, Ken H; Patten, Nancy; Truong, Sim;

    2009-01-01

    mutations) had significantly decreased median OS (17 months) when compared to patients with Loop L2 (16% of all mutations) or loop-sheet-helix motifs (Loop L1-S10-H2, 20% of all mutations) with median OS of 49 and 50 months, respectively. In contrast to our previous CHOP series study, median survival was...... ratio of 0.69 (GCB vs ABC, 95% CI 0.49-0.98) and 1.60 (TP53 vs wt-TP53, 95% CI 1.10-2.31), respectively. Similar to our previous CHOP study, the TP53 mutation profile, regardless of location, was found to stratify GCB-DLBCL, but not ABC-DLBCL, into molecularly distinct subsets with different clinical...... either the CHOP or Rituxan-CHOP regimen. These findings also provide the rationale and strategies for p53 targeted therapeutic intervention in DLBCL patients. Disclosures: Kahl: Milllennium: Consultancy, Research Funding; Cephalon: Consultancy, Research Funding....

  8. Novel Therapies for Aggressive B-Cell Lymphoma

    Directory of Open Access Journals (Sweden)

    Kenneth A. Foon

    2012-01-01

    Full Text Available Aggressive B-cell lymphoma (BCL comprises a heterogeneous group of malignancies, including diffuse large B-cell lymphoma (DLBCL, Burkitt lymphoma, and mantle cell lymphoma (MCL. DLBCL, with its 3 subtypes, is the most common type of lymphoma. Advances in chemoimmunotherapy have substantially improved disease control. However, depending on the subtype, patients with DLBCL still exhibit substantially different survival rates. In MCL, a mature B-cell lymphoma, the addition of rituximab to conventional chemotherapy regimens has increased response rates, but not survival. Burkitt lymphoma, the most aggressive BCL, is characterized by a high proliferative index and requires more intensive chemotherapy regimens than DLBCL. Hence, there is a need for more effective therapies for all three diseases. Increased understanding of the molecular features of aggressive BCL has led to the development of a range of novel therapies, many of which target the tumor in a tailored manner and are summarized in this paper.

  9. Ocular Adnexal Diffuse Large B-cell LymphomaA Multicenter International Study

    DEFF Research Database (Denmark)

    Munch-Petersen, Helga D; Rasmussen, Peter K; Coupland, Sarah E;

    2015-01-01

    IMPORTANCE: The clinical features of diffuse large B-cell lymphoma (DLBCL) subtype of ocular adnexal lymphoma have not previously been evaluated in a large cohort to our knowledge. OBJECTIVE: To investigate the clinical features of ocular adnexal DLBCL (OA-DLBCL). DESIGN, SETTING, AND PARTICIPANT...

  10. B-cell lymphoma, unclassifiable, with features intermediate between diffuse large B-cell lymphoma and Burkitt lymphoma: Report of a case in the oral cavity

    Directory of Open Access Journals (Sweden)

    Jumana M Jaradat

    2013-01-01

    Full Text Available B-cell lymphoma, unclassifiable, with features intermediate between diffuse large B-cell lymphoma and Burkitt lymphoma (DLBCL/BL is a new category of B-cell lymphoma according to the 4 th edition of the World Health Organization Classification of Tumours of Haematopoietic and Lymphoid Tissues (2008. The following report presents a case of this rare, newly described entity on the palate of a 59 year-old male.

  11. Aggressive B-cell lymphomas: how many categories do we need?

    OpenAIRE

    Said, Jonathan W.

    2012-01-01

    Aggressive B-cell lymphomas are diverse group of neoplasms that arise at different stages of B-cell development and by various mechanisms of neoplastic transformation. The aggressive B-cell lymphomas include many types, subtypes and variants of diffuse large B-cell lymphoma (DLBCL), Burkitt lymphoma (BL), mantle cell lymphoma and its blastoid variant, and B lymphoblastic lymphoma. Differences in histology, cytogenetic and molecular abnormalities, as well as the relationship with the tumor mic...

  12. MYC Negative Rectal B-Cell Lymphoma, Unclassifiable, with Features Intermediate between Diffuse Large B-Cell Lymphoma and Burkitt’s Lymphoma in an Immunocompetent Patient

    OpenAIRE

    Parikh, Jignesh G.; Ted Strom; Ilya Stone

    2013-01-01

    B-cell lymphoma, unclassifiable, with features intermediate between diffuse large B-cell lymphoma and Burkitt’s lymphoma (BLUI) is a recently added entity to the World Health Organization (WHO) classification to address a grey zone between large B-cell lymphoma (DLBCL) and Burkitt’s lymphoma (BL). These are rare aggressive lymphomas, which were previously also known as Burkitt’s-like lymphoma (BLL). BL and BLUI/BLL of the colon mostly involve the ileocecal region. In the rectum, BL and BLUI/B...

  13. B-cell lymphoma, unclassifiable, with features intermediate between diffuse large B-cell lymphoma and classical Burkitt's lymphoma: A case report and review

    Directory of Open Access Journals (Sweden)

    Tabita Joy Chettiankandy

    2016-01-01

    Full Text Available B-cell lymphoma, unclassifiable, with features intermediate between diffuse large B-cell lymphoma (DLBCL and classical Burkitt's lymphoma (BL, is a diagnostic provisional category in the World Health Organization 2008 classification of lymphomas. This category was designed as a measure to accommodate borderline cases that cannot be reliably classified into a single distinct disease entity after all available morphological, immunophenotypical and molecular studies have been performed. Typically, these cases share features intermediate between DLBCL and classical BL or include characteristics of both lymphomas. The rarity of such cases poses a tremendous challenge to both pathologists and oncologists because its differential diagnosis has direct implications for management strategies. In this article, we present a “classical unclassifiable lymphoma with features intermediate between DLBCL and BL” in a young male patient and review of literature.

  14. MicroRNA signatures in B-cell lymphomas

    International Nuclear Information System (INIS)

    Accurate lymphoma diagnosis, prognosis and therapy still require additional markers. We explore the potential relevance of microRNA (miRNA) expression in a large series that included all major B-cell non-Hodgkin lymphoma (NHL) types. The data generated were also used to identify miRNAs differentially expressed in Burkitt lymphoma (BL) and diffuse large B-cell lymphoma (DLBCL) samples. A series of 147 NHL samples and 15 controls were hybridized on a human miRNA one-color platform containing probes for 470 human miRNAs. Each lymphoma type was compared against the entire set of NHLs. BL was also directly compared with DLBCL, and 43 preselected miRNAs were analyzed in a new series of routinely processed samples of 28 BLs and 43 DLBCLs using quantitative reverse transcription-polymerase chain reaction. A signature of 128 miRNAs enabled the characterization of lymphoma neoplasms, reflecting the lymphoma type, cell of origin and/or discrete oncogene alterations. Comparative analysis of BL and DLBCL yielded 19 differentially expressed miRNAs, which were confirmed in a second confirmation series of 71 paraffin-embedded samples. The set of differentially expressed miRNAs found here expands the range of potential diagnostic markers for lymphoma diagnosis, especially when differential diagnosis of BL and DLBCL is required

  15. Gene expression-based risk score in diffuse large B-cell lymphoma.

    OpenAIRE

    Bret, Caroline; Klein, Bernard; Moreaux, Jérôme

    2012-01-01

    International audience Diffuse large B-cell lymphoma (DLBCL) is the most common type of non-Hodgkin lymphoma and displays heterogeneous clinical and molecular characteristics. In this study, high throughput gene expression profiling of DLBCL tumor samples was used to design a 12-gene expression-based risk score (GERS) predictive for patient's overall survival. GERS allowed identifying a high-risk group comprising 46,4% of the DLBCL patients in two independent cohorts (n=414 and n=69). GERS...

  16. Genetic Landscapes of Relapsed and Refractory Diffuse Large B-Cell Lymphomas

    DEFF Research Database (Denmark)

    Morin, Ryan D; Assouline, Sarit; Alcaide, Miguel; Mohajeri, Arezoo; Johnston, Rebecca L; Chong, Lauren; Grewal, Jasleen; Yu, Stephen; Fornika, Daniel; Bushell, Kevin; Nielsen, Torsten Holm; Petrogiannis-Haliotis, Tina; Crump, Michael; Tosikyan, Axel; Grande, Bruno M; MacDonald, David; Rousseau, Caroline; Bayat, Maryam; Sesques, Pierre; Froment, Remi; Albuquerque, Marco; Monczak, Yury; Oros, Kathleen Klein; Greenwood, Celia; Riazalhosseini, Yasser; Arseneault, Madeleine; Camlioglu, Errol; Constantin, André; Pan-Hammarstrom, Qiang; Peng, Roujun; Mann, Koren K; Johnson, Nathalie A

    2015-01-01

    PURPOSE: Relapsed or refractory diffuse large B-cell lymphoma (rrDLBCL) is fatal in 90% of patients, and yet little is known about its biology. EXPERIMENTAL DESIGN: Using exome sequencing, we characterized the mutation profiles of 38 rrDLBCL biopsies obtained at the time of progression after...

  17. Efficacy of adjusted BACOD regimen on the treatment of relapsed refractory diffuse large B cell lymphoma

    Institute of Scientific and Technical Information of China (English)

    龚格格

    2014-01-01

    Objective To compare the efficacy and adverse events of adjusted BACOD(bleomycin,doxorubicin,cyclophosphamide,vincristine,dexamethasone)regimen(continuous intravenous infusion)and conventional BACOD regimen(conventional intravenous drip)in the treatment of relapsed and refractory diffuse large B cell lymphoma(DLBCL).Methods Retrospective analysis of63 cases of relapsed or refractory DLBCL patients was performed,32 patients received conventional BACOD

  18. MYC/BCL2 protein coexpression contributes to the inferior survival of activated B-cell subtype of diffuse large B-cell lymphoma and demonstrates high-risk gene expression signatures

    DEFF Research Database (Denmark)

    Hu, Shimin; Xu-Monette, Zijun Y; Tzankov, Alexander;

    2013-01-01

    Diffuse large B-cell lymphoma (DLBCL) is stratified into prognostically favorable germinal center B-cell (GCB)-like and unfavorable activated B-cell (ABC)-like subtypes based on gene expression signatures. In this study, we analyzed 893 de novo DLBCL patients treated with R-CHOP (rituximab, cyclo...

  19. Prevalence and Clinical Implications of Epstein-Barr Virus Infection in De Novo Diffuse Large B-Cell Lymphoma in Western Countries

    NARCIS (Netherlands)

    Ok, C.Y.; Li, L; Xu-Monette, Z.Y.; Visco, C.; Tzankov, A.; Manyam, G.C.; Montes-Moreno, S.; Dybaer, K.; Chiu, A.; Orazi, A.; Zu, Y.; Bhagat, G.; Chen, J.; Richards, K.L.; Hsi, E.D.; Choi, W.W.; Krieken, J.H.J.M. van; Huh, J.; Ai, W.; Ponzoni, M.; Ferreri, A.J.; Farnen, J.P.; Moller, M.B.; Bueso-Ramos, C.E.; Miranda, R.N.; Winter, J.N.; Piris, M.A.; Medeiros, L.J.; Young, K.H.

    2014-01-01

    PURPOSE: Epstein-Barr virus-positive (EBV+) diffuse large B-cell lymphoma (DLBCL) of the elderly is a variant of DLBCL with worse outcome that occurs most often in East-Asian countries and is uncommon in the Western hemisphere. We studied the largest cohort of EBV+ DLBCL, independent of age, treated

  20. Diffuse large B-cell lymphoma: clinical implications of extranodal versus nodal presentation--a population-based study of 1575 cases

    DEFF Research Database (Denmark)

    Møller, Michael B; Pedersen, Niels T; Christensen, Bjarne E

    2004-01-01

    Differences in genetic origin between nodal and extranodal diffuse large B-cell lymphomas (DLBCL) exist. Using population-based data from the registry of the Danish Lymphoma Group, the present study is the first to analyse clinical implications of nodal versus extranodal presentation of DLBCL. Of...... 4786 newly diagnosed non-Hodgkin's lymphoma patients in a 16-year period, 1575 (33%) had DLBCL. The annual incidence rate was 2.9 per 100 000; 40% were extranodal. The clinical profile of patients with extranodal DLBCL was different from the nodal DLBCL patients. Extranodal DLBCL was associated with...... older age and poorer performance score, but also lower tumour burden. In extranodal DLBCL, 51% of the cases were stage I and 36% were stage IV, whereas the patients were relatively equally distributed between the four stages in nodal DLBCL. For stage I patients, extranodal DLBCL was independently...

  1. Recent Advances in Aggressive Large B-cell Lymphomas: A Comprehensive Review.

    Science.gov (United States)

    Korkolopoulou, Penelope; Vassilakopoulos, Theodoros; Milionis, Vassilios; Ioannou, Maria

    2016-07-01

    Diffuse large B-cell lymphoma (DLBCL) is an aggressive disease with considerable heterogeneity reflected in the 2008 World Health Organization classification. In recent years, genome-wide assessment of genetic and epigenetic alterations has shed light upon distinct molecular subsets linked to dysregulation of specific genes or pathways. Besides fostering our knowledge regarding the molecular complexity of DLBCL types, these studies have unraveled previously unappreciated genetic lesions, which may be exploited for prognostic and therapeutic purposes. Following the last World Health Organization classification, we have witnessed the emergence of new variants of specific DLBCL entities, such as CD30 DLBCL, human immunodeficiency virus-related and age-related variants of plasmablastic lymphoma, and EBV DLBCL arising in young patients. In this review, we will present an update on the clinical, pathologic, and molecular features of DLBCL incorporating recently gained information with respect to their pathobiology and prognosis. We will emphasize the distinctive features of newly described or emerging variants and highlight advances in our understanding of entities presenting a diagnostic challenge, such as T-cell/histiocyte-rich large B-cell lmphoma and unclassifiable large B-cell lymphomas. Furthermore, we will discuss recent advances in the genomic characterization of DLBCL, as they may relate to prognostication and tailored therapeutic intervention. The information presented in this review derives from English language publications appearing in PubMed throughout December 2015. For a complete outline of this paper, please visit: http://links.lww.com/PAP/A12. PMID:27271843

  2. B-cell-specific conditional expression of Myd88p.L252P leads to the development of diffuse large B-cell lymphoma in mice.

    Science.gov (United States)

    Knittel, Gero; Liedgens, Paul; Korovkina, Darya; Seeger, Jens M; Al-Baldawi, Yussor; Al-Maarri, Mona; Fritz, Christian; Vlantis, Katerina; Bezhanova, Svetlana; Scheel, Andreas H; Wolz, Olaf-Oliver; Reimann, Maurice; Möller, Peter; López, Cristina; Schlesner, Matthias; Lohneis, Philipp; Weber, Alexander N R; Trümper, Lorenz; Staudt, Louis M; Ortmann, Monika; Pasparakis, Manolis; Siebert, Reiner; Schmitt, Clemens A; Klatt, Andreas R; Wunderlich, F Thomas; Schäfer, Stephan C; Persigehl, Thorsten; Montesinos-Rongen, Manuel; Odenthal, Margarete; Büttner, Reinhard; Frenzel, Lukas P; Kashkar, Hamid; Reinhardt, H Christian

    2016-06-01

    The adaptor protein MYD88 is critical for relaying activation of Toll-like receptor signaling to NF-κB activation. MYD88 mutations, particularly the p.L265P mutation, have been described in numerous distinct B-cell malignancies, including diffuse large B-cell lymphoma (DLBCL). Twenty-nine percent of activated B-cell-type DLBCL (ABC-DLBCL), which is characterized by constitutive activation of the NF-κB pathway, carry the p.L265P mutation. In addition, ABC-DLBCL frequently displays focal copy number gains affecting BCL2 Here, we generated a novel mouse model in which Cre-mediated recombination, specifically in B cells, leads to the conditional expression of Myd88(p.L252P) (the orthologous position of the human MYD88(p.L265P) mutation) from the endogenous locus. These mice develop a lymphoproliferative disease and occasional transformation into clonal lymphomas. The clonal disease displays the morphologic and immunophenotypical characteristics of ABC-DLBCL. Lymphomagenesis can be accelerated by crossing in a further novel allele, which mediates conditional overexpression of BCL2 Cross-validation experiments in human DLBCL samples revealed that both MYD88 and CD79B mutations are substantially enriched in ABC-DLBCL compared with germinal center B-cell DLBCL. Furthermore, analyses of human DLBCL genome sequencing data confirmed that BCL2 amplifications frequently co-occurred with MYD88 mutations, further validating our approach. Finally, in silico experiments revealed that MYD88-mutant ABC-DLBCL cells in particular display an actionable addiction to BCL2. Altogether, we generated a novel autochthonous mouse model of ABC-DLBCL that could be used as a preclinical platform for the development and validation of novel therapeutic approaches for the treatment of ABC-DLBCL. PMID:27048211

  3. Differential regulation of mTOR signaling determines sensitivity to AKT inhibition in diffuse large B cell lymphoma

    OpenAIRE

    Ezell, Scott A.; Wang, Suping; Bihani, Teeru; Lai, Zhongwu; Grosskurth, Shaun E.; Tepsuporn, Suprawee; Davies, Barry R; Huszar, Dennis; Byth, Kate F.

    2016-01-01

    Agents that target components of the PI3K/AKT/mTOR pathway are under investigation for the treatment of diffuse large B cell lymphoma (DLBCL). Given the highly heterogeneous nature of DLBCL, it is not clear whether all subtypes of DLBCL will be susceptible to PI3K pathway inhibition, or which kinase within this pathway is the most favorable target. Pharmacological profiling of a panel of DLBCL cell lines revealed a subset of DLBCL that was resistant to AKT inhibition. Strikingly, sensitivity ...

  4. Investigation of MGMT and DAPK1 methylation patterns in diffuse large B-cell lymphoma using allelic MSP-pyrosequencing

    DEFF Research Database (Denmark)

    Kristensen, Lasse Sommer; Treppendahl, Marianne Bach; Asmar, Fazila;

    2013-01-01

    The tumor suppressor genes MGMT and DAPK1 become methylated in several cancers including diffuse large B-cell lymphoma (DLBCL). However, allelic methylation patterns have not been investigated in DLBCL. We developed a fast and cost-efficient method for the analysis of allelic methylation based on...

  5. Clinicopathological characteristics and prognostic analysis of 92 cases with primary gastrointestinal diffuse large B-cell lymphoma

    Institute of Scientific and Technical Information of China (English)

    冯佳

    2014-01-01

    Objective To analyze the clinical and pathological features,molecular biological markers and prognosis of primary gastrointestinal diffuse large B-cell lymphoma(DLBCL).Methods A retrospective study was conducted in 92 cases of primary gastrointestinal DLBCL.The data of clinical characteristics,pathological and immunohistochemical features were analyzed.The relationship between different factors at diagnosis and prognosis were

  6. Mutational and structural analysis of diffuse large B-cell lymphoma using whole genome sequencing | Office of Cancer Genomics

    Science.gov (United States)

    Abstract: Diffuse large B-cell lymphoma (DLBCL) is a genetically heterogeneous cancer comprising at least two molecular subtypes that differ in gene expression and distribution of mutations. Recently, application of genome/exome sequencing and RNA-seq to DLBCL has revealed numerous genes that are recurrent targets of somatic point mutation in this disease.

  7. Inhibition of COP9-signalosome (CSN) deneddylating activity and tumor growth of diffuse large B-cell lymphomas by doxycycline

    OpenAIRE

    Pulvino, Mary; Chen, Luojing; Oleksyn, David; Li, Jing; Compitello, George; Rossi, Randy; Spence, Stephen; Balakrishnan, Vijaya; Jordan, Craig; Poligone, Brian; Casulo, Carla; Burack, Richard; Shapiro, Joel L.; Bernstein, Steven; Friedberg, Jonathan W.

    2015-01-01

    In searching for small-molecule compounds that inhibit proliferation and survival of diffuse large B-cell lymphoma (DLBCL) cells and may, therefore, be exploited as potential therapeutic agents for this disease, we identified the commonly used and well-tolerated antibiotic doxycycline as a strong candidate. Here, we demonstrate that doxycycline inhibits the growth of DLBCL cells both in vitro and in mouse xenograft models. In addition, we show that doxycycline accumulates in DLBCL cells to hi...

  8. Clinical and biological aspects of aggressive B-cell non-Hodgkin lymphoma in adolescents and young adults

    OpenAIRE

    Coso D; Garciaz S; Bouabdallah R

    2015-01-01

    Diane Coso, Sylvain Garciaz, Réda BouabdallahDepartment of Hematology, Cancer Center Institut J. Paoli-I. Calmettes, University of La Méditerranée, Marseille, FranceAbstract: Non-Hodgkin lymphomas (NHLs) are one of the most frequent malignancies in adolescents and young adults (AYA). Among NHLs, Burkitt's lymphoma (BL) represents approximately 40% while diffuse large B-cell lymphoma (DLBCL) accounts for nearly 20% of cases. Primary mediastinal B-cell lymphoma is a var...

  9. The relationship between HLA class II polymorphisms and somatic deletions in testicular B cell lymphomas of Dutch patients

    NARCIS (Netherlands)

    Riemersma, SA; Jordanova, ES; Haasnoot, GW; Drabbels, J; Schuuring, E; Schreuder, GMT; Kluin, PM

    2006-01-01

    Several risk factors including immune deficiencies, infections, and autoimmune diseases have been established for non-Hodgkin's lymphoma (NHL). For diffuse large B cell lymphoma (DLBCL), the most common type of lymphoma, no risk factors have been described, which may be due to the intrinsic heteroge

  10. Pathophysiological significance and therapeutic targeting of germinal center kinase in diffuse large B-cell lymphoma.

    Science.gov (United States)

    Matthews, Julie Marie; Bhatt, Shruti; Patricelli, Matthew P; Nomanbhoy, Tyzoon K; Jiang, Xiaoyu; Natkunam, Yasodha; Gentles, Andrew J; Martinez, Ezequiel; Zhu, Daxing; Chapman, Jennifer Rose; Cortizas, Elena; Shyam, Ragini; Chinichian, Shideh; Advani, Ranjana; Tan, Li; Zhang, Jianming; Choi, Hwan Geun; Tibshirani, Robert; Buhrlage, Sara J; Gratzinger, Dita; Verdun, Ramiro; Gray, Nathanael S; Lossos, Izidore S

    2016-07-14

    Diffuse large B-cell lymphoma (DLBCL) is the most common subtype of non-Hodgkin lymphoma, yet 40% to 50% of patients will eventually succumb to their disease, demonstrating a pressing need for novel therapeutic options. Gene expression profiling has identified messenger RNAs that lead to transformation, but critical events transforming cells are normally executed by kinases. Therefore, we hypothesized that previously unrecognized kinases may contribute to DLBCL pathogenesis. We performed the first comprehensive analysis of global kinase activity in DLBCL, to identify novel therapeutic targets, and discovered that germinal center kinase (GCK) was extensively activated. GCK RNA interference and small molecule inhibition induced cell-cycle arrest and apoptosis in DLBCL cell lines and primary tumors in vitro and decreased the tumor growth rate in vivo, resulting in a significantly extended lifespan of mice bearing DLBCL xenografts. GCK expression was also linked to adverse clinical outcome in a cohort of 151 primary DLBCL patients. These studies demonstrate, for the first time, that GCK is a molecular therapeutic target in DLBCL tumors and that inhibiting GCK may significantly extend DLBCL patient survival. Because the majority of DLBCL tumors (∼80%) exhibit activation of GCK, this therapy may be applicable to most patients. PMID:27151888

  11. Microarray-based classification of diffuse large B-cell lymphoma

    DEFF Research Database (Denmark)

    Poulsen, Christian Bjørn; Borup, Rehannah; Nielsen, Finn Cilius;

    2005-01-01

    OBJECTIVE: Hierarchical clusterings of diffuse large B-cell lymphoma (DLBCL) based on gene expression signatures have previously been used to classify DLBCL into Germinal Center B-cell (GCB) and Activated B-cell (ABC) types. To examine if it was feasible to perform a cross-platform validation on...... of classifier genes was generated by analysis of 34 patients that were consistently classified as GCB or ABC in the above analyses. Seventy-eight genes were selected and demonstrated on two previously published data sets (Shipp et al. Nat Med 2002;8:68-74 and Houldsworth et al. Blood 2004...

  12. Colorimetric In Situ Hybridization Identifies MYC Gene Signal Clusters Correlating With Increased Copy Number, mRNA, and Protein in Diffuse Large B-cell Lymphoma

    OpenAIRE

    Valentino, Carlo; Kendrick, Samantha; Johnson, Nathalie; Gascoyne, Randy; Chan, Wing C.; Weisenburger, Dennis; Braziel, Rita; Cook, James R.; Tubbs, Raymond; Campo, Elias; Rosenwald, Andreas; Ott, German; Delabie, Jan; Jaffe, Elaine; Zhang, Wenjun

    2013-01-01

    Abnormalities of the MYC oncogene on chromosome 8 are characteristic of Burkitt lymphoma and other aggressive B-cell lymphomas, including diffuse large B-cell lymphoma (DLBCL). We recently described a colorimetric in situ hybridization (CISH) method for detecting extra copies of the MYC gene in DLBCL and the frequent occurrence of excess copies of discrete MYC signals in the context of diploidy or polyploidy of chromosome 8, which correlated with increased mRNA signals. We further observed en...

  13. Expressions of glucose transporter Types 1 and 3 and hexokinase-II in diffuse large B-cell lymphoma and other B-cell non-Hodgkin's lymphomas

    Energy Technology Data Exchange (ETDEWEB)

    Shim, Hye Kyung [Department of Nuclear Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine (Korea, Republic of); Lee, Won Woo [Department of Nuclear Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine (Korea, Republic of); Institute of Radiation Medicine, Medical Research Center, Seoul National University (Korea, Republic of)], E-mail: wwlee@snu.ac.kr; Park, So Yeon [Department of Nuclear Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine (Korea, Republic of); Kim, Haeryoung [Department of Pathology, Seoul National University Bundang Hospital, Seoul National University College of Medicine (Korea, Republic of); So, Young [Department of Nuclear Medicine, Konkuk University School of Medicine (Korea, Republic of); Kim, Sang Eun [Department of Nuclear Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine (Korea, Republic of); Institute of Radiation Medicine, Medical Research Center, Seoul National University (Korea, Republic of)

    2009-02-15

    Introduction: Diffuse large B-cell lymphoma (DLBCL) has been reported to show higher uptake of 2-deoxy-2-F18-fluoro-D-glucose (FDG) by positron emission tomography than other B-cell non-Hodgkin's lymphomas (non-DLBCL). The authors addressed the mechanism of FDG uptake in DLBCL by immunostaining for glucose transporter Types 1 (Glut-1) and 3 (Glut-3) and hexokinase-II (HK-II) in excised lymphoma tissues. Methods: Sixteen B-cell non-Hodgkin's lymphoma patients (11 DLBCL and 5 non-DLBCL patients) were included in the study because the lymphoma tissues obtained by excision were eligible for immunostaining. The expressions of Glut-1, Glut-3 and HK-II were assessed regarding the percentages of positively stained lymphoma cells (%expression), the staining intensities (none=0, weak=1, moderate=2 and strong=3) and the staining patterns (membranous or cytoplasmic) and compared between DLBCL and non-DLBCL. Results: Glut-1 was not expressed at all in DLBCL or non-DLBCL, and their Glut-3 expressions were not significantly different (P>.05) with respect to %expression (mean{+-}S.E.M., 73.6{+-}7.3% vs. 72.0{+-}3.7%), staining intensity (2.5{+-}0.2 vs. 2.6{+-}0.2) and staining pattern (membranous pattern dominant; 54.5% vs. 60.0%). However, DLBCL expressed more HK-II than non-DLBCL, i.e., %expression (45.2{+-}11.5% vs. 17.0{+-}15.8%, P=.0275) and staining intensity (2.3{+-}0.2 vs. 0.6{+-}0.4, P=.0032). HK-II showed a cytoplasmic location in DLBCL and non-DLBCL. Conclusions: HK-II and Glut-3 contribute significantly to FDG uptake in DLBCL. DLBCL may have higher FDG uptake because it expresses more HK-II, whereas Glut-1 appears to play no role in FDG uptake in B-cell non-Hodgkin's lymphoma.

  14. Clinicopathological Analysis of B Cell Lymphomas, Unclassifiable; with Features Intermediate Between Diffuse Large B-Cell Lymphoma and Burkitt Lymphoma in a Tertiary Care Hospital in Southern India.

    Science.gov (United States)

    Selvi, Subramanian Kalaivani; Kar, Rakhee; Basu, Debdatta; Jacob, Sajini Elizabeth; Dubashi, Biswajit

    2016-06-01

    B-cell lymphomas, unclassifiable; with features intermediate between large B-cell lymphoma and Burkitt lymphoma (BCLu-DLBCL/BL) is a new entity included in the recent World Health Organization (WHO) classification of Tumours of the Hematopoietic and Lymphoid Tissues (2008) to overcome the problems of difficulty in classifying certain lymphomas having overlapping morphological, immunophenotypical and genetic features. To study the clinicopathological profile of BCLu-DLBCL/BL. Cross-sectional study over 3 year period in the Haematology section of Department of Pathology in a large teaching hospital in Southern India from January 2011 to December 2013. All the cases reported as BCLu-DLBCL/BL were collected and the clinical, morphological and immunohistochemical parameters were analyzed. Descriptive statistics. There were seven cases, four males and three females, of age ranging from 20 to 70 years. Five cases had extranodal involvement. Four cases had Burkitt morphology with strong Bcl2 positivity and absent CD10 expression. One case had the morphology and immunophenotype that of typical BL, along with strong positivity to Bcl2 suggesting a double hit hypothesis. Two cases had morphology and immunophenotype of BL with low Ki 67. Three patients on follow up had adverse outcome. BCLu-DLBCL/BL, a provisional category in WHO 2008 is useful in classifying the cases not meeting the criteria for classical BL or DLBCL. Each of these cases was interesting with different sites of involvement, different morphological features and immunophenotype with most of the patients on follow up ending with a grave prognosis. PMID:27065578

  15. Prognostic significance of peripheral monocytic myeloid-derived suppressor cells and monocytes in patients newly diagnosed with diffuse large b-cell lymphoma

    OpenAIRE

    Wu, Chongyang; Wu, Xiangyang; Zhang, Xiaoni; Chai, Ye; Guo, Qi; Li, Lijuan; Yue, Lingling; Bai, Jun; Wang, Zhiping; Zhang, Liansheng

    2015-01-01

    Objective: The revised International Prognostic Index (R-IPI) aids in predicting the prognosis of patients with diffuse large B cell lymphoma (DLBCL), but R-IPI yields no significant differences in assessing different subtypes of DLBCL. It is necessary to identify patients with a high-risk of DLBCL and alternative therapy should be delivered as early as possible. Methods: In total, 144 patients newly diagnosed with DLBCL including 63 GCB-DLBCL and 81 non-GCB-DLBCL and 30 healthy controls were...

  16. Outcome of children and adolescents with Burkitt lymphoma and diffuse large B cell lymphoma treated with a modified NHL-BFM-90 protocol

    Institute of Scientific and Technical Information of China (English)

    孙晓非

    2014-01-01

    Objective To evaluate the efficacy of a modified NHL-BFM-90 protocol in childhood and adolescence with Burkitt lymphoma(BL)and diffuse large B-cell lymphoma(DLBCL).Methods A total of 138 de novo patients with BL and DLBCL were enrolled.All patients were stratified into low(R1),intermediate(R2)and high risk(R3)groups based on the stage,chemotherapy

  17. Clinical and biological aspects of aggressive B-cell non-Hodgkin lymphoma in adolescents and young adults

    OpenAIRE

    Bouabdallah, Réda

    2015-01-01

    Diane Coso, Sylvain Garciaz, Réda BouabdallahDepartment of Hematology, Cancer Center Institut J. Paoli-I. Calmettes, University of La Méditerranée, Marseille, FranceAbstract: Non-Hodgkin lymphomas (NHLs) are one of the most frequent malignancies in adolescents and young adults (AYA). Among NHLs, Burkitt's lymphoma (BL) represents approximately 40% while diffuse large B-cell lymphoma (DLBCL) accounts for nearly 20% of cases. Primary mediastinal B-cell l...

  18. Combinatorial BTK and MALT1 inhibition augments killing of CD79 mutant diffuse large B cell lymphoma

    OpenAIRE

    Nagel, Daniel; Bognar, Miriam; Eitelhuber, Andrea C; Kutzner, Kerstin; Vincendeau, Michelle; Krappmann, Daniel

    2015-01-01

    Survival of activated B cell-subtype (ABC) of diffuse large B cell lymphoma (DLBCL) is driven by chronic B cell receptor (BCR) signaling that activates the canonical NF-κB pathway. Inhibition of BTK by Ibrutinib has been shown to kill ABC DLBCL cells that carry activating mutations in the BCR adaptor CD79. However, mutations in BTK or in downstream components such as CARMA1/CARD11 can render lymphomas Ibrutinib resistant. Therefore, we assessed here the simultaneous inhibition of BTK and the ...

  19. Clinical Implications of Phosphorylated STAT3 Expression in de novo Diffuse Large B-cell Lymphoma

    DEFF Research Database (Denmark)

    Ok, Chi Y; Chen, Jiayu; Xu-Monette, Ziju;

    2014-01-01

    phosphorylated STAT3 (pSTAT3) on prognosis are limited. EXPERIMENTAL DESIGN: We evaluated expression of pSTAT3 in de novo DLBCL using immunohistochemistry, gene expression profiling (GEP), and gene set enrichment analysis (GSEA). Results were analyzed in correlation with cell-of-origin (COO), critical lymphoma......PURPOSE: Activated signal transducer and activator of transcription 3 (STAT3) regulates tumor growth, invasion, cell proliferation, angiogenesis, immune response, and survival. Data regarding expression of phosphorylated (activated) STAT3 in diffuse large B-cell lymphoma (DLBCL) and the impact of...... biomarkers, and genetic translocations. RESULTS: pSTAT3 expression was observed in 16% of DLBCL and was associated with advanced stage, multiple extranodal sites of involvement, activated B-cell-like (ABC) subtype, MYC expression, and MYC/BCL2 expression. Expression of pSTAT3 predicted inferior overall...

  20. Diffuse large B-cell lymphoma of the ocular adnexal region

    DEFF Research Database (Denmark)

    Rasmussen, Peter Kristian; Ralfkiaer, Elisabeth; Prause, Jan U;

    2013-01-01

    Purpose: To characterize the clinicopathological features of diffuse large B-cell lymphoma (DLBCL) of the ocular adnexal region. Methods: The present series of orbital and adnexal DLBCLs were found by searching the Danish Registry of Pathology between 1980 and 2009. Histological specimens were re......-evaluated using a panel of monoclonal antibodies. Clinical files from all patients with confirmed DLBCL were collected. Results: A total of 34 patients with DLBCL of the ocular adnexal region were identified. Eighteen of the patients were men. The patients had a median age of 78 years (range 35-97 years). Ninety......, concordant bone marrow involvement and the International Prognostic Index (IPI) score were prognostic factors for OS. Conclusions: Diffuse large B-cell lymphoma of the ocular adnexal region is mainly prevalent in elderly patients. Most patients had unilateral orbital involvement. The overall prognosis is...

  1. Safety and Tolerability Study of PCI-32765 in B Cell Lymphoma and Chronic Lymphocytic Leukemia

    Science.gov (United States)

    2016-04-26

    B-cell Chronic Lymphocytic Leukemia; Small Lymphocytic Lymphoma; Diffuse Well-differentiated Lymphocytic Lymphoma; B Cell Lymphoma; Follicular Lymphoma,; Mantle Cell Lymphoma; Non-Hodgkin's Lymphoma; Waldenstrom Macroglobulinemia; Burkitt Lymphoma; B-Cell Diffuse Lymphoma

  2. Diffuse large B-cell lymphoma patient-derived xenograft models capture the molecular and biological heterogeneity of the disease.

    Science.gov (United States)

    Chapuy, Bjoern; Cheng, Hongwei; Watahiki, Akira; Ducar, Matthew D; Tan, Yuxiang; Chen, Linfeng; Roemer, Margaretha G M; Ouyang, Jing; Christie, Amanda L; Zhang, Liye; Gusenleitner, Daniel; Abo, Ryan P; Farinha, Pedro; von Bonin, Frederike; Thorner, Aaron R; Sun, Heather H; Gascoyne, Randy D; Pinkus, Geraldine S; van Hummelen, Paul; Wulf, Gerald G; Aster, Jon C; Weinstock, David M; Monti, Stefano; Rodig, Scott J; Wang, Yuzhuo; Shipp, Margaret A

    2016-05-01

    Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous disease defined by transcriptional classifications, specific signaling and survival pathways, and multiple low-frequency genetic alterations. Preclinical model systems that capture the genetic and functional heterogeneity of DLBCL are urgently needed. Here, we generated and characterized a panel of large B-cell lymphoma (LBCL) patient-derived xenograft (PDX) models, including 8 that reflect the immunophenotypic, transcriptional, genetic, and functional heterogeneity of primary DLBCL and 1 that is a plasmablastic lymphoma. All LBCL PDX models were subjected to whole-transcriptome sequencing to classify cell of origin and consensus clustering classification (CCC) subtypes. Mutations and chromosomal rearrangements were evaluated by whole-exome sequencing with an extended bait set. Six of the 8 DLBCL models were activated B-cell (ABC)-type tumors that exhibited ABC-associated mutations such as MYD88, CD79B, CARD11, and PIM1. The remaining 2 DLBCL models were germinal B-cell type, with characteristic alterations of GNA13, CREBBP, and EZH2, and chromosomal translocations involving IgH and either BCL2 or MYC Only 25% of the DLBCL PDX models harbored inactivating TP53 mutations, whereas 75% exhibited copy number alterations of TP53 or its upstream modifier, CDKN2A, consistent with the reported incidence and type of p53 pathway alterations in primary DLBCL. By CCC criteria, 6 of 8 DLBCL PDX models were B-cell receptor (BCR)-type tumors that exhibited selective surface immunoglobulin expression and sensitivity to entospletinib, a recently developed spleen tyrosine kinase inhibitor. In summary, we have established and characterized faithful PDX models of DLBCL and demonstrated their usefulness in functional analyses of proximal BCR pathway inhibition. PMID:26773040

  3. Clinicopathological prognostic factors of 24 patients with B-cell lymphoma, unclassifiable, with features intermediate between diffuse large B-cell lymphoma and Burkitt lymphoma.

    Science.gov (United States)

    Miyamoto, Ken-Ichi; Kobayashi, Yukio; Maeshima, Akiko Miyagi; Taniguchi, Hirokazu; Nomoto, Junko; Kitahara, Hideaki; Fukuhara, Suguru; Munakata, Wataru; Maruyama, Dai; Tobinai, Kensei

    2016-06-01

    B-cell lymphoma, unclassifiable, with features intermediate between diffuse large B-cell lymphoma and Burkitt lymphoma (iBL/DLBCL), is a rare, but an aggressive subtype. In iBL/DLBCL, clinicopathological prognostic factors, including MYC and BCL2 translocations (double hit translocation, DHT) and the expression of both MYC and BCL2 (double hit score 2, DHS2), have not been studied thoroughly. We retrospectively analyzed the prognostic impact of clinicopathological factors, including MYC split, IGH/BCL2 fusion, MYC and BCL2 expressions, in 24 iBL/DLBCL patients (median age: 47 years). Fifteen patients (62 %) underwent intensive chemotherapy, and nine patients (38 %) underwent rituximab-cyclophosphamide, doxorubicin, vincristine, and prednisolone (R-CHOP). The 5-year progression-free (PFS) and overall survival (OS) rates of intensive chemotherapy and R-CHOP were 57 and 72 %, respectively. PFS was significantly shorter in patients with high IPI score (P < .0001), stage IV (P = .001), aged ≥60 years (P = .042), IGH/BCL2 fusion (P = .029), DHS2 (P = .015), and DHT (P = .03). OS was significantly shorter in patients with high IPI score (P < .0001) and aged ≥60 years (P = .008). In iBL/DLBCL, IGH/BCL2 fusion, DHS2, and DHT were pathological prognostic factors for poor PFS, while IPI remained as more predictive for PFS and OS. PMID:27095041

  4. 18F-fluorodeoxyglucose-positron emission tomography/computed tomography after one cycle of chemotherapy in patients with diffuse large B-cell lymphoma

    DEFF Research Database (Denmark)

    Mylam, Karen Juul; Kostakoglu, Lale; Hutchings, Martin;

    2015-01-01

    We evaluated the predictive value of interim positon emission tomography (I-PET) after one course of chemoimmunotherapy in patients with newly diagnosed diffuse large B-cell lymphoma (DLBCL). One hundred and twelve patients with DLBCL were enrolled. All patients had PET/computed tomography (CT) s...

  5. MDM2 phenotypic and genotypic profiling, respective to TP53 genetic status, in diffuse large B-cell lymphoma patients treated with rituximab-CHOP immunochemotherapy

    DEFF Research Database (Denmark)

    Xu-Monette, Zijun Y; Møller, Michael; Tzankov, Alexander; Montes-Moreno, Santiago; Hu, Wenwei; Manyam, Ganiraju C; Kristensen, Louise; Fan, Lei; Visco, Carlo; Dybkær, Karen; Chiu, April; Tam, Wayne; Zu, Youli; Bhagat, Govind; Richards, Kristy L; Hsi, Eric D; Choi, William W L; van Krieken, J Han; Huang, Qin; Huh, Jooryung; Ai, Weiyun; Ponzoni, Maurilio; Ferreri, Andrés J M; Winter, Jane N; Wu, Lin; Zhao, Xiaoying; Go, Ronald S; Wang, Sa A; Bueso-Ramos, Carlos E; Li, Yong; Piris, Miguel A; Medeiros, L Jeffrey; Young, Ken H

    2013-01-01

    MDM2 is a key negative regulator of the tumor suppressor p53, however, the prognostic significance of MDM2 overexpression in diffuse large B-cell lymphoma (DLBCL) has not been defined convincingly. In a p53-genetically defined large cohort of de novo DLBCL patients treated with R-CHOP chemotherap...

  6. Significance of microRNA-146b-5p in dif-fuse large B-cell lymphoma and its relationship with risk assessment

    Institute of Scientific and Technical Information of China (English)

    曹其伟

    2013-01-01

    Objective To study the expression of miR-146b-5p in diffuse large B cell lymphoma(DLBCL),and its rela-tionship with risk assessment. Methods 62 cases of nod-al DLBCL with follow-up data were collected from Shanxi

  7. High-resolution copy number analysis of paired normal-tumor samples from diffuse large B cell lymphoma.

    Science.gov (United States)

    Sebastián, Elena; Alcoceba, Miguel; Martín-García, David; Blanco, Óscar; Sanchez-Barba, Mercedes; Balanzategui, Ana; Marín, Luis; Montes-Moreno, Santiago; González-Barca, Eva; Pardal, Emilia; Jiménez, Cristina; García-Álvarez, María; Clot, Guillem; Carracedo, Ángel; Gutiérrez, Norma C; Sarasquete, M Eugenia; Chillón, Carmen; Corral, Rocío; Prieto-Conde, M Isabel; Caballero, M Dolores; Salaverria, Itziar; García-Sanz, Ramón; González, Marcos

    2016-01-01

    Copy number analysis can be useful for assessing prognosis in diffuse large B cell lymphoma (DLBCL). We analyzed copy number data from tumor samples of 60 patients diagnosed with DLBCL de novo and their matched normal samples. We detected 63 recurrent copy number alterations (CNAs), including 33 gains, 30 losses, and nine recurrent acquired copy number neutral loss of heterozygosity (CNN-LOH). Interestingly, 20 % of cases acquired CNN-LOH of 6p21 locus, which involves the HLA region. In normal cells, there were no CNAs but we observed CNN-LOH involving some key lymphoma regions such as 6p21 and 9p24.1 (5 %) and 17p13.1 (2.5 %) in DLBCL patients. Furthermore, a model with some specific CNA was able to predict the subtype of DLBCL, 1p36.32 and 10q23.31 losses being restricted to germinal center B cell-like (GCB) DLBCL. In contrast, 8p23.3 losses and 11q24.3 gains were strongly associated with the non-GCB subtype. A poor prognosis was associated with biallelic inactivation of TP53 or 18p11.32 losses, while prognosis was better in cases carrying 11q24.3 gains. In summary, CNA abnormalities identify specific DLBCL groups, and we describe CNN-LOH in germline cells from DLBCL patients that are associated with genes that probably play a key role in DLBCL development. PMID:26573278

  8. Primary Breast Mucosa-Associated Lymphoid Tissue (MALT Lymphoma Transformation to Diffuse Large B-cell Lymphoma: A Case Report

    Directory of Open Access Journals (Sweden)

    Şerife Hülya Arslan

    2012-09-01

    Full Text Available Primary non-Hodgkin’s lymphoma (NHL of the breast constitutes 0.04%-0.53% of all malignancies and 2.2% of extra nodal lymphomas. In total, 7%-8% of all B-cell lymphomas are the mucosa-associated lymphoid tissue (MALT type, of which up to 50% of primary gastric MALT lymphoma. Herein we present a patient with breast MALT lymphoma that transformed to diffuse large B-cell lymphoma (DLBCL. A 69-year-old female presented with a mass on her left breast. Physical examination showed a 3 × 3-cm mass located 1 cm from the areola on the upper lateral quadrant of the breast at the 1 o’clock position, which was fixed and firm. Excisional biopsy was performed and pathologic examination of the specimen showed MALT lymphoma transformation to DLBCL. The patient was staged as II-EA. The rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone (R-CHOP protocol was scheduled as treatment. Following 6 courses of R-CHOP, 2 additional courses of rituximab were administered. Positron emission tomography (PET-CT was done at the end of the treatment. PET showed that the patient was in complete remission. At the time this report was written, the patient was being followed-up at the outpatient clinic on a regular basis. Lymphoma of the breast is a rarity among malignant tumors of the breast. The most common type of lymphoma is DLBCL. Breast MALT lymphoma is extremely rare. Primary MALT lymphoma of the breast can transform from low grade to high grade and recurrence is possible; therefore, such patients should be monitored carefully for transformation.

  9. The CXCR4 antagonist plerixafor enhances the effect of rituximab in diffuse large B-cell lymphoma cell lines

    DEFF Research Database (Denmark)

    Reinholdt, Linn; Laursen, Maria Bach; Schmitz, Alexander;

    2016-01-01

    strategies are needed. Antagonizing the CXCR4 receptor might be promising since the CXCR4-CXCL12 axis is implicated in several aspects of tumor pathogenesis as well as in protection from chemotherapeutic response. In Burkitt lymphoma, the CXCR4 antagonist plerixafor has already been shown to enhance the......BACKGROUND: Diffuse large B-cell lymphoma (DLBCL) is an aggressive disease with variable clinical outcome, accounting for at least 25-30 % of adult non-Hodgkin lymphomas. Approximately one third of DLBCL patients are not cured by the currently used treatment regimen, R-CHOP. Hence, new treatment...

  10. Primary Hepatosplenic Large B-Cell Lymphoma

    Directory of Open Access Journals (Sweden)

    M.R. Morales-Polanco

    2008-03-01

    Full Text Available Diffuse large B-cell lymphoma is the most common form of lymphoma. It usually begins in the lymph nodes; up to 40% may have an extranodal presentation. According to a definition of primary extranodal lymphoma with presentation only in extranodal sites, there are reports of large B-cell lymphomas limited to liver or spleen as separate entities, and to date there have been only three documented cases of primary hepatosplenic presentation. This paper reports a fourth case. Due to a review of the literature and the clinical course of the case reported, we conclude that primary hepatosplenic large B-cell lymphoma has been found predominantly in females older than 60 years. The patients reported had <2 months of evolution prior to diagnosis, prominent B symptoms, splenomegaly in three and hepatomegaly in two, none with lymph node involvement. All had thrombocytopenia and abnormal liver function tests; three had anemia and elevated serum lactic dehydrogenase levels, two with hemophagocytosis in bone marrow. Because of the previously mentioned data, it can be stated that primary hepatosplenic lymphoma is an uncommon and aggressive form of disease that requires immediate recognition and treatment.

  11. Analysis of survival and prognsis in 409 newly diagnosed patients with diffuse large B-cell lymphoma

    Institute of Scientific and Technical Information of China (English)

    文菁菁

    2014-01-01

    Objective To explore the poor prognostic factors of diffuse large B-cell lymphoma(DLBCL).Methods The clinical data of 409 newly diagnosed patients with DLBCL from January 2000 to December 2010 were collected,and the prognostic factors by univariate and multivariate stratification were analyzed.Results Of the 409 DLBCL patients,244 were males and 165 females,the median age was 56(16-89)years old,the median follow-up time was 23(2-108)months.In univariate analysis,

  12. [The role of PET/CT investigation in the management of patients with diffuse large B-cell lymphoma].

    Science.gov (United States)

    Paksi, Melinda; Demeter, Judit; Szabó, Péter

    2016-06-01

    Diffuse large B-cell lymphoma (DLBCL) is the most common type of non-Hodgkin's lymphoma (NHL). Although this lymphoma is curable, 40% of patients with DLBCL will die of relapsed or refractory disease. 18F-Fluoro-deoxyglucose positron emission tomography (FDG-PET) is a noninvasive, 3-dimensional, functional imaging modality. When combined with the anatomical imaging tool computed tomography (CT), PET/CT can differentiate among others necrotic masses and viable tumors. PET scan has become a basic clinical tool for staging and response assessment in aggressive lymphomas, such as DLBCL. It has been evaluated in pretreatment staging, restaging, monitoring during therapy, post-therapy surveillance and assessment of transformation. Based on the preliminary results of several studies FDG-PET scans play an important role in the early assessment of treatment response, in planning of the treatment including radiation therapy and in the estimation of prognosis. PMID:27275637

  13. Diffuse large B-cell lymphoma: sub-classification by massive parallel quantitative RT-PCR.

    Science.gov (United States)

    Xue, Xuemin; Zeng, Naiyan; Gao, Zifen; Du, Ming-Qing

    2015-01-01

    Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous entity with remarkably variable clinical outcome. Gene expression profiling (GEP) classifies DLBCL into activated B-cell like (ABC), germinal center B-cell like (GCB), and Type-III subtypes, with ABC-DLBCL characterized by a poor prognosis and constitutive NF-κB activation. A major challenge for the application of this cell of origin (COO) classification in routine clinical practice is to establish a robust clinical assay amenable to routine formalin-fixed paraffin-embedded (FFPE) diagnostic biopsies. In this study, we investigated the possibility of COO-classification using FFPE tissue RNA samples by massive parallel quantitative reverse transcription PCR (qRT-PCR). We established a protocol for parallel qRT-PCR using FFPE RNA samples with the Fluidigm BioMark HD system, and quantified the expression of the COO classifier genes and the NF-κB targeted-genes that characterize ABC-DLBCL in 143 cases of DLBCL. We also trained and validated a series of basic machine-learning classifiers and their derived meta classifiers, and identified SimpleLogistic as the top classifier that gave excellent performance across various GEP data sets derived from fresh-frozen or FFPE tissues by different microarray platforms. Finally, we applied SimpleLogistic to our data set generated by qRT-PCR, and the ABC and GCB-DLBCL assigned showed the respective characteristics in their clinical outcome and NF-κB target gene expression. The methodology established in this study provides a robust approach for DLBCL sub-classification using routine FFPE diagnostic biopsies in a routine clinical setting. PMID:25418578

  14. Body mass index and other anthropometric parameters in patients with diffuse large B-cell lymphoma: physiopathological significance and predictive value in the immunochemotherapy era.

    Science.gov (United States)

    Sarkozy, Clémentine; Camus, Vincent; Tilly, Hervé; Salles, Gilles; Jardin, Fabrice

    2015-07-01

    Diffuse large B-cell lymphoma (DLBCL) is the most common form of aggressive non-Hodgkin lymphoma, accounting for 30-40% of newly diagnosed cases. Obesity is a well-defined risk factor for DLBCL. However, the impact of body mass index (BMI) on DLBCL prognosis is controversial. Recent studies suggest that skeletal muscle wasting (sarcopenia) or loss of fat mass can be detected by computed tomography (CT) images and is useful for predicting the clinical outcome in several types of cancer including DLBCL. Several hypotheses have been proposed to explain the differences in DLBCL outcome according to BMI or weight that include tolerance to treatment, inflammatory background and chemotherapy or rituximab metabolism. In this review, we summarize the available literature, addressing the impact and physiopathological relevance of simple anthropometric tools including BMI and tissue distribution measurements. We also discuss their relationship with other nutritional parameters and their potential role in the management of patients with DLBCL. PMID:25363401

  15. Tumor necrosis at FDG-PET is an independent predictor of outcome in diffuse large B-cell lymphoma

    NARCIS (Netherlands)

    Adams, Hugo J A; De Klerk, John M H; Fijnheer, Rob; Heggelman, Ben G F; Dubois, Stefan V.; Nievelstein, Rutger A J; Kwee, Thomas C.

    2016-01-01

    Purpose To determine the prognostic performance of tumor necrosis at FDG-PET in patients with newly diagnosed diffuse large B-cell lymphoma (DLBCL) who are treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) therapy. Materials and methods 108 patients with new

  16. Differential expression of Toll-like receptor (TLR) and B cell receptor (BCR) signaling molecules in primary diffuse large B-cell lymphoma of the central nervous system.

    Science.gov (United States)

    Akhter, Ariz; Masir, Noraidah; Elyamany, Ghaleb; Phang, Kean-Chang; Mahe, Etienne; Al-Zahrani, Ali Matar; Shabani-Rad, Meer-Taher; Stewart, Douglas Allan; Mansoor, Adnan

    2015-01-01

    Primary diffuse large B-cell lymphoma of the central nervous system (CNS DLBCL) is a distinct and aggressive lymphoma that is confined to CNS. Since, central nervous system is barrier-protected and immunologically silent; role of TLR/BCR signaling in pathogenesis and biology of CNS DLBCL is intriguing. Genomic mutations in key regulators of TLR/BCR signaling pathway (MYD88/CD79B/CARD11) have recently been reported in this disease. These observations raised possible implications in novel targeted therapies; however, expression pattern of molecules related to TLR/BCR pathways in this lymphoma remains unknown. We have analyzed the expression of 19 genes encoding TLR/BCR pathways and targets in CNS DLBCLs (n = 20) by Nanostring nCounter™ analysis and compared it with expression patterns in purified reactive B-lymphocytes and systemic diffuse large B cell lymphoma (DLBCL) (n = 20). Relative expression of TLR4, TLR5, TLR9, CD79B and BLNK was higher in CNS DLBCLs than in control B-lymphocytes; where as TLR7, MALT1, BCL10, CD79A and LYN was lower in CNS DLBCLs (P 1.5 fold change; P < 0.01). The B cell receptor molecules like BLNK and CD79B were also associated with higher expression of MYD88 dependent TLRs (TLR4/5/9). In conclusion, we have shown over expression of TLR/BCR related genes or their targets, where genomic mutations have commonly been identified in CNS DLBCL. We have also demonstrated that TLR over expression closely relate with up regulation of genes associated with BCR pathway like CD79B/BLNK and CARD11, which play an important role in NF-kB pathway activation. Our results provide an important insight into the possibility of TLR and/or B-cell receptor signaling molecules as possible therapeutic targets in CNS DLBCL. PMID:25391967

  17. Clinical and biological aspects of aggressive B-cell non-Hodgkin lymphoma in adolescents and young adults

    Directory of Open Access Journals (Sweden)

    Coso D

    2015-11-01

    Full Text Available Diane Coso, Sylvain Garciaz, Réda BouabdallahDepartment of Hematology, Cancer Center Institut J. Paoli-I. Calmettes, University of La Méditerranée, Marseille, FranceAbstract: Non-Hodgkin lymphomas (NHLs are one of the most frequent malignancies in adolescents and young adults (AYA. Among NHLs, Burkitt's lymphoma (BL represents approximately 40% while diffuse large B-cell lymphoma (DLBCL accounts for nearly 20% of cases. Primary mediastinal B-cell lymphoma is a variant of DLBCL, which preferentially concerns young patients. Biology of B-NHLs is well known and several pathways involving chromosomal translocations, gene rearrangements, and molecular profiling are the subject of continuous investigations. AYA with B-NHL have inferior survival when compared with children. The reasons for this unfavorable outcome are multifactorial, but disease-related biological characteristics of the tumor represent a powerful factor influencing survival. The choice of optimal strategy in the management of B-NHL in patients of 15–29 years old remains controversial and depends on the treating institution and its physicians. Although children and younger adolescents benefit from pediatric approaches using intensive treatment, older adolescents are often treated with adult rituximab-based chemotherapy. In this review, we focus on the current knowledge relevant to AYA with DLBCL and primary mediastinal B-cell lymphoma.Keywords: DLBCL, PMBCL, AYA, prognosis, treatment

  18. Pregnancy and cavernous sinus syndrome in diffuse large B-cell lymphoma

    Directory of Open Access Journals (Sweden)

    Juan Wang

    2013-01-01

    Full Text Available Diffuse large B-cell lymphoma (DLBCL usually present with rapidly growing lymph nodes or extra-nodal masses. Central nerve system involvement and pregnancy are rare in DLBCL. Here, we report an unusual case of DLBCL with cavernous sinus syndrome during pregnancy. A 24-year-old woman presented cavernous sinus syndrome as the initial presentation during pregnancy. Magnetic resonance imaging (MRI revealed enlargement of bilateral cavernous sinus. Tonsil and ovary biopsy indicated malignant lymphoma-DLBCL. Bone marrow smear showed infiltration by tumor cells. The case delivered a viable baby by cesarean section and then took chemotherapy of rituxan, cyclophosphamide, adriamycin, eldisine and dexamethasone. The disease deteriorated rapidly, especially after the pregnancy was terminated. Fortunately, a complete response was achieved after six cycles of chemotherapy. With the accumulation of clinical practice of such cases, we would be able to recognize minimal symptoms of DLBCL at the beginning and confirm the most suitable timing of the initiation of chemotherapy during pregnancy.

  19. [Central nervous system relapse in diffuse large B cell lymphoma: Risk factors].

    Science.gov (United States)

    Sancho, Juan-Manuel; Ribera, Josep-Maria

    2016-01-15

    Central nervous system (CNS) involvement by lymphoma is a complication associated, almost invariably, with a poor prognosis. The knowledge of the risk factors for CNS relapse is important to determine which patients could benefit from prophylaxis. Thus, patients with very aggressive lymphomas (such as lymphoblastic lymphoma or Burkitt's lymphoma) must systematically receive CNS prophylaxis due to a high CNS relapse rate (25-30%), while in patients with indolent lymphoma (such as follicular lymphoma or marginal lymphoma) prophylaxis is unnecessary. However, the question about CNS prophylaxis in patients with diffuse large B-cell lymphoma (DLBCL), the most common type of lymphoma, remains controversial. The information available is extensive, mainly based on retrospective and heterogeneous studies. There seems that immunochemotherapy based on rituximab reduces the CNS relapse rate. On the other hand, patients with increased serum lactate dehydrogenase plus more than one extranodal involvement seem to have a higher risk of CNS relapse, but a prophylaxis strategy based only on the presence of these 2 factors does not prevent all CNS relapses. Patients with involvement of testes or breast have high risk of CNS relapse and prophylaxis is mandatory. Finally, CNS prophylaxis could be considered in patients with DLBCL and renal or epidural space involvement, as well as in those cases with MYC rearrangements, although additional studies are necessary. PMID:25817451

  20. Prevalence and clinical implications of epstein-barr virus infection in de novo diffuse large B-cell lymphoma in Western countries

    DEFF Research Database (Denmark)

    Ok, Chi Young; Li, Ling; Xu-Monette, Zijun Y;

    2014-01-01

    , treated with rituximab combined with CHOP (R-CHOP) in developed Western countries. EXPERIMENTAL DESIGN: A large cohort (n = 732) of patients with DLBCL treated with R-CHOP chemotherapy is included from the multicenter consortium. This study group has been studied for expression of different biomarkers......PURPOSE: Epstein-Barr virus-positive (EBV(+)) diffuse large B-cell lymphoma (DLBCL) of the elderly is a variant of DLBCL with worse outcome that occurs most often in East-Asian countries and is uncommon in the Western hemisphere. We studied the largest cohort of EBV(+) DLBCL, independent of age...

  1. Deregulation of COMMD1 Is Associated with Poor Prognosis in Diffuse Large B-cell Lymphoma

    DEFF Research Database (Denmark)

    Taskinen, M.; Louhimo, R.; Koivula, S.;

    2014-01-01

    Background: Despite improved survival for the patients with diffuse large B-cell lymphoma (DLBCL), the prognosis after relapse is poor. The aim was to identify molecular events that contribute to relapse and treatment resistance in DLBCL. Methods: We analysed 51 prospectively collected pretreatment...... associated with unfavourable survival. The 2p15 aberration harboured COMMD1 gene, whose expression had a significant adverse prognostic impact on survival. Immunohistochemical analysis of COMMD1 expression in two series confirmed the association of COMMD1 expression with poor prognosis. Conclusion: COMMD1 is...... a potential novel prognostic factor in DLBCLs. The results highlight the value of integrated comprehensive analysis to identify prognostic markers and genetic driver events not previously implicated in DLBCL....

  2. Primary bladder lymphoma, diffuse large B-cell type: Case report and literature review of 26 cases

    OpenAIRE

    W Greg Simpson; Armando Lopez; Paurush Babbar; Lynnetta Faith Payne

    2015-01-01

    Primary lymphoma of the urinary bladder is exceedingly rare, representing 0.2% of all extranodal non-Hodgkin′s lymphoma. Although Matsuno et al. and others state the most common type is mucosa-associated lymphoid tissue (MALT) lymphoma, 20% of all the primary lymphomas of the urinary bladder are considered to be high grade neoplasms; the majority being diffuse large B-cell lymphoma (DLBCL). This is a case report of a 48-year-old man that presented with hematuria, frequency, nocturia, and flan...

  3. EBV, HHV8 and HIV in B cell non Hodgkin lymphoma in Kampala, Uganda

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    Pileri Stefano A

    2010-06-01

    Full Text Available Abstract Background B cell non Hodgkin lymphomas account for the majority of lymphomas in Uganda. The commonest is endemic Burkitt lymphoma, followed by diffuse large-B-cell lymphoma (DLBCL. There has been an increase in incidence of malignant lymphoma since the onset of the HIV/AIDS pandemic. However, the possible linkages of HHV8 and EBV to the condition of impaired immunity present in AIDS are still not yet very clearly understood. Objectives 1. To describe the prevalence of Epstein-Barr virus, Human Herpes virus 8 and Human Immunodeficiency Virus-1 in B cell non Hodgkin lymphoma biopsy specimens in Kampala, Uganda. 2. To describe the histopathology of non Hodgkin lymphoma by HIV serology test result in Kampala, Uganda Method Tumour biopsies specimens from 119 patients with B cell non Hodgkin lymphoma were classified according to the WHO classification. Immunohistochemistry was used for detection of HHV8 and in situ hybridization with Epstein Barr virus encoded RNA (EBER for EBV. Real time and nested PCR were used for the detection of HIV. The patients from whom the 1991-2000 NHL biopsies had been taken did not have HIV serology results therefore 145 patients biopsies where serology results were available were used to describe the association of HIV with non Hodgkin lymphoma type during 2008-2009. Results In this study, the majority (92% of the Burkitt lymphomas and only 34.8% of the diffuse large B cell lymphomas were EBV positive. None of the precursor B lymphoblastic lymphomas or the mantle cell lymphomas showed EBV integration in the lymphoma cells. None of the Burkitt lymphoma biopsies had HIV by PCR. Of the 121 non Hodgkin B cell lymphoma patients with HIV test results, 19% had HIV. However, only 1(0.04% case of Burkitt lymphoma had HIV. All the tumours were HHV8 negative. Conclusions The majority of the Burkitt lymphomas and two fifths of the diffuse large B cell lymphomas had EBV. All the tumours were HHV8 negative. Generally, the

  4. Transformation of a Cutaneous Follicle Center Lymphoma to a Diffuse Large B-Cell Lymphoma—An Unusual Presentation

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    J. Dias Coelho

    2010-01-01

    Full Text Available Primary cutaneous follicle center lymphoma (PCFCL is characterized by a proliferation of follicle center cells in the skin. A definitive diagnosis is frequently delayed because of difficulties in interpretation of the histopathologic findings. It has an excellent prognosis with a 5-year survival over 95% and its risk of transformation has not been established. We describe a case report of man with a gastric diffuse large B-cell lymphoma (DLBCL referred to our clinic because of nodules in the back that had gradually developed over a period of 10 years. A biopsy performed 3 years before was interpreted as reactive follicular hyperplasia. A new skin biopsy revealed a diffuse large B-cell lymphoma and immunoglobulin heavy chain gene rearrangements from the initial skin biopsy (PCBCL and the DLBCL gastric biopsy were studied by polymerase chain reaction and an identical clonal rearrangement was detected which was highly suggestive of a transformation lymphoma.

  5. Primary uterine diffuse large B-cell lymphoma involving the urinary bladder with urinary cytology mimicking carcinomas: A case report

    OpenAIRE

    Sumiyo Adachi; Kazuto Yamazaki; Shan-Guang Liang; Yasuo Ishida

    2015-01-01

    We report a rare case of a 69-year-old woman in whom diffuse large B-cell lymphoma (DLBCL) originated from the uterus and involved the urinary bladder. The cervical smears of the case mostly consisted of discohesive atypical round cells, which were highly suggestive of lymphoma; however, in voided urine smears, a majority of the cells formed large aggregates of degenerated cells, mimicking those of urothelial carcinoma (UC). The smears also represented some small loose clusters, in which tumo...

  6. Primary Mediastinal Large B-Cell Lymphoma during Pregnancy

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    Cesar A. Perez

    2012-01-01

    Full Text Available Non-Hodgkin’s Lymphoma (NHL rarely presents during pregnancy and primary mediastinal large B-cell lymphoma (PMLBCL accounts for approximately 2.5% of patients with NHL. The case of a 22-year-old woman who was diagnosed with Stage IIA PMLBCL during week 13 of her intrauterine pregnancy is described. The staging consisted in computed tomography (CT of the chest and magnetic resonance imaging (MRI of the abdomen and pelvis. She was managed with R-CHOP regimen (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone for a total of six cycles and, because of the early presentation during the second trimester, she received the entire chemotherapy course during the pregnancy. She delivered a healthy baby at 34 weeks of pregnancy and a 18FDG-PET/CT scan demonstrated complete remission after delivery. After 20 months of follow up she remains with no evidence of disease and her 1-year-old son has shown no developmental delays or physical abnormalities. PMLBCL, although an uncommon subgroup of DLBCL, may present during pregnancy and R-CHOP should be considered as one suitable option in this complex scenario.

  7. In Situ Hepatitis C NS3 Protein Detection Is Associated with High Grade Features in Hepatitis C-Associated B-Cell Non-Hodgkin Lymphomas.

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    Danielle Canioni

    Full Text Available Hepatitis C Virus (HCV infection is associated with the B-cell non-Hodgkin lymphomas (NHL, preferentially marginal zone lymphomas (MZL and diffuse large B-cell lymphomas (DLBCL. While chronic antigenic stimulation is a main determinant of lymphomagenesis in marginal zone lymphomas (MZL, a putative role of HCV infection of B-cells is supported by in vitro studies. We performed a pathological study within the "ANRS HC-13 LymphoC" observational study focusing on in situ expression of the oncogenic HCV non structural 3 (NS3 protein. Lympho-C study enrolled 116 HCV-positive patients with B-NHL of which 86 histological samples were collected for centralized review. Main histological subtypes were DLBCL (36% and MZL (34%. Almost half of DLBCL (12/26 were transformed from underlying small B-cell lymphomas. NS3 immunostaining was found positive in 17 of 37 tested samples (46%. There was a striking association between NS3 detection and presence of high grade lymphoma features: 12 out of 14 DLBCL were NS3+ compared to only 4 out of 14 MZL (p = 0.006. Moreover, 2 among the 4 NS3+ MZL were enriched in large cells. Remarkably, this study supports a new mechanism of transformation with a direct oncogenic role of HCV proteins in the occurrence of high-grade B lymphomas.

  8. In Situ Hepatitis C NS3 Protein Detection Is Associated with High Grade Features in Hepatitis C-Associated B-Cell Non-Hodgkin Lymphomas

    Science.gov (United States)

    Rabiega, Pascaline; Molina, Thierry J.; Charlotte, Frédéric; Lazure, Thierry; Davi, Frédéric; Settegrana, Catherine; Berger, Françoise; Alric, Laurent; Cacoub, Patrice; Terrier, Benjamin; Suarez, Felipe; Sibon, David; Dupuis, Jehan; Feray, Cyrille; Tilly, Hervé; Pol, Stanislas; Deau Fischer, Bénédicte; Roulland, Sandrine; Thieblemont, Catherine; Leblond, Véronique; Carrat, Fabrice; Hermine, Olivier; Besson, Caroline

    2016-01-01

    Hepatitis C Virus (HCV) infection is associated with the B-cell non-Hodgkin lymphomas (NHL), preferentially marginal zone lymphomas (MZL) and diffuse large B-cell lymphomas (DLBCL). While chronic antigenic stimulation is a main determinant of lymphomagenesis in marginal zone lymphomas (MZL), a putative role of HCV infection of B-cells is supported by in vitro studies. We performed a pathological study within the "ANRS HC-13 LymphoC" observational study focusing on in situ expression of the oncogenic HCV non structural 3 (NS3) protein. Lympho-C study enrolled 116 HCV-positive patients with B-NHL of which 86 histological samples were collected for centralized review. Main histological subtypes were DLBCL (36%) and MZL (34%). Almost half of DLBCL (12/26) were transformed from underlying small B-cell lymphomas. NS3 immunostaining was found positive in 17 of 37 tested samples (46%). There was a striking association between NS3 detection and presence of high grade lymphoma features: 12 out of 14 DLBCL were NS3+ compared to only 4 out of 14 MZL (p = 0.006). Moreover, 2 among the 4 NS3+ MZL were enriched in large cells. Remarkably, this study supports a new mechanism of transformation with a direct oncogenic role of HCV proteins in the occurrence of high-grade B lymphomas. PMID:27257992

  9. Primary Diffuse Large B-Cell Lymphoma of the Liver in a Patient with Sjogren Syndrome

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    Vadim Gorodetskiy

    2016-01-01

    Full Text Available Sjögren’s syndrome (SS has the highest incidence of malignant lymphoproliferative disorders transformation among autoimmune diseases. We present a case of extranodal high grade lymphoma of the liver in a 52-year-old patient with long history of SS. Lymphoma manifested with sharp significant pain in the right hypochondrium, weakness, and profuse night sweats. Contrast-enhanced computed tomography scan (CT-scan of the abdomen revealed multiple low density foci with homogeneous structure and clear contours in both lobes of the liver. Histologically, proliferation of medium sized lymphoma cells with round-oval and slightly irregular nuclei with fine chromatin was shown. Immunohistochemical and molecular features of the tumors allowed diagnosis of diffuse large B-cell lymphoma (DLBCL. To exclude secondary liver lesion by non-Hodgkin lymphoma, chest and small pelvis CT-scan, endoscopy of upper and lower gastrointestinal tract and study of bone marrow were performed. After 8 cycles of R-CHOP chemotherapy (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone, the complete remission was achieved, which persists after 45 months of follow-up. Primary hepatic lymphomas are extremely rare, and previously only low-grade hepatic lymphomas have been described in SS. To our knowledge, the patient described here represents the first reported case of DLBCL with primary liver involvement in SS.

  10. Rituximab in Combination with CHOP, an Effective and Well-tolerated Salvage Regimen for Diffuse Large B-Cell Lymphoma

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    OBJECTIVE To evaluate the clinical effect of the R-CHOP regimen (rituximab in combination with cyclophosphamide, epirubicin, vincristine and prednisone) in treating refractory or relapsed diffuse large B-cell lymphoma (DLBCL), as a salvage therapy for DLBCL.METHODS Eighteen patients with refractory or relapsed DLBCL who were treated with the R-CHOP regimen from 2001 to 2006 in hospitals in Jilin Province were analyzed retrospectively. The response rate, change of serum lactate dehydrogenase (LDH), time to progression (TTP) and toxicity were observed.RESULTS The R-CHOP regimen can achieve a higher response rate, decrease serum LDH to a larger extent and obtain longer TTP than a conventional secondary regimen. The main adverse effects were similar to conventional chemotherapy.CONCLUSION The R-CHOP regimen is one of the most effective secondary therapies for DLBCL.

  11. Translocations activating IRF4 identify a subtype of germinal center-derived B-cell lymphoma affecting predominantly children and young adults.

    Science.gov (United States)

    Salaverria, Itziar; Philipp, Claudia; Oschlies, Ilske; Kohler, Christian W; Kreuz, Markus; Szczepanowski, Monika; Burkhardt, Birgit; Trautmann, Heiko; Gesk, Stefan; Andrusiewicz, Miroslaw; Berger, Hilmar; Fey, Miriam; Harder, Lana; Hasenclever, Dirk; Hummel, Michael; Loeffler, Markus; Mahn, Friederike; Martin-Guerrero, Idoia; Pellissery, Shoji; Pott, Christiane; Pfreundschuh, Michael; Reiter, Alfred; Richter, Julia; Rosolowski, Maciej; Schwaenen, Carsten; Stein, Harald; Trümper, Lorenz; Wessendorf, Swen; Spang, Rainer; Küppers, Ralf; Klapper, Wolfram; Siebert, Reiner

    2011-07-01

    The prognosis of germinal center-derived B-cell (GCB) lymphomas, including follicular lymphoma and diffuse large-B-cell lymphoma (DLBCL), strongly depends on age. Children have a more favorable outcome than adults. It is not known whether this is because of differences in host characteristics, treatment protocols, or tumor biology, including the presence of chromosomal alterations. By screening for novel IGH translocation partners in pediatric and adult lymphomas, we identified chromosomal translocations juxtaposing the IRF4 oncogene next to one of the immunoglobulin (IG) loci as a novel recurrent aberration in mature B-cell lymphoma. FISH revealed 20 of 427 lymphomas to carry an IG/IRF4-fusion. Those were predominantly GCB-type DLBCL or follicular lymphoma grade 3, shared strong expression of IRF4/MUM1 and BCL6, and lacked PRDM1/BLIMP1 expression and t(14;18)/BCL2 breaks. BCL6 aberrations were common. The gene expression profile of IG/IRF4-positive lymphomas differed from other subtypes of DLBCL. A classifier for IG/IRF4 positivity containing 27 genes allowed accurate prediction. IG/IRF4 positivity was associated with young age and a favorable outcome. Our results suggest IRF4 translocations to be primary alterations in a molecularly defined subset of GCB-derived lymphomas. The probability for this subtype of lymphoma significantly decreases with age, suggesting that diversity in tumor biology might contribute to the age-dependent differences in prognosis of lymphoma. PMID:21487109

  12. Epstein-Barr virus-positive diffuse large B-cell lymphoma in children: a disease reminiscent of Epstein-Barr virus-positive diffuse large B-cell lymphoma of the elderly.

    Science.gov (United States)

    Uccini, Stefania; Al-Jadiry, Mazin F; Scarpino, Stefania; Ferraro, Daniela; Alsaadawi, Adel R; Al-Darraji, Amir F; Moleti, Maria Luisa; Testi, Anna Maria; Al-Hadad, Salma A; Ruco, Luigi

    2015-05-01

    Pediatric Epstein-Barr virus (EBV)-positive diffuse large B-cell lymphoma (EBV+ DLBCL) is a rare disease in nonimmunocompromised hosts. In a review of 231 cases of malignant lymphoma (87 Hodgkin lymphoma and 144 non-Hodgkin lymphoma) occurring in Iraqi children, 7 cases (5% of NHLs) were classified as EBV+ DLBCL. Six children presented with nodal disease, and 1 presented with extranodal localization (bone). In all cases, the disease was at an advanced clinical stage (III/IV). Evidence of immunodeficiency (Evans syndrome and selective IgA deficiency) was observed in a single case. Two cases were "monomorphic" with immunoblastic histology, and 5 cases were "polymorphic" with histologic aspects reminiscent of nodular lymphocyte-predominant Hodgkin lymphoma (2 cases) and of CD30+ classical Hodgkin lymphoma (3 cases). In all cases, tumor cells were EBV infected (EBER+/LMP-1+), were medium-large B-cells (CD20+/CD79a+/PAX-5+/BOB-1+/OCT-2+) of non-germinal center (non-GC) origin (CD10-/MUM-1+), and had high proliferative activity (50%-70%). Chromosomal translocations involving BCL2, MYC, and IGH genes were not observed. IGH monoclonality could be demonstrated in 3 of 3 investigated cases. Six cases of EBV-negative DLBCL (4% of NHL) were present in the same series. All had monomorphic histology with centroblastic/immunoblastic morphology; 3 cases were of GC type and 3 of non-GC type. Our findings indicate that in Iraq, DLBCLs are 9% of NHLs. Moreover, 2 different types of the disease do exist; the EBV-positive cases, with strong histologic and immunohistochemical resemblance with EBV+ DLBCL of the elderly, and the EBV-negative cases, which are similar to the pediatric DLBCL usually observed in Western populations. PMID:25704629

  13. Comparison of Three Chemotherapy Regimens in Elderly Patients with Diffuse Large B Cell Lymphoma: Experience at a Single National Reference Center in Mexico

    OpenAIRE

    Diana Nolasco-Medina; Nancy Reynoso-Noveron; Alejandro Mohar-Betancourt; Alejandro Aviles-Salas; Osvaldo García-Perez; Myrna Candelaria

    2016-01-01

    Background. Although chemotherapy added to rituximab is a standard of care for diffuse large B cell lymphoma (DLBCL), treatment of patients ≥65 years of age remains controversial due to comorbidities. Methods. This is a retrospective, comparative, nonrandomized study of patients ≥65 years of age, who were diagnosed with DLBCL but not previously treated. Demographic characteristics and comorbidities were analyzed. Three rituximab-containing treatment regimens (standard RCHOP, anthracycline dos...

  14. Routine imaging for diffuse large B-cell lymphoma in first remission is not associated with better survival

    DEFF Research Database (Denmark)

    El-Galaly, Tarec; Jakobsen, Lasse Hjort; Hutchings, Martin;

    2015-01-01

    (HR 2.3, P <0.01), B-symptoms (HR 1.6, P = 0.02), and ECOG performance >2 (HR 1.8, P = 0.04) at diagnosis were associated with inferior post-remission OS in multivariate Cox analysis, whereas an imaging-based FU strategy (country of FU) was not prognostic. An imaging-based FU strategy also had no......Background: Routine surveillance imaging plays a limited role in detecting recurrent diffuse large B-cell lymphoma (DLBCL), and the value of routine imaging is controversial. The present population-based study compares the post-remission survival of Danish and Swedish DLBCL patients......-two neighbouring countries with comparable treatment guidelines but with completely different traditions for routine surveillance imaging. Methods: Patients enroled in the Danish (LYFO) and Swedish population-based lymphoma registries were included by following criteria: (a) newly diagnosed DLBCL in the period...

  15. Gastric infiltration of diffuse large B-cell lymphoma: Endoscopic diagnosis and improvement of lesions after chemotherapy

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    Diffuse large B-cell lymphoma (DLBCL) is the most common histologic subtype of the non-Hodgkin's lymphoma (NHL) accounting for about 40% of all NHLs. This is a case report about the endoscopic appearance of a DLBCL with infiltration to the stomach in a 39-year-old female. She had a 6-me history of lumbar and left upper quadrant pain with intermittent episodes of melena. A computer tomograghy (CT) scan showed mural thickening of the gastric antrum. Endoscopic examination revealed multiple gastric ulcers. Definite diagnosis could be made by endoscopic biopsies and the patient had a good response to chemotherapy. This response correlated well with a further endoscopic follow-up. A follow-up endoscopic examination could be considered to evaluate a good response to chemotherapy in DLBCL patients with secondary gastric dissemination.

  16. Composite B-cell and T-cell non-Hodgkin lymphoma of the tibia.

    Science.gov (United States)

    Kaleem, Zahid; McGuire, Michael H; Caracioni, Adrian C; Leonard, Ronald L; Pathan, M Hanif; Lessmann, Ellen A; Chan, Wing C

    2005-02-01

    We report a unique case of de novo composite lymphoma in the tibia of a 35-year-old man who presented with increasingly frequent and intense pain in the right upper leg. He was otherwise healthy without significant medical history. A plain radiograph of the right leg showed a permeative lesion with alternating areas of radiolucency and radiodensity in the upper third of the tibia. Magnetic resonance imaging showed a large, heterogeneous enhancing lesion involving the medullary and cortical bone of the proximal tibia with cortical disruption and extension into the adjacent soft tissue. A biopsy showed sheets and clusters of large cells, punctuated by clusters of small, irregular lymphocytes. Flow cytometry and immunohistochemical analysis showed composite lymphoma: diffuse large B-cell lymphoma (DLBCL) and peripheral T-cell non-Hodgkin lymphoma with predominantly small cell morphologic features. The DLBCL expressed CD19, CD20, CD79a, CD5, CD10, CD23, CD38, CD117, bcl-2, and bcl-6, with monotypic expression of immunoglobulin kappa light chain. The T cells expressed CD2, CD3, CD5, CD7, and CD8, with partial loss of CD4. Clonal rearrangement of T-cell receptor gamma chain gene was found. Neither the large B cells nor the small T cells expressed Epstein-Barr virus-encoded RNA. Physical examination and radiologic studies showed no evidence of lymphadenopathy, organomegaly, or other mass lesions in the body. No peripheral lymphocytosis or bone marrow involvement was present. PMID:15842045

  17. Case Report of Diffuse Large B Cell Lymphoma of Uterine Cervix Treated at a Semiurban Cancer Centre in North India

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    Vibhor Sharma

    2016-01-01

    Full Text Available Lymphoma of the uterine cervix is very rare. We report a case of diffuse large B cell lymphoma (DLBCL involving the uterine cervix treated at a newly commissioned semiurban cancer centre in north India in 2015. Data for this study was obtained from the hospital electronic medical records and the patient’s case file. We also reviewed published case reports of uterine and cervical lymphoma involving forty-one patients. We treated a case of stage IV DLBCL cervix with six cycles of R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone and intrathecal methotrexate followed by consolidation with radiotherapy. The patient showed complete response to chemotherapy. We conclude that, in advanced stage lymphoma involving uterus and cervix, combination of chemotherapy and radiotherapy is effective in short term.

  18. High nuclear expression of STAT3 is associated with unfavorable prognosis in diffuse large B-cell lymphoma

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    Zhu J

    2011-08-01

    Full Text Available Abstract Background The purpose of the study was to investigate the expression and prognostic value of STAT3 in diffuse large B-cell lymphoma (DLBCL. Methods Seventy-four DLBCL patients from 2001 to 2007 were reviewed in the study. The STAT3 expression in their tumor tissues was examined using the immunohistochemistry (IHC method, and evaluated for its association with clinicopathological parameters. Results Strong nuclear staining of STAT3 and phosphorylated-STAT3tyr705 (P-STAT3 were observed in 19 cases (25.7% and 24 cases (32.4%, respectively, and the expression levels were highly consistent between them (P = 0.001. The high nuclear expression of STAT3 was more frequent in the non-germinal center B cell-like (non-GCB DLBCL than that in the GCB subtype, but not reaching significance (P P = 0.005. Multivariate Cox regression analysis showed that the STAT3 expression was an independent prognostic factor for DLBCL patients regardless of CHOP or R-CHOP regimen used as the first-line therapy. Conclusion STAT3 is more frequently expressed in non-GCB DLBCL than that in GCB subtype, and its strong nuclear expression is correlated with poor OS in DLBCL.

  19. Double-hit BCL2/MYC translocations in a consecutive cohort of patients with large B-cell lymphoma - a single centre's experience

    DEFF Research Database (Denmark)

    Pedersen, Mette Ø; Gang, Anne O; Poulsen, Tim S;

    2012-01-01

    large B-cell lymphoma (DLBCL) or B-cell lymphoma, unclassifiable, with features intermediate between diffuse large B-cell lymphoma and Burkitt lymphoma (BCLU). The incidence of DH was 11% in the total cohort, 7% of primary LBCL and 21% of transformed LBCL. DH lymphomas were all GCB immunophenotype and......Concurrent BCL2 and MYC translocations, so called double hit (DH), are a rare finding in large B-cell lymphoma (LBCL). Based on data from retrospective series, DH has been correlated with aggressive clinical behaviour and poor outcome. We conducted a consecutive study of DH incidence and...... were more often BCLU. No clinical characteristics were correlated with the presence of DH, which also had no impact on overall response rate (ORR), relapse rate or overall survival (OS). However, sub-stratification of DH lymphomas by FISH indicated a possible inferior survival related to immunoglobulin...

  20. Use of subsequent PET/CT in diffuse large B-cell lymphoma patients in complete remission following primary therapy

    OpenAIRE

    Xu Zhang; Wei Fan; Zhong-Jun Xia; Ying-Ying Hu; Xiao-Ping Lin; Ya-Rui Zhang; Zhi-Ming Li; Pei-Yan Liang; Yuan-Hua Li

    2015-01-01

    Interim 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (I-PET/CT) is a powerful tool for monitoring the response to therapy in diffuse large B-cell lymphoma (DLBCL). This retrospective study aimed to determine when and how to use I-PET/CT in DLBCL. A total of 197 patients treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) were enrolled between October 2005 and July 2011; PET/CT was performed at the time of diagnosis (PET/...

  1. Genomic signatures in B-cell lymphoma: How can these improve precision in diagnosis and inform prognosis?

    Science.gov (United States)

    Iqbal, Javeed; Naushad, Hina; Bi, Chengfeng; Yu, Jiayu; Bouska, Alyssa; Rohr, Joseph; Chao, Wang; Fu, Kai; Chan, Wing C; Vose, Julie M

    2016-03-01

    Current genomic technologies have immensely improved disease classification and prognostication of major subtypes of B-cell lymphomas. This novel genetic information has not only aided in diagnosis, but has also revealed a landscape of critical molecular events that determine the biological and clinical behavior of a lymphoma. In this review, we summarized the genetic characteristics of major subtypes of B-cell lymphomas, including diffuse large B cell lymphoma (DLBCL), follicular lymphoma (FL), Burkitt lymphoma (BL), and mantle cell lymphoma (MCL). We illustrated how genomic profiling had identified molecular subgroups in DLBCL with varied clinical outcomes, and how a subset of genes defined prognosis in MCL and aided in BL diagnoses. We also highlighted some Phase II/III clinical trials using new therapeutic agents to determine clinical efficacy in novel molecular subgroups with distinct gene expression patterns. We believe that refinement of genomic signatures will require more intensive efforts from the biomedical research community to improve targeted therapy designs and bring a substantial change in the treatment decisions. In the next era of genomic medicine, we anticipate that a clinically and biologically relevant molecular profile of each tumor will be obtained at diagnosis to guide therapy. PMID:26432520

  2. Diffuse large B-cell lymphoma with combined TP53 mutation and MIR34A methylation

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    Asmar, Fazila; Hother, Christoffer; Kulosman, Gorjan;

    2014-01-01

    MiR34A, B and C have been implicated in lymphomagenesis, but information on their role in normal CD19+ B-cells (PBL-B) and de novo diffuse large B-cell lymphoma (DLBCL) is limited. We show that in normal and activated B-cells miR34A-5p plays a dominant role compared to other miR34 family members....

  3. Two-Dimensional Matrix Algorithm Using Detrended Fluctuation Analysis to Distinguish Burkitt and Diffuse Large B-Cell Lymphoma

    Directory of Open Access Journals (Sweden)

    Rong-Guan Yeh

    2012-01-01

    Full Text Available A detrended fluctuation analysis (DFA method is applied to image analysis. The 2-dimensional (2D DFA algorithms is proposed for recharacterizing images of lymph sections. Due to Burkitt lymphoma (BL and diffuse large B-cell lymphoma (DLBCL, there is a significant different 5-year survival rates after multiagent chemotherapy. Therefore, distinguishing the difference between BL and DLBCL is very important. In this study, eighteen BL images were classified as group A, which have one to five cytogenetic changes. Ten BL images were classified as group B, which have more than five cytogenetic changes. Both groups A and B BLs are aggressive lymphomas, which grow very fast and require more intensive chemotherapy. Finally, ten DLBCL images were classified as group C. The short-term correlation exponent α1 values of DFA of groups A, B, and C were 0.370±0.033, 0.382±0.022, and 0.435±0.053, respectively. It was found that α1 value of BL image was significantly lower (P<0.05 than DLBCL. However, there is no difference between the groups A and B BLs. Hence, it can be concluded that α1 value based on DFA statistics concept can clearly distinguish BL and DLBCL image.

  4. Insights into the Molecular Pathogenesis of Activated B-Cell-like Diffuse Large B-Cell Lymphoma and Its Therapeutic Implications

    Directory of Open Access Journals (Sweden)

    Georg Lenz

    2015-05-01

    Full Text Available Within the last couple of years, the understanding of the molecular mechanisms that drive the pathogenesis of diffuse large B-cell lymphoma (DLBCL has significantly improved. Large-scale gene expression profiling studies have led to the discovery of several molecularly defined subtypes that are characterized by specific oncogene addictions and significant differences in their outcome. Next generation sequencing efforts combined with RNA interference screens frequently identify crucial oncogenes that lead to constitutive activation of various signaling pathways that drive lymphomagenesis. This review summarizes our current understanding of the molecular pathogenesis of the activated B-cell-like (ABC DLBCL subtype that is characterized by poor prognosis. A special emphasis is put on findings that might impact therapeutic strategies of affected patients.

  5. Insights into the Molecular Pathogenesis of Activated B-Cell-like Diffuse Large B-Cell Lymphoma and Its Therapeutic Implications

    Energy Technology Data Exchange (ETDEWEB)

    Lenz, Georg [Translational Oncology, Department of Medicine A, Albert-Schweitzer Campus 1, University Hospital Münster, 48149 Münster (Germany); Cluster of Excellence EXC 1003, Cells in Motion, 48149 Münster (Germany)

    2015-05-22

    Within the last couple of years, the understanding of the molecular mechanisms that drive the pathogenesis of diffuse large B-cell lymphoma (DLBCL) has significantly improved. Large-scale gene expression profiling studies have led to the discovery of several molecularly defined subtypes that are characterized by specific oncogene addictions and significant differences in their outcome. Next generation sequencing efforts combined with RNA interference screens frequently identify crucial oncogenes that lead to constitutive activation of various signaling pathways that drive lymphomagenesis. This review summarizes our current understanding of the molecular pathogenesis of the activated B-cell-like (ABC) DLBCL subtype that is characterized by poor prognosis. A special emphasis is put on findings that might impact therapeutic strategies of affected patients.

  6. Biomarkers of diffuse large B-cell lymphoma: impact on diagnosis, treatment, and prognosis

    Directory of Open Access Journals (Sweden)

    Coutinho R

    2013-02-01

    Full Text Available Rita Coutinho, John GribbenCentre for Haemato-Onocology, Barts Cancer Institute, Queen Mary, University of London, London, United KingdomAbstract: Introduction of immunochemotherapy as frontline treatment for diffuse large B-cell lymphoma (DLBCL has significantly increased survival. However, patients refractory to rituximab-containing regimens have a very poor survival. These differences in clinical behavior might lie behind the biological heterogeneity well recognized in this disease. Advanced molecular research has helped us to define DLBCL subgroups which harbor distinct oncogenic events and response to immunochemotherapy. The field of biomarker discovery in DLBCL has become more complex over the last decade and a broad up-to-date review on this topic is lacking. The aim for this review was to offer the hematology community a comprehensive overview of clinical and biological markers which have a diagnostic and prognostic potential and that might be amenable to therapeutic targeting. Some well known markers are reassessed in light of recent findings.Keywords: DLBCL, immunochemotherapy, rituximab, biomarkers

  7. Human Leukocyte Antigen Class I and II Alleles and Overall Survival in Diffuse Large B-Cell Lymphoma and Follicular Lymphoma

    OpenAIRE

    Yani Lu; Amr M Abdou; Cerhan, James R.; Morton, Lindsay M.; Richard K Severson; Scott Davis; Wendy Cozen; Nathaniel Rothman; Leslie Bernstein; Stephen Chanock; Patricia Hartge; Wang, Sophia S.

    2011-01-01

    Genetic variation in the 6p21 chromosomal region, including human leukocyte antigen (HLA) genes and tumor necrosis factor (TNF), has been linked to both etiology and clinical outcomes of lymphomas. We estimated the effects of HLA class I (A, B, and C), class II DRB1 alleles, and the ancestral haplotype (AH) 8.1 (HLAA*01-B*08-DRB1*03-TNF-308A) on overall survival (OS) among patients with diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL) in a population-based study of non-Hodgk...

  8. Massive transcriptional perturbation in subgroups of diffuse large B-cell lymphomas.

    Directory of Open Access Journals (Sweden)

    Maciej Rosolowski

    Full Text Available Based on the assumption that molecular mechanisms involved in cancerogenesis are characterized by groups of coordinately expressed genes, we developed and validated a novel method for analyzing transcriptional data called Correlated Gene Set Analysis (CGSA. Using 50 extracted gene sets we identified three different profiles of tumors in a cohort of 364 Diffuse large B-cell (DLBCL and related mature aggressive B-cell lymphomas other than Burkitt lymphoma. The first profile had high level of expression of genes related to proliferation whereas the second profile exhibited a stromal and immune response phenotype. These two profiles were characterized by a large scale gene activation affecting genes which were recently shown to be epigenetically regulated, and which were enriched in oxidative phosphorylation, energy metabolism and nucleoside biosynthesis. The third and novel profile showed only low global gene activation similar to that found in normal B cells but not cell lines. Our study indicates novel levels of complexity of DLBCL with low or high large scale gene activation related to metabolism and biosynthesis and, within the group of highly activated DLBCLs, differential behavior leading to either a proliferative or a stromal and immune response phenotype.

  9. High-throughput combinatorial screening identifies drugs that cooperate with ibrutinib to kill activated B-cell-like diffuse large B-cell lymphoma cells.

    Science.gov (United States)

    Mathews Griner, Lesley A; Guha, Rajarshi; Shinn, Paul; Young, Ryan M; Keller, Jonathan M; Liu, Dongbo; Goldlust, Ian S; Yasgar, Adam; McKnight, Crystal; Boxer, Matthew B; Duveau, Damien Y; Jiang, Jian-Kang; Michael, Sam; Mierzwa, Tim; Huang, Wenwei; Walsh, Martin J; Mott, Bryan T; Patel, Paresma; Leister, William; Maloney, David J; Leclair, Christopher A; Rai, Ganesha; Jadhav, Ajit; Peyser, Brian D; Austin, Christopher P; Martin, Scott E; Simeonov, Anton; Ferrer, Marc; Staudt, Louis M; Thomas, Craig J

    2014-02-11

    The clinical development of drug combinations is typically achieved through trial-and-error or via insight gained through a detailed molecular understanding of dysregulated signaling pathways in a specific cancer type. Unbiased small-molecule combination (matrix) screening represents a high-throughput means to explore hundreds and even thousands of drug-drug pairs for potential investigation and translation. Here, we describe a high-throughput screening platform capable of testing compounds in pairwise matrix blocks for the rapid and systematic identification of synergistic, additive, and antagonistic drug combinations. We use this platform to define potential therapeutic combinations for the activated B-cell-like subtype (ABC) of diffuse large B-cell lymphoma (DLBCL). We identify drugs with synergy, additivity, and antagonism with the Bruton's tyrosine kinase inhibitor ibrutinib, which targets the chronic active B-cell receptor signaling that characterizes ABC DLBCL. Ibrutinib interacted favorably with a wide range of compounds, including inhibitors of the PI3K-AKT-mammalian target of rapamycin signaling cascade, other B-cell receptor pathway inhibitors, Bcl-2 family inhibitors, and several components of chemotherapy that is the standard of care for DLBCL. PMID:24469833

  10. SILAC-Based Quantitative Proteomic Analysis of Diffuse Large B-Cell Lymphoma Patients

    Directory of Open Access Journals (Sweden)

    Ulla Rüetschi

    2015-01-01

    Full Text Available Diffuse large B-cell lymphoma (DLBCL, the most common lymphoma, is a heterogeneous disease where the outcome for patients with early relapse or refractory disease is very poor, even in the era of immunochemotherapy. In order to describe possible differences in global protein expression and network patterns, we performed a SILAC-based shotgun (LC-MS/MS quantitative proteomic analysis in fresh-frozen tumor tissue from two groups of DLBCL patients with totally different clinical outcome: (i early relapsed or refractory and (ii long-term progression-free patients. We could identify over 3,500 proteins; more than 1,300 were quantified in all patients and 87 were significantly differentially expressed. By functional annotation analysis on the 66 proteins overexpressed in the progression-free patient group, we found an enrichment of proteins involved in the regulation and organization of the actin cytoskeleton. Also, five proteins from actin cytoskeleton regulation, applied in a supervised regression analysis, could discriminate the two patient groups. In conclusion, SILAC-based shotgun quantitative proteomic analysis appears to be a powerful tool to explore the proteome in DLBCL tumor tissue. Also, as progression-free patients had a higher expression of proteins involved in the actin cytoskeleton protein network, such a pattern indicates a functional role in the sustained response to immunochemotherapy.

  11. Addition of rituximab to chemotherapy overcomes the negative prognostic impact of cyclin E expression in diffuse large B-cell lymphoma

    DEFF Research Database (Denmark)

    Frei, E; Visco, C; Xu-Monette, Z Y;

    2013-01-01

    High levels of cyclin E (CCNE) are accompanied by shorter survival in cyclophosphamide, hydroxydaunorubicin, oncovin and prednisone (CHOP)-treated diffuse large B-cell lymphomas (DLBCL), independent of the international prognostic index (IPI). Data on the prognostic role of CCNE in the 'rituximab...

  12. Multiplex polymerase chain reaction-based prognostic models in diffuse large B-cell lymphoma patients treated with R-CHOP

    DEFF Research Database (Denmark)

    Green, Tina M; Jensen, Andreas K; Holst, René;

    2016-01-01

    We present a multiplex analysis for genes known to have prognostic value in an attempt to design a clinically useful classification model in patients with diffuse large B-cell lymphoma (DLBCL). Real-time polymerase chain reaction was used to measure transcript levels of 28 relevant genes in 194 de...

  13. Phase III study of ACVBP versus ACVBP plus rituximab for patients with localized low-risk diffuse large B-cell lymphoma (LNH03-1b)

    OpenAIRE

    Ketterer, N; Coiffier, B.; Thieblemont, C.; Fermé, C.; Brière, J; Casasnovas, O.; Bologna, S.; Christian, B.; Connerotte, T.; Récher, C; Bordessoule, D; Fruchart, C.; Delarue, R.; Bonnet, Christophe; Morschhauser, F.

    2013-01-01

    Background The superiority of a chemotherapy with doxorubicin, cyclophosphamide, vindesine, bleomycin and prednisone (ACVBP) in comparaison with cyclophosphamide, doxorubicin, vincristin and prednisone plus radiotherapy for Young patients with localized diffuse large B-cell lymphoma (DLBCL) was previously demonstrated. We report the results of a trial which évaluâtes the role of rituximab combined with ACVBP (R- ACVBP) in these patients. ...

  14. Ran GTPase-activating protein 1 is a therapeutic target in diffuse large B-cell lymphoma.

    Directory of Open Access Journals (Sweden)

    Kung-Chao Chang

    Full Text Available Lymphoma-specific biomarkers contribute to therapeutic strategies and the study of tumorigenesis. Diffuse large B-cell lymphoma (DLBCL is the most common type of malignant lymphoma. However, only 50% of patients experience long-term survival after current treatment; therefore, developing novel therapeutic strategies is warranted. Comparative proteomic analysis of two DLBCL lines with a B-lymphoblastoid cell line (LCL showed differential expression of Ran GTPase-activating protein 1 (RanGAP1 between them, which was confirmed using immunoblotting. Immunostaining showed that the majority of DLBCLs (92%, 46/50 were RanGAP1(+, while reactive lymphoid hyperplasia (n = 12 was RanGAP1(+ predominantly in germinal centers. RanGAP1 was also highly expressed in other B-cell lymphomas (BCL, n = 180 with brisk mitotic activity (B-lymphoblastic lymphoma/leukemia: 93%, and Burkitt lymphoma: 95% or cell-cycle dysregulation (mantle cell lymphoma: 83%, and Hodgkin's lymphoma 91%. Interestingly, serum RanGAP1 level was higher in patients with high-grade BCL (1.71 ± 2.28 ng/mL, n = 62 than in low-grade BCL (0.75 ± 2.12 ng/mL, n = 52 and healthy controls (0.55 ± 1.58 ng/mL, n = 75 (high-grade BCL vs. low-grade BCL, p = 0.002; high-grade BCL vs. control, p < 0.001, Mann-Whitney U test. In vitro, RNA interference of RanGAP1 showed no effect on LCL but enhanced DLBCL cell death (41% vs. 60%; p = 0.035 and cell-cycle arrest (G0/G1: 39% vs. 49%, G2/M: 19.0% vs. 7.5%; p = 0.030 along with decreased expression of TPX2 and Aurora kinases, the central regulators of mitotic cell division. Furthermore, ON 01910.Na (Estybon, a multikinase inhibitor induced cell death, mitotic cell arrest, and hyperphosphorylation of RanGAP1 in DLBCL cell lines but no effects in normal B and T cells. Therefore, RanGAP1 is a promising marker and therapeutic target for aggressive B-cell lymphoma, especially DLBCL.

  15. ctDNA DLBCL Detection Lancet Oncology

    Science.gov (United States)

    Measurement of circulating tumor DNA in blood can be used to detect disease recurrence in patients with a curable form of cancer known as diffuse large B-cell lymphoma (DLBCL). In most patients, measurement of ctDNA enabled detection of microscopic diseas

  16. Role of microRNAs and microRNA machinery in the pathogenesis of diffuse large B-cell lymphoma

    International Nuclear Information System (INIS)

    Deregulation of microRNA (miRNA) expression has been documented in diffuse large B-cell lymphoma (DLBCL). However, the impact of miRNAs and their machinery in DLBCL is not fully determined. Here, we assessed the role of miRNA expression and their processing genes in DLBCL development. Using microarray and RT-qPCR approaches, we quantified global miRNAs and core components of miRNA-processing genes expression in 75 DLBCLs (56 de novo and 19 transformed) and 10 lymph nodes (LN). Differential miRNA signatures were identified between DLBCLs and LNs, or between the de novo and transformed DLBCLs. We also identified subsets of miRNAs associated with germinal center B-cell phenotype, BCL6 and IRF4 expression, and clinical staging. In addition, we showed a significant over-expression of TARBP2 in de novo DLBCLs as compared with LNs, and decreased expression of DROSHA, DICER, TARBP2 and PACT in transformed as compared with de novo cases. Interestingly, cases with high TARBP2 and DROSHA expression had a poorer chemotherapy response. We further showed that TARBP2 can regulate miRNA-processing efficiency in DLBCLs, and its expression inhibition decreases cell growth and increases apoptosis in DLBCL cell lines. Our findings provide new insights for the understanding of miRNAs and its machinery in DLBCL

  17. Rituximab plus Ifosfamide, Carboplatin and Etoposide for T-Cell/Histiocyte-Rich B-Cell Lymphoma Arising in Nodular Lymphocyte-Predominant Hodgkin’s Lymphoma

    Directory of Open Access Journals (Sweden)

    Hyung-Chul Park

    2012-08-01

    Full Text Available A small subset of patients with nodular lymphocyte-predominant Hodgkin’s lymphoma (NLPHLs develop a non-Hodgkin lymphoma either concurrently or subsequently, usuallyT-cell/histiocyte-rich B-cell lymphomas (T/HRBCL, which are subtypes of diffuse large B-cell lymphomas (DLBCL. The standard treatment of DLBCL patients is rituximab-based chemotherapy with cyclophosphamide, adriamycin, vincristine and prednisolone. However, the administration of this chemotherapy regimen to patients with DLBCL arising in NLPHL brings concern about the cardiac toxicity of anthracycline because the majority of these patients had already received anthracycline-based chemotherapy with doxorubicin, bleomycin, vinblastine and dacarbazine at the time of NLPHL. Herein, we report 2 patients with sequential transformation of NLPHL to T/HRBCL. They initially presented with limited-stage NLPHL and subsequently developed T/HRBCL after 16 and 8 months, respectively. At the time of T/HRBCL, they were treated with rituximab, ifosfamide, carboplatin and etoposide, and complete responses were obtained.

  18. Gastrointestinal B-cell lymphomas: From understanding B-cell physiology to classification and molecular pathology

    OpenAIRE

    2012-01-01

    The gut is the most common extranodal site where lymphomas arise. Although all histological lymphoma types may develop in the gut, small and large B-cell lymphomas predominate. The sometimes unexpected finding of a lymphoid lesion in an endoscopic biopsy of the gut may challenge both the clinician (who is not always familiar with lymphoma pathogenesis) and the pathologist (who will often be hampered in his/her diagnostic skill by the limited amount of available tissue). Moreover, the past 2 d...

  19. MUM-1 and bcl-2 Positive Primary Diffuse Large B Cell Non-Hodgkin's Lymphoma of the Colon.

    Science.gov (United States)

    Jurisić, Vladimir; Plećić, Mirjana; Colović, Natasa; Čemerikić-Martinović, Vesna; Janković, Marko; Čolović, Milica

    2016-04-01

    Primary diffuse large B cell lymphoma (DLBCL) presents as a nodal and extranodal disease. The most common extranodal site is the gastrointestinal tract (GI), with the stomach most frequently involved, followed by the small bowel. Primary DLBCL of the large bowel accounts for 0.2%-1.2% of all colonic tumors. We present two patients who underwent radical resections of right colonic tumors. They were diagnosed with primary colonic DLBCL following histological and immunohistochemical testing of the excised tissues, and were determined as being in stage IIE of the disease. The tumors expressed CD20 markers. Both received multi-agent chemotherapy with combined immunotherapy and remain in complete remission at 4 and 5 years. PMID:27041528

  20. Study of BKM120 & Rituximab in Patients With Relapsed or Refractory Indolent B-Cell Lymphoma

    Science.gov (United States)

    2016-06-14

    Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Nodal Marginal Zone B-cell Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Splenic Marginal Zone Lymphoma; Waldenström Macroglobulinemia

  1. Alisertib and Romidepsin in Treating Patients With Relapsed or Refractory B-Cell or T-Cell Lymphomas

    Science.gov (United States)

    2016-06-15

    Recurrent B-Cell Non-Hodgkin Lymphoma; Recurrent Burkitt Lymphoma; Recurrent Diffuse Large B-Cell Lymphoma; Recurrent Follicular Lymphoma; Recurrent Hodgkin Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Mature T- and NK-Cell Non-Hodgkin Lymphoma; Refractory B-Cell Non-Hodgkin Lymphoma; Refractory Burkitt Lymphoma; Refractory Diffuse Large B-Cell Lymphoma; Refractory Follicular Lymphoma; Refractory Hodgkin Lymphoma; Refractory Mantle Cell Lymphoma; Refractory Mature T-Cell and NK-Cell Non-Hodgkin Lymphoma

  2. Diffuse Large B Cell Lymphoma of the Breast

    OpenAIRE

    Feryal Karaca; Vehbi Ercolak; Cigdem Usul Afsar; Meral Gunaldi

    2015-01-01

    Primary breast lymphoma is rarely encountered in Non-Hodgkin Lymphomas. However, if early diagnosis is made, and treatment is started immediately in patients with low grade and stage, patient survival is increased. 39-year old female patient applied us due to a palpable mass. She was diagnosed with the Non-Hodgkin Lymphoma Diffuse Large B Cell Lymphoma after the investigations. Curative external radiotherapy was applied after 6 courses of CHOP-R chemotherapy to the patient with Stage-IIE favo...

  3. Prognostic value of tumor necrosis at CT in diffuse large B-cell lymphoma

    Energy Technology Data Exchange (ETDEWEB)

    Adams, Hugo J.A., E-mail: h.j.a.adams@gmail.com [Department of Radiology and Nuclear Medicine, University Medical Center Utrecht, Utrecht (Netherlands); Klerk, John M.H. de [Department of Nuclear Medicine, Meander Medical Center, Amersfoort (Netherlands); Fijnheer, Rob [Department of Hematology, Meander Medical Center, Amersfoort (Netherlands); Dubois, Stefan V. [Department of Pathology, Meander Medical Center, Amersfoort (Netherlands); Nievelstein, Rutger A.J.; Kwee, Thomas C. [Department of Radiology and Nuclear Medicine, University Medical Center Utrecht, Utrecht (Netherlands)

    2015-03-15

    Highlights: •CT is compulsory for staging newly diagnosed DLBCL. •Approximately 13.7% of DLBCL patients have tumor necrosis at CT. •Tumor necrosis status at CT is not associated with any NCCN-IPI factor. •Patients with tumor necrosis at CT have a significantly worse outcome. -- Abstract: Objective: To determine the prognostic value of tumor necrosis at computed tomography (CT) in newly diagnosed diffuse large B-cell lymphoma (DLBCL). Materials and methods: This retrospective study included 51 patients with newly diagnosed DLBCL who had undergone both unenhanced and intravenous contrast-enhanced CT before R-CHOP (rituximab, cyclophosphamide, hydroxydaunorubicin, oncovin and prednisolone) chemo-immunotherapy. Presence of tumor necrosis was visually and quantitatively assessed at CT. Associations between tumor necrosis status at CT and the National Comprehensive Cancer Network (NCCN) International Prognostic Index (IPI) factors were assessed. Cox regression analysis was used to determine the prognostic impact of NCCN-IPI scores and tumor necrosis status at CT. Results: There were no correlations between tumor necrosis status at CT and the NCCN-IPI factors categorized age (ρ = −0.042, P = 0.765), categorized lactate dehydrogenase (LDH) ratio (ρ = 0.201, P = 0.156), extranodal disease in major organs (φ = −0.245, P = 0.083), Ann Arbor stage III/IV disease (φ = −0.208, P = 0.141), and Eastern Cooperative Oncology Group (ECOG) performance status (φ = 0.015, P = 0.914). In the multivariate Cox proportional hazards model, only tumor necrosis status at CT was an independent predictive factor of progression-free survival (P = 0.003) and overall survival (P = 0.004). Conclusion: The findings of this study indicate the prognostic potential of tumor necrosis at CT in newly diagnosed DLBCL.

  4. Prognostic value of tumor necrosis at CT in diffuse large B-cell lymphoma

    International Nuclear Information System (INIS)

    Highlights: •CT is compulsory for staging newly diagnosed DLBCL. •Approximately 13.7% of DLBCL patients have tumor necrosis at CT. •Tumor necrosis status at CT is not associated with any NCCN-IPI factor. •Patients with tumor necrosis at CT have a significantly worse outcome. -- Abstract: Objective: To determine the prognostic value of tumor necrosis at computed tomography (CT) in newly diagnosed diffuse large B-cell lymphoma (DLBCL). Materials and methods: This retrospective study included 51 patients with newly diagnosed DLBCL who had undergone both unenhanced and intravenous contrast-enhanced CT before R-CHOP (rituximab, cyclophosphamide, hydroxydaunorubicin, oncovin and prednisolone) chemo-immunotherapy. Presence of tumor necrosis was visually and quantitatively assessed at CT. Associations between tumor necrosis status at CT and the National Comprehensive Cancer Network (NCCN) International Prognostic Index (IPI) factors were assessed. Cox regression analysis was used to determine the prognostic impact of NCCN-IPI scores and tumor necrosis status at CT. Results: There were no correlations between tumor necrosis status at CT and the NCCN-IPI factors categorized age (ρ = −0.042, P = 0.765), categorized lactate dehydrogenase (LDH) ratio (ρ = 0.201, P = 0.156), extranodal disease in major organs (φ = −0.245, P = 0.083), Ann Arbor stage III/IV disease (φ = −0.208, P = 0.141), and Eastern Cooperative Oncology Group (ECOG) performance status (φ = 0.015, P = 0.914). In the multivariate Cox proportional hazards model, only tumor necrosis status at CT was an independent predictive factor of progression-free survival (P = 0.003) and overall survival (P = 0.004). Conclusion: The findings of this study indicate the prognostic potential of tumor necrosis at CT in newly diagnosed DLBCL

  5. Composite diffuse large B-cell lymphoma and follicular B-cell lymphoma - case report and review of literature.

    Science.gov (United States)

    Turbatu, Andrei; Stoian, Marilena; Brezean, Iulian; Stoica, Victor Constantin Ion; Colita, Andrei; Dobrea, Camelia; State, Nicoleta; Ionescu, Cosmin; Ivanescu, Ana-Maria; Oprea, Madalina; Ghimici, Cecilia; Lupu, Anca Roxana

    2014-06-01

    Composite lymphoma refers to the co-occurrence of two or more morphologically and immunophenotypically separate lymphomas in the same topographic site at the time of clinical presentation. It is an infrequent type of lymphoid neoplasm, present in lymphoid tissue and may be due to the existence of two genetically related neoplasms such as transformation of a single lymphoma into another more aggressive lymphoma or be due to the presence of two clonally unrelated lymphomas. This paper is presenting a case of diffuse non-Hodgkin large B-cell lymphoma with areas of low grade and high grade follicular non-Hodgkin B-cell lymphoma in a retroperitoneal lymph node and spleen of an 62 year old woman. Histopathological examination and immunohistochemistry features proved the diagnosis of composite lymphoma. PMID:25705280

  6. Composite Diffuse Large B-Cell Lymphoma and Follicular B-Cell Lymphoma – Case Report and Review of Literature

    Science.gov (United States)

    TURBATU, Andrei; STOIAN, Marilena; BREZEAN, Iulian; STOICA, Victor Constantin Ion; COLITA, Andrei; DOBREA, Camelia; STATE, Nicoleta; IONESCU, Cosmin; IVANESCU, Ana-Maria; OPREA, Madalina; GHIMICI, Cecilia; LUPU, Anca Roxana

    2014-01-01

    Composite lymphoma refers to the co-occurrence of two or more morphologically and immunophenotypically separate lymphomas in the same topographic site at the time of clinical presentation. It is an infrequent type of lymphoid neoplasm, present in lymphoid tissue and may be due to the existence of two genetically related neoplasms such as transformation of a single lymphoma into another more aggressive lymphoma or be due to the presence of two clonally unrelated lymphomas. This paper is presenting a case of diffuse non-Hodgkin large B-cell lymphoma with areas of low grade and high grade follicular non-Hodgkin B-cell lymphoma in a retroperitoneal lymph node and spleen of an 62 year old woman. Histopathological examination and immunohistochemistry features proved the diagnosis of composite lymphoma. PMID:25705280

  7. Mature B-cell lymphoma and leukemia in children and adolescents-review of standard chemotherapy regimen and perspectives.

    Science.gov (United States)

    Worch, Jennifer; Rohde, Marius; Burkhardt, Birgit

    2013-09-01

    Mature B-cell non-Hodgkin lymphoma (B-NHL) comprises more than 50% of all non-Hodgkin lymphoma (NHL) in children and adolescents. Many B-NHL subtypes frequently observed in adults are rarely diagnosed in children and adolescents. In this age group, Burkitt lymphoma (BL), Burkitt leukemia or FAB L3 leukemia (B-AL), diffuse large B-cell lymphoma (DLBCL), primary mediastinal large B-cell lymphoma (PMLBL), follicular lymphoma (FL), and aggressive mature B-NHL not further classifiable (B-NHL nfc) are the most common subtypes. Diverse clinical trials demonstrated similar results of current combination chemotherapy regimens succeeding in overall survival rates of more than 80%. However, treatment-related toxicity and the poor prognosis of relapse are serious concerns. Furthermore, specific histological B-NHL subtypes are rare in children and optimal treatment is not established. New treatment modalities are urgently needed for these patient groups. Rituximab, a monoclonal antibody that is already established in the treatment of adults with mature B-NHL, demonstrated promising results in pediatric patients. The definitive role of rituximab in the treatment of children and adolescents with B-NHL needs to be evaluated in prospective controlled clinical trials. This review provides a comprehensive overview of chemotherapy regimens and the perspectives for children and adolescents with mature B-cell lymphoma and leukemia. PMID:23570584

  8. Preclinical Evaluation of the Novel BTK Inhibitor Acalabrutinib in Canine Models of B-Cell Non-Hodgkin Lymphoma.

    Directory of Open Access Journals (Sweden)

    Bonnie K Harrington

    Full Text Available Acalabrutinib (ACP-196 is a second-generation inhibitor of Bruton agammaglobulinemia tyrosine kinase (BTK with increased target selectivity and potency compared to ibrutinib. In this study, we evaluated acalabrutinib in spontaneously occurring canine lymphoma, a model of B-cell malignancy similar to human diffuse large B-cell lymphoma (DLBCL. First, we demonstrated that acalabrutinib potently inhibited BTK activity and downstream effectors in CLBL1, a canine B-cell lymphoma cell line, and primary canine lymphoma cells. Acalabrutinib also inhibited proliferation in CLBL1 cells. Twenty dogs were enrolled in the clinical trial and treated with acalabrutinib at dosages of 2.5 to 20mg/kg every 12 or 24 hours. Acalabrutinib was generally well tolerated, with adverse events consisting primarily of grade 1 or 2 anorexia, weight loss, vomiting, diarrhea and lethargy. Overall response rate (ORR was 25% (5/20 with a median progression free survival (PFS of 22.5 days. Clinical benefit was observed in 30% (6/20 of dogs. These findings suggest that acalabrutinib is safe and exhibits activity in canine B-cell lymphoma patients and support the use of canine lymphoma as a relevant model for human non-Hodgkin lymphoma (NHL.

  9. Ibrutinib Before and After Stem Cell Transplant in Treating Patients With Relapsed or Refractory Diffuse Large B-cell Lymphoma

    Science.gov (United States)

    2016-09-01

    Activated B-Cell-Like Diffuse Large B-Cell Lymphoma; B-Cell Lymphoma, Unclassifiable, With Features Intermediate Between Diffuse Large B-Cell Lymphoma and Burkitt Lymphoma; Recurrent Diffuse Large B-Cell Lymphoma; Refractory Diffuse Large B-Cell Lymphoma

  10. EBV-positive diffuse large B-cell lymphoma of the elderly: 2016 update on diagnosis, risk-stratification, and management.

    Science.gov (United States)

    Castillo, Jorge J; Beltran, Brady E; Miranda, Roberto N; Young, Ken H; Chavez, Julio C; Sotomayor, Eduardo M

    2016-05-01

    Epstein-Barr virus (EBV)-positive diffuse large B-cell lymphoma (DLBCL) of the elderly is a provisional entity included in the 2008 WHO classification of lymphoid neoplasms. It is a disease typically seen in the elderly and thought to be associated with chronic EBV infection and severe immunosuppression with a component of immunosenescence. Recent research, however, has suggested that EBV-positive DLBCL can be seen in younger, immunocompetent patients. The diagnosis of EBV-positive DLBCL of the elderly is made through a careful pathological evaluation. The differential diagnosis includes infectious mononucleosis (specifically in younger patients), lymphomatoid granulomatosis, Hodgkin lymphoma, and gray zone lymphoma, among others. Detection of EBV-encoded RNA (EBER) is considered standard for diagnosis; however, a clear cutoff for positivity has not been defined. The International Prognostic Index (IPI), and the Oyama score can be used for risk-stratification. The Oyama score includes age >70 years and presence of B symptoms. The expression of CD30 is emerging as a potential adverse, and targetable, prognostic factor. Patients with EBV-positive DLBCL should be staged and managed following similar guidelines than patients with EBV-negative DLBCL. It has been suggested, however, that EBV-positive patients have a worse prognosis than EBV-negative counterparts in the era of chemoimmunotherapy. There is an opportunity to study and develop targeted therapy in the management of patients with EBV-positive DLBCL. Am. J. Hematol. 91:530-537, 2016. © 2016 Wiley Periodicals, Inc. PMID:27093913

  11. Diffuse large B-Cell lymphoma: a clinico- pathologic and prognostic study on 1470 biopsy specimens

    Directory of Open Access Journals (Sweden)

    Sadighi S

    2009-11-01

    Full Text Available "n Normal 0 false false false EN-US X-NONE AR-SA MicrosoftInternetExplorer4 /* Style Definitions */ table.MsoNormalTable {mso-style-name:"Table Normal"; mso-tstyle-rowband-size:0; mso-tstyle-colband-size:0; mso-style-noshow:yes; mso-style-priority:99; mso-style-qformat:yes; mso-style-parent:""; mso-padding-alt:0in 5.4pt 0in 5.4pt; mso-para-margin:0in; mso-para-margin-bottom:.0001pt; mso-pagination:widow-orphan; font-size:11.0pt; font-family:"Calibri","sans-serif"; mso-ascii-font-family:Calibri; mso-ascii-theme-font:minor-latin; mso-fareast-font-family:"Times New Roman"; mso-fareast-theme-font:minor-fareast; mso-hansi-font-family:Calibri; mso-hansi-theme-font:minor-latin; mso-bidi-font-family:Arial; mso-bidi-theme-font:minor-bidi;} Background: Diffuse large B Cell lymphoma (DLBCL is the most common subtype of non-Hogkin lymphoma (NHL. We performed a retrospective study of patients with de novo DLBCL treated in the Medical Oncology department of Cancer Institute of Iran, Tehran to assess the clinicopathologic and immunohistochemistry correlation and prognosis of the patients. "n"nMethods: World Health Organization (WHO classification was used to reexamine 1470 biopsy specimens related to the years 1985-2006. After excluding five cases of T Cell large cell lymphoma, 50 Patients diagnosed as DLBCL. "n"nResults: Median age of the patients was 45.5(20-85 years: 60% were male and 30% had primary extranodal disease. The most common extranodal sites were bone, gastrointestinal tract and Head and neck areas. The most common stages were stage II (32%, stage III (32%, stage IV (20% and stage I (16% retrospectively and 33% had B-symptoms. All of The Patients received chemotherapy (83% CHOP regimen and 46% treated by radiotherapy after chemotherapy. With a mean follow up time of 32 months, median survival time was 34 (95% CI 24-40 months. Prognostic factors for survival were tumor stage, B-symptoms and early relapse (less than 6 months."n"nConclusions: Our

  12. Gastrointestinal B-cell lymphomas: From understanding B-cell physiology to classification and molecular pathology.

    Science.gov (United States)

    Sagaert, Xavier; Tousseyn, Thomas; Yantiss, Rhonda K

    2012-12-15

    The gut is the most common extranodal site where lymphomas arise. Although all histological lymphoma types may develop in the gut, small and large B-cell lymphomas predominate. The sometimes unexpected finding of a lymphoid lesion in an endoscopic biopsy of the gut may challenge both the clinician (who is not always familiar with lymphoma pathogenesis) and the pathologist (who will often be hampered in his/her diagnostic skill by the limited amount of available tissue). Moreover, the past 2 decades have spawned an avalanche of new data that encompasses both the function of the reactive B-cell as well as the pathogenic pathways that lead to its neoplastic counterpart, the B-cell lymphoma. Therefore, this review aims to offer clinicians an overview of B-cell lymphomas in the gut, and their pertinent molecular features that have led to new insights regarding lymphomagenesis. It addresses the question as how to incorporate all presently available information on normal and neoplastic B-cell differentiation, and how this knowledge can be applied in daily clinical practice (e.g., diagnostic tools, prognostic biomarkers or therapeutic targets) to optimalise the managment of this heterogeneous group of neoplasms. PMID:23443141

  13. Low HIP1R mRNA and protein expression are associated with worse survival in diffuse large B-cell lymphoma patients treated with R-CHOP

    DEFF Research Database (Denmark)

    Wong, K. K.; Ch'ng, E. S.; Loo, S. K.;

    2015-01-01

    Huntingtin-interacting protein 1-related (HIP1R) is an endocytic protein involved in receptor trafficking, including regulating cell surface expression of receptor tyrosine kinases. We have previously shown that low HIP1R protein expression was associated with poorer survival in diffuse large B......-cell lymphoma (DLBCL) patients from Denmark treated with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone). In this multicenter study, we extend these findings and validate the prognostic and subtyping utility of HIP1R expression at both transcript and protein level. Using data mining......<0.05) in a microarray-profiled DLBCL dataset At the protein level examined by immunohistochemistry, HIP1R expression at 30% cut-off was associated with GCB-DLBCL molecular subtype (P = 0.0004; n = 42), and predictive of OS (P = 0.0006) and PFS (P = 0.0230) in de novo DLBCL patients treated with R...

  14. Gene Mutation Profiles in Primary Diffuse Large B Cell Lymphoma of Central Nervous System: Next Generation Sequencing Analyses.

    Science.gov (United States)

    Todorovic Balint, Milena; Jelicic, Jelena; Mihaljevic, Biljana; Kostic, Jelena; Stanic, Bojana; Balint, Bela; Pejanovic, Nadja; Lucic, Bojana; Tosic, Natasa; Marjanovic, Irena; Stojiljkovic, Maja; Karan-Djurasevic, Teodora; Perisic, Ognjen; Rakocevic, Goran; Popovic, Milos; Raicevic, Sava; Bila, Jelena; Antic, Darko; Andjelic, Bosko; Pavlovic, Sonja

    2016-01-01

    The existence of a potential primary central nervous system lymphoma-specific genomic signature that differs from the systemic form of diffuse large B cell lymphoma (DLBCL) has been suggested, but is still controversial. We investigated 19 patients with primary DLBCL of central nervous system (DLBCL CNS) using the TruSeq Amplicon Cancer Panel (TSACP) for 48 cancer-related genes. Next generation sequencing (NGS) analyses have revealed that over 80% of potentially protein-changing mutations were located in eight genes (CTNNB1, PIK3CA, PTEN, ATM, KRAS, PTPN11, TP53 and JAK3), pointing to the potential role of these genes in lymphomagenesis. TP53 was the only gene harboring mutations in all 19 patients. In addition, the presence of mutated TP53 and ATM genes correlated with a higher total number of mutations in other analyzed genes. Furthermore, the presence of mutated ATM correlated with poorer event-free survival (EFS) (p = 0.036). The presence of the mutated SMO gene correlated with earlier disease relapse (p = 0.023), inferior event-free survival (p = 0.011) and overall survival (OS) (p = 0.017), while mutations in the PTEN gene were associated with inferior OS (p = 0.048). Our findings suggest that the TP53 and ATM genes could be involved in the molecular pathophysiology of primary DLBCL CNS, whereas mutations in the PTEN and SMO genes could affect survival regardless of the initial treatment approach. PMID:27164089

  15. Gene Mutation Profiles in Primary Diffuse Large B Cell Lymphoma of Central Nervous System: Next Generation Sequencing Analyses

    Science.gov (United States)

    Todorovic Balint, Milena; Jelicic, Jelena; Mihaljevic, Biljana; Kostic, Jelena; Stanic, Bojana; Balint, Bela; Pejanovic, Nadja; Lucic, Bojana; Tosic, Natasa; Marjanovic, Irena; Stojiljkovic, Maja; Karan-Djurasevic, Teodora; Perisic, Ognjen; Rakocevic, Goran; Popovic, Milos; Raicevic, Sava; Bila, Jelena; Antic, Darko; Andjelic, Bosko; Pavlovic, Sonja

    2016-01-01

    The existence of a potential primary central nervous system lymphoma-specific genomic signature that differs from the systemic form of diffuse large B cell lymphoma (DLBCL) has been suggested, but is still controversial. We investigated 19 patients with primary DLBCL of central nervous system (DLBCL CNS) using the TruSeq Amplicon Cancer Panel (TSACP) for 48 cancer-related genes. Next generation sequencing (NGS) analyses have revealed that over 80% of potentially protein-changing mutations were located in eight genes (CTNNB1, PIK3CA, PTEN, ATM, KRAS, PTPN11, TP53 and JAK3), pointing to the potential role of these genes in lymphomagenesis. TP53 was the only gene harboring mutations in all 19 patients. In addition, the presence of mutated TP53 and ATM genes correlated with a higher total number of mutations in other analyzed genes. Furthermore, the presence of mutated ATM correlated with poorer event-free survival (EFS) (p = 0.036). The presence of the mutated SMO gene correlated with earlier disease relapse (p = 0.023), inferior event-free survival (p = 0.011) and overall survival (OS) (p = 0.017), while mutations in the PTEN gene were associated with inferior OS (p = 0.048). Our findings suggest that the TP53 and ATM genes could be involved in the molecular pathophysiology of primary DLBCL CNS, whereas mutations in the PTEN and SMO genes could affect survival regardless of the initial treatment approach. PMID:27164089

  16. Primary bladder lymphoma, diffuse large B-cell type: Case report and literature review of 26 cases

    Directory of Open Access Journals (Sweden)

    W Greg Simpson

    2015-01-01

    Full Text Available Primary lymphoma of the urinary bladder is exceedingly rare, representing 0.2% of all extranodal non-Hodgkin′s lymphoma. Although Matsuno et al. and others state the most common type is mucosa-associated lymphoid tissue (MALT lymphoma, 20% of all the primary lymphomas of the urinary bladder are considered to be high grade neoplasms; the majority being diffuse large B-cell lymphoma (DLBCL. This is a case report of a 48-year-old man that presented with hematuria, frequency, nocturia, and flank pain that was found to have high grade DLBCL. Twenty-six other cases of both low and high grade primary bladder lymphomas were selected in order to provide a thorough comparison of different treatment modalities. Of the cases reviewed, bladder lymphoma was more common in females (2:1. The average age at diagnosis was 63.9 years old (low grade: 68.7 years old, high grade: 58.8 years old. The most common low-grade neoplasm was MALT lymphoma (85.7%. For the low-grade malignancies, the most successful treatments were simple therapies (2 transurethral resection of a bladder tumour [TURBT], 1 antibiotics, solitary chemotherapy, and combination TURBT/chemo; all 3 of which achieved 100% clinical remission (CR in the cases reviewed. The most common high grade neoplasm was DLBCL (76.9%. The most successful therapies used to treat high grade lesions were solitary chemotherapy (cyclophosphamide, duanorubacin, vincristine, prednisolone [CHOP] or ritoximab, CHOP [R-CHOP] and combination therapies (2 radiation/CHOP, 2 surgery/CHOP. In the agreement with the current literature, this review has shown that simple therapies (TURBT are equally as effective as aggressive treatments (chemotherapy, radiation and should therefore be used as first line treatment in low grade tumors. For high grade malignancies, chemotherapy (R-CHOP or CHOP alone or combination therapy (CHOP/surgery or CHOP/radiation is recommended.

  17. Microenvironment-Centred Dynamics in Aggressive B-Cell Lymphomas

    Directory of Open Access Journals (Sweden)

    Matilde Cacciatore

    2012-01-01

    Full Text Available Aggressive B-cell lymphomas share high proliferative and invasive attitudes and dismal prognosis despite heterogeneous biological features. In the interchained sequence of events leading to cancer progression, neoplastic clone-intrinsic molecular events play a major role. Nevertheless, microenvironment-related cues have progressively come into focus as true determinants for this process. The cancer-associated microenvironment is a complex network of nonneoplastic immune and stromal cells embedded in extracellular components, giving rise to a multifarious crosstalk with neoplastic cells towards the induction of a supportive milieu. The immunological and stromal microenvironments have been classically regarded as essential partners of indolent lymphomas, while considered mainly negligible in the setting of aggressive B-cell lymphomas that, by their nature, are less reliant on external stimuli. By this paper we try to delineate the cardinal microenvironment-centred dynamics exerting an influence over lymphoid clone progression in aggressive B-cell lymphomas.

  18. Primary Testicular B-cell Lymphoma

    OpenAIRE

    Aykut Buğra Şentürk; Musa Ekici; Hamit Ersoy

    2015-01-01

    Primary testicular lymphoma constitutes only 1-7% of all testicular neoplasms and less than 1% of all non-Hodgkin lymphoma. We report a 69-year-old man who presented with a painful right testicular mass. Treatment modalities consist of surgical excision, chemotherapy and radiation therapy, however there are no standardized treatment options.

  19. Primary Testicular B-cell Lymphoma

    Directory of Open Access Journals (Sweden)

    Aykut Buğra Şentürk

    2015-12-01

    Full Text Available Primary testicular lymphoma constitutes only 1-7% of all testicular neoplasms and less than 1% of all non-Hodgkin lymphoma. We report a 69-year-old man who presented with a painful right testicular mass. Treatment modalities consist of surgical excision, chemotherapy and radiation therapy, however there are no standardized treatment options.

  20. PET Scans for Staging and Restaging in Diffuse Large B-Cell and Follicular Lymphomas.

    Science.gov (United States)

    Barrington, Sally F; Mikhaeel, N George

    2016-06-01

    Positron emission tomography (PET)-CT was recommended in updated international guidelines for staging/restaging of diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL). In FL, PET was previously regarded as a research application only. This review concentrates on new publications related to PET in these diseases. In DLBCL, PET appears appropriate for staging using prognostic indices established with CT and baseline PET parameters, e.g. metabolic tumour volume, are prognostic of outcome. Early complete metabolic response (CMR) predicts end-of-treatment CMR with excellent prognosis. Patients without CMR at interim should not have treatment altered, but have a worse prognosis, and patients with other high risk features may need closer monitoring. The end-of-treatment scan is confirmed as the standard for remission assessment using Deauville criteria, which are also predictive for patients undergoing ASCT. In FL, PET is more sensitive for staging than CT but misses bone marrow involvement. PET-CT identifies patients at risk of progression after induction chemotherapy better than CT. PMID:27095319

  1. Comparative Study on Rituximab Combined with Chemotherapy and Single Chemotherapy for Diffuse Large B Cell Lymphoma

    Institute of Scientific and Technical Information of China (English)

    FENG Ji-feng

    2015-01-01

    Objective:To explore the clinical efifcacy and safety of rituximab combined with chemotherapy and single chemotherapy for diffuse large B cell lymphoma (DLBCL). Methods:A total of 97 patients with DLBCL were selected. Patients treated by single chemotherapy were designed as control group, while those by rituximab combined with chemotherapy as observational group. All patients were treated for at least 4 cycles. The short-term and long-term efifcacy and related adverse reactions of 2 groups were observed. Results:The rate of complete remission (CR) in observational group was signiifcantly higher than in control group (χ2=4.6589,P=0.0309). However, there was no signiifcant difference in objective remission rate (ORR) between 2 groups (P=0.3651). The rates of 3-year overall survival (OS), progression-free survival (PFS) and disease-free survival (DFS) were 80.30% (53/66), 69.70% (46/66) and 59.09% (39/66) in observational group, and 61.29% (19/31), 58.06% (18/31) and 58.06% (18/31) in control group, respectively. The OS in observational group was signiifcantly longer than in control group (P=0.035). However, there was no signiifcant difference in PFS, DFS and rate adverse reactions between 2 groups (P=0.089;P=0.438;χ2=0.1562,P=0.6927). Conclusion: Rituximab combined with chemotherapy can improve the efficacy of DLBCL without increasing the adverse reactions, which can be used as the ifrst-line treatment for DLBCL, thus deserving to be widely applied in clinic.

  2. Sarcopenia is an independent prognostic factor in male patients with diffuse large B-cell lymphoma.

    Science.gov (United States)

    Nakamura, Nobuhiko; Hara, Takeshi; Shibata, Yuhei; Matsumoto, Takuro; Nakamura, Hiroshi; Ninomiya, Soranobu; Kito, Yusuke; Kitagawa, Junichi; Kanemura, Nobuhiro; Goto, Naoe; Shiraki, Makoto; Miyazaki, Tatsuhiko; Takeuchi, Tamotsu; Shimizu, Masahito; Tsurumi, Hisashi

    2015-12-01

    Sarcopenia reportedly predicts poor outcomes in elderly patients with diffuse large B-cell lymphoma (DLBCL). However, because previous studies only involved elderly patients, it is difficult to generalize these results to all patients with DLBCL. We retrospectively analyzed 207 patients with DLBCL who received the R-CHOP or R-THP-COP regimen between June 2004 and May 2014. Sarcopenia was measured by the analysis of CT images at the L3 level before treatment. The surface of muscular tissues was selected according to the CT Hounsfield unit. This value was normalized for stature in order to calculate the L3 skeletal muscle index (L3 SMI, cm(2)/m(2)). Median age at diagnosis in the 121 males and 86 females was 67 years (range, 19-86 years). The sex-specific cutoffs for the L3 SMI were determined by receiver operator curve (ROC) analysis. Sarcopenic patients were older than non-sarcopenic patients, with a median age of 70 and 65 years, respectively (p sarcopenic and non-sarcopenic patients. With a median follow-up of 50.4 months, the 3-year overall survival (OS) was 70 % in the sarcopenic group and 85 % in the non-sarcopenic group (p = 0.0260). In a subgroup analysis by gender, there was a significant difference in the OS when comparing sarcopenic and non-sarcopenic patients in males but not in females (p = 0.0003, p = 0.4440, respectively). Sarcopenia is an independent prognostic factor in male patients with DLBCL. PMID:26385388

  3. R-ICE and Lenalidomide in Treating Patients With First-Relapse/Primary Refractory Diffuse Large B-Cell Lymphoma

    Science.gov (United States)

    2015-12-30

    Diffuse Large B-Cell Lymphoma; Recurrent Diffuse Large B-Cell Lymphoma; Recurrent Mediastinal (Thymic) Large B-Cell Cell Lymphoma; Refractory Diffuse Large B-Cell Lymphoma; Refractory Mediastinal (Thymic) Large B-Cell Cell Lymphoma; Transformed Recurrent Non-Hodgkin Lymphoma

  4. Immunoproliferative Small Intestinal Disease Associated with Overwhelming Polymicrobial Gastrointestinal Infection with Transformation to Diffuse Large B-cell Lymphoma.

    Science.gov (United States)

    Ewers, Evan C; Sheffler, Robert L; Wang, James; Ngauy, Viseth

    2016-05-01

    Immunoproliferative small intestinal disease (IPSID) is an extra-nodal B-cell lymphoma most commonly described in the Mediterranean, Africa, and Asia. It is associated with poverty and poor sanitation, and is rarely encountered in developed countries. A 26-year-old previously healthy, Marshallese male was transferred to our facility with a 6-month history of watery diarrhea, weakness, and cachexia refractory to multiple short courses of oral antibiotics. Stool cultures grew Campylobacter jejuni and Vibrio fluvialis. Endoscopic evaluation showed histologic evidence of Helicobacter pylori gastritis and gross evidence of whipworm infection found in the colon. Mesenteric lymph node biopsy cultures grew Escherichia coli. Histopathology and immunohistochemical stains of the small intestine were consistent with IPSID. He subsequently transformed to diffuse large B-cell lymphoma (DLBCL) with tonsillar involvement despite treatment with rituximab and an extended course of antibiotics. Systemic chemotherapy with six cycles of rituximab, cyclophosphamide, vincristine, doxorubicin, prednisone, and lenalidomide, resulted in remission of his diffuse B cell lymphoma. This case is illustrative of IPSID developing in a previously healthy individual due to overwhelming polymicrobial gastrointestinal infection by C. jejuni and other enteric pathogens with subsequent transformation to an aggressive DLBCL. IPSID should be considered in residents of developing countries presenting with refractory chronic diarrhea, weight loss, and mesenteric lymphadenopathy. PMID:26903604

  5. PMA/IONO affects diffuse large B-cell lymphoma cell growth through upregulation of A20 expression.

    Science.gov (United States)

    Yang, Wenxiu; Li, Yi; Li, Pinhao; Wang, Lingling

    2016-08-01

    Diffuse large B-cell lymphoma (DLBCL) is a common non-Hodgkin lymphoma. A20 and mucosa-associated lymphoid tissue lymphoma translocation gene 1 (MALT1) are known to be related to DLBCL pathogenesis and progression. This study aimed to assess the effects of phorbol myristate acetate/ionomycin (PMA/IONO) on the growth and apoptosis of the DLBCL cell line OCI-LY1, and their associations with A20, MALT1 and survivin levels. Cell viability was assessed by MTT assay. Cell cycle distribution and apoptosis were evaluated using flow cytometry after incubation with Annexin V-FITC/propidium iodide (PI) and RNase/PI, respectively. Gene and protein expression levels were determined by quantitative real-time PCR and western blotting, respectively. To further determine the role of A20, this gene was silenced in the OCI-LY1 cell line by specific siRNA transfection. A20 protein levels were higher in the OCI-LY1 cells treated with PMA/IONO compared with the controls, and were positively correlated with the concentration and treatment time of IONO, but not with changes of PMA and MALT1. Meanwhile, survivin expression was reduced in the OCI-LY1 cells after PMA/IONO treatment. In addition, OCI-LY1 proliferation was markedly inhibited, with a negative correlation between cell viability and IONO concentration. In concordance, apoptosis rates were higher in the OCI-LY1 cells after PMA + IONO treatment. Cell cycle distribution differed between the OCI-LY1 cells with and without PMA/IONO treatment only at 24 h, with increased cells in the G0/G1 stage after PMA/IONO treatment. These findings indicate that PMA/IONO promotes the apoptosis and inhibits the growth of DLBCL cells, in association with A20 upregulation. Thus, A20 may be a potential therapeutic target for DLBCL. PMID:27349720

  6. The histone lysine methyltransferase KMT2D sustains a gene expression program that represses B cell lymphoma development

    Science.gov (United States)

    Ortega-Molina, Ana; Boss, Isaac W.; Canela, Andres; Pan, Heng; Jiang, Yanwen; Zhao, Chunying; Jiang, Man; Hu, Deqing; Agirre, Xabier; Niesvizky, Itamar; Lee, Ji-Eun; Chen, Hua-Tang; Ennishi, Daisuke; Scott, David W.; Mottok, Anja; Hother, Christoffer; Liu, Shichong; Cao, Xing-Jun; Tam, Wayne; Shaknovich, Rita; Garcia, Benjamin A.; Gascoyne, Randy D.; Ge, Kai; Shilatifard, Ali; Elemento, Olivier; Nussenzweig, Andre; Melnick, Ari M.; Wendel, Hans-Guido

    2015-01-01

    The lysine-specific histone methyltransferase KMT2D has emerged as one of the most frequently mutated genes in follicular lymphoma (FL) and diffuse large B cell lymphoma (DLBCL). However, the biological consequences of KMT2D mutations on lymphoma development are not known. Here we show that KMT2D functions as a bona fide tumor suppressor and that its genetic ablation in B cells promotes lymphoma development in mice. KMT2D deficiency also delays germinal center (GC) involution, impedes B cell differentiation and class switch recombination (CSR). Integrative genomic analyses indicate that KMT2D affects H3K4 methylation and expression of a specific set of genes including those in the CD40, JAK-STAT, Toll-like receptor, and B cell receptor pathways. Notably, other KMT2D target genes include frequently mutated tumor suppressor genes such as TNFAIP3, SOCS3, and TNFRSF14. Therefore, KMT2D mutations may promote malignant outgrowth by perturbing the expression of tumor suppressor genes that control B cell activating pathways. PMID:26366710

  7. Diagnosis and therapy of primary lung diffuse large B cell lymphoma: a case report%原发性肺大B细胞淋巴瘤诊断治疗一例报道

    Institute of Scientific and Technical Information of China (English)

    Lei Zhou; Li Duan; Min Hu

    2009-01-01

    Objective: We studied the diagnosis and therapy of primary lung diffuse large B cell lymphoma (DLBCL). Meth-ods: Analysis the clinical manifestations, pathologic character and immunohistochemical character of one tung diffuse B cell lymphoma patent. Results: In visual observation, it's a gray irregular Iobulated mass, section was gray, fish-like, and number of necrotic foci. Observed under the microscope, subepithelial respiratory center oocyte-like cells diffuse proliferative, infiltra-tion in lung tissue. Immunohistochemistry: CDJ0 (+), CD790 (+), CD3 (-), CD45RO (-), PCK (-). Conclusion: Diffuse large B cell lymphoma is the most common subtype in non-Hodgkin lymphoma, but the primary lung diffuse large B cell lymphoma is rare. This disease is lack of typical clinical manifestations, so easily misdiagnosed. The diagnosis of diffuse large B cell lymphoma should be based on pathology and immunohistochemistry.

  8. 复发难治性弥漫大B细胞淋巴瘤的生物靶向治疗%Biological targeted treatment of refractory / relapsed diffuse large B-cell lymphoma

    Institute of Scientific and Technical Information of China (English)

    刘宁

    2016-01-01

    含有利妥昔单抗的化疗方案能改善弥漫大B细胞淋巴瘤(DLBCL)患者的预后,然而仍有部分患者在一线应用R-CHOP方案后转为复发难治性DLBCL(RR-DLBCL),且预后不良.对DLBCL及其相关肿瘤基因表达研究证实基因水平的生物靶向治疗能改善RR-DLBCL患者的预后.目前,一些新的靶向治疗成为研究热点.文章就RR-DLBCL的生物靶向治疗进展进行综述.%Diffuse large B-cell lymphoma (DLBCL) is the aggressive non-Hodgkin's lymphoma.Rituximab in combination with chemotherapy had improved the outcomes,however,a substantial proportion of these patients transfer into refractory or eventually relapsed lymphoma after using R-CHOP as a front-line treatment regimen with poor prognosis.With the research development on DLBCL and its related gene,it is confirmed that gene biological targeted therapy can improve the prognosis of patients with refractory /relapsed DLBCL (RR-DLBCL).Recently,some new targeted therapies become research hotspots.This review will focus on recent development and future direction of biological targeted treatment in RR-DLBCL.

  9. Immunohistochemical and molecular characteristics with prognostic significance in diffuse large B-cell lymphoma.

    Directory of Open Access Journals (Sweden)

    Carmen Bellas

    Full Text Available Diffuse large B-cell lymphoma (DLBCL is an aggressive non-Hodgkin lymphoma with marked biologic heterogeneity. We analyzed 100 cases of DLBCL to evaluate the prognostic value of immunohistochemical markers derived from the gene expression profiling-defined cell origin signature, including MYC, BCL2, BCL6, and FOXP1 protein expression. We also investigated genetic alterations in BCL2, BCL6, MYC and FOXP1 using fluorescence in situ hybridization and assessed their prognostic significance. BCL6 rearrangements were detected in 29% of cases, and BCL6 gene alteration (rearrangement and/or amplification was associated with the non-germinal center B subtype (non-GCB. BCL2 translocation was associated with the GCB phenotype, and BCL2 protein expression was associated with the translocation and/or amplification of 18q21. MYC rearrangements were detected in 15% of cases, and MYC protein expression was observed in 29% of cases. FOXP1 expression, mainly of the non-GCB subtype, was demonstrated in 37% of cases. Co-expression of the MYC and BCL2 proteins, with non-GCB subtype predominance, was observed in 21% of cases. We detected an association between high FOXP1 expression and a high proliferation rate as well as a significant positive correlation between MYC overexpression and FOXP1 overexpression. MYC, BCL2 and FOXP1 expression were significant predictors of overall survival. The co-expression of MYC and BCL2 confers a poorer clinical outcome than MYC or BCL2 expression alone, whereas cases negative for both markers had the best outcomes. Our study confirms that DLBCL, characterized by the co-expression of MYC and BCL2 proteins, has a poor prognosis and establishes a significant positive correlation with MYC and FOXP1 over-expression in this entity.

  10. Y-box-binding protein-1 (YB-1) promotes cell proliferation, adhesion and drug resistance in diffuse large B-cell lymphoma.

    Science.gov (United States)

    Miao, Xiaobing; Wu, Yaxun; Wang, Yuchan; Zhu, Xinghua; Yin, Haibing; He, Yunhua; Li, Chunsun; Liu, Yushan; Lu, Xiaoyun; Chen, Yali; Shen, Rong; Xu, Xiaohong; He, Song

    2016-08-15

    YB-1 is a multifunctional protein, which has been shown to correlate with resistance to treatment of various tumor types. This study investigated the expression and biologic function of YB-1 in diffuse large B-cell lymphoma (DLBCL). Immunohistochemical analysis showed that the expression statuses of YB-1 and pYB-1(S102) were reversely correlated with the clinical outcomes of DLBCL patients. In addition, we found that YB-1 could promote the proliferation of DLBCL cells by accelerating the G1/S transition. Ectopic expression of YB-1 could markedly increase the expression of cell cycle regulators cyclin D1 and cyclin E. Furthermore, we found that adhesion of DLBCL cells to fibronectin (FN) could increase YB-1 phosphorylation at Ser102 and pYB-1(S102) nuclear translocation. In addition, overexpression of YB-1 could increase the adhesion of DLBCL cells to FN. Intriguingly, we found that YB-1 overexpression could confer drug resistance through cell-adhesion dependent and independent mechanisms in DLBCL. Silencing of YB-1 could sensitize DLBCL cells to mitoxantrone and overcome cell adhesion-mediated drug resistance (CAM-DR) phenotype in an AKT-dependent manner. PMID:27397581

  11. SPIB and BATF provide alternate determinants of IRF4 occupancy in diffuse large B-cell lymphoma linked to disease heterogeneity.

    Science.gov (United States)

    Care, Matthew A; Cocco, Mario; Laye, Jon P; Barnes, Nicholas; Huang, Yuanxue; Wang, Ming; Barrans, Sharon; Du, Ming; Jack, Andrew; Westhead, David R; Doody, Gina M; Tooze, Reuben M

    2014-07-01

    Interferon regulatory factor 4 (IRF4) is central to the transcriptional network of activated B-cell-like diffuse large B-cell lymphoma (ABC-DLBCL), an aggressive lymphoma subgroup defined by gene expression profiling. Since cofactor association modifies transcriptional regulatory input by IRF4, we assessed genome occupancy by IRF4 and endogenous cofactors in ABC-DLBCL cell lines. IRF4 partners with SPIB, PU.1 and BATF genome-wide, but SPIB provides the dominant IRF4 partner in this context. Upon SPIB knockdown IRF4 occupancy is depleted and neither PU.1 nor BATF acutely compensates. Integration with ENCODE data from lymphoblastoid cell line GM12878, demonstrates that IRF4 adopts either SPIB- or BATF-centric genome-wide distributions in related states of post-germinal centre B-cell transformation. In primary DLBCL high-SPIB and low-BATF or the reciprocal low-SPIB and high-BATF mRNA expression links to differential gene expression profiles across nine data sets, identifying distinct associations with SPIB occupancy, signatures of B-cell differentiation stage and potential pathogenetic mechanisms. In a population-based patient cohort, SPIBhigh/BATFlow-ABC-DLBCL is enriched for mutation of MYD88, and SPIBhigh/BATFlow-ABC-DLBCL with MYD88-L265P mutation identifies a small subgroup of patients among this otherwise aggressive disease subgroup with distinct favourable outcome. We conclude that differential expression of IRF4 cofactors SPIB and BATF identifies biologically and clinically significant heterogeneity among ABC-DLBCL. PMID:24875472

  12. Outcome and pathologic classification of children and adolescents with mediastinal large B-cell lymphoma treated with FAB/LMB96 mature B-NHL therapy

    OpenAIRE

    Gerrard, Mary; Waxman, Ian M.; Sposto, Richard; Auperin, Anne; Perkins, Sherrie L.; Goldman, Stanton; Harrison, Lauren; Pinkerton, Ross; McCarthy, Keith; Raphael, Martine; Patte, Catherine; Cairo, Mitchell S

    2013-01-01

    Mediastinal large B-cell lymphoma (MLBL) represents 2% of mature B-cell non-Hodgkin lymphoma in patients ≤ 18 years of age. We analyzed data from childhood and adolescent patients with stage III MLBL (n = 42) and non-MLBL DLBCL (n = 69) treated with Group B therapy in the French-American-British/Lymphome Malins de Burkitt (FAB/LMB) 96 study. MLBL patients had a male/female 26/16; median age, 15.7 years (range, 12.5-19.7); and LDH < 2 versus ≥ 2 × the upper limit of normal, 23:19. Six MLBL pat...

  13. Alisertib With and Without Rituximab in Treating Patients With Relapsed or Refractory B-Cell Non-Hodgkin Lymphoma

    Science.gov (United States)

    2016-07-15

    Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Nodal Marginal Zone B-cell Lymphoma; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Splenic Marginal Zone Lymphoma; Waldenström Macroglobulinemia

  14. MLN0905, a small-molecule plk1 inhibitor, induces antitumor responses in human models of diffuse large B-cell lymphoma.

    Science.gov (United States)

    Shi, Judy Quiju; Lasky, Kerri; Shinde, Vaishali; Stringer, Bradley; Qian, Mark G; Liao, Debra; Liu, Ray; Driscoll, Denise; Nestor, Michelle Tighe; Amidon, Benjamin S; Rao, Youlan; Duffey, Matt O; Manfredi, Mark G; Vos, Tricia J; D' Amore, Natalie; Hyer, Marc L

    2012-09-01

    Diffuse large B-cell lymphoma (DLBCL) is the most common of the non-Hodgkin lymphomas, accounting for up to 30% of all newly diagnosed lymphoma cases. Current treatment options for this disease are effective, but not always curative; therefore, experimental therapies continue to be investigated. We have discovered an experimental, potent, and selective small-molecule inhibitor of PLK1, MLN0905, which inhibits cell proliferation in a broad range of human tumor cells including DLBCL cell lines. In our report, we explored the pharmacokinetic, pharmacodynamic, and antitumor properties of MLN0905 in DLBCL xenograft models grown in mice. These studies indicate that MLN0905 modulates the pharmacodynamic biomarker phosphorylated histone H3 (pHisH3) in tumor tissue. The antitumor activity of MLN0905 was evaluated in three human subcutaneous DLBCL xenograft models, OCI LY-10, OCI LY-19, and PHTX-22L (primary lymphoma). In each model, MLN0905 yielded significant antitumor activity on both a continuous (daily) and intermittent dosing schedule, underscoring dosing flexibility. The antitumor activity of MLN0905 was also evaluated in a disseminated xenograft (OCI LY-19) model to better mimic human DLBCL disease. In the disseminated model, MLN0905 induced a highly significant survival advantage. Finally, MLN0905 was combined with a standard-of-care agent, rituximab, in the disseminated OCI LY-19 xenograft model. Combining rituximab and MLN0905 provided both a synergistic antitumor effect and a synergistic survival advantage. Our findings indicate that PLK1 inhibition leads to pharmacodynamic pHisH3 modulation and significant antitumor activity in multiple DLBCL models. These data strongly suggest evaluating PLK1 inhibitors as DLBCL anticancer agents in the clinic. PMID:22609854

  15. Small B cell lymphocytic lymphoma presenting as obstructive sleep apnea

    Directory of Open Access Journals (Sweden)

    Chang Weng-Cheng

    2004-07-01

    Full Text Available Abstract Background Most lymphomas that involve the tonsil are large B cell lymphomas. Large B-cell lymphoma is a high grade malignancy which progresses rapidly. Tonsillar lymphoma usually presents as either a unilaterally enlarged palatine tonsil or as an ulcerative and fungating lesion over the tonsillar area. Small lymphocytic lymphomas (SLL of the Waldeyer's ring are uncommon. Case presentation We report a 41-year-old male who presented with a ten-year history of snoring. Physical examination revealed smooth bilateral symmetrically enlarged tonsils without abnormal surface change or cervical lymphadenopathy. Palatal redundancy and a narrowed oropharyngeal airway were also noted. The respiratory disturbance index (RDI was 66 per hour, and severe obstruction sleep apnea (OSA was suspected. No B symptoms, sore throat, odynophagia or dysphagia was found. We performed uvulopalatopharyngoplasty (UPPP and pathological examination revealed incidental small B-cell lymphocytic lymphoma (SLL. Conclusion It is uncommon for lymphoma to initially present as OSA. SLL is an indolent malignancy and is not easy to detect in the early stage. We conclude that SLL may be a contributing factor of OSA in the present case.

  16. Mutational profile and prognostic significance of TP53 in diffuse large B-cell lymphoma patients treated with rituximab-CHOP

    DEFF Research Database (Denmark)

    Xu-Monette, Zijun Y; Wu, Lin; Visco, Carlo;

    2012-01-01

    . In the present study of a large cohort of DLBCL patients treated with rituximab plus CHOP (R-CHOP), we show that those with TP53 mutations had worse overall and progression-free survival compared with those without. Unlike earlier studies of patients treated with CHOP, TP53 mutation has predictive value for R......TP53 mutation is an independent marker of poor prognosis in patients with diffuse large B-cell lymphoma (DLBCL) treated with cyclophosphamide, hydroxydaunorubicin, vincristine, and prednisone (CHOP) therapy. However, its prognostic value in the rituximab immunochemotherapy era remains undefined...

  17. A phase I/II study of bortezomib plus CHOP every 2 weeks (CHOP-14) in patients with advanced-stage diffuse large B-cell lymphomas

    OpenAIRE

    Kim, Jeong Eun; Yoon, Dok Hyun; Jang, Geundoo; Lee, Dae Ho; Kim, Shin; Park, Chan-Sik; Huh, Jooryung; Kim, Won Seog; Park, Jinny; Lee, Jae Hoon; LEE, SOON IL; Suh, Cheolwon

    2012-01-01

    Background Bortezomib targets molecular dysregulation of nuclear factor-κB activation and cell cycle control, which are characteristic features of diffuse large B-cell lymphoma (DLBCL). We evaluated the safety and efficacy of bortezomib treatment with dose-dense cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) every 2 weeks (CHOP-14). Methods Untreated DLBCL patients were enrolled. A phase I dose-escalation study with 1.0, 1.3, and 1.6 mg/m2 bortezomib administration on day 1...

  18. Study of ADCT-402 in Patients With Relapsed or Refractory B-cell Lineage Non Hodgkin Lymphoma (B-NHL)

    Science.gov (United States)

    2016-07-04

    Non-Hodgkin Lymphoma; Burkitt's Lymphoma; Chronic Lymphocytic Leukemia; Small Lymphocytic Lymphoma; Lymphoma, Large B-Cell, Diffuse; Lymphoma, Follicular; Lymphoma, Mantle-Cell; Lymphoma, Marginal Zone; Waldenstrom Macroglobulinemia

  19. Genetically Engineered Lymphocytes, Cyclophosphamide, and Aldesleukin in Treating Patients With Relapsed or Refractory Mantle Cell Lymphoma or Indolent B-Cell Non-Hodgkin Lymphoma

    Science.gov (United States)

    2014-08-04

    B-cell Chronic Lymphocytic Leukemia; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Nodal Marginal Zone B-cell Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Small Lymphocytic Lymphoma; Refractory Chronic Lymphocytic Leukemia; Splenic Marginal Zone Lymphoma; Waldenström Macroglobulinemia

  20. Pineal Diffuse Large B-Cell Lymphoma Concomitant With Pituitary Prolactinoma: Possible Correlation Between 2 Distinguished Pathologies: A Case Report.

    Science.gov (United States)

    Kim, Yeong-Jin; Kim, Hee Kyung; Yang, Deok-Hwan; Jung, Shin; Noh, Myung-Giun; Lee, Jae-Hyuk; Lee, Kyung-Hwa; Moon, Kyung-Sub

    2016-02-01

    This is the first reported case of pineal lymphoma with concomitant prolactin-producing pituitary adenoma.A 51-year-old male experienced worsening headaches accompanied by nausea, diplopia, and memory loss for 1 month. Cranial nerve examination revealed bilateral upward gaze limitation with convergence impairment, which is known as Parinaud syndrome. Magnetic resonance images revealed a mass in the pineal gland with a coexisting mass within the enlarged sella fossa. Hormone analysis revealed hyperprolactinemia. The pineal mass was removed without injuring the hypothalamus, brain stem, or any neighboring vessels. Pathology examination confirmed the diagnosis of diffuse large B-cell lymphoma (DLBCL) involving the pineal gland. After further studies, the pineal lymphoma was determined to be a secondary tumor from a gastric primary tumor. The patient died 6 months after diagnosis due to systemic progression of DLBCL.Although the mechanistic link between hyperprolactinemia and lymphoma progression has not been clarified on a clinical basis, high prolactin levels may contribute to the rapid progression and therapeutic resistance of the lymphoma. PMID:26937937

  1. Pineal Diffuse Large B-Cell Lymphoma Concomitant With Pituitary Prolactinoma: Possible Correlation Between 2 Distinguished Pathologies

    Science.gov (United States)

    Kim, Yeong-Jin; Kim, Hee Kyung; Yang, Deok-Hwan; Jung, Shin; Noh, Myung-Giun; Lee, Jae-Hyuk; Lee, Kyung-Hwa; Moon, Kyung-Sub

    2016-01-01

    Abstract This is the first reported case of pineal lymphoma with concomitant prolactin-producing pituitary adenoma. A 51-year-old male experienced worsening headaches accompanied by nausea, diplopia, and memory loss for 1 month. Cranial nerve examination revealed bilateral upward gaze limitation with convergence impairment, which is known as Parinaud syndrome. Magnetic resonance images revealed a mass in the pineal gland with a coexisting mass within the enlarged sella fossa. Hormone analysis revealed hyperprolactinemia. The pineal mass was removed without injuring the hypothalamus, brain stem, or any neighboring vessels. Pathology examination confirmed the diagnosis of diffuse large B-cell lymphoma (DLBCL) involving the pineal gland. After further studies, the pineal lymphoma was determined to be a secondary tumor from a gastric primary tumor. The patient died 6 months after diagnosis due to systemic progression of DLBCL. Although the mechanistic link between hyperprolactinemia and lymphoma progression has not been clarified on a clinical basis, high prolactin levels may contribute to the rapid progression and therapeutic resistance of the lymphoma. PMID:26937937

  2. The impact of FcγRIIa and FcγRIIIa gene polymorphisms on responses to RCHOP chemotherapy in diffuse large B-cell lymphoma patients

    Science.gov (United States)

    ROŽMAN, SAMO; NOVAKOVIĆ, SRDJAN; GRABNAR, IZTOK; CERKOVNIK, PETRA; NOVAKOVIĆ, BARBARA JEZERŠEK

    2016-01-01

    Rituximab is a monoclonal antibody routinely used in the treatment of B-cell non-Hodgkin lymphomas. It mediates antibody-dependent cellular cytotoxicity of B lymphocytes by bridging them with Fcγ receptors (FcγR) on effector cells. Several polymorphisms in the FcγR genes have been identified to influence rituximab binding to FcγR, thus altering its antitumor effect in indolent lymphomas. In the present study, the impact of FcγRIIa and FcγRIIIa polymorphisms on the survival and response to immunochemotherapy consisting of rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone was evaluated in diffuse large B-cell lymphoma (DLBCL) patients. A total of 29 Slovenian DLBCL patients were studied. Genotyping was conducted for FcγRIIa-27, FcγRIIa-131, FcγRIIIa-48 and FcγRIIIa-158 polymorphisms. The median follow-up time was 29.7 months (range, 9.7–45.4 months). No significant impact of the genotypes was observed on the treatment response, progression-free or overall survival of DLBCL patients. There was a non-significant trend of an improved response to chemotherapy without additional irradiation in patients homozygous for Val at FCγIIIa-158 compared to Phe carriers. The findings of the present study indicate that FcγR polymorphisms have no influence on the survival of DLBCL patients.

  3. Molecular pathology of lymphoma

    OpenAIRE

    Coupland, S E

    2012-01-01

    Ocular lymphomas can be divided into intraocular lymphomas and ocular adnexal lymphomas. The vitreoretinal lymphoma—usually a diffuse large B-cell lymphoma (DLBCL) of high-grade malignancy—is the most common lymphoid malignancy arising in the eye, while the extranodal marginal zone B-cell lymphoma (EMZL), an indolent often recurrent tumour, occurs most frequently in the ocular adnexal tissue. The two lymphoma subtypes differ significantly in their clinical presentation, subsequent course and ...

  4. MAGE-A3 expression is an adverse prognostic factor in diffuse large B-cell lymphoma.

    Science.gov (United States)

    Olarte, Irma; Martinez, Adolfo; Ramos-Peñafiel, Christian; Castellanos-Sinco, Humberto; Zamora, Jorge; Collazo-Jaloma, Juan; Gutiérrez, Mario; Gutiérrez-Kobeh, Laila; Chavez-Olmos, Pedro; Manzanilla, Hugo; Garrido-Guerrero, Efraín; Ordoñez-Razo, Rosa M; Miranda, Enrique I

    2011-11-01

    This study evaluates the prognostic value of MAGE-A3 expression in 28 diffuse large B-cell lymphoma (DLBCL) patients. A significant association was observed between MAGE-A3 expressions, assessed by quantitative real-time RT-polymerase chain reaction (PCR), with advanced stages of disease (P < 0.05). Elevated serum lactate dehydrogenase (LDH) levels and International Prognostic Index (IPI) score were significantly higher in MAGE-A3-positive patients (P = 0.025 and P = 0.004, respectively). Expression of MAGE-A3 was associated with poor response to treatment and a significantly shorter overall survival (P < 0.001). Our data address new information in the association of MAGE-A3 expression and poor prognosis in DLBCL patients. PMID:22183072

  5. Prognostic value of interim 18F-FDG PET/CT in diffuse large B-cell lymphoma

    Institute of Scientific and Technical Information of China (English)

    Zhitao Ying; Xuejuan Wang; Yuqin Song; Wen Zheng; Xiaopei Wang; Yan Xie; Ningjing Lin

    2013-01-01

    Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous disease.The prognostic factor currently used is not accurate enough to predict the outcomes of patients with DLBCL.The prognostic significance of interim PET/CT in DLBCL remains controversial.The aim of this study is to determine the predictive value of interim 18F-FDG PET/CT after first-line treatment in patients with DLBCL.Methods:Thirty-two patients with DLBCL underwent baseline,interim and post-treatment 18F-FDG PET/CT scans.Imaging results were analyzed for the survival of patients via software SPSS 13.0,retrospectively.Results:Thirty-one of the 32 patients were treated with R-CHOP regimen,and interim 18F-FDG PET/CT of 24 patients was performed after 2 cycles of treatment.After a median follow-up period of 16.7 months,the 2-year progression-free survival (PFS) rates were significandy different between the groups above and below SUVmax cut-off value of 2.5 (P=0.039).No significant differences were found in the 2-year PFS rates if SUVmax cut-offvalues were set as 2.0 and 3.0,respectively (P=0.360; P=0.113).Conclusions:Interim PET/CT could predict the prognosis of DLBCL patients with the SUVmax cut-off value of 2.5,but more clinical data should be concluded to confirm this conclusion.

  6. The expression of CD30 based on immunohistochemistry predicts inferior outcome in patients with diffuse large B-cell lymphoma.

    Directory of Open Access Journals (Sweden)

    Xiaoxiao Hao

    Full Text Available The prognostic value of CD30 expression in diffuse large B-cell lymphoma (DLBCLremains controversial. Herein, we performed this retrospective study to investigate the clinical and prognostic significance of CD30 expression in patients with DLBCL.Among all the 146 patients, the expression of CD30 was observed in 23 cases (15.7%.The DLBCL patients with CD30 expression showed more likely to present B symptoms, bone marrow involvement, non-germinal centre B-cell-like (Non-GCB DLBCL, BCL-2 and Ki-67 overexpression (p<0.05. Patients with CD30 expression showed significantly poor overall and event-free survival compared with CD30 negative patients(p = 0.031 and 0.041, respectively, especially those with the high intermediate/high-risk international prognostic index (IPI(p = 0.001 and 0.007, respectively. The prognostic value of CD30 expression retained in DLBCL patients treated with either CHOP (cyclophosphamide, doxorubicin, vincristine,prednisone or R-CHOP(rituximab+CHOP. The multivariate analysis revealed that the expression of CD30 remained an unfavorable factor for both overall and event-free survival (p = 0.001 and 0.002, respectively. In conclusion, these data suggest that CD30 is expressed predominantly in Non-GCBDLBCL. The expression of CD30 implied poor outcome in DLBCL patients treated with either CHOP or R-CHOP, especially those with the high intermediate/high-risk IPI, possibly indicating that anti-CD30 monoclonal antibody could be of clinical interest.

  7. Prognosis of patients with diffuse large B cell lymphoma not reaching complete response or relapsing after frontline chemotherapy or immunochemotherapy

    OpenAIRE

    Rovira, Jordina; Valera, Alexandra; Colomo, Lluis; Setoain, Xavier; Rodríguez, Sonia; Martínez-Trillos, Alejandra; Giné, Eva; Dlouhy, Ivan; Magnano, Laura; Gaya, Anna; Martínez, Daniel; Martínez, Antonio; Campo, Elías; López-Guillermo, Armando

    2014-01-01

    A retrospective study was performed to assess the outcome of patients with diffuse large B cell lymphoma (DLBCL) who did not achieve complete response or who relapsed before and after the use of rituximab. Clinical features and outcome of 816 (425 M/391 F; median age 63 years) patients diagnosed from 1991 to 2001 (pre-rituximab era, N = 348) and from 2002 to 2012 (rituximab era, N = 468) in a single institution were evaluated. Five hundred fifty-three patients achieved complete remission (CR)...

  8. Sclerosing encapsulating peritonitis (abdominal cocoon) associated with liver cirrhosis and diffuse large B-cell lymphoma: autopsy case.

    Science.gov (United States)

    Yamada, Sohsuke; Tanimoto, Akihide; Matsuki, Yasumasa; Hisada, Yuji; Sasaguri, Yasuyuki

    2009-09-01

    A case of sclerosing encapsulating peritonitis (SEP) associated with liver cirrhosis (LC) and complicated by diffuse large B-cell lymphoma (DLBCL) is reported herein. A 49-year-old Japanese man had undergone peritoneo-venous shunt against refractory ascites due to hepatitis C virus-positive uncompensated LC for 2 years. After he received a diagnosis of DLBCL of the left neck lymph node 3 months before his death, palliative care was given because of his poor general condition. He developed severe abdominal distention and pain over 1 week and was found to have marked ascites and whole bowel lumped together on abdominal CT. At autopsy, the peritoneum was covered with a thick white membrane and the bowel could not be distinguished, which was macroscopically characterized by a cocoon-like appearance. Histology indicated a proliferation of diffusely thickened or hyalinized fibrocollagenous tissue in the entire peritoneum with a slight chronic inflammatory infiltrate and without remarkable change of mucosa. A diagnosis of SEP, also known as abdominal cocoon, was established based on these features. Additionally, in the abdominal cavity, a large amount of serous ascites and multiple peritoneal nodules or masses involved by DLBCL were recognized. To the authors' knowledge this is the first case report of SEP associated with LC and complicated by the invasion of DLBCL in the abdominal cavity. PMID:19712139

  9. High-Dose Y-90-Ibritumomab Tiuxetan Added to Reduced-Intensity Allogeneic Stem Cell Transplant Regimen for Relapsed or Refractory Aggressive B-Cell Lymphoma

    Science.gov (United States)

    2016-07-08

    Post-Transplant Lymphoproliferative Disorder; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent B-Cell Non-Hodgkin Lymphoma; Recurrent Burkitt Lymphoma; Refractory B-Cell Non-Hodgkin Lymphoma; Refractory Burkitt Lymphoma; Refractory Diffuse Large B-Cell Lymphoma

  10. Inhibition of the PI3K/Akt/mTOR Signaling Pathway in Diffuse Large B-Cell Lymphoma: Current Knowledge and Clinical Significance

    Directory of Open Access Journals (Sweden)

    Agata Majchrzak

    2014-09-01

    Full Text Available Diffuse large B-cell lymphoma (DLBCL is one of the most common non-Hodgkin lymphomas in adults. The disease is very heterogeneous in its presentation, that is DLBCL patients may differ from each other not only in regard to histology of tissue infiltration, clinical course or response to treatment, but also in respect to diversity in gene expression profiling. A growing body of knowledge on the biology of DLBCL, including abnormalities in intracellular signaling, has allowed the development of new treatment strategies, specifically directed against lymphoma cells. The phosphoinositide 3-kinase (PI3K/protein kinase B (Akt/mammalian target of rapamycin (mTOR signaling pathway plays an important role in controlling proliferation and survival of tumor cells in various types of malignancies, including DLBCL, and therefore it may be a promising target for therapeutic intervention. Currently, novel anticancer drugs are undergoing assessment in different phases of clinical trials in aggressive lymphomas, with promising outcomes. In this review we present a state of art review on various classes of small molecule inhibitors selectively involving PI3K/Akt/mTOR pathway and their clinical potential in this disease.

  11. Diffuse large B-cell lymphoma in the elderly: a review of potential difficulties.

    Science.gov (United States)

    Sarkozy, Clémentine; Coiffier, Bertrand

    2013-04-01

    Half of patients with diffuse large B-cell lymphoma (DLBCL) are more than 65 years old. These elderly patients frequently have other diseases, some of them severe, which may alter their ability to receive standard curative therapy. However, these associated diseases are heterogeneous and only a few contraindicate chemotherapy treatments. We reviewed all potential difficulties, such as the evaluation of comorbidities, the heterogeneous functional status of this population, and the consequences of the aging process that might be associated with treating these patients, and now propose solutions. As standard rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) chemotherapy may cure the majority of patients, it must always be the first proposed option. With this approach, elderly patients with DLBCL treated with a curative intent can reach a complete remission and have a similar outcome as younger patients. Reduced dose intensity must be applied for very elderly patients or those unfit for full-dose anthracycline. The critical question for a physician is why these patients cannot be treated with the standard regimen, namely R-CHOP. PMID:23339126

  12. Treatment of B-cells non-Hodgkin lymphomas with combined immunochemotherapy: ability to treatment optimization

    Directory of Open Access Journals (Sweden)

    N. V. Smirnova

    2015-01-01

    Full Text Available The results of two consecutive multicenter clinical trials enrolled 241 patient with childhood mature B-cells non-Hodgkin lymphomas/leukemia are presented. Patients received treatment according B-NHL 2004mab protocol (n = 83 and B-NHL 2010M (n = 158 with combined immunochemotherapy (ICT in Russian and Belarus pediatric clinics from 2004 to 2015 years. Primary patients with different mature B-NHL (Burkitt lymphoma/leukemia, diffuse large B-cell lymphoma and primary mediastinal B-cell lymphoma (DLBCL and PMBCL aged from 2 to 18 years are included in the studies.Protocol B-NHL 2004mab for treatment of children and adolescents with B-NHL/B-AL, stage III and IV, includes a combination of chemotherapy (PCT and rituximab – an antibody against the B-cells receptor CD20. PCT courses similar to those in the B-NHL BFM90 protocol (group III with the exception of methotrexate dose in induction courses, reduced to 1 g/m2 /24 h in order to reduce toxicity. Rituximab (Mabthera, 375 mg/m2 /h used for the first time in the treatment of children and adolescents with B-NHL. Of the 83 patients included, clinical remission was achieved in 77 (92.8 %. With a median follow time of 51.6 months, remission continued in 23 (85.2 % patients with B-AL, in 32 (88.9 % patients with LB and 19 (95.0 % patients – with DLBCL. With median follow time of 65.2 months, event-free and overall survival was 84 ± 6 and 82 ± 8 %, respectively.Based on previous experience in order to further optimize B-NHL treatment, new protocol B-NHL 2010M with effect-adapted therapy and improvement of stratification risk group criteria was proposed. Overall survival in patients of 1st and 2nd risk groups with full implementation of diagnosis and treatment is approaching 100 %. In interim analysis of 3rd risk group patients, pOS was 88 ± 3 %. The incidence of induction death (infections, metabolic complications remains within 2.7 % (n = 4; refractory cases (n = 2; 1.3 % and relapses (n = 4; 2

  13. Risk factors and patterns of lymph node involvement in primary gastric large B-cell lymphoma: implications for target definition

    Directory of Open Access Journals (Sweden)

    Zhang X

    2016-07-01

    Full Text Available Ximei Zhang, Peiguo Wang, Lujun Zhao, Zhiyong Yuan, Ping Wang Department of Radiation Oncology, Tianjin’s Clinical Research Center for Cancer and Key Laboratory of Cancer Prevention and Therapy, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, People’s Republic of China Background: The aim of this study was to identify the appropriate radiation volume for primary gastric diffuse large B-cell lymphoma (PG-DLBCL.Methods: We retrospectively analyzed the clinical and pathological findings of 68 patients treated with total gastrectomy and D2 lymphadenectomy.Results: There were 23, 14, and 29 patients with stage I, stage II, and stage IIE disease, respectively, and 30 patients had lymph node involvement. Primary tumor location, as well as the depth of invasion, was significantly associated with lymph node involvement. When the tumor was limited to the muscularis, the involved lymph nodes were found to be perigastric nodes. For tumors invading beyond the muscularis, regional lymph nodes were involved.Conclusion: The optimal radiation volume for patients with PG-DLBCL is largely dependent on the primary location and depth of invasion. Larger series and longer follow-up are needed to further delineate the radiation volumes for PG-DLBCL. Keywords: primary gastric lymphoma, failure patterns, radiotherapy, chemotherapy, prognosis

  14. The rGel/BLyS Fusion Toxin Inhibits Diffuse Large B-cell Lymphoma Growth In Vitro and In Vivo

    Directory of Open Access Journals (Sweden)

    Mi-Ae Lyu

    2010-05-01

    Full Text Available Diffuse large B-cell lymphoma (DLBCL is an aggressive subtype of B-cell non-Hodgkin lymphoma (NHL and accounts for 30%to 40%of NHL. Molecules targeting nuclear factor-κB (NF-κB are expected to be of therapeutic value in those tumors where NF-κB seems to play a unique survival role such as activated B-cell (ABC-subtype DLBCL. We previously generated a rGel/BLyS fusion toxin for receptor-mediated delivery of the rGel toxin specifically to malignant B cells. In this study, we examined this fusion toxin for its ability to suppress DLBCL growth in vitro and in vivo. rGel/BLyS was specifically cytotoxic to DLBCL lines expressing all three BLyS receptors and constitutively active NF-κB. Treatment with rGel/BLyS induced down-regulation of the phosphorylation of inhibitory subunit of NF-κB (IκB-α, inhibition of NF-κB DNA-binding activity, and accumulation of IκB-α. In agreement with these results, we additionally found that rGel/BLyS downregulated levels of several NF-κB targets including Bcl-xL, Mcl-1, survivin, and x-chromosome linked inhibitor-of-apoptosis. Treatment also induced up-regulation of Bax and apoptosis through caspase-3 activation and poly ADP-ribose polymerase cleavage. Importantly, rGel/BLyS significantly inhibited tumor growth (P < .05 in a DLBCL xenograft model. Thus, our results indicate that rGel/BLyS is an excellent candidate for the treatment of aggressive NHLs that are both dependent on NF-κB and are resistant to conventional chemotherapeutic regimens.

  15. M2 tumour-associated macrophages contribute to tumour progression via legumain remodelling the extracellular matrix in diffuse large B cell lymphoma.

    Science.gov (United States)

    Shen, Long; Li, Honghao; Shi, Yuzhi; Wang, Dekun; Gong, Junbo; Xun, Jing; Zhou, Sifan; Xiang, Rong; Tan, Xiaoyue

    2016-01-01

    Effects of M2 tumour-associated macrophages on the pathogenesis of diffuse large B cell lymphoma (DLBCL) are still controversial. Our data showed that the number of CD163-positive M2 macrophages correlated negatively with DLBCL prognosis. Macrophage depletion by clodronate liposomes significantly suppressed tumour growth in a xenograft mouse model of DLBCL using OCI-Ly3 cells. Moreover, M2 polarization of macrophages induced legumain expression in U937 cells. Exogenous legumain promoted degradation of fibronectin and collagen I, which was abolished by administration of a legumain inhibitor RR-11a. Overexpression of legumain in Raw 264.7 cells also induced tube formation of endothelial cells in matrigel. In the xenograft mouse model of DLBCL, decreased fibronectin and collagen I, as well as increased legumain expression and angiogenesis were found at the late stage tumours compared with early stage tumours. Co-localization of legumain and fibronectin was observed in the extracellular matrix of tumour tissues. Administration of the legumain inhibitor to the xenograft DLBCL model suppressed tumour growth, angiogenesis and collagen deposition compared with the control. Taken together, our results suggest that M2 tumour-associated macrophages affect degradation of the extracellular matrix and angiogenesis via overexpression of legumain, and therefore play an active role in the progression of DLBCL. PMID:27464733

  16. The value of routine bone marrow biopsy in patients with diffuse large B-cell lymphoma staged with PET/CT

    DEFF Research Database (Denmark)

    Alzahrani, M; El-Galaly, T C; Hutchings, M;

    2016-01-01

    BACKGROUND: The added diagnostic and prognostic value of routine bone marrow biopsy (BMB) in patients with diffuse large B-cell lymphoma (DLBCL) undergoing PET/CT staging is controversial. PATIENTS AND METHODS: Patients with newly-diagnosed DLBCL who underwent both staging PET/CT and BMB were...... marrow (BM) lesions on PET/CT and 87 (16%) had positive BMB. 52 of 146 patients (36%) with positive PET/CT had a positive BMB (39 DLBCL, 13 indolent non-Hodgkin lymphoma [iNHL]), while 35 of 384 patients (9%) with negative PET/CT had positive BMB (12 DLBCL, 23 iNHL). BMB upstaged 12/209 (6%) of stage I....../II patients to stage IV, although this was the case for only 3 (1%) patients with DLBCL in the BMB. PET/CT identified bone marrow involvement by BMB with sensitivity 60%, specificity 79%, positive predictive value 36%, and negative predictive value 91%. Concordant histological involvement of the bone marrow...

  17. Diffuse large B-cell lymphoma of the breast: prognostic factors and treatment outcomes

    Directory of Open Access Journals (Sweden)

    Sun Y

    2016-04-01

    Full Text Available Yao Sun,1 Monika Joks,2 Li-Ming Xu,1 Xiu-Li Chen,1 Dong Qian,1 Jin-Qiang You,1 Zhi-Yong Yuan1 1Department of Radiation Oncology, CyberKnife Center, Key Laboratory of Cancer Prevention and Therapy, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin, People’s Republic of China; 2Department of Hematology and Bone Marrow Transplantation, Poznan University of Medical Science, Poznan, Poland Background: The breast is a rare site of extranodal involvement of diffuse large B-cell lymphoma (DLBCL. We aimed to assess the clinical characteristics, prognostic factors, and treatment outcomes of breast DLBCL.Patients and methods: We retrospectively analyzed 113 patients (from our institution and the literature between 1973 and 2014. The primary end point was overall survival (OS. Kaplan–Meier OS curves were compared with the log-rank test. Cox regression analysis was applied to determine the prognostic factors for OS, progression-free survival (PFS, local control (LC, and cause-specific survival (CSS.Results: A total of 113 patients were included in the study: 42 cases from our hospital and 71 cases from 12 publications. The median age at diagnosis was 58 years. With a median follow-up time of 39.2 months, the estimated 5-year OS, PFS, LC, and CSS were 71.4%, 58.8%, 75.6%, and 74.9%, respectively. In multivariate analysis, more than four cycles of chemotherapy, having localized cancer, lumpectomy with or without axillary lymph node (ALN dissection, and low to low-to-intermediate International Prognostic Index were favorable factors for OS. For PFS, significant prognostic factors were rituximab use, B symptoms, and tumor size. As for the local group, lumpectomy with or without ALN dissection and more than four cycles of chemotherapy were favorable factors for OS. Tumor size >4 cm and nonuse of rituximab were adverse factors for PFS. Twenty-one patients (18.6% developed local relapse and 33 (29

  18. Treatment and Outcomes in Patients With Primary Cutaneous B-Cell Lymphoma: The BC Cancer Agency Experience

    Energy Technology Data Exchange (ETDEWEB)

    Hamilton, Sarah N., E-mail: shamilton7@bccancer.bc.ca [University of British Columbia, Vancouver (Canada); Radiation Therapy Program, BC Cancer Agency, Vancouver (Canada); Wai, Elaine S. [Radiation Therapy Program, BC Cancer Agency, Victoria (Canada); Tan, King [Department of Pathology, BC Cancer Agency, Vancouver (Canada); Alexander, Cheryl [Radiation Therapy Program, BC Cancer Agency, Victoria (Canada); Gascoyne, Randy D. [University of British Columbia, Vancouver (Canada); Department of Pathology, BC Cancer Agency, Vancouver (Canada); Centre for Lymphoid Cancer, BC Cancer Agency, Vancouver (Canada); Connors, Joseph M. [University of British Columbia, Vancouver (Canada); Centre for Lymphoid Cancer, BC Cancer Agency, Vancouver (Canada)

    2013-11-15

    Purpose: To review the treatment and outcomes of patients with primary cutaneous B-cell lymphoma (CBCL). Methods and Materials: Clinical characteristics, treatment, and outcomes were analyzed for all patients referred to our institution from 1981 through 2011 with primary CBCL without extracutaneous or distant nodal spread at diagnosis (n=136). Hematopathologists classified 99% of cases using the World Health Organization-European Organization for Research and Treatment of Cancer (WHO-EORTC) guidelines. Results: Median age at diagnosis was 62 years. Classification was 18% diffuse large B-cell leg-type (DLBCL-leg), 32% follicle center (FCCL), 45% marginal zone (MZL), and 6% nonclassifiable (OTHER). Of the 111 subjects with indolent lymphoma (FCCL, MZL, OTHER), 79% received radiation alone (RT), 11% surgery alone, 3% chemotherapy alone, 4% chemotherapy followed by RT, and 3% observation. Following treatment, 29% of subjects relapsed. In-field recurrence occurred in 2% treated with RT and in 33% treated with surgery alone. Of the 25 subjects with DLBCL-leg, 52% received chemotherapy followed by RT, 24% chemotherapy, 20% RT, and 4% surgery alone. Seventy-nine percent received CHOP-type chemotherapy (cyclophosphamide, doxorubicin or epirubicin, vincristine, prednisone), 47% with rituximab added. Overall and disease-specific survival and time to progression at 5 years were 81%, 92%, and 69% for indolent and 26%, 61%, and 54% for DLBCL-leg, respectively. On Cox regression analysis of indolent subjects, RT was associated with better time to progression (P=.05). RT dose, chemo, age >60 y, and >1 lesion were not significantly associated with time to progression. For DLBCL-leg, disease-specific survival at 5 years was 100% for those receiving rituximab versus 67% for no rituximab (P=.13). Conclusions: This review demonstrates better outcomes for indolent histology compared with DLBCL-leg, validating the prognostic utility of the WHO-EORTC classification. In the indolent group

  19. Diffuse Large B Cell Lymphoma of the Breast

    Directory of Open Access Journals (Sweden)

    Feryal Karaca

    2015-03-01

    Full Text Available Primary breast lymphoma is rarely encountered in Non-Hodgkin Lymphomas. However, if early diagnosis is made, and treatment is started immediately in patients with low grade and stage, patient survival is increased. 39-year old female patient applied us due to a palpable mass. She was diagnosed with the Non-Hodgkin Lymphoma Diffuse Large B Cell Lymphoma after the investigations. Curative external radiotherapy was applied after 6 courses of CHOP-R chemotherapy to the patient with Stage-IIE favorable, and B symptoms. After 48-month follow up, patient follow up is being continued without any progression, or recurrence or metastasis. [Cukurova Med J 2015; 40(1.000: 151-157

  20. Cross-Platform Assessment of Genomic Imbalance Confirms the Clinical Relevance of Genomic Complexity and Reveals Loci with Potential Pathogenic Roles in Diffuse Large B-Cell Lymphoma

    Science.gov (United States)

    Dias, Lizalynn M.; Thodima, Venkata; Friedman, Julia; Ma, Charles; Guttapalli, Asha; Mendiratta, Geetu; Siddiqi, Imran N.; Syrbu, Sergei; Chaganti, R. S. K.; Houldsworth, Jane

    2016-01-01

    Genomic copy number alterations (CNAs) in diffuse large B-cell lymphoma (DLBCL) have roles in disease pathogenesis but overall clinical relevance remains unclear. Herein, an unbiased algorithm was uniformly applied across three genome profiling datasets comprising 392 newly-diagnosed DLBCL specimens that defined 32 overlapping CNAs, involving 36 minimal common regions (MCRs). Scoring criteria were established for 50 aberrations within the MCRs while considering peak gains/losses. Application of these criteria to independent datasets revealed novel candidate genes with coordinated expression, such as CNOT2, potentially with pathogenic roles. No one single aberration significantly associated with patient outcome across datasets, but genomic complexity, defined by imbalance in more than one MCR, significantly portended adverse outcome in two of three independent datasets. Thus, the standardized scoring of CNAs currently developed can be uniformly applied across platforms, affording robust validation of genomic imbalance and complexity in DLBCL and overall clinical utility as biomarkers of patient outcome. PMID:26294112

  1. Differential Expression of miR-155 and miR-21 in Tumor and Stroma Cells in Diffuse Large B-Cell Lymphoma

    DEFF Research Database (Denmark)

    Munch-Petersen, Helga D; Ralfkiaer, Ulrik; Sjö, Lene D;

    2015-01-01

    OncomiRs miR-21 and miR-155 have been linked to lymphomagenesis, but information on their implication in diffuse large B-cell lymphoma (DLBCL) is limited. Here, we used locked nucleic acid-based in situ hybridization (ISH) detection techniques on formalin-fixed paraffin-embedded DLBCL tissue...... samples to identify miR-155 and miR-21 at the cellular level in 56 patients diagnosed with DLBCL, and compared them to miR array data. miR-155 was observed in tumor cells in 19/56 (33.9%) of the samples evaluated by ISH. miR-21 was localized to the stromal compartment in 41/56 (73.2%). A subset of these...

  2. Efficacy and Tolerability of Anthracycline-Based Therapy in Elderly Patients With Diffuse Large B-Cell Lymphoma

    Science.gov (United States)

    Davis, Christine C.; Cohen, Jonathon B.; Shah, Katherine S.; Hutcherson, Don A.; Surati, Minal J.; Valla, Kelly; Panjic, Elyse H.; Handler, Caitlin E.; Switchenko, Jeffrey M.; Flowers, Christopher R.

    2016-01-01

    We examined treatment with or without anthracyclines in 72 eldery diffuse large B-cell lymphoma patients (age ≥ 65 years) in a retrospective cohort analysis. Factors leading to treatment without an anthracycline included age and ejection fraction, whereas markers of tolerability were similar between groups. This study highlights the details of anthracycline tolerability in elderly lymphoma patients. Introduction Although diffuse large B-cell lymphoma (DLBCL) can be cured with rituximab and anthracycline-based therapy, within the elderly population there are additional factors to consider in selecting a treatment regimen including comorbid conditions, decreased drug metabolism, decreased hematologic reserve, reduced performance status, and regimen-related toxicity. Patients and Methods We performed a retrospective cohort analysis of patients with DLBCL aged ≥ 65 years at time of diagnosis treated with either an anthracycline-containing regimen (ACR; n = 59) or a non-ACR (n = 13) to assess factors that led to treatment selection, tolerability, and outcomes. Results The mean age was 73 years in the ACR and 77 years in the non-ACR group (P = .009), and median left ventricular ejection fraction (LVEF) at diagnosis was 60% in the ACR group and 45% in the non-ACR group (P < .001). With an ACR, elderly DLBCL patients had a median overall survival of 28 months and a 2-year progression-free survival (PFS) of 64%. After an ACR, 14 patients [24%] (out of 59 total patients) had a decrease in LVEF, 7 patients [15%] (% is based off of those who we had the data collected, so this is out of 45 with this specific data) required a dose reduction of the anthracycline, and 15 patients [33%] (% is based off of those who we had the data collected, so this is out of 45 with this specific data) could not complete the regimen as planned. Hospitalization due to toxicity occurred in 20 patients [44%] (% is based off of those who we had the data collected, so this is out of 45 with data

  3. MicroRNA-142 is mutated in about 20% of diffuse large B-cell lymphoma

    International Nuclear Information System (INIS)

    MicroRNAs (miRNAs) are short 18–23 nucleotide long noncoding RNAs that posttranscriptionally regulate gene expression by binding to mRNA. Our previous miRNA profiling of diffuse large B-cell lymphoma (DLBCL) revealed a mutation in the seed sequence of miR-142-3p. Further analysis now showed that miR-142 was mutated in 11 (19.64%) of the 56 DLBCL cases. Of these, one case had a mutation in both alleles, with the remainder being heterozygous. Four mutations were found in the mature miR-142-5p, four in the mature miR-142-3p, and three mutations affected the miR-142 precursor. Two mutations in the seed sequence redirected miR-142-3p to the mRNA of the transcriptional repressor ZEB2 and one of them also targeted the ZEB1 mRNA. However, the other mutations in the mature miR-142-3p did not influence either the ZEB1 or ZEB2 3′ untranslated region (3′ UTR). On the other hand, the mutations affecting the seed sequence of miR-142-3p resulted in a loss of responsiveness in the 3′ UTR of the known miR-142-3p targets RAC1 and ADCY9. In contrast to the mouse p300 gene, the human p300 gene was not found to be a target for miR-142-5p. In one case with a mutation of the precursor, we observed aberrant processing of the miR-142-5p. Our data suggest that the mutations in miR-142 probably lead to a loss rather than a gain of function. This is the first report describing mutations of a miRNA gene in a large percentage of a distinct lymphoma subtype

  4. Oxidative stress and redox state-regulating enzymes have prognostic relevance in diffuse large B-cell lymphoma

    Directory of Open Access Journals (Sweden)

    Peroja Pekka

    2012-03-01

    Full Text Available Abstract Background Oxidative stress and redox-regulating enzymes may have roles both in lymphomagenesis and resistance to lymphoma therapy. Previous studies from the pre-rituximab era suggest that antioxidant enzyme expression is related to prognosis in diffuse large B-cell lymphoma (DLBCL, although these results cannot be extrapolated to patient populations undergoing modern treatment modalities. In this study we assessed expression of the oxidative stress markers 8-hydroxydeoxyguanosine (8-OHdG and nitrotyrosine and the antioxidant enzymes thioredoxin (Trx, manganese superoxide dismutase (MnSOD and glutamate-cysteine ligase (GCL via immunohistochemistry in 106 patients with DLBCL. All patients were treated with CHOP-like therapy combined with rituximab. Immunostaining results were correlated with progression-free survival, disease-specific survival and traditional prognostic factors of DLBCL. Results Strong 8-OHdG immunostaining intensity was associated with extranodal involvement (p = 0.00002, a high International Prognostic Index (p = 0.002 and strong Trx (p = 0.011 and GCL (p = 0.0003 expression. Strong Trx staining intensity was associated with poor progression-free survival (p = 0.046 and poor disease-specific survival (p = 0.015. Strong GCL immunostaining intensity predicted poor progression-free survival (p = 0.049. Patients with either strong Trx or strong nitrotyrosine expression showed significantly poorer progression-free survival (p = 0.003 and disease-specific survival (p = 0.031 compared with the other patients. Conclusions The redox state-regulating enzymes GCL and Trx are promising markers in the evaluation of DLBCL prognosis in the era of modern immunochemotherapy.

  5. Diffuse large B-cell lymphoma of the thyroid: Seven cases with review of the literature from India

    Directory of Open Access Journals (Sweden)

    K. Govind Babu

    2015-02-01

    Full Text Available Background: Diffuse large B - cell lymphoma (DLBCL is the most frequent subtype of nonHodgkin’s lymphoma globally with frequent extra nodal involvement. There is sporadic data available on thyroid DLBCL in Indian population and hence we undertook this retrospective observational study at Kidwai Memorial Institute of Oncology, a tertiary care oncology center in India to analyze the clinico biological features of this disease. Methodology: A total of 7 consecutive cases diagnosed as DLBCL by appropriate lymph node biopsy with evidence of thyroid involvement on fine‑needle aspiration cytology of thyroid or thyroid histopathology (following thyroidectomy were confirmed by immunohistochemistry (WHO classification between January 2008 and September 2013 were included in this study. Results: A total of 7 patients were included in the study. Median age was 65 - years (range: 50–72 years, and all were females. Six out of seven were in stage IIAE and one was in stage IVAE. The distribution according to the international prognostic index was as follows: 3 were in low risk, 1 in low - intermediate, 2 in high - intermediate and 1 in high risk group. Regarding treatment, 5 received CHOP, 1 received COP and 1 received no treatment. 5 patients received radiotherapy. 2 patients underwent subtotal thyroidectomy. Of the 6 patients who received chemotherapy ± radiotherapy, 4 had complete response, 2 had partial response. The median survival was 15 months (3-32 months. Conclusions: Extranodal thyroid DLBCL presents common in elderly age group and in females. A multimodality treatment approach is used to treat this entity and may improve survival compared with unimodality approach

  6. Secondary cutaneous Epstein-Barr virus-associated diffuse large B-cell lymphoma in a patient with angioimmunoblastic T-cell lymphoma: a case report and review of literature.

    Science.gov (United States)

    Yang, Qing-Xu; Pei, Xiao-Juan; Tian, Xiao-Ying; Li, Yang; Li, Zhi

    2012-01-01

    Only a few cases of extranodal Epstein-Barr virus (EBV)-associated B-cell lymphomas arising from patients with angioimmunoblastic T-cell lymphoma (AITL) have been described. We report a case of AITL of which secondary cutaneous EBV-associated diffuse large B-cell lymphoma (DLBCL) developed after the initial diagnosis of AITL. A 65-year-old Chinese male patient was diagnosed as AITL based on typical histological and immunohistochemical characteristics in biopsy of the enlarged right inguinal lymph nodes. The patient initially received 6 cycles of chemotherapy with CHOP regimen (cyclophosphamide, vincristine, adriamycin, prednisone), but his symptoms did not disappear. Nineteen months after initial diagnosis of AITL, the patient was hospitalized again because of multiple plaques and nodules on the skin. The skin biopsy was performed, but this time the tumor was composed of large, polymorphous population of lymphocytes with CD20 and CD79a positive on immunohistochemical staining. The tumor cells were strong positive for EBER by in situ hybridization. The findings of skin biopsy were compatible with EBV-associated DLBCL. CHOP-R chemotherapy (cyclophosphamide, doxorubicin, vincristine, prednisone and rituximab) was then administered, resulting in partial response of the disease with pancytopenia and suppression of cellular immunity. To our knowledge, this is the first case of cutaneous EBV-associated DLBCL originated from AITL in Chinese pepole. We suggest the patients with AITL should perform lymph node and skin biopsies regularly in the course of the disease to detect the progression of secondary lymphomas. PMID:22260632

  7. [Lymphomas].

    Science.gov (United States)

    Lohri, Andreas

    2016-01-01

    Although malignant lymphoma is split in over 60 distinct entities, four of them, diffuse large B cell lymphoma, follicular-, Hodgkin's- and mantle cell lymphoma constitute more than half of all new cases. A recent major revision of the Ann Arbor staging system restricts the suffix “A” and “B” just to Hodgkin's lymphoma. Bone marrow exams are abandonned in Hodgkin's and restricted in DLBCL. PET exams at different time points are crucial. PET guided therapy will lead to a reduction of the use of chemo- and radiation therapy. Many new targeted drugs have been introduced. Their therapeutic index is impressive as is their price tag. The radiation and chemotherapy free treatment of malignant lymphoma is within reach. PMID:26732717

  8. CPI-613, Bendamustine Hydrochloride, and Rituximab in Treating Patients With Relapsed or Refractory B-Cell Non-Hodgkin Lymphoma

    Science.gov (United States)

    2016-07-26

    B-cell Adult Acute Lymphoblastic Leukemia; B-cell Chronic Lymphocytic Leukemia; Cutaneous B-cell Non-Hodgkin Lymphoma; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Intraocular Lymphoma; Nodal Marginal Zone B-cell Lymphoma; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Grade III Lymphomatoid Granulomatosis; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Mycosis Fungoides/Sezary Syndrome; Recurrent Small Lymphocytic Lymphoma; Refractory Chronic Lymphocytic Leukemia; Refractory Hairy Cell Leukemia; Small Intestine Lymphoma; Splenic Marginal Zone Lymphoma; Testicular Lymphoma; Waldenström Macroglobulinemia

  9. Benefit of Consolidative Radiation Therapy for Primary Bone Diffuse Large B-Cell Lymphoma

    Energy Technology Data Exchange (ETDEWEB)

    Tao, Randa; Allen, Pamela K. [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Rodriguez, Alma [Department of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Shihadeh, Ferial; Pinnix, Chelsea C.; Arzu, Isadora; Reed, Valerie K. [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Oki, Yasuhiro; Westin, Jason R.; Fayad, Luis E.; Medeiros, L. Jeffrey [Department of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Dabaja, Bouthaina, E-mail: bdabaja@mdanderson.org [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States)

    2015-05-01

    Purpose: Outcomes for patients with diffuse large B-cell lymphoma (DLBCL) differ according to the site of presentation. With effective chemotherapy, the need for consolidative radiation therapy (RT) is controversial. We investigated the influence of primary bone presentation and receipt of consolidative RT on progression-free survival (PFS) and overall survival (OS) in patients with DLBCL. Methods and Materials: We identified 102 patients with primary bone DLBCL treated consecutively from 1988 through 2013 and extracted clinical, pathologic, and treatment characteristics from the medical records. Survival outcomes were calculated by the Kaplan-Meier method, with factors affecting survival determined by log-rank tests. Univariate and multivariate analyses were done with a Cox regression model. Results: The median age was 55 years (range, 16-87 years). The most common site of presentation was in the long bones. Sixty-five patients (63%) received R-CHOP–based chemotherapy, and 74 (72%) received rituximab. RT was given to 67 patients (66%), 47 with stage I to II and 20 with stage III to IV disease. The median RT dose was 44 Gy (range, 24.5-50 Gy). At a median follow-up time of 82 months, the 5-year PFS and OS rates were 80% and 82%, respectively. Receipt of RT was associated with improved 5-year PFS (88% RT vs 63% no RT, P=.0069) and OS (91% vs 68%, P=.0064). On multivariate analysis, the addition of RT significantly improved PFS (hazard ratio [HR] = 0.14, P=.014) with a trend toward an OS benefit (HR=0.30, P=.053). No significant difference in PFS or OS was found between patients treated with 30 to 35 Gy versus ≥36 Gy (P=.71 PFS and P=.31 OS). Conclusion: Patients with primary bone lymphoma treated with standard chemotherapy followed by RT can have excellent outcomes. The use of consolidative RT was associated with significant benefits in both PFS and OS.

  10. Benefit of Consolidative Radiation Therapy for Primary Bone Diffuse Large B-Cell Lymphoma

    International Nuclear Information System (INIS)

    Purpose: Outcomes for patients with diffuse large B-cell lymphoma (DLBCL) differ according to the site of presentation. With effective chemotherapy, the need for consolidative radiation therapy (RT) is controversial. We investigated the influence of primary bone presentation and receipt of consolidative RT on progression-free survival (PFS) and overall survival (OS) in patients with DLBCL. Methods and Materials: We identified 102 patients with primary bone DLBCL treated consecutively from 1988 through 2013 and extracted clinical, pathologic, and treatment characteristics from the medical records. Survival outcomes were calculated by the Kaplan-Meier method, with factors affecting survival determined by log-rank tests. Univariate and multivariate analyses were done with a Cox regression model. Results: The median age was 55 years (range, 16-87 years). The most common site of presentation was in the long bones. Sixty-five patients (63%) received R-CHOP–based chemotherapy, and 74 (72%) received rituximab. RT was given to 67 patients (66%), 47 with stage I to II and 20 with stage III to IV disease. The median RT dose was 44 Gy (range, 24.5-50 Gy). At a median follow-up time of 82 months, the 5-year PFS and OS rates were 80% and 82%, respectively. Receipt of RT was associated with improved 5-year PFS (88% RT vs 63% no RT, P=.0069) and OS (91% vs 68%, P=.0064). On multivariate analysis, the addition of RT significantly improved PFS (hazard ratio [HR] = 0.14, P=.014) with a trend toward an OS benefit (HR=0.30, P=.053). No significant difference in PFS or OS was found between patients treated with 30 to 35 Gy versus ≥36 Gy (P=.71 PFS and P=.31 OS). Conclusion: Patients with primary bone lymphoma treated with standard chemotherapy followed by RT can have excellent outcomes. The use of consolidative RT was associated with significant benefits in both PFS and OS

  11. Hepatitis C virus - associated B cell non-Hodgkin's lymphoma

    Science.gov (United States)

    Mihăilă, Romeo-Gabriel

    2016-01-01

    The hepatitis C virus (HCV) infected patients are prone to develop bone marrow or various tissue infiltrates with monoclonal B cells, monoclonal B lymphocytosis or different types of B cell non-Hodgkin’s lymphoma (BCNHL), of which the most common are splenic marginal zone BCNHL, diffuse large BCNHL and follicular lymphoma. The association between chronic HCV infection and non Hodgkin’s lymphoma has been observed especially in areas with high prevalence of this viral infection. Outside the limitations of some studies that have been conducted, there are also geographic, environmental, and genetic factors that contribute to the epidemiological differences. Various microenvironmental signals, such as cytokines, viral antigenic external stimulation of lymphocyte receptors by HCV antigens, and intercellular interactions contribute to B cell proliferation. HCV lymphotropism and chronic antigenic stimulation are involved in B-lymphocyte expansion, as mixted cryoglobulinemia or monoclonal gammopathy of undetermined significance, which can progress to BCNHL. HCV replication in B lymphocytes has oncogenic effect mediated by intracellular HCV proteins. It is also involved in an important induction of reactive oxygen species that can lead to permanent B lymphocyte damage, as DNA mutations, after binding to surface B-cell receptors. Post-transplant lymphoproliferative disorder could appear and it has a multiclonal potentiality that may develop into different types of lymphomas. The hematopoietic stem cell transplant made for lymphoma in HCV-infected patients can increase the risk of earlier progression to liver fibrosis and cirrhosis. HCV infected patients with indolent BCNHL who receive antiviral therapy can be potentially cured. Viral clearance was related to lymphoma response, fact that highlights the probable involvement of HCV in lymphomagenesis. Direct acting antiviral drugs could be a solution for the patients who did not tolerate or respond to interferon, as they

  12. CD20-negative de novo diffuse large B-cell lymphoma in HIV-negative patients: A matched case-control analysis in a single institution

    Directory of Open Access Journals (Sweden)

    Li Ya-Jun

    2012-05-01

    Full Text Available Abstract Background HIV-negative, CD20-negative de novo diffuse large B-cell lymphoma (DLBCL patients has rarely been reported. To elucidate the nature of this entity, we retrospectively reviewed the data of 1,456 consecutive de novo DLBCL patients who were treated at Sun Yat-Sen University Cancer Center between January 1999 and March 2011. Methods The pathologic characteristics of CD20-negative patients, clinical features, response to initial treatment, and outcomes of 28 patients with available clinical data (n = 21 were reviewed. Then, a matched case-control (1:3 analysis was performed to compare patients with CD20-negative and -positive DLBCL. Results The median age of the 28 CD20-negative DLBCL patients was 48 years, with a male-female ratio of 20:8. Seventeen of 22 (77.3% CD20-negative DLBCL cases were of the non-germinal centre B-cell (non-GCB subtype. High Ki67 expression (≥80%, an index of cell proliferation, was demonstrated in 17 of 24 (70.8% cases. Extranodal involvement (≥ 1 site was observed in 76.2% of the patients. Following initial therapy, 9 of 21 (42.9% cases achieved complete remission, 4 (19% achieved partial remission, 1 (4.8% had stable disease, and 7 (33.3% had disease progression. The median overall survival was 23 months. The 3-year progression-free survival (PFS and overall survival (OS rates were 30.5% and 35%, respectively. A matched case-control analysis showed that patients with CD20-negative and -positive DLBCL did not exhibit a statistically significant difference with respect to the main clinical characteristics (except extranodal involvement, whereas the patients with CD20-positive DLBCL had a better survival outcome with 3-year PFS (P = 0.008 and OS (P = 0.008 rates of 52% and 74.1%, respectively. Conclusions This study suggests that HIV-negative, CD20-negative de novo DLBCL patients have a higher proportion of non-GCB subtype, a higher proliferation index, more frequent extranodal involvement, a poorer

  13. Pretherapy metabolic tumour volume is an independent predictor of outcome in patients with diffuse large B-cell lymphoma

    Energy Technology Data Exchange (ETDEWEB)

    Sasanelli, Myriam; Meignan, Michel; Haioun, Corinne; Itti, Emmanuel [Paris-Est University, Nuclear Medicine and Lymphoid Malignancies Unit, Henri Mondor Hospital, Creteil (France); Berriolo-Riedinger, Alina; Casasnovas, Rene-Olivier [Nuclear Medicine and Hematology, Georges-Francois Leclerc Center, Le Bocage Hospital, Dijon (France); Biggi, Alberto; Gallamini, Andrea [Nuclear Medicine and Hematology, Santa Croce e Carle Hospital, Cuneo (Italy); Siegel, Barry A.; Cashen, Amanda F. [Washington University School of Medicine, Nuclear Medicine and Oncology, Siteman Cancer Center, St. Louis, MO (United States); Vera, Pierre; Tilly, Herve [Nuclear Medicine and Hematology, Henri Becquerel Center, Rouen (France); Versari, Annibale [Nuclear Medicine, Santa Maria Nuova Hospital-IRCCS, Reggio Emilia (Italy)

    2014-11-15

    We investigated the prognostic value of total metabolic tumour volume (TMTV) in diffuse large B-cell lymphoma (DLBCL). TMTV was measured in 114 patients with newly diagnosed DLBCL who underwent {sup 18}F-FDG PET/CT at baseline before immunochemotherapy. TMTV was computed by summing the volumes of all lymphomatous lesions after applying the local SUVmax threshold of 41 % using semiautomatic software. Prognostic value was assessed by Kaplan-Meier estimates of progression-free survival (PFS) and overall survival (OS). Median follow-up was 39 months. Average pretherapy TMTV was 509 ± 568 cm{sup 3}. The 3-year estimates of PFS were 77 % in the low metabolic burden group (TMTV ≤550 cm{sup 3}) and 60 % in the high metabolic burden group (TMTV >550 cm{sup 3}, p = 0.04), and prediction of OS was even better (87 % vs. 60 %, p = 0.0003). Cox regression showed independence of TMTV for OS prediction (p = 0.002) compared with other pretherapy indices of tumour burden, such as tumour bulk and the International Prognostic Index. Pretherapy TMTV is an independent predictor of outcome in patients with DLBCL. (orig.)

  14. Pretherapy metabolic tumour volume is an independent predictor of outcome in patients with diffuse large B-cell lymphoma

    International Nuclear Information System (INIS)

    We investigated the prognostic value of total metabolic tumour volume (TMTV) in diffuse large B-cell lymphoma (DLBCL). TMTV was measured in 114 patients with newly diagnosed DLBCL who underwent 18F-FDG PET/CT at baseline before immunochemotherapy. TMTV was computed by summing the volumes of all lymphomatous lesions after applying the local SUVmax threshold of 41 % using semiautomatic software. Prognostic value was assessed by Kaplan-Meier estimates of progression-free survival (PFS) and overall survival (OS). Median follow-up was 39 months. Average pretherapy TMTV was 509 ± 568 cm3. The 3-year estimates of PFS were 77 % in the low metabolic burden group (TMTV ≤550 cm3) and 60 % in the high metabolic burden group (TMTV >550 cm3, p = 0.04), and prediction of OS was even better (87 % vs. 60 %, p = 0.0003). Cox regression showed independence of TMTV for OS prediction (p = 0.002) compared with other pretherapy indices of tumour burden, such as tumour bulk and the International Prognostic Index. Pretherapy TMTV is an independent predictor of outcome in patients with DLBCL. (orig.)

  15. Serum nuclear magnetic resonance-based metabolomics and outcome in diffuse large B-cell lymphoma patients - a pilot study.

    Science.gov (United States)

    Stenson, Martin; Pedersen, Anders; Hasselblom, Sverker; Nilsson-Ehle, Herman; Karlsson, Bengt Göran; Pinto, Rui; Andersson, Per-Ola

    2016-08-01

    The prognosis for diffuse large B-cell lymphoma (DLBCL) patients with early relapse or refractory disease is dismal. To determine if clinical outcome correlated to diverse serum metabolomic profiles, we used (1)H nuclear magnetic resonance (NMR) spectroscopy and compared two groups of DLBCL patients treated with immunochemotherapy: i) refractory/early relapse (REF/REL; n=27) and ii) long-term progression-free (CURED; n = 60). A supervised multivariate analysis showed a separation between the groups. Among discriminating metabolites higher in the REF/REL group were the amino acids lysine and arginine, the degradation product cadaverine and a compound in oxidative stress (2-hydroxybutyrate). In contrast, the amino acids aspartate, valine and ornithine, and a metabolite in the glutathione cycle, pyroglutamate, were higher in CURED patients. Together, our data indicate that NMR-based serum metabolomics can identify a signature for DLBCL patients with high-risk of failing immunochemotherapy, prompting for larger validating studies which could lead to more individualized treatment of this disease. PMID:26887805

  16. Investigation of MGMT and DAPK1 methylation patterns in diffuse large B-cell lymphoma using allelic MSP-pyrosequencing

    Science.gov (United States)

    Kristensen, Lasse Sommer; Treppendahl, Marianne Bach; Asmar, Fazila; Girkov, Mia Seremet; Nielsen, Helene Myrtue; Kjeldsen, Tina Ellegaard; Ralfkiaer, Elisabeth; Hansen, Lise Lotte; Grønbæk, Kirsten

    2013-01-01

    The tumor suppressor genes MGMT and DAPK1 become methylated in several cancers including diffuse large B-cell lymphoma (DLBCL). However, allelic methylation patterns have not been investigated in DLBCL. We developed a fast and cost-efficient method for the analysis of allelic methylation based on pyrosequencing of methylation specific PCR (MSP) products including a SNP. Allelic methylation patterns were reliably analyzed in standards of known allelic methylation status even when diluted in unmethylated DNA to below 1% methylation. When studying 148 DLBCL patients MGMT and DAPK1 methylation was observed in 19% and 89%, respectively, and among methylated and heterozygous patients 29% and 55%, respectively, were biallelically methylated. An association between the T-allele of the rs16906252 SNP and MGMT methylation was observed (p-value = 0.04), and DAPK1 methylation of the A-allele was associated with shorter overall survival (p-value = 0.006). In future cancer research allelic MSP-pyrosequencing may be used to study a wide range of other loci. PMID:24071855

  17. Cyclin Dl expression in B-cell non Hodgkin lymphoma.

    Science.gov (United States)

    Aref, Salah; Mossad, Y; El-Khodary, T; Awad, M; El-Shahat, E

    2006-10-01

    Disorders of the cell cycle regulatory machinery play a key role in the pathogenesis of cancer. Over-expression of cyclin D1 protein has been reported in several solid tumors and certain lymphoid malignancies, but little is known about the effect of its expression on clinical behavior and outcome in B-cell Non-Hodgkin lymphoma (NHL). In this study, we investigated the expression of cyclin Dl in group of patients with NHL and correlated the results with the clinical and laboratory data. The degree of expression of cyclin Dl protein was evaluated by flow cytometry in a group of NHL patients (n = 46) and in normal control group (n = 10). Cyclin Dl over expression was detected in 10 out of 46 (21.7%) patients; they were 5/5-mantle cell lymphoma (MCL) (100%) and 5/28 large B-cell lymphoma (17.8%). All other NHL subtypes showed normal cyclin D1 expression. The clinical signs (hepatomegaly, splenomegaly and B-symptoms, clinical staging) and laboratory data (hemoglobin, white cell count (WBCs), platelet count, and bone marrow infiltration) were not significantly different between NHL subgroup with cyclin Dl over expression and that with normal cyclin Dl expression. Serum lactic dehydrogenase (LDH) levels and lymphadenopathy were significantly higher in NHL group with cyclin D1 over expression as compared to those without. Also, cyclin D1 over expression is associated with poor outcome of NHL patients. Cyclin Dl over expression was evident among all cases of MCL and few cases of large B-cell lymphoma. Cyclin Dl over expression might be used as adjuvant tool for diagnosis of MCL; has role in NHL biology and is bad prognostic index in NHL. PMID:17607588

  18. Prognostic factors in primary diffuse large B-cell lymphoma of adrenal gland treated with rituximab-CHOP chemotherapy from the Consortium for Improving Survival of Lymphoma (CISL

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    Kim Yu

    2012-08-01

    Full Text Available Abstract Background The objective of this study was to identify prognostic factors for survival in patients with primary diffuse large B-cell lymphoma (DLBCL of the adrenal gland. Methods Thirty one patients diagnosed with primary adrenal DLBCL from 14 Korean institutions and treated with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone were analyzed. Results Complete remission (CR and overall response rate after R-CHOP chemotherapy were 54.8% and 87.0%. The 2-year estimates of overall survival (OS and progression-free survival (PFS were 68.3% and 51.1%. In patients achieving CR, significant prolongations of OS (P = 0.029 and PFS (P = 0.005 were observed. Ann Arbor stage had no influence on OS. There was no significant difference in OS between patients with unilateral involvement of adrenal gland and those with bilateral involvement. When staging was modified to include bilateral adrenal involvement as one extranodal site, early stage (I or II significantly correlated with longer OS (P = 0.021 and PFS (P 0.001. Conclusions Contrary to prior reports, our data suggests that outcomes of primary adrenal DLBCL are encouraging using a regimen of R-CHOP, and that achieving CR after R-CHOP is predictive of survival. Likewise, our modified staging system may have prognostic value.

  19. Dominant neurologic symptomatology in intravascular large B-cell lymphoma.

    Science.gov (United States)

    Kubisova, K; Martanovic, P; Sisovsky, V; Tomleinova, Z; Steno, A; Janega, P; Rychly, B; Babal, P

    2016-01-01

    Intravascular large B-cell lymphoma (IVLBCL) is a rare variant of extranodal large B-cell lymphoma and it is characterized by selective intravascular proliferation of malignant cells. Typical features of the disease include aggressive behavior, rapid and frequently fatal course. Clinical picture is non-specific and heterogeneous, depending on the affected organ. It is not uncommon that this unique type of lymphoma is diagnosed post mortem. Herein, we report two cases of IVLBCL with neurologic symptomatology. In our clinical study patient 1 was an 80-year-old male with mixed paraparesis of lower extremities and difficulties with sphincter control. Patient 2 (56-year-old male) had vision malfunction, mental status changes and defect in phatic and motor functions. In both cases definite diagnosis was established by histological examination of necroptic material. We propose to include IVLBCL in differential diagnostic considerations in patients presenting with gradually impairing neurological status and spinal cord damage of unknown etiology (Fig. 2, Ref. 9). PMID:27546361

  20. Outcome of R-CHOP or CHOP Regimen for Germinal Center and Nongerminal Center Subtypes of Diffuse Large B-Cell Lymphoma of Chinese Patients

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    Ying Huang

    2012-01-01

    Full Text Available 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. We studied 204 patients with de novo DLBCL (107 treated with first-line CHOP; 97 treated with first-line 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 (IHC were studied. The 5-year overall survival (OS in the CHOP and R-CHOP groups 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 or not (65.0% versus 40.9%; P=0.011. In contrast, there is no difference in the 5-year OS for the GCB and non-GCB with R-CHOP (76.5% versus 61.3%; P=0.141. In non-GCB subtype, additional rituximab improved survival better than CHOP (61.3% versus 40.9%; P=0.0303. These results indicated that addition of rituximab to standard chemotherapy eliminates the prognostic value of IHC-defined GCB and non-GCB phenotypes in DLBCL by improving the prognostic value of non-GCB subtype of DLBCL.

  1. Clinical analysis of unclassifiable B-cell lymphoma intermediates between diffuse lage B-cell lymphoma and Burkitt lymphoma%介于弥漫大B细胞淋巴瘤和伯基特淋巴瘤之间的未分类淋巴瘤

    Institute of Scientific and Technical Information of China (English)

    李素彩; 南飞飞; 贾思思; 曹婧语; 樊姗姗; 张超; 张明智; 张蕾

    2016-01-01

    目的:分析介于弥漫大B细胞淋巴瘤和伯基特淋巴瘤之间的未分类的B细胞淋巴瘤(B-cell lymphoma,unclassifiable,with features intermediate between DLBCL and Burkitt lymphoma,DLBCL/BL)的临床特点、治疗与预后,增加对该病的认识。方法:收集郑州大学第一附属医院2013年1月至2014年12月收治的13例DLBCL/BL患者临床病理资料,采用Kaplan-Meier法进行生存分析,采用Log rank检验对临床分期、年龄、LDH水平、IPI评分、初治化疗方案等进行单因素分析。结果:13例患者中12例存在结外侵犯,13例患者的中位OS为10个月,中位PFS为6个月。单因素分析显示IPI评分、LDH水平与预后有统计学相关性,行CHOP、CHOP样与高强度化疗方案患者之间生存差异具有统计学意义(P=0.054)。结论:DLBCL/BL恶性程度高,生存期短,结外侵犯多见,对CHOP及CHOP样方案治疗反应差,高强度化疗可能改善预后,IPI评分≥3分及LDH升高是其不良预后因素。%Objective:To analyze clinical characteristics, treatment, and prognosis of B-cell lymphoma, unclassifiable, with features in-termediate between diffuse large B-cell lymphoma and Burkitt lymphoma (DLBCL/BL). Methods:The clinical and pathological data of 13 DLBCL/BL patients, who were treated in the First Affiliated Hospital of Zhengzhou University between January 2013 and December 2014, were collected. Overall survival (OS) and progression-free survival (PFS) were estimated by the Kaplan-Meier method. Through the log-rank test, survival curves were compared among groups classified by clinical stage, age, serum lactate dehydrogenase (LDH) lev-el, international prognostic index (IPI) score, or first chemotherapy regimen. Results:Among the 13 patients with DLBCL/BL, 12 pa-tients showed extra-nodal involvement. The median OS and PFS were only 10 and 6 months, respectively. Univariate analysis showed that the LDH levels and IPI scores exerted

  2. Primary cardiac diffuse large B-cell lymphoma with activated B-cell-like phenotype

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    Vijaya Gadage

    2011-01-01

    Full Text Available Primary cardiac lymphoma (PCL is a rare and fatal disorder. It may often mimic other common cardiac tumors like cardiac myxoma because of similarities in the clinical presentation. We report a case of PCL of diffuse large B-cell type, in a 38-year-old, immunocompetent male who presented with superior vena cava syndrome that was excised as a myxoma. Histology revealed a large cell population diffusely and strongly expressing CD45, CD20, MUM1/IRF4 and FOXP1 hinting at an activated B-cell (ABC-like phenotype. After four cycles of Rituximab with CHOP (cyclophosphamide, hydroxydaunorubicin, Oncovin, and prednisolone the tumor regressed completely but the patient had a relapse and subsequently succumbed to the disease confirming the aggressive nature. The aggressive behavior of PCL may be possibly linked to its ABC-like origin.

  3. Epstein-Barr Virus-Positive Diffuse Large B-Cell Lymphoma in the Elderly: A Matched Case-Control Analysis.

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    Chen-Ge Song

    Full Text Available Epstein-Barr virus (EBV-positive diffuse large B-cell lymphoma (DLBCL in the elderly has rarely been reported. This study aimed to explore the clinical characteristics and prognosis of this entity.In situ hybridization (ISH analysis of Epstein-Barr virus (EBV and immunohistochemistry was performed in 230 tumor specimens from consecutive de novo DLBCL patients over 50 years old. A matched-case control analysis (1:3 was utilized to compare EBV-positive and EBV-negative DLBCL in the elderly.A total of 16 patients (7.0% were diagnosed with EBV-positive DLBCL. Of these 16 cases, the median age was 62 years, with a male to female ratio of 11:5. Elderly EBV-positive DLBCL patients had a higher incidence of non-germinal center B-cell (non-GCB subtypes (87.5% and high Ki67 (75% and CD30 expression (93.8%. For EBV-positive patients undergoing initial chemotherapy, 7 of 16 (43.8% had complete remission, 2 (12.5% had partial remission, 2 (12.5% had stable disease, and 5 (31.3% had progressive disease. The median overall survival was 9 months for the EBV-positive patients. A matched-case control analysis suggested that EBV-positive patients had inferior survival outcomes compared with EBV-negative patients (3-year progression-free survival [PFS]: 25% vs. 76.7%, respectively; 3-year overall survival [OS]: 25% vs. 77.4%, respectively; P<0.001.EBV-positive DLBCL of the elderly is associated with an inferior clinical course and inferior survival outcomes. The role of EBV in this disease and the optimal management of this subgroup warrants further investigation.

  4. Sphingosine-1-phosphate receptor 1 as a prognostic biomarker and therapeutic target for patients with primary testicular diffuse large B-cell lymphoma.

    Science.gov (United States)

    Koresawa, Risa; Yamazaki, Kazuto; Oka, Daigo; Fujiwara, Hideyo; Nishimura, Hirotake; Akiyama, Takashi; Hamasaki, Shuji; Wada, Hideho; Sugihara, Takashi; Sadahira, Yoshito

    2016-07-01

    Sphingosine-1-phosphate (S1P) is a potent lipid mediator that is produced during the metabolism of sphingolipid by sphingosine kinase. S1P has been implicated in the migration and trafficking of lymphocytes and several lymphoid malignancies through S1P receptors. Moreover, the overexpression of sphingosine-1-phosphate receptor 1 (S1PR1) has been correlated with the constitutive activation of signal transducer and activator of transcription (STAT)3 and poor prognosis of diffuse large B-cell lymphoma (DLBCL). Thus, in this study, we examined the expression of S1PR1 in 198 DLBCL samples collected from nodal and various extranodal sites and sub-classified formalin-fixed paraffin-embedded tissue samples into germinal centre B-cell-like (GCB) and non-GCB subgroups using immunohistochemistry. These analyses showed S1PR1 overexpression in 15·7% of all cases with DLBCL and in 54·2% of 24 cases with primary testicular (PT)-DLBCL; S1PR1 expression correlated with S1PR1mRNA expression and STAT3 phosphorylation in fresh samples. Analyses of data from a single institution suggested that S1PR1 overexpression was an independent negative prognostic marker in 68 patients with DLBCL of clinical stages I and II. The present high prevalence of S1PR1 overexpression warrants the consideration of PT-DLBCL as a distinct disease subtype and suggests the potential of the S1P/S1PR1 axis as a therapeutic target. PMID:27061580

  5. Comprehensive Assessment and Classification of High-Grade B-cell Lymphomas.

    Science.gov (United States)

    Behdad, Amir; Bailey, Nathanael G

    2016-03-01

    High-grade B-cell lymphomas (HGBCLs) are a heterogeneous group of neoplasms that include subsets of diffuse large B-cell lymphoma, Burkitt lymphoma, and lymphomas with features intermediate between diffuse large B-cell lymphoma and Burkitt lymphoma. Morphologically indistinguishable HGBCLs may demonstrate variable clinical courses and responses to therapy. The morphologic evaluation and classification of these neoplasms must be followed by further genetic and immunophenotypic work-up. These additional diagnostic modalities lead to a comprehensive stratification of HGBCL that determines the prognosis and optimal therapy. This article reviews the well-established and emerging biomarkers that are most relevant to the clinical management of HGBCL. PMID:26940267

  6. Global gene expression changes of in vitro stimulated human transformed germinal centre B cells as surrogate for oncogenic pathway activation in individual aggressive B cell lymphomas

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    Schrader Alexandra

    2012-12-01

    Full Text Available Abstract Background Aggressive Non-Hodgkin lymphomas (NHL are a group of lymphomas derived from germinal centre B cells which display a heterogeneous pattern of oncogenic pathway activation. We postulate that specific immune response associated signalling, affecting gene transcription networks, may be associated with the activation of different oncogenic pathways in aggressive Non-Hodgkin lymphomas (NHL. Methodology The B cell receptor (BCR, CD40, B-cell activating factor (BAFF-receptors and Interleukin (IL 21 receptor and Toll like receptor 4 (TLR4 were stimulated in human transformed germinal centre B cells by treatment with anti IgM F(ab2-fragments, CD40L, BAFF, IL21 and LPS respectively. The changes in gene expression following the activation of Jak/STAT, NF-кB, MAPK, Ca2+ and PI3K signalling triggered by these stimuli was assessed using microarray analysis. The expression of top 100 genes which had a change in gene expression following stimulation was investigated in gene expression profiles of patients with Aggressive non-Hodgkin Lymphoma (NHL. Results αIgM stimulation led to the largest number of changes in gene expression, affecting overall 6596 genes. While CD40L stimulation changed the expression of 1194 genes and IL21 stimulation affected 902 genes, only 283 and 129 genes were modulated by lipopolysaccharide or BAFF receptor stimulation, respectively. Interestingly, genes associated with a Burkitt-like phenotype, such as MYC, BCL6 or LEF1, were affected by αIgM. Unique and shared gene expression was delineated. NHL-patients were sorted according to their similarity in the expression of TOP100 affected genes to stimulated transformed germinal centre B cells The αIgM gene module discriminated individual DLBCL in a similar manner to CD40L or IL21 gene modules. DLBCLs with low module activation often carry chromosomal MYC aberrations. DLBCLs with high module activation show strong expression of genes involved in cell

  7. Integrating understanding of epidemiology and genomics in B-cell non-Hodgkin lymphoma as a pathway to novel management strategies.

    Science.gov (United States)

    Glass, Samantha; Phan, Anh; Williams, Jessica N; Flowers, Christopher R; Koff, Jean L

    2016-03-01

    Non-Hodgkin lymphomas include a biologically and clinically heterogeneous group of cancers distinguished by genetics, histology, and treatment outcomes. New discoveries regarding the genomic alterations and epidemiological exposures associated with these lymphomas have enhanced our understanding of factors that contribute to lymphomagenesis for specific subtypes. We explore the impact of normal B-cell biology engineered for recognizing a wide variety of antigens on the development of specific lymphoma subtypes, review lymphoma genetics, and examine the epidemiology of B-cell NHLs including recent investigations of risk factors for particular lymphoma subtypes based on large pooled analyses. Burkitt lymphoma, an aggressive form of B-cell NHL involving translocation of the MYC gene and an immunoglobulin gene has been associated with a history of eczema, hepatitis C, and occupation as a cleaner. Increased risk of diffuse large B-cell lymphoma has been associated with increased young adult body mass index, history of B-cell-activating autoimmune diseases, hepatitis C, and several single nucleotide variants involving the human leukocyte antigen (HLA) region of chromosome 6 and non-HLA loci near EXOC2, PVT1, MYC, and NCOA1. Tumor sequencing studies suggest that multiple pathways are involved in the development of DLBCL. Additional studies of epidemiological exposures, genome wide associations, and tumor sequencing in follicular, lymphoplasmacytic, marginal zone, and mantle cell lymphoma demonstrate overlapping areas of increased risk factors and unique factors for specific subtypes. Integrating these findings is important for constructing comprehensive models of NHL pathogenesis, which could yield novel targets for therapy and strategies for lymphoma prevention in certain populations. PMID:27115168

  8. Diffuse large B-cell lymphoma of the oral cavity

    International Nuclear Information System (INIS)

    The authors report a case of diffuse large B-cell lymphoma (DLBL) of the oral cavity. The patient was a 73-year-old white man who first presented at the Division of Stomatology with a large nodular mass in the hard palate and a nodular lesion in the upper lip, which were diagnosed as DLBL. The patient was treated with eight cycles of CHOP chemotherapy (cyclophosphamide, doxorubicin, vincristine and prednisone), but the disease recurred 22 months after the end of the therapy. Both primary sites hard palate and upper lip were involved again and the patient was resubmitted to chemotherapy. (author)

  9. Prevalence of targetable oncogenic mutations and genomic alterations in Epstein-Barr virus-associated diffuse large B-cell lymphoma of the elderly.

    Science.gov (United States)

    Gebauer, Niklas; Gebauer, Judith; Hardel, Tim Tristan; Bernard, Veronica; Biersack, Harald; Lehnert, Hendrik; Rades, Dirk; Feller, Alfred Christian; Thorns, Christoph

    2015-04-01

    Epstein-Barr virus (EBV)-associated diffuse large B-cell lymphoma (DLBCL) of the elderly constitutes a provisional clinicopathological entity in the current World Health Organization (WHO) classification and its genomic features remain sparsely characterized. We investigated a cohort of 26 cases of untreated de novo EBV-positive DLBCL of the elderly by high-resolution array-based comparative genomic profiling and fluorescence in situ hybridization (FISH). Moreover, we screened for activating mutations affecting nuclear factor (NF)-κB pathway signaling and chromatin remodeling (EZH2, CD79B, CARD11 and MYD88) due to their impact of gene expression signatures and postulated upcoming therapeutic targetability. We identified an overlap between genomic aberrations previously described to be exclusive features of plasmablastic lymphoma (PL), post-transplant lymphoproliferative disorder (PTLD) and DLBCL, respectively, indicating a close cytogenetic relationship between these entities. Few mutations affecting CD79B and CARD11 and no MYD88 mutations were detectable, hinting at EBV-mediated activation of NF-κB as an alternative to pathologically enforced B-cell receptor signaling in this rare entity. PMID:25030036

  10. De novo CD5+ diffuse large B-cell lymphoma: Adverse outcomes with and without stem cell transplantation in a large, multicenter, rituximab treated cohort.

    Science.gov (United States)

    Alinari, Lapo; Gru, Alejandro; Quinion, Carl; Huang, Ying; Lozanski, Arletta; Lozanski, Gerard; Poston, Jacqueline; Venkataraman, Girish; Oak, Eunhye; Kreisel, Friederike; Park, Steven I; Matthews, Stephanie; Abramson, Jeremy S; Iris Lim, Hana; Martin, Peter; Cohen, Jonathon B; Evens, Andrew; Al-Mansour, Zeina; Singavi, Arun; Fenske, Timothy S; Blum, Kristie A

    2016-06-01

    De novo CD5+ diffuse large B-cell lymphomas (DLBCL) are a distinct subgroup of DLBCL with poor prognosis. However the role of rituximab-containing therapy and salvage stem cell transplantation in this patients' population remain to be defined. We retrospectively reviewed clinical features and outcomes of 102 patients with de novo CD5+ DLBCL treated with rituximab-containing therapy at nine different institutions. By Hans' criteria, 64 patients had activated B-cell (ABC) subtype, 24 germinal center B-cell (GCB) subtype, and 14 were not evaluated. No patients had a myc translocation. Eighty-three patients were treated with rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone (R-CHOP), 7 with rituximab, etoposide, cyclophosphamide, doxorubicin, vincristine, prednisone (R-EPOCH), and 6 with R-CHOP with methotrexate, 3 g/m(2) . The overall response rate to front-line therapy was 85%. The 3-year progression free survival (PFS) and overall survival (OS) for all patients were 40 and 65%, respectively. The 3-year PFS for ABC- and GCB-subtypes was 34 and 45%, respectively. The 3-year OS for ABC- and GCB-subtypes was 62 and 67%, respectively. The median time to second treatment failure was 3 months and 1 month for ABC- and GCB-subtypes, respectively. Twenty of 28 (71%) transplanted patients with autologous, allogeneic, or both, relapsed. This study confirms the poor prognosis of de novo CD5+ DLBCL in a large multi-center cohort despite initial rituximab-containing chemotherapy and suggests that stem cell transplantation fails to salvage the majority of these patients. Approaches to prevent recurrence and/or novel therapies for relapsed disease are needed for this subgroup of DLBCL patients. Am. J. Hematol. 91:395-399, 2016. © 2016 Wiley Periodicals, Inc. PMID:26800311

  11. Expression of CD40 is a positive prognostic factor of diffuse large B-cell lymphoma treated with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone

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    Song G

    2016-06-01

    Full Text Available Guoqi Song,1 Huiyun Ni,1 Linqing Zou,2 Shukui Wang,3 Fuliang Tian,4 Hong Liu,1 William C Cho5 1Department of Hematology, Affiliated Hospital of Nantong University, Nantong, 2Department of Human Anatomy, Nantong University, Nantong, 3Central Laboratory of Nanjing First Hospital, Nanjing Medical University, Nanjing, 4Maternal and Child Health Hospital of Lianyungang, Lianyungang, Jiangsu, People’s Republic of China; 5Department of Clinical Oncology, Queen Elizabeth Hospital, Kowloon, Hong Kong Objectives: The objective of this study was to investigate the expression level of CD40 and its role in the prognosis of patients with diffuse large B-cell lymphoma (DLBCL who were treated with rituximab-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone.Design and methods: The immunohistochemical expressions of CD40 in 186 well-characterized DLBCL patients were evaluated by tissue microarrays, thereby revealing the relationship of the molecule CD40 with known tumor, patient-related variables, and survival rates.Results: The results showed that CD40 expressions were not statistically different between the germinal center B-cell-like (GCB type and the non-GCB type. We also analyzed the relationships of CD40 expression with overall survival (OS and progression-free survival (PFS in DLBCL patients who were uniformly treated with R-CHOP. A low expression of CD40 compared to high expression is related to poor OS and PFS. Conclusion: Our findings indicate that the CD40 level at onset acts as an independent prognostic predictor of DLBCL patients treated with R-CHOP. Keywords: CD40, diffuse large B-cell lymphoma, R-CHOP, prognostic factor

  12. Rituximab in Treating Patients Undergoing Donor Peripheral Blood Stem Cell Transplant for Relapsed or Refractory B-cell Lymphoma

    Science.gov (United States)

    2015-11-23

    B-cell Adult Acute Lymphoblastic Leukemia; B-cell Childhood Acute Lymphoblastic Leukemia; B-cell Chronic Lymphocytic Leukemia; Childhood Burkitt Lymphoma; Childhood Diffuse Large Cell Lymphoma; Childhood Immunoblastic Large Cell Lymphoma; Cutaneous B-cell Non-Hodgkin Lymphoma; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Intraocular Lymphoma; Nodal Marginal Zone B-cell Lymphoma; Post-transplant Lymphoproliferative Disorder; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Grade III Lymphomatoid Granulomatosis; Recurrent Adult Hodgkin Lymphoma; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Childhood Acute Lymphoblastic Leukemia; Recurrent Childhood Grade III Lymphomatoid Granulomatosis; Recurrent Childhood Large Cell Lymphoma; Recurrent Childhood Lymphoblastic Lymphoma; Recurrent Childhood Small Noncleaved Cell Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Small Lymphocytic Lymphoma; Recurrent/Refractory Childhood Hodgkin Lymphoma; Refractory Chronic Lymphocytic Leukemia; Refractory Hairy Cell Leukemia; Small Intestine Lymphoma; Splenic Marginal Zone Lymphoma; Testicular Lymphoma; Waldenström Macroglobulinemia

  13. The B-cell receptor orchestrates environment-mediated lymphoma survival and drug resistance in B-cell malignancies

    OpenAIRE

    Shain, KH; Tao, J.

    2013-01-01

    Specific niches within the lymphoma tumor microenvironment (TME) provide sanctuary for subpopulations of tumor cells through stromal cell–tumor cell interactions. These interactions notably dictate growth, response to therapy and resistance of residual malignant B cells to therapeutic agents. This minimal residual disease (MRD) remains a major challenge in the treatment of B-cell malignancies and contributes to subsequent disease relapse. B-cell receptor (BCR) signaling has emerged as essenti...

  14. Routine use of ancillary investigations in staging diffuse large B-cell lymphoma improves the International Prognostic Index (IPI

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    Shadbolt Bruce

    2009-11-01

    Full Text Available Abstract Background The International Prognostic Index (IPI is used to determine prognosis in diffuse large B-cell lymphoma (DLBCL. One of the determinants of IPI is the stage of disease with bone marrow involvement being classified as stage IV. For the IPI, involvement on bone marrow is traditionally defined on the basis of histology with ancillary investigations used only in difficult cases to aid histological diagnosis. This study aimed to determine the effect of the routine use of flow cytometry, immunohistochemistry and molecular studies in bone marrow staging upon the IPI. Results Bone marrow trephines of 156 histologically proven DLBCL cases at initial diagnosis were assessed on routine histology, and immunohistochemistry using two T-cell markers (CD45RO and CD3, two B-cell markers (CD20 and CD79a and kappa and lambda light chains. Raw flow cytometry data on all samples were reanalysed and reinterpreted blindly. DNA extracted from archived paraffin-embedded trephine biopsy samples was used for immunoglobulin heavy chain and light chain gene rearrangement analysis. Using immunophenotyping (flow cytometry and immunohistochemistry, 30 (19.2% cases were upstaged to stage IV. A further 8 (5.1% cases were upstaged using molecular studies. A change in IPI was noted in 18 cases (11.5% on immunophenotyping alone, and 22 (14.1% cases on immunophenotyping and molecular testing. Comparison of two revised IPI models, 1 using immunophenotyping alone, and 2 using immunophenotyping with molecular studies, was performed with baseline IPI using a Cox regression model. It showed that the revised IPI model using immunophenotyping provides the best differentiation between the IPI categories. Conclusion Improved bone marrow staging using flow cytometry and immunohistochemistry improves the predictive value of the IPI in patients with DLBCL and should be performed routinely in all cases.

  15. Anticancer Effect of Curcumin on B Cell non- Hodgkin's Lymphoma

    Institute of Scientific and Technical Information of China (English)

    SUN Chunyan; LIU Xinyue; CHEN Yan; LIU Fang

    2005-01-01

    To explore the anticancer effect of curcumin on human B cell non-Hodgkin's lymphoma and compare its effects on human B cell non-Hodgkin's lymphoma cells and normal peripheral blood mononuclear cells (NPBMNCs). MTT assay was used to study the effect of curcumin on the growth of Raji cells and NPBMNCs. The effect of curcumin on the apoptosis of Raji cells and NPBMNC were studied by flow cytometry and TDT-mediated dUTP nick and labeling (TUNEL). The effect of curcumin on the cell cycle of Raji cells were examined by propidium iodide staining flow cytometry. The results showed that curcumin strongly inhibited ±1.82 μmol/L and curcumin induced Raji cell apoptosis in a time- and dose-dependent manner. Raji cells treated with curcumin showed curcumin did not demonstrate apparent proliferation inhibition and apoptosis induction in NPBMNCs. It was concluded that curcumin is able to inhibit the proliferation of Raji cells by regulating the cell cycle and inducing the cell apoptosis. Morever, curcumin has low toxicity on NPBMNCs but can selectively induce apoptosis in Raji cells.

  16. Cellular Immunotherapy Following Chemotherapy in Treating Patients With Recurrent Non-Hodgkin Lymphomas, Chronic Lymphocytic Leukemia or B-Cell Prolymphocytic Leukemia

    Science.gov (United States)

    2016-07-29

    Post-transplant Lymphoproliferative Disorder; B-Cell Prolymphocytic Leukemia; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Small Lymphocytic Lymphoma; Refractory Chronic Lymphocytic Leukemia; Refractory Hairy Cell Leukemia; B-Cell Lymphoma, Unclassifiable, With Features Intermediate Between Diffuse Large B-Cell Lymphoma and Burkitt Lymphoma; B-Cell Lymphoma, Unclassifiable, With Features Intermediate Between Diffuse Large B-Cell Lymphoma and Classical Hodgkin Lymphoma; Recurrent Lymphoplasmacytic Lymphoma

  17. Rituximab, Romidepsin, and Lenalidomide in Treating Patients With Recurrent or Refractory B-cell Non-Hodgkin Lymphoma

    Science.gov (United States)

    2016-01-07

    B-cell Adult Acute Lymphoblastic Leukemia; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Intraocular Lymphoma; Nodal Marginal Zone B-cell Lymphoma; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Grade III Lymphomatoid Granulomatosis; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Small Lymphocytic Lymphoma; Refractory Hairy Cell Leukemia; Small Intestine Lymphoma; Splenic Marginal Zone Lymphoma; Testicular Lymphoma; Waldenström Macroglobulinemia

  18. Diffuse large B-cell lymphoma in patient after treatment of angioimmunoblastic T-cell lymphoma.

    Science.gov (United States)

    Skugor, Nives Dzeko; Perić, Zinaida; Vrhovac, Radovan; Radić-Kristo, Delfa; Kardum-Skelin, Ika; Jaksić, Branimir

    2010-03-01

    Relatively few cases of Epstein-Barr (EBV)-positive B-cell lymphomas arising in patients with angioimmunoblastic T-cell lymphoma (AITL) have been reported. We report a case of AITL in which diffuse large B-cell lymphoma arose 13 months after the initial diagnosis of AITL. In a 36-year-old female patient, evaluated for moderate leukocytosis, peripheral and abdominal lymphadenopathy AITL was diagnosed in March 2008, based on results of fine-needle aspiration cytology (FNAC) of the enlarged cervical and supraclavicular lymph nodes. The diagnosis was also confirmed by immunophenotyping and histopathology of the cervical lymph nodes. The patient initially recieved FED chemotherapy (fludarabine, cyclophosphamide, dexamethasone) followed by elective autologous hematopoietic stem cell transplantation. In April 2009 the patient was hospitalized because of fever, pancytopenia, hyperbilirubinemia and peripheral lymphadenopathy. The FNAC of the enlarged cervical lymph nodes was performed again, but this time the smears were composed of polymorphous population of lymphocytes with the predomination of large cells, CD20+ on immunocytochemical stains. The immunophenotyping confirmed a predomination of monoclonal mature B-cells. Patient had high number of EBV DNA copies in plasma and serologic testing revealed increased titers of EBV VCA IgG and EBV EBNA IgG. CHOP-R chemotherapy (cyclophosphamide, doxorubicin, vincristine, prednisone and rituximab) was then administered, resulting in good partial response of the disease. Reduced intensity allogeneic stem cell transplantation performed thereafter, resulted in complete remission of the disease. AITL is a rare lymphoproliferative disorder in which the neoplastic T-cells represent the minority of the lymph node cell population and almost all cases harbor EBV-infected B-cells. Various authors postulated that immunodeficiency in AITL patients together with immunosuppressive effects of cytotoxic drugs, may be responsible for EBV

  19. Primary uterine diffuse large B-cell lymphoma involving the urinary bladder with urinary cytology mimicking carcinomas: A case report

    Directory of Open Access Journals (Sweden)

    Sumiyo Adachi

    2015-01-01

    Full Text Available We report a rare case of a 69-year-old woman in whom diffuse large B-cell lymphoma (DLBCL originated from the uterus and involved the urinary bladder. The cervical smears of the case mostly consisted of discohesive atypical round cells, which were highly suggestive of lymphoma; however, in voided urine smears, a majority of the cells formed large aggregates of degenerated cells, mimicking those of urothelial carcinoma (UC. The smears also represented some small loose clusters, in which tumor cells formed short chains with nuclear molding, mimicking those of small cell carcinoma. The cytodiagnosis got definitive when we identified the atypical cells that showed CD20+/CD3-/cytokeratin-/NSE- immunophenotype. These are of particular concern as they may have misleading similarities to other epithelial neoplasms when examining lymphoma involving the urinary bladder. Accordingly, this case highlights the importance of immunocytochemistry to rule out malignant lymphoma when encountering large and/or small loose clusters of atypical round cells on urinary cytology.

  20. Primary uterine diffuse large B-cell lymphoma involving the urinary bladder with urinary cytology mimicking carcinomas: A case report.

    Science.gov (United States)

    Adachi, Sumiyo; Yamazaki, Kazuto; Liang, Shan-Guang; Ishida, Yasuo

    2015-01-01

    We report a rare case of a 69-year-old woman in whom diffuse large B-cell lymphoma (DLBCL) originated from the uterus and involved the urinary bladder. The cervical smears of the case mostly consisted of discohesive atypical round cells, which were highly suggestive of lymphoma; however, in voided urine smears, a majority of the cells formed large aggregates of degenerated cells, mimicking those of urothelial carcinoma (UC). The smears also represented some small loose clusters, in which tumor cells formed short chains with nuclear molding, mimicking those of small cell carcinoma. The cytodiagnosis got definitive when we identified the atypical cells that showed CD20+/CD3-/cytokeratin-/NSE- immunophenotype. These are of particular concern as they may have misleading similarities to other epithelial neoplasms when examining lymphoma involving the urinary bladder. Accordingly, this case highlights the importance of immunocytochemistry to rule out malignant lymphoma when encountering large and/or small loose clusters of atypical round cells on urinary cytology. PMID:26729979

  1. Intravascular Large B-Cell Lymphoma: A Difficult Diagnostic Challenge.

    Science.gov (United States)

    Khan, Maria S; McCubbin, Mark; Nand, Sucha

    2014-01-01

    Case Presentation. A 69-year-old Hispanic male, with a past history of diabetes and coronary disease, was admitted for fever, diarrhea, and confusion of 4 weeks duration. Physical examination showed a disoriented patient with multiple ecchymoses, possible ascites, and bilateral scrotal swelling. Hemoglobin was 6.7, prothrombin time (PT) 21.4 seconds with international normalized ratio 2.1, partial thromboplastin time (PTT) 55.6 seconds, fibrin split 10 µg/L, and lactate dehydrogenase (LDH) 1231 IU/L. Except for a positive DNA test for Epstein-Barr virus (EBV) infection, extensive diagnostic workup for infections, malignancy, or a neurological cause was negative. Mixing studies revealed a nonspecific inhibitor of PT and PTT but Factor VIII levels were normal. The patient was empirically treated with antibiotics but developed hypotension and died on day 27 of admission. At autopsy, patient was found to have intravascular diffuse large B-cell lymphoma involving skin, testes, lung, and muscles. The malignant cells were positive for CD20, CD791, Mum-1, and Pax-5 and negative for CD3, CD5, CD10, CD30, and Bcl-6. The malignant cells were 100% positive for Ki-67. Discussion. Intravascular large cell B-cell lymphoma (IVLBCL) is rare form of diffuse large B-cell lymphoma and tends to proliferate within small blood vessels, particularly capillaries and postcapillary venules. The cause of its affinity for vascular bed remains unknown. In many reports, IVLBCL was associated with HIV, HHV8, and EBV infections. The fact that our case showed evidence of EBV infection lends support to the association of this diagnosis to viral illness. The available literature on this subject is scant, and in many cases, the diagnosis was made only at autopsy. The typical presentation of this disorder is with B symptoms, progressive neurologic deficits, and skin findings. Bone marrow, spleen, and liver are involved in a minority of patients. Nearly all patients have elevated LDH, and about 65% are

  2. Prognostic Significance of Monocytes and Monocytic Myeloid-Derived Suppressor Cells in Diffuse Large B-Cell Lymphoma Treated with R-CHOP

    Directory of Open Access Journals (Sweden)

    Chongyang Wu

    2016-07-01

    Full Text Available Background/Aims: To evaluate the prognostic significance of monocytes and monocytic myeloid-derived suppressor cells (M-MDSCs for patients with diffuse large B-cell lymphoma (DLBCL under R-CHOP chemotherapy. Methods: Flow cytometry (FCM was applied to measure M-MDSCs (CD14+ HLA-DRlow/− M-MDSCs. Results: Analysis of 144 patients with DLBCL under R-CHOP treatment showed that the 5-year overall survival rate was 61.09% (95% CI: 43.72%-72.56% and the average survival time of patients with monocytes (% ≥ 8% was shorter than those with monocytes (% 2 (P = 0.0397, meanwhile, there was no significant difference in survival of patients with monocytes (% ≥ 8% compared to patients with monocytes (% Conclusion: Our results indicated that monocytes (% and M-MDSCs combined with R-IPI may be a simple and efficient immunological index to evaluate prognosis.

  3. A COMPARISON OF HLA-IDENTICAL SIBLING ALLOGENEIC VERSUS AUTOLOGOUS TRANSPLANTATION FOR DIFFUSE LARGE B-CELL LYMPHOMA: A REPORT FROM THE CIBMTR

    Science.gov (United States)

    Lazarus, Hillard M.; Zhang, Mei-Jie; Carreras, Jeanette; Hayes-Lattin, Brandon M.; Ataergin, Asli Selmin; Bitran, Jacob D.; Bolwell, Brian J.; Freytes, César O.; Gale, Robert Peter; Goldstein, Steven C.; Hale, Gregory A.; Inwards, David J.; Klumpp, Thomas R.; Marks, David I.; Maziarz, Richard T.; McCarthy, Philip L.; Pavlovsky, Santiago; Rizzo, J Douglas; Shea, Thomas C.; Schouten, Harry C.; Slavin, Shimon; Winter, Jane N.; van Besien, Koen; Vose, Julie M.; Hari, Parameswaran N.

    2010-01-01

    We compared outcomes of 916 diffuse large B cell lymphoma (DLBCL) patients age ≥ 18 years undergoing first autologous (n=837) or myeloablative allogeneic hematopoietic cell transplant (HCT) (n=79) between 1995–2003 reported to the CIBMTR. Median follow-up was 81 months for allogeneic HCT vs. 60 months for autologous. Allogeneic HCT recipients were more likely to have high risk disease features including higher stage, more prior chemotherapy regimens and resistant disease. Allogeneic HCT was associated with a higher 1 year treatment-related mortality (TRM) (RR 4.88, 95% CI, 3.21–7.40, p50 years), lower performance score, chemoresistance and earlier year of transplant. In a cohort of mainly high risk DLBCL patients, upfront myeloablative allogeneic HCT while associated with increased early mortality was associated with a similar risk of disease progression compared to lower risk patients receiving autologous HCT. PMID:20053330

  4. The B-cell receptor orchestrates environment-mediated lymphoma survival and drug resistance in B-cell malignancies.

    Science.gov (United States)

    Shain, K H; Tao, J

    2014-08-01

    Specific niches within the lymphoma tumor microenvironment (TME) provide sanctuary for subpopulations of tumor cells through stromal cell-tumor cell interactions. These interactions notably dictate growth, response to therapy and resistance of residual malignant B cells to therapeutic agents. This minimal residual disease (MRD) remains a major challenge in the treatment of B-cell malignancies and contributes to subsequent disease relapse. B-cell receptor (BCR) signaling has emerged as essential mediator of B-cell homing, survival and environment-mediated drug resistance (EMDR). Central to EMDR are chemokine- and integrin-mediated interactions between lymphoma and the TME. Further, stromal cell-B cell adhesion confers a sustained BCR signaling leading to chemokine and integrin activation. Recently, the inhibitors of BCR signaling have garnered a substantial clinical interest because of their effectiveness in B-cell disorders. The efficacy of these agents is, at least in part, attributed to attenuation of BCR-dependent lymphoma-TME interactions. In this review, we discuss the pivotal role of BCR signaling in the integration of intrinsic and extrinsic determinants of TME-mediated lymphoma survival and drug resistance. PMID:24037527

  5. A rare cytological diagnosis of primary non-Hodgkin lymphoma of the parotid gland

    Science.gov (United States)

    Dey, Biswajit; Goyal, Vasudha; Bharti, Jyotsna Naresh; Mahajan, Nidhi; Jain, Shyama

    2016-01-01

    Primary lymphoma of the parotid gland is relatively rare and constitutes about 4-5% of extranodal lymphomas. The majority of them is non-Hodgkin lymphoma (NHL) and is B cell in nature. We report a case of primary diffuse large B-cell lymphoma (DLBCL) of the parotid gland in an elderly male. The case was diagnosed on fine needle aspiration cytology (FNAC) of the right parotid gland as high grade B-cell NHL and confirmed on histopathology as DLBCL. In correlation with the clinicoradiological findings, the case was diagnosed as primary parotid DLBCL. The case highlights the role of FNAC as a timely and useful diagnostic tool. PMID:27279690

  6. Digital PCR for quantification of recurrent and potentially actionable somatic mutations in circulating free DNA from patients with diffuse large B-cell lymphoma.

    Science.gov (United States)

    Camus, Vincent; Sarafan-Vasseur, Nasrin; Bohers, Elodie; Dubois, Sydney; Mareschal, Sylvain; Bertrand, Philippe; Viailly, Pierre-Julien; Ruminy, Philippe; Maingonnat, Catherine; Lemasle, Emilie; Stamatoullas, Aspasia; Picquenot, Jean-Michel; Cornic, Marie; Beaussire, Ludivine; Bastard, Christian; Frebourg, Thierry; Tilly, Hervé; Jardin, Fabrice

    2016-09-01

    Diffuse large B-cell lymphoma (DLBCL) is an aggressive and heterogeneous malignancy harboring frequent targetable activating somatic mutations. Emerging evidence suggests that circulating cell-free DNA (cfDNA) can be used to detect somatic variants in DLBCL using Next-Generation Sequencing (NGS) experiments. In this proof-of-concept study, we chose to develop simple and valuable digital PCR (dPCR) assays for the detection of recurrent exportin-1 (XPO1) E571K, EZH2 Y641N, and MYD88 L265P mutations in DLBCL patients, thereby identifying patients most likely to potentially benefit from targeted therapies. We demonstrated that our dPCR assays were sufficiently sensitive to detect rare XPO1, EZH2, and MYD88 mutations in plasma cfDNA, with a sensitivity of 0.05%. cfDNA somatic mutation detection by dPCR seems to be a promising technique in the management of DLBCL, in addition to NGS experiments. PMID:26883583

  7. Prognostic significance of PRAME expression based on immunohistochemistry for diffuse large B-cell lymphoma patients treated with R-CHOP therapy.

    Science.gov (United States)

    Mitsuhashi, Kenjiro; Masuda, Akihiro; Wang, Yan-Hua; Shiseki, Masayuki; Motoji, Toshiko

    2014-07-01

    The preferentially expressed antigen of melanoma (PRAME), a tumor-associated antigen, is considered a prognostic marker for various human malignancies. The prognostic significance of PRAME expression for diffuse large B-cell lymphoma (DLBCL) patients treated with rituximab-containing chemotherapy has not been evaluated to date, and the ability of immunohistochemistry (IHC) to detect PRAME expression in these patients has not yet been studied, although IHC is simple to perform in clinical practice. We evaluated the prognostic significance of PRAME expression based on IHC analysis in 160 DLBCL patients treated with R-CHOP therapy. There was a significant association between higher PRAME expression and shorter progression-free survival (PFS), and a trend toward shorter overall survival (OS) in patients with higher PRAME expression than that in patients with lower PRAME expression (5-year PFS, 48.1 vs. 61.1 %; 5-year OS, 65.6 vs. 79.1 %). Patients with high PRAME expression tended to have lower chemotherapeutic responses. Thus, IHC is useful for detecting and assessing PRAME expression in DLBCL. Further, we found a positive correlation between IHC and quantitative real-time RT-PCR measurements of PRAME expression. Our findings indicate that IHC results of PRAME expression can be a novel prognostic maker in DLBCL patients treated with R-CHOP therapy. PMID:24820636

  8. Heart of Lymphoma: Primary Mediastinal Large B-Cell Lymphoma with Endomyocardial Involvement

    Directory of Open Access Journals (Sweden)

    Elisa Rogowitz

    2013-01-01

    Full Text Available Primary mediastinal B-cell lymphoma (PMBCL is an uncommon aggressive subset of diffuse large B-cell lymphomas. Although PMBCL frequently spreads locally from the thymus into the pleura or pericardium, it rarely invades directly through the heart. Herein, we report a case of a young Mexican female diagnosed with PMBCL with clear infiltration of lymphoma through the cardiac wall and into the right atrium and tricuspid valve leading to tricuspid regurgitation. This was demonstrated by cardiac MRI and transthoracic echocardiogram. In addition, cardiac MRI and CT scan of the chest revealed the large mediastinal mass completely surrounding and eroding into the superior vena cava (SVC wall causing a collar of stokes. The cardiac and SVC infiltration created a significant therapeutic challenge as lymphomas are very responsive to chemotherapy, and treatment could potentially lead to vascular wall rupture and hemorrhage. Despite the lack of conclusive data on chemotherapy-induced hemodynamic compromise in such scenarios, her progressive severe SVC syndrome and respiratory distress necessitated urgent intervention. In addition to the unique presentation of this rare lymphoma, our case report highlights the safety of R-CHOP treatment.

  9. Selective loss of B-cell phenotype in lymphocyte predominant Hodgkin lymphoma.

    NARCIS (Netherlands)

    Tedoldi, S.; Mottok, A.; Ying, J.; Paterson, J.C.; Cui, Y.; Facchetti, F.; Krieken, J.H.J.M. van; Ponzoni, M.; Ozkal, S.; Masir, N.; Natkunam, Y.; Pileri, S.; Hansmann, M.L.; Mason, D.; Tao, Q.; Marafioti, T.

    2007-01-01

    The neoplastic Reed-Sternberg cells characteristic of classical Hodgkin's lymphoma (cHL) are of B-cell origin but they almost always show striking loss of a range of B-cell-associated molecules. In contrast, the neoplastic cells found in lymphocyte predominant Hodgkin's lymphoma (LPHL) (L&H cells) a

  10. Machine learning-based classification of diffuse large B-cell lymphoma patients by eight gene expression profiles.

    Science.gov (United States)

    Zhao, Shuangtao; Dong, Xiaoli; Shen, Wenzhi; Ye, Zhen; Xiang, Rong

    2016-05-01

    Gene expression profiling (GEP) had divided the diffuse large B-cell lymphoma (DLBCL) into molecular subgroups: germinal center B-cell like (GCB), activated B-cell like (ABC), and unclassified (UC) subtype. However, this classification with prognostic significance was not applied into clinical practice since there were more than 1000 genes to detect and interpreting was difficult. To classify cancer samples validly, eight significant genes (MYBL1, LMO2, BCL6, MME, IRF4, NFKBIZ, PDE4B, and SLA) were selected in 414 patients treated with CHOP/R-CHOP chemotherapy from Gene Expression Omnibus (GEO) data sets. Cutoffs for each gene were obtained using receiver-operating characteristic curves (ROC) new model based on the support vector machine (SVM) estimated the probability of membership into one of two subgroups: GCB and Non-GCB (ABC and UC). Furtherly, multivariate analysis validated the model in another two cohorts including 855 cases in all. As a result, patients in the training and validated cohorts were stratified into two subgroups with 94.0%, 91.0%, and 94.4% concordance with GEP, respectively. Patients with Non-GCB subtype had significantly poorer outcomes than that with GCB subtype, which agreed with the prognostic power of GEP classification. Moreover, the similar prognosis received in the low (0-2) and high (3-5) IPI scores group demonstrated that the new model was independent of IPI as well as GEP method. In conclusion, our new model could stratify DLBCL patients with CHOP/R-CHOP regimen matching GEP subtypes effectively. PMID:26869285

  11. Multifocal Extranodal Involvement of Diffuse Large B-Cell Lymphoma

    Directory of Open Access Journals (Sweden)

    Devrim Cabuk

    2013-01-01

    Full Text Available Endobronchial involvement of extrapulmonary malignant tumors is uncommon and mostly associated with breast, kidney, colon, and rectum carcinomas. A 68-year-old male with a prior diagnosis of colon non-Hodgkin lymphoma (NHL was admitted to the hospital with a complaint of cough, sputum, and dyspnea. The chest radiograph showed right hilar enlargement and opacity at the right middle zone suggestive of a mass lesion. Computed tomography of thorax revealed a right-sided mass lesion extending to thoracic wall with the destruction of the third and the fourth ribs and a right hilar mass lesion. Fiberoptic bronchoscopy was performed in order to evaluate endobronchial involvement and showed stenosis with mucosal tumor infiltration in right upper lobe bronchus. The pathological examination of bronchoscopic biopsy specimen reported diffuse large B-cell lymphoma and the patient was accepted as the endobronchial recurrence of sigmoid colon NHL. The patient is still under treatment of R-ICE (rituximab-ifosfamide-carboplatin-etoposide chemotherapy and partial regression of pulmonary lesions was noted after 3 courses of treatment.

  12. Alisertib in Combination With Vorinostat in Treating Patients With Relapsed or Recurrent Hodgkin Lymphoma, B-Cell Non-Hodgkin Lymphoma, or Peripheral T-Cell Lymphoma

    Science.gov (United States)

    2016-07-12

    Adult B Acute Lymphoblastic Leukemia; Adult T Acute Lymphoblastic Leukemia; Anaplastic Large Cell Lymphoma; Angioimmunoblastic T-Cell Lymphoma; Chronic Lymphocytic Leukemia; Cutaneous B-Cell Non-Hodgkin Lymphoma; Extranodal Marginal Zone Lymphoma of Mucosa-Associated Lymphoid Tissue; Hepatosplenic T-Cell Lymphoma; Intraocular Lymphoma; Lymphomatous Involvement of Non-Cutaneous Extranodal Site; Mature T-Cell and NK-Cell Non-Hodgkin Lymphoma; Nodal Marginal Zone Lymphoma; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Grade III Lymphomatoid Granulomatosis; Recurrent Adult Hodgkin Lymphoma; Recurrent Adult Immunoblastic Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Adult T-Cell Leukemia/Lymphoma; Recurrent Cutaneous T-Cell Non-Hodgkin Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Mycosis Fungoides and Sezary Syndrome; Recurrent Small Lymphocytic Lymphoma; Refractory Chronic Lymphocytic Leukemia; Refractory Hairy Cell Leukemia; Small Intestinal Lymphoma; Splenic Marginal Zone Lymphoma; T-Cell Large Granular Lymphocyte Leukemia; Testicular Lymphoma; Waldenstrom Macroglobulinemia

  13. Colonic Diffuse Large B-Cell Lymphoma in a Liver Transplant Patient with Historically Very Low Tacrolimus Levels

    Directory of Open Access Journals (Sweden)

    Christopher M. Moore

    2012-01-01

    Full Text Available Posttransplant lymphoproliferative disorders (PTLDs comprise a wide spectrum of hematologic malignancies that are found increasingly in orthotopic liver transplant (OLT patients given the rising frequency of these surgeries and their long-term success. PTLDs are highly correlated with both the Epstein-Barr virus (EBV infection and the degree of immunosuppression involved. Herein is reported a case of a 53-year-old male with successfully treated hepatitis C virus genotype 4 and hepatocellular carcinoma who underwent OLT and developed symptoms of weakness and poor appetite 4 years later while on tacrolimus 3 mg b.i.d. with historically very low plasma levels. He was found to be anemic and colonoscopy revealed a 4.5 cm cecal diffuse large B-cell lymphoma (DLBCL. Further workup revealed mesenteric lymph node enlargement consistent and nodal DLBCL dissemination. He was treated with cyclophosphamide-hydroxyldaunorubicin-oncovin-prednisone-rituximab (CHOP-R chemotherapy and his tacrolimus dose was lowered. Additionally, he manifested PTLD-associated cryoglobulinemia leading to acute kidney injury. After a prolonged hospitalization he was discharged with close followup.

  14. Colonic diffuse large B-cell lymphoma in a liver transplant patient with historically very low tacrolimus levels.

    Science.gov (United States)

    Moore, Christopher M; Lamzabi, Ihab; Bartels, Anne K; Jakate, Shriram; Van Thiel, David H

    2012-01-01

    Posttransplant lymphoproliferative disorders (PTLDs) comprise a wide spectrum of hematologic malignancies that are found increasingly in orthotopic liver transplant (OLT) patients given the rising frequency of these surgeries and their long-term success. PTLDs are highly correlated with both the Epstein-Barr virus (EBV) infection and the degree of immunosuppression involved. Herein is reported a case of a 53-year-old male with successfully treated hepatitis C virus genotype 4 and hepatocellular carcinoma who underwent OLT and developed symptoms of weakness and poor appetite 4 years later while on tacrolimus 3 mg b.i.d. with historically very low plasma levels. He was found to be anemic and colonoscopy revealed a 4.5 cm cecal diffuse large B-cell lymphoma (DLBCL). Further workup revealed mesenteric lymph node enlargement consistent and nodal DLBCL dissemination. He was treated with cyclophosphamide-hydroxyldaunorubicin-oncovin-prednisone-rituximab (CHOP-R) chemotherapy and his tacrolimus dose was lowered. Additionally, he manifested PTLD-associated cryoglobulinemia leading to acute kidney injury. After a prolonged hospitalization he was discharged with close followup. PMID:23259146

  15. Radiotherapy dose–response analysis for diffuse large B-cell lymphoma with a complete response to chemotherapy

    Directory of Open Access Journals (Sweden)

    Dorth Jennifer A

    2012-06-01

    Full Text Available Abstract Objective To examine the efficacy of different radiation doses after achievement of a complete response to chemotherapy in diffuse large B-cell lymphoma (DLBCL. Methods Patients with stage I-IV DLBCL treated from 1995–2009 at Duke Cancer Institute who achieved a complete response to chemotherapy were reviewed. In-field control, event-free survival, and overall survival were calculated using the Kaplan-Meier method. Dose response was evaluated by grouping treated sites by delivered radiation dose. Results 105 patients were treated with RT to 214 disease sites. Chemotherapy (median 6 cycles was R-CHOP (65%, CHOP (26%, R-CNOP (2%, or other (7%. Post-chemotherapy imaging was PET/CT (88%, gallium with CT (1%, or CT only (11%. The median RT dose was 30 Gy (range, 12–40 Gy. The median radiation dose was higher for patients with stage I-II disease compared with patients with stage III-IV disease (30 versus 24.5 Gy, p  Conclusion In-field control was excellent with a combined modality approach when a complete response was achieved after chemotherapy without a clear radiation dose response.

  16. Clinical outcomes and prognostic factors in patients with breast diffuse large B cell lymphoma; Consortium for Improving Survival of Lymphoma (CISL study

    Directory of Open Access Journals (Sweden)

    Lee Je-Jung

    2010-06-01

    Full Text Available Abstract Background The breast is a rare extranodal site of non-Hodgkin lymphoma, and primary breast lymphoma (PBL has been arbitrarily defined as disease localized to one or both breasts with or without regional lymph nodes involvement. The aim of this study was to evaluate the clinical outcomes in patients with diffuse large B cell lymphoma (DLBCL and breast involvement, and to find the criteria of PBL reflecting the outcome and prognosis. Methods We retrospectively analyzed data from 68 patients, newly diagnosed with DLBCL and breast involvement at 16 Korean institutions between January 1994 and June 2009. Results Median age at diagnosis was 48 years (range, 20-83 years. Forty-three (63.2% patients were PBL according to previous arbitrary criteria, sixteen (23.5% patients were high-intermediate to high risk of international prognostic index. The patients with one extranodal disease in the breast (OED with or without nodal disease were 49 (72.1%, and those with multiple extranodal disease (MED were 19 (27.9%. During median follow-up of 41.5 months (range, 2.4-186.0 months, estimated 5-year progression-free survival (PFS was 53.7 ± 7.6%, and overall survival (OS was 60.3 ± 7.2%. The 5-year PFS and OS was significantly higher for patients with the OED group than those with the MED group (5-year PFS, 64.9 ± 8.9% vs. 27.5 ± 11.4%, p = 0.001; 5-year OS, 74.3 ± 7.6% vs. 24.5 ± 13.0%, p Conclusions Our results show that the patients included in OED group, reflecting different treatment outcome, prognosis and pattern of progression, should be considered as PBL in the future trial. Further studies are warranted to validate our suggested criteria.

  17. Bone marrow involvement in diffuse large B-cell lymphoma: correlation between FDG-PET uptake and type of cellular infiltrate

    International Nuclear Information System (INIS)

    To assess, in patients with diffuse large B-cell lymphoma (DLBCL), whether the low sensitivity of 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) for bone marrow assessment may be explained by histological characteristics of the cellular infiltrate. From a prospective cohort of 110 patients with newly diagnosed aggressive lymphoma, 21 patients with DLBCL had bone marrow involvement. Pretherapeutic FDG-PET images were interpreted visually and semiquantitatively, then correlated with the type of cellular infiltrate and known prognostic factors. Of these 21 patients, 7 (33%) had lymphoid infiltrates with a prominent component of large transformed lymphoid cells (concordant bone marrow involvement, CBMI) and 14 (67%) had lymphoid infiltrates composed of small cells (discordant bone marrow involvement, DBMI). Only 10 patients (48%) had abnormal bone marrow FDG uptake, 6 of the 7 with CBMI and 4 of the 14 with DBMI. Therefore, FDG-PET positivity in the bone marrow was significantly associated with CBMI, while FDG-PET negativity was associated with DBMI (Fisher's exact test, p=0.024). There were no significant differences in gender, age and overall survival between patients with CBMI and DBMI, while the international prognostic index was significantly higher in patients with CBMI. Our study suggests that in patients with DLBCL with bone marrow involvement bone marrow FDG uptake depends on two types of infiltrate, comprising small (DBMI) or large (CBMI) cells. This may explain the apparent low sensitivity of FDG-PET previously reported for detecting bone marrow involvement. (orig.)

  18. Radioimmunotherapy with {sup 131}I-Rituximab in a Patient with Diffuse Large B-Cell Lymphoma Relapsed After Treatment with {sup 90}Y-Ibritumomab Tiuxetan

    Energy Technology Data Exchange (ETDEWEB)

    Kang, Geon Wook; Kang, Hye Jin; Shin, Dongyeop; Gu, Ha Ra; Choi, Hong Seok; Lim, Sang Moo [Korea Cancer Center Hospital, Seoul (Korea, Republic of)

    2013-12-15

    We report a case that demonstrates the efficacy of radioimmunotherapy (RIT) with radioiodinated rituximab ({sup 131}I-rituximab) for relapsed diffuse large B-cell lymphoma (DLBCL). A 79-year-old male patient with DLBCL initially achieved a complete response (CR) after six cycles of RCHOP (rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone) therapy. However, the lymphoma relapsed 20 months later. Although the patient had achieved a second and a third CR after two cycles of {sup 90}Y-ibritumomab tiuxetan, he experienced a third relapse approximately 3 years later. Between March and June 2011, the patient received three cycles of {sup 131}I-rituximab. Although he had achieved partial response after the second cycle, the disease progressed after the third cycle, and the total progression. Free survival was thus 5 months. The patient suffered only relatively mild toxicity (grade 1 thrombocytopenia) during treatment. RIT with {sup 131}I-rituximab is therefore potentially effective in patients with relapsed DLBCL, even after the failure of {sup 90}Y-ibritumomab tiuxetan therapy.

  19. EBV-positive diffuse large B-cell lymphoma in a patient with primary Sjögren’s syndrome and membranous glomerulonephritis

    Directory of Open Access Journals (Sweden)

    Kim Chang

    2012-11-01

    Full Text Available Abstract Background Sjögren’s syndrome is a systemic autoimmune disease in which lymphatic cells destroy the salivary and lacrimal glands. Glomerulonephritis is thought to be a rare occurrence in primary Sjögren’s syndrome. Furthermore, concurrent glomerular involvement and lymphoma in patients with Sjögren’s syndrome has seldom been reported. Case presentation A 52-year-old woman with primary Sjögren’s syndrome developed membranous glomerulonephritis and Epstein-Barr virus-positive diffuse large B-cell lymphoma (DLBCL. She was diagnosed with Sjögren’s syndrome based on the dry eyes, dry mouth, positive anti-nuclear antibody test, anti-Ro (SS-A antibody, salivary gland biopsy, and salivary scintigraphy. Moreover, renal biopsy confirmed the diagnosis of membranous glomerulonephritis. Three months later, her small bowel was perforated with pneumoperitoneum, and the biopsy revealed Epstein-Barr virus-positive DLBCL. Conclusions We observed the first case of primary Sjögren’s syndrome associated with Epstein-Barr Virus-positive DLBCL and membranous glomerulonephritis. Because of the possibility of malignancy-associated membranous glomerulonephritis in patients with primary Sjögren’s syndrome, we should be careful and examine such patients for hidden malignancy.

  20. Different sensitivity of germinal center B cell-like diffuse large B cell lymphoma cells towards ibrutinib treatment

    OpenAIRE

    Zheng, Xiaohui; Ding, Ning; Song, Yuqin; Feng, Lixia; Zhu, Jun

    2014-01-01

    Background Although rituximab in the combination of CHOP chemotherapy has been widely used as the standard treatment for several kinds of B-cell non-Hodgkin lymphoma (B-NHL), a great number of B-NHL patients treated with this immunotherapy still develop primary and secondary resistance. Recently Bruton’s tyrosine kinase (Btk) inhibitor ibrutinib showed promising therapeutic effect in relapsed/refractory CLL and B-cell NHL, which provided essential alternatives for these patients. Methods The ...

  1. Diffuse Large B Cell Lymphoma in a Patient with Hypocomplementemic Urticarial Vasculitis

    Directory of Open Access Journals (Sweden)

    Calvo-Romero J

    2003-01-01

    Full Text Available Hypocomplementemic urticarial vasculitis (HUV is known to be associated with malignancies. Urticarial vasculitis has been linked to lymphomas, but to our knowledge, the association of HUV and non-Hodgkin lymphoma has not been described so far. A patient with HUV who developed 10 years later a diffuse large B cell lymphoma is reported here.

  2. Diffuse Large B Cell Lymphoma in a Patient with Hypocomplementemic Urticarial Vasculitis

    OpenAIRE

    Calvo-Romero J

    2003-01-01

    Hypocomplementemic urticarial vasculitis (HUV) is known to be associated with malignancies. Urticarial vasculitis has been linked to lymphomas, but to our knowledge, the association of HUV and non-Hodgkin lymphoma has not been described so far. A patient with HUV who developed 10 years later a diffuse large B cell lymphoma is reported here.

  3. Coordinate suppression of B cell lymphoma by PTEN and SHIP phosphatases

    DEFF Research Database (Denmark)

    Miletic, Ana V; Anzelon-Mills, Amy N; Mills, David M; Omori, Sidne A; Pedersen, Irene M; Shin, Dong-Mi; Ravetch, Jeffrey V; Bolland, Silvia; Morse, Herbert C; Rickert, Robert C

    2010-01-01

    , follicular or centroblastic lymphoma. bPTEN/SHIP(-/-) B cells exhibit enhanced survival and express more MCL1 and less Bim. These cells also express low amounts of p27(kip1) and high amounts of cyclin D3 and thus appear poised to undergo proliferative expansion. Unlike normal B cells, bPTEN/SHIP(-/-) B cells...

  4. Secondary cutaneous Epstein-Barr virus-associated diffuse large B-cell lymphoma in a patient with angioimmunoblastic T-cell lymphoma: a case report and review of literature

    Directory of Open Access Journals (Sweden)

    Yang Qing-Xu

    2012-01-01

    Full Text Available Abstract Only a few cases of extranodal Epstein-Barr virus (EBV-associated B-cell lymphomas arising from patients with angioimmunoblastic T-cell lymphoma (AITL have been described. We report a case of AITL of which secondary cutaneous EBV-associated diffuse large B-cell lymphoma (DLBCL developed after the initial diagnosis of AITL. A 65-year-old Chinese male patient was diagnosed as AITL based on typical histological and immunohistochemical characteristics in biopsy of the enlarged right inguinal lymph nodes. The patient initially received 6 cycles of chemotherapy with CHOP regimen (cyclophosphamide, vincristine, adriamycin, prednisone, but his symptoms did not disappear. Nineteen months after initial diagnosis of AITL, the patient was hospitalized again because of multiple plaques and nodules on the skin. The skin biopsy was performed, but this time the tumor was composed of large, polymorphous population of lymphocytes with CD20 and CD79a positive on immunohistochemical staining. The tumor cells were strong positive for EBER by in situ hybridization. The findings of skin biopsy were compatible with EBV-associated DLBCL. CHOP-R chemotherapy (cyclophosphamide, doxorubicin, vincristine, prednisone and rituximab was then administered, resulting in partial response of the disease with pancytopenia and suppression of cellular immunity. To our knowledge, this is the first case of cutaneous EBV-associated DLBCL originated from AITL in Chinese pepole. We suggest the patients with AITL should perform lymph node and skin biopsies regularly in the course of the disease to detect the progression of secondary lymphomas. Virtual slides The virtual slide(s for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1197421158639299

  5. Functional Imaging Using 18-Fluorodeoxyglucose PET in the Management of Primary Mediastinal Large B-Cell Lymphoma: The Contributions of the International Extranodal Lymphoma Study Group.

    Science.gov (United States)

    Cavalli, Franco; Ceriani, Luca; Zucca, Emanuele

    2016-01-01

    Primary mediastinal large B-cell lymphoma (PMLBCL) is recognized as a distinct disease entity. Treatment outcomes appear better than in other diffuse large B-cell lymphoma (DLBCL) types, partly because of their earlier stage at presentation and the younger age of most patients. If initial treatment fails, however, the results of salvage chemotherapy and myeloablative treatment are poor. The need to avoid relapses after initial therapy has led to controversy over the extent of front-line therapy, particularly whether consolidation radiotherapy to the mediastinum is always required and whether the 18-fluorodeoxyglucose ((18)F-FDG) uptake detected by PET-CT scan can be used to determine its requirements. Functional imaging using PET-CT generally allows distinguishing of residual mediastinal masses containing active lymphoma from those with only sclerotic material remaining. The International Extranodal Lymphoma Study Group (IELSG) conducted the prospective IELSG-26 study, which showed that a five-point visual scale can be used to define metabolic response after immunochemotherapy and that a cut point based on liver uptake discriminates effectively between high or low risk of failure, with 5-year progression-free survival (PFS) of 99% versus 68% and 5-year overall survival (OS) of 100% versus 83%. This study also showed that a baseline quantitative PET parameter, namely the total lesion glycolysis describing the metabolic tumor burden, can be a powerful predictor of PMLBCL outcomes and warrants further validation as a biomarker. The ongoing IELSG-37 randomized study addresses the need for consolidation mediastinal radiotherapy in patients in whom a complete metabolic response (CMR) can be seen on PET scans after standard immunochemotherapy. PMID:27249743

  6. Identification of highly methylated genes across various types of B-cell non-hodgkin lymphoma.

    Directory of Open Access Journals (Sweden)

    Nicole Bethge

    Full Text Available Epigenetic alterations of gene expression are important in the development of cancer. In this study, we identified genes which are epigenetically altered in major lymphoma types. We used DNA microarray technology to assess changes in gene expression after treatment of 11 lymphoma cell lines with epigenetic drugs. We identified 233 genes with upregulated expression in treated cell lines and with downregulated expression in B-cell lymphoma patient samples (n = 480 when compared to normal B cells (n = 5. The top 30 genes were further analyzed by methylation specific PCR (MSP in 18 lymphoma cell lines. Seven of the genes were methylated in more than 70% of the cell lines and were further subjected to quantitative MSP in 37 B-cell lymphoma patient samples (diffuse large B-cell lymphoma (activated B-cell like and germinal center B-cell like subtypes, follicular lymphoma and Burkitt`s lymphoma and normal B lymphocytes from 10 healthy donors. The promoters of DSP, FZD8, KCNH2, and PPP1R14A were methylated in 28%, 67%, 22%, and 78% of the 36 tumor samples, respectively, but not in control samples. Validation using a second series of healthy donor controls (n = 42; normal B cells, peripheral blood mononuclear cells, bone marrow, tonsils and follicular hyperplasia and fresh-frozen lymphoma biopsies (n = 25, confirmed the results. The DNA methylation biomarker panel consisting of DSP, FZD8, KCNH2, and PPP1R14A was positive in 89% (54/61 of all lymphomas. Receiver operating characteristic analysis to determine the discriminative power between lymphoma and healthy control samples showed a c-statistic of 0.96, indicating a possible role for the biomarker panel in monitoring of lymphoma patients.

  7. Primary cutaneous diffuse large B-cell lymphoma of the upper limb: A fascinating entity

    Directory of Open Access Journals (Sweden)

    Manoj Madakshira Gopal

    2013-01-01

    Full Text Available Primary cutaneous lymphomas are defined as lymphoid neoplasms that present themselves clinically on the skin and do not have extra-cutaneous disease, when the diagnosis is made or even after 6 months of the diagnosis. Primary cutaneous lymphomas of B-cells are less frequent than lymphomas of T-cells. Primary B-cell lymphomas have a better prognosis than secondary B-cell lymphomas. Primary B-cell cutaneous lymphomas are classified into five types according to the World Health Organization and European Organization for Research and Treatment of Cancer classification. The primary diffuse large B-cell cutaneous lymphoma - leg type corresponds to approximately 5-10% of the B-cell cutaneous lymphomas. It is predominantly seen in elderly people and has a female preponderance. Skin lesions can be single, multiple, and even grouped. A 5-year survival rate ranges from 36 to 100% of the cases. The expression of Bcl-2, presence of multiple lesions, and involvement of both the upper limbs lead to a worse prognosis. Very few cases have been described in the literature.

  8. My treatment approach to patients with diffuse large B-cell lymphoma.

    Science.gov (United States)

    Armitage, James O

    2012-02-01

    My favored treatment approach for patients with diffuse large B-cell lymphoma continues to evolve. Diffuse large B-cell lymphoma can now be cured in more than 50% of patients. This is a result of improved definitions of the disease, improved diagnostic capabilities, better staging and restaging techniques, a useful prognostic index to guide therapeutic decisions, and the development of increasingly effective therapies. Positron emission tomographic scans have improved the accuracy of both staging and restaging. Findings on a positron emission tomographic scan at the end of therapy are the best predictors of a good treatment outcome. Numerous subtypes of diffuse large B-cell lymphoma have been identified that require specific treatment approaches. For example, plasmablastic lymphoma typically lacks CD20 and does not benefit from treatment with rituximab. Diffuse large B-cell lymphoma originating in specific extranodal sites such as the central nervous system, testes, and skin presents special problems and requires specific treatment approaches. A subgroup of diffuse large B-cell lymphoma with a very high proliferative rate seems to have a poor outcome when treated with CHOP-R and does better with regimens used for patients with Burkitt lymphoma. New insights into the biology of these disorders are likely to further change treatment approaches. Recognition that diffuse large B-cell lymphoma is not one disease, but a variety of clinicopathologic syndromes provides the opportunity to further improve our ability to benefit patients. PMID:22305028

  9. Farnesyl transferase inhibitors induce extended remissions in transgenic mice with mature B cell lymphomas

    Directory of Open Access Journals (Sweden)

    Refaeli Yosef

    2008-05-01

    Full Text Available Abstract Background We have used a mouse model based on overexpression of c-Myc in B cells genetically engineered to be self-reactive to test the hypothesis that farnesyl transferase inhibitors (FTIs can effectively treat mature B cell lymphomas. FTIs are undergoing clinical trials to treat both lymphoid and non-lymphoid malignancies and we wished to obtain evidence to support the inclusion of B cell lymphomas in future trials. Results We report that two FTIs, L-744,832 and SCH66336, blocked the growth of mature B cell lymphoma cells in vitro and in vivo. The FTI treatment affected the proliferation and survival of the transformed B cells to a greater extent than naïve B cells stimulated with antigen. In syngeneic mice transplanted with the transgenic lymphoma cells, L-744,832 treatment prevented the growth of the tumor cells and the morbidity associated with the resulting lymphoma progression. Tumors that arose from transplantation of the lymphoma cells regressed with as little as three days of treatment with L-744,832 or SCH66336. Treatment of these established lymphomas with L-744,832 for seven days led to long-term remission of the disease in approximately 25% of animals. Conclusion FTI treatment can block the proliferation and survival of self-reactive transformed B cells that overexpress Myc. In mice transplanted with mature B cell lymphomas, we found that FTI treatment led to regression of disease. FTIs warrant further consideration as therapeutic agents for mature B cell lymphomas and other lymphoid tumors.

  10. Treatment of B-cells non-Hodgkin lymphomas with combined immunochemotherapy: ability to treatment optimization

    OpenAIRE

    Smirnova, N. V.; N. V. Myakova; M. B. Belogurova; O. V. Ryskal; O. E. Nikonova; G. R. Sharapova; A. S. Fedorova; N. A. Grigorieva; A. V. Shamardina; N. I. Ponomareva; D. S. Abramov; D. M. Konovalov; M. E. Dubrovina; A. A. Maschan; E. V. Samochatova

    2015-01-01

    The results of two consecutive multicenter clinical trials enrolled 241 patient with childhood mature B-cells non-Hodgkin lymphomas/leukemia are presented. Patients received treatment according B-NHL 2004mab protocol (n = 83) and B-NHL 2010M (n = 158) with combined immunochemotherapy (ICT) in Russian and Belarus pediatric clinics from 2004 to 2015 years. Primary patients with different mature B-NHL (Burkitt lymphoma/leukemia, diffuse large B-cell lymphoma and primary mediastinal B-cell lympho...

  11. The B cell antigen receptor and overexpression of MYC can cooperate in the genesis of B cell lymphomas.

    Directory of Open Access Journals (Sweden)

    Yosef Refaeli

    2008-06-01

    Full Text Available A variety of circumstantial evidence from humans has implicated the B cell antigen receptor (BCR in the genesis of B cell lymphomas. We generated mouse models designed to test this possibility directly, and we found that both the constitutive and antigen-stimulated state of a clonal BCR affected the rate and outcome of lymphomagenesis initiated by the proto-oncogene MYC. The tumors that arose in the presence of constitutive BCR differed from those initiated by MYC alone and resembled chronic B cell lymphocytic leukemia/lymphoma (B-CLL, whereas those that arose in response to antigen stimulation resembled large B-cell lymphomas, particularly Burkitt lymphoma (BL. We linked the genesis of the BL-like tumors to antigen stimulus in three ways. First, in reconstruction experiments, stimulation of B cells by an autoantigen in the presence of overexpressed MYC gave rise to BL-like tumors that were, in turn, dependent on both MYC and the antigen for survival and proliferation. Second, genetic disruption of the pathway that mediates signaling from the BCR promptly killed cells of the BL-like tumors as well as the tumors resembling B-CLL. And third, growth of the murine BL could be inhibited by any of three distinctive immunosuppressants, in accord with the dependence of the tumors on antigen-induced signaling. Together, our results provide direct evidence that antigenic stimulation can participate in lymphomagenesis, point to a potential role for the constitutive BCR as well, and sustain the view that the constitutive BCR gives rise to signals different from those elicited by antigen. The mouse models described here should be useful in exploring further the pathogenesis of lymphomas, and in preclinical testing of new therapeutics.

  12. Ibrutinib in Treating Relapsed or Refractory B-Cell Non-Hodgkin Lymphoma in Patients With HIV Infection

    Science.gov (United States)

    2015-08-18

    Adult B Acute Lymphoblastic Leukemia; Chronic Lymphocytic Leukemia; Cutaneous B-Cell Non-Hodgkin Lymphoma; Extranodal Marginal Zone Lymphoma of Mucosa-Associated Lymphoid Tissue; HIV Infection; Intraocular Lymphoma; Multicentric Angiofollicular Lymphoid Hyperplasia; Nodal Marginal Zone Lymphoma; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Grade III Lymphomatoid Granulomatosis; Recurrent Adult Immunoblastic Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Small Lymphocytic Lymphoma; Refractory Chronic Lymphocytic Leukemia; Refractory Hairy Cell Leukemia; Refractory Plasma Cell Myeloma; Small Intestinal Lymphoma; Splenic Marginal Zone Lymphoma; Testicular Lymphoma; Waldenstrom Macroglobulinemia

  13. Excellent outcomes and lack of prognostic impact of cell of origin for localized diffuse large B-cell lymphoma in the rituximab era.

    Science.gov (United States)

    Kumar, Anita; Lunning, Matthew A; Zhang, Zhigang; Migliacci, Jocelyn C; Moskowitz, Craig H; Zelenetz, Andrew D

    2015-12-01

    Therapeutic options for limited-stage diffuse large B cell lymphoma (DLBCL) include short- or full-course R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisolone) ± radiotherapy. The optimal treatment remains unclear. The prognostic value of cell-of-origin (COO) in early stage DLBCL is unknown. Patients with limited-stage DLBCL (stage I or stage II, non-bulky) treated with R-CHOP ± involved field radiotherapy (IFRT) from 1999 to 2012 were included. COO by the Hans algorithm was analysed in a subset of patients. Of 261 patients, 30% were stage I (N = 82), 37% stage IE (N = 96), IIE (N = 37). The stage-modified International Prognostic Index stratified patients into prognostically relevant groups. There was no significant difference in progression-free survival (PFS) or overall survival (OS) for patients in the germinal centre B-cell-like (GCB; n = 65) and non-GCB cohorts (n = 22). Seventeen patients received R-CHOP × 3-4 cycles (Arm A), 147 received R-CHOP × 3-4 cycles + IFRT (Arm B), 48 received R-CHOP × 6 cycles (Arm C), and 50 received R-CHOP × 6 cycles + IFRT (Arm D). The outcomes were excellent, with 5-year PFS of 82% and 5-year OS of 93%, and were similar across the 4 treatment groups. In the rituximab era, outcomes for limited-stage DLBCL, regardless of treatment approach, were excellent. Baseline COO was not a significant prognostic factor in patients treated with short-course R-CHOP + IFRT. PMID:26456939

  14. Increased risk of gastric adenocarcinoma after treatment of primary gastric diffuse large B-cell lymphoma

    International Nuclear Information System (INIS)

    There have been sporadic reports about synchronous as well as metachronous gastric adenocarcinoma and primary gastric lymphoma. Many reports have dealt with metachronous gastric adenocarcinoma in mucosa-associated lymphoid tissue lymphoma of stomach. But to our knowledge, there have been no reports that document the increased incidence of metachronous gastric adenocarcinoma in patients with gastric diffuse large B-cell lymphoma. This retrospective study was conducted to estimate the incidence of metachronous gastric adenocarcinoma after primary gastric lymphoma treatment, especially in diffuse large B-cell lymphoma. The retrospective cohort study of 139 primary gastric lymphoma patients treated with radiotherapy at our hospital. Mean observation period was 61.5 months (range: 3.7-124.6 months). Patients profile, characteristics of primary gastric lymphoma and metachronous gastric adenocarcinoma were retrieved from medical records. The risk of metachronous gastric adenocarcinoma was compared with the risk of gastric adenocarcinoma in Japanese population. There were 10 (7.2%) metachronous gastric adenocarcinoma patients after treatment of primary gastric lymphomas. It was quite high risk compared with the risk of gastric carcinoma in Japanese population of 54.7/100,000. Seven patients of 10 were diffuse large B-cell lymphoma and other 3 patients were mixed type of diffuse large B-cell lymphoma and mucosa associated lymphoid tissue lymphoma. Four patients of 10 metachronous gastric adenocarcinomas were signet-ring cell carcinoma and two patients died of gastric adenocarcinoma. Metachronous gastric adenocarcinoma may have a more malignant potential than sporadic gastric adenocarcinoma. Old age, Helicobacter pylori infection and gastric mucosal change of chronic gastritis and intestinal metaplasia were possible risk factors for metachronous gastric adenocarcinoma. There was an increased risk of gastric adenocarcinoma after treatment of primary gastric lymphoma

  15. Identification and validation of a two-gene expression index for subtype classification and prognosis in Diffuse Large B-Cell Lymphoma.

    Science.gov (United States)

    Xu, Qinghua; Tan, Cong; Ni, Shujuan; Wang, Qifeng; Wu, Fei; Liu, Fang; Ye, Xun; Meng, Xia; Sheng, Weiqi; Du, Xiang

    2015-01-01

    The division of diffuse large B-cell lymphoma (DLBCL) into germinal center B-cell-like (GCB) and activated B-cell-like (ABC) subtypes based on gene expression profiling has proved to be a landmark in understanding the pathogenesis of the disease. This study aims to identify a novel biomarker to facilitate the translation of research into clinical practice. Using a training set of 350 patients, we identified a two-gene expression signature, "LIMD1-MYBL1 Index", which is significantly associated with cell-of-origin subtypes and clinical outcome. This two-gene index was further validated in two additional dataset. Tested against the gold standard method, the LIMD1-MYBL1 Index achieved 81% sensitivity, 89% specificity for ABC group and 81% sensitivity, 87% specificity for GCB group. The ABC group had significantly worse overall survival than the GCB group (hazard ratio = 3.5, P = 0.01). Furthermore, the performance of LIMD1-MYBL1 Index was satisfactory compared with common immunohistochemical algorithms. Thus, the LIMD1-MYBL1 Index had considerable clinical value for DLBCL subtype classification and prognosis. Our results might prompt the further development of this two-gene index to a simple assay amenable to routine clinical practice. PMID:25940947

  16. Leukocytoclastic vasculitis as early manifestation of Epstein-Barr virus-positive diffuse large B-cell lymphoma of the elderly.

    Science.gov (United States)

    Zoroquiain, Pablo; González, Sergio; Molgó, Montserrat; Rodríguez, Alejandra; Valbuena, José R

    2012-05-01

    Extensive necrotizing vasculitis (ENV) is a rare paraneoplastic phenomenon, and the majority of cases reported are associated with hematolymphoid neoplasms. Histologically, most cases of ENV represent leukocytoclastic vasculitis (LCV). Here we report the clinicopahological features of a 68-year-old man with ENV associated to a Epstein Barr virus-positive diffuse large B-cell lymphoma (EBV+DLBCL) of the elderly, a newly recognized lymphoproliferative disorder, most likely representing a paraneoplastic manifestation. The patient was treated with standard chemotherapy regimen for malignant lymphoma. Due to the extensive involvement of the extremities by ENV, surgical debridement was not feasible and a novel therapy based on CHITOSAN apposits was initiated with overall good response and subsequent re-epithelization of the skin lesions. The patient died of sepsis secondary to a Pseudomona pneumonia 17 months after diagnosis. PMID:22197862

  17. Lenalidomide And Rituximab as Maintenance Therapy in Treating Patients With B-Cell Non-Hodgkin Lymphoma

    Science.gov (United States)

    2015-11-25

    Adult Non-Hodgkin Lymphoma; Adult Grade III Lymphomatoid Granulomatosis; Contiguous Stage II Adult Burkitt Lymphoma; Contiguous Stage II Adult Diffuse Large Cell Lymphoma; Contiguous Stage II Adult Diffuse Mixed Cell Lymphoma; Contiguous Stage II Adult Diffuse Small Cleaved Cell Lymphoma; Contiguous Stage II Adult Immunoblastic Large Cell Lymphoma; Contiguous Stage II Adult Lymphoblastic Lymphoma; Contiguous Stage II Grade 1 Follicular Lymphoma; Contiguous Stage II Grade 2 Follicular Lymphoma; Contiguous Stage II Grade 3 Follicular Lymphoma; Contiguous Stage II Mantle Cell Lymphoma; Contiguous Stage II Marginal Zone Lymphoma; Contiguous Stage II Small Lymphocytic Lymphoma; Cutaneous B-cell Non-Hodgkin Lymphoma; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Nodal Marginal Zone B-cell Lymphoma; Noncontiguous Stage II Adult Burkitt Lymphoma; Noncontiguous Stage II Adult Diffuse Large Cell Lymphoma; Noncontiguous Stage II Adult Diffuse Mixed Cell Lymphoma; Noncontiguous Stage II Adult Diffuse Small Cleaved Cell Lymphoma; Noncontiguous Stage II Adult Immunoblastic Large Cell Lymphoma; Noncontiguous Stage II Adult Lymphoblastic Lymphoma; Noncontiguous Stage II Grade 1 Follicular Lymphoma; Noncontiguous Stage II Grade 2 Follicular Lymphoma; Noncontiguous Stage II Grade 3 Follicular Lymphoma; Noncontiguous Stage II Mantle Cell Lymphoma; Noncontiguous Stage II Marginal Zone Lymphoma; Noncontiguous Stage II Small Lymphocytic Lymphoma; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Grade III Lymphomatoid Granulomatosis; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent

  18. Composite Diffuse Large B-Cell Lymphoma and Follicular B-Cell Lymphoma – Case Report and Review of Literature

    OpenAIRE

    TURBATU, Andrei; Marilena STOIAN; BREZEAN, Iulian; STOICA, Victor Constantin Ion; COLITA, Andrei; Dobrea, Camelia; STATE, Nicoleta; IONESCU, Cosmin; IVANESCU, Ana-Maria; OPREA, Madalina; GHIMICI, Cecilia; LUPU, Anca Roxana

    2014-01-01

    Composite lymphoma refers to the co-occurrence of two or more morphologically and immunophenotypically separate lymphomas in the same topographic site at the time of clinical presentation. It is an infrequent type of lymphoid neoplasm, present in lymphoid tissue and may be due to the existence of two genetically related neoplasms such as transformation of a single lymphoma into another more aggressive lymphoma or be due to the presence of two clonally unrelated lymphomas. This paper is presen...

  19. Importance of gallium-67 scintigraphy in primary cutaneous B-cell lymphoma: report of two cases

    International Nuclear Information System (INIS)

    The authors describe two cases of cutaneous B-cell lymphoma where correct staging, treatment and follow-up could be achieved through a combination of conventional imaging studies and gallium-67 scintigraphy. (author)

  20. Novel lymphoid neoplasms – the borderland between diffuse large B-cell lymphoma and Burkitt’s lymphoma

    OpenAIRE

    de Jong, Daphne

    2009-01-01

    The recent update of the WHO classification of tumors of the lymphoid tissue has recognized a category with overlapping features between Burkitt lymphoma and diffuse large B-cell lymphoma. In this perspective article, Dr. de Jong reviews the conceptual basis and practical impact of this diagnosis. See related paper on page 935.

  1. Detection of Asymptomatic Cardiac Metastasis and Successful Salvage Chemotherapy Comprising a Prednisone, Etoposide, Procarbazine, and Cyclophosphamide Regimen in an Elderly Japanese Patient Suffering from a Delayed Recurrence of Diffuse Large B-Cell Lymphoma

    Directory of Open Access Journals (Sweden)

    Keita Tagami

    2012-01-01

    Full Text Available We report a case of facial diffuse large B-cell lymphoma (DLBCL associated with recurrent metastasis in the heart and other sites in a 76-year-old Japanese woman. Initially, she developed DLBCL in her left upper eyelid that spread into the left orbit (Ann Arbor classification stage I. The lesion went into clinical regression after 4 cycles of rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone chemotherapy followed by radiotherapy. More than 3 years later, the lymphoma recurred in her facial skin, together with metastases in the mediastinal lymph nodes and the heart; the tumor in the heart was successfully detected by PET/CT and cardiac MRI. To treat the recurrent lesions, we performed a salvage chemotherapy regimen comprising prednisone, etoposide, procarbazine, and cyclophosphamide, which successfully induced tumor regression.

  2. Use of subsequent PET/CT in diffuse large B-cell lymphoma patients in complete remission following primary therapy

    Institute of Scientific and Technical Information of China (English)

    Xu Zhang; Wei Fan; Zhong-Jun Xia; Ying-Ying Hu; Xiao-Ping Lin; Ya-Rui Zhang; Zhi-Ming Li; Pei-Yan Liang; Yuan-Hua Li

    2015-01-01

    Interim 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (I-PET/CT) is a powerful tool for monitoring the response to therapy in diffuse large B-cell lymphoma (DLBCL). This retrospective study aimed to determine when and how to use I-PET/CT in DLBCL. A total of 197 patients treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) were enrolled between October 2005 and July 2011; PET/CT was performed at the time of diagnosis (PET/CT0), after 2 and 4 cycles of chemotherapy (PET/CT2 and PET/CT4, respectively), and at the end of treatment (F-PET/CT). According to the International Harmonization Project for Response Criteria in Lymphoma, 110 patients had negative PET/CT2 scans, and 87 had positive PET/CT2 scans. The PET/CT2-negative patients had significantly higher 3-year progression-free survival rate (75.8% vs. 38.2%) and 3-year overal survival rate (93.5%vs. 55.6%) than PET/CT2-positive patients. Al PET/CT2-negative patients remained negative at PET/CT4, but 3 were positive at F-PET/CT. Among the 87 PET/CT2-positive patients, 57 remained positive at F-PET/CT, and 32 progressed during chemotherapy (15 at PET/CT4 and 17 at F-PET/CT). Comparing PET/CT4 with PET/CT0, 7 patients exhibited progression, and 8 achieved partial remission. Comparing F-PET/CT with PET/CT0, 10 patients exhibited progression, and 7 achieved partial remission. In conclusion, our results indicate that I-PET/CT should be performed after 2 rather than 4 cycles of immunochemotherapy in DLBCL patients. There is a limited role for subsequent PET/CT in the detection of relapse in PET/CT2-negative patients, but repeat PET/CT is required if the PET/CT2 findings are positive.

  3. TLR9 Agonist SD-101, Ipilimumab, and Radiation Therapy in Treating Patients With Low-Grade Recurrent B-cell Lymphoma

    Science.gov (United States)

    2016-04-23

    Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Nodal Marginal Zone B-cell Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Small Lymphocytic Lymphoma; Splenic Marginal Zone Lymphoma

  4. Does the presence of tumor-induced cortical bone destruction at CT have any prognostic value in newly diagnosed diffuse large B-cell lymphoma?

    Energy Technology Data Exchange (ETDEWEB)

    Adams, Hugo J.A.; Nievelstein, Rutger A.J.; Kwee, Thomas C. [University Medical Center Utrecht, Department of Radiology and Nuclear Medicine, Utrecht (Netherlands); Klerk, John M.H. de [Meander Medical Center, Department of Nuclear Medicine, Amersfoort (Netherlands); Fijnheer, Rob [Meander Medical Center, Department of Hematology, Amersfoort (Netherlands); Heggelman, Ben G.F. [Meander Medical Center, Department of Radiology, Amersfoort (Netherlands); Dubois, Stefan V. [Meander Medical Center, Department of Pathology, Amersfoort (Netherlands)

    2015-05-01

    To determine the prognostic value of tumor-induced cortical bone destruction at computed tomography (CT) in newly diagnosed diffuse large B-cell lymphoma (DLBCL). This retrospective study included 105 patients with newly diagnosed DLBCL who had undergone CT and bone marrow biopsy (BMB) before R-CHOP (rituximab, cyclophosphamide, hydroxydaunorubicin, Oncovin, and prednisolone) chemo-immunotherapy. Cox regression analyses were used to determine the associations of cortical bone status at CT (absence vs. presence of tumor-induced cortical bone destruction), BMB findings (negative vs. positive for lymphomatous involvement), and dichotomized National Comprehensive Cancer Network International Prognostic Index (NCCN-IPI) strata (low risk vs. high risk) with progression-free survival (PFS) and overall survival (OS). Univariate Cox regression analysis indicated that cortical bone status at CT was no significant predictor of either PFS or OS (p = 0.358 and p = 0.560, respectively), whereas BMB findings (p = 0.002 and p = 0.013, respectively) and dichotomized NCCN-IPI risk strata (p = 0.002 and p = 0.003, respectively) were significant predictors of both PFS and OS. In the multivariate Cox proportional hazards model, only the dichotomized NCCN-IPI score was an independent predictive factor of PFS and OS (p = 0.004 and p = 0.003, respectively). The presence of tumor-induced cortical bone destruction at CT was not found to have any prognostic implications in newly diagnosed DLBCL. (orig.)

  5. A new extranodal scoring system based on the prognostically relevant extranodal sites in diffuse large B-cell lymphoma, not otherwise specified treated with chemoimmunotherapy.

    Science.gov (United States)

    Hwang, Hee Sang; Yoon, Dok Hyun; Suh, Cheolwon; Huh, Jooryung

    2016-08-01

    Extranodal involvement is a well-known prognostic factor in patients with diffuse large B-cell lymphomas (DLBCL). Nevertheless, the prognostic impact of the extranodal scoring system included in the conventional international prognostic index (IPI) has been questioned in an era where rituximab treatment has become widespread. We investigated the prognostic impacts of individual sites of extranodal involvement in 761 patients with DLBCL who received rituximab-based chemoimmunotherapy. Subsequently, we established a new extranodal scoring system based on extranodal sites, showing significant prognostic correlation, and compared this system with conventional scoring systems, such as the IPI and the National Comprehensive Cancer Network-IPI (NCCN-IPI). An internal validation procedure, using bootstrapped samples, was also performed for both univariate and multivariate models. Using multivariate analysis with a backward variable selection, we found nine extranodal sites (the liver, lung, spleen, central nervous system, bone marrow, kidney, skin, adrenal glands, and peritoneum) that remained significant for use in the final model. Our newly established extranodal scoring system, based on these sites, was better correlated with patient survival than standard scoring systems, such as the IPI and the NCCN-IPI. Internal validation by bootstrapping demonstrated an improvement in model performance of our modified extranodal scoring system. Our new extranodal scoring system, based on the prognostically relevant sites, may improve the performance of conventional prognostic models of DLBCL in the rituximab era and warrants further external validation using large study populations. PMID:27167532

  6. Consolidation Radiotherapy in Stage IE- IIE, Non-Bulky Primary Gastric Diffuse Large B-Cell Lymphoma with Post-Chemotherapy Complete Remission.

    Directory of Open Access Journals (Sweden)

    Qiwen Li

    Full Text Available To investigate the effects of consolidation radiation in patients with stage IE-IIE, non-bulky primary gastric diffuse large B-cell lymphoma (DLBCL.A cohort consisted of 71 consecutive patients with stage IE-IIE, non-bulky primary gastric DLBCL was retrospectively analyzed. All of them had been in complete remission after receiving at least four cycles of chemotherapy, containing rituximab or not. Consolidation radiation was delivered thereafter in 28 patients while other 43 received clinical observation only. Locoregional relapse-free survival (LRFS, disease-free survival (DFS, overall survival (OS and distant metastasis-free survival (DMFS were compared between patients with or without radiotherapy.The 10-year LRFS, DFS, OS and DMFS were 100% and 81.4% (p = 0.028, 91.7% and 77.1% (p = 0.14, 91.7% and 77.8% (p = 0.67, 91.7% and 78.0% (p = 0.42 for patients with or without radiotherapy.Radiotherapy is associated with improved locoregional control of patients with early stage primary gastric DLBCL, who have achieved complete remission following at least four cycles of chemotherapy.

  7. R-CHOP regimen can significantly decrease the risk of disease relapse and progression in patients with non-germinal center B-cell subtype diffuse large B-cell lymphoma

    Institute of Scientific and Technical Information of China (English)

    Xiao-Hui He; Mei Dong; Sheng-Yu Zhou; Jian-Liang Yang; Peng Liu; Chang-Gong Zhang; Yan Qin; Feng-Yi Feng; Yuan-Kai Shi; Bo Li; Sheng Yang; Ning Lu; Xun Zhang; Shuang-Mei Zou; Ye-Xiong Li; Yong-Wen Song; Shan Zheng

    2012-01-01

    To further explore the role of rituximab when added to the CHOP-like regimen in the treatment of immunohistochemically defined non-germinal center B-cell subtype (non-GCB) diffuse large B-cell lymphoma (DLBCL),159 newly diagnosed DLBCL patients were studied retrospectively based on the immunohistochemical evaluation of CD10,Bcl-6,MUM-1,and Bcl-2.Altogether,110 patients underwent the CHOP-like regimen,and rituximab was added for the other 49 patients.Cox regression analysis showed that compared with the CHOP-like regimen,the rituximab-based regimen (R-CHOP regimen)significantly decreased the risk of disease relapse and progression in CD10-negative patients (P =0.001),Bcl-6-negative patients (P =0.01),and MUM-1-positive patients (P =0.003).The risk of disease relapse in patients with non-GCB subtype (P =0.002) also decreased.In contrast,patients with the opposite immunohistochemical marker expression profile and GCB subtype did not benefit from treatment with the R-CHOP regimen.In addition,non-GCB subtype patients had a significantly higher expression rate of Bcl-2than GCB subtype patients (P =0.042).Although univariate analysis found that both Bcl-2-positive and -negative patients had significantly higher event-free survival rates with the R-CHOP regimen,only Bcl-2positivity (P =0.004) maintained significance in the Cox regression analysis.We conclude that the addition of rituximab can significantly improve the prognosis of patients with non-GCB subtype DLBCL,which is closely related to the expression of CD10,Bcl-6,MUM-1,and Bcl-2.

  8. Secondary pancreatic involvement by a diffuse large B-cell lymphoma presenting as acute pancreatitis

    Institute of Scientific and Technical Information of China (English)

    M Wasif Saif; Sapna Khubchandani; Marek Walczak

    2007-01-01

    Diffuse large B-cell lymphoma is the most common type of non-Hodgkin's lymphoma. More than 50% of patients have some site of extra-nodal involvement at diagnosis,including the gastrointestinal tract and bone marrow.However, a diffuse large B-cell lymphoma presenting as acute pancreatitis is rare. A 57-year-old female presented with abdominal pain and matted lymph nodes in her axilla. She was admitted with a diagnosis of acute pancreatitis. Abdominal computed tomography (CT) scan showed diffusely enlarged pancreas due to infiltrative neoplasm and peripancreatic lymphadenopathy. Biopsy of the axillary mass revealed a large B-cell lymphoma.The patient was classified as stage Ⅳ, based on the Ann Arbor Classification, and as having a high-risk lymphoma,based on the International Prognostic Index. She was started on chemotherapy with CHOP (cyclophosphamide,doxorubicin, vincristine and prednisone). Within a week after chemotherapy, the patient's abdominal pain resolved. Follow-up CT scan of the abdomen revealed a marked decrease in the size of the pancreas and peripancreatic lymphadenopathy. A literature search revealed only seven cases of primary involvement of the pancreas in B-cell lymphoma presenting as acute pancreatitis. However, only one case of secondary pancreatic involvement by B-cell lymphoma presenting as acute pancreatitis has been published. Our case appears to be the second report of such a manifestation.Both cases responded well to chemotherapy.

  9. Primary diffuse large B-cell lymphoma of the ascending colon

    Directory of Open Access Journals (Sweden)

    Alan D. Gilman

    2013-04-01

    Full Text Available Primary colorectal lymphoma is a rare malignancy accounting for 3% of all gastrointestinal lymphomas and 0.1-0.5% of all colorectal malignancies. Among primary colorectal lymphomas, the most common histological subtype of colorectal lymphoma is diffuse large B-cell lymphoma. We report a case of an 84-year old Caucasian female who was admitted to the hospital because of a 2 days history of altered mental status. In the emergency department the patient was found to have acute kidney injury and hypercalcemia. On physical examination a large lower quadrant abdominal mass was palpated. Computed tomography scan of abdomen confirmed the presence of a mass along the cecum and proximal ascending colon. Colonoscopy showed a large ulcerated mass and biopsy was consistent with diffuse large B-cell lymphoma. The patient underwent colectomy but refused to receive chemotherapy.

  10. Frequent disruption of the RB1 pathway in diffuse large B cell lymphoma

    DEFF Research Database (Denmark)

    Møller, M B; Kania, Per Walter; Ino, Y;

    2000-01-01

    In the present study, we analysed 34 de novo diffuse large B cell lymphoma (DLCL) from a population-based lymphoma registry for alterations of the RB1 pathway at the genetic (RB1 and CDK4) and protein (pRb, cyclin D1, cyclin D3, CDK4, and E2F-1) level. The results were correlated with the data fr...

  11. Reactivation of hepatitis D virus after chemotherapy for diffuse large B cell lymphoma despite lamivudine prophylaxis

    DEFF Research Database (Denmark)

    Andersen, Ellen Sloth; Gerstoft, Jan; Weis, Nina Margrethe

    2010-01-01

    We describe a case of reactivation of hepatitis D virus (HDV) in a patient treated with chemotherapy for a diffuse large B cell lymphoma despite lamivudine prophylaxis. This case suggests that previously cleared HDV should be considered when administering chemotherapy to patients with lymphoma....

  12. Primary central nervous system B-cell lymphoma in a young dog

    OpenAIRE

    Kim, Na-Hyun; Ciesielski, Thomas; Kim, Jung H; Yhee, Ji-Young; Im, Keum-Soon; Nam, Hae-Mi; Kim, Il-Hwan; Kim, Jong-Hyuk; Sur, Jung-Hyang

    2012-01-01

    This report describes a primary central nervous system B-cell lymphoma in a 3-year-old intact female Maltese dog. Canine primary central nervous system lymphomas constitute about 4% of all intracranial primary neoplasms, but comprehensive histopathologic classifications have rarely been carried out. This is the first report of this disease in a young adult dog.

  13. Relationships among hepatitis C virus, hepatocellular carcinoma, and diffuse large B cell lymphoma: A case report

    Energy Technology Data Exchange (ETDEWEB)

    Byun, Hyuk Jun; Kim, Seong Hoon [Dept. of Radiology, Daegu Fatima Hospital, Daegu (Korea, Republic of)

    2015-07-15

    Hepatitis C virus (HCV) is one of the main causes of hepatocellular carcinoma (HCC). Recent studies have reported various associations between HCV and the incidence of non-Hodgkin's lymphoma. We report the radiologic findings in a rare case of simultaneous occurrence of HCC and diffuse large B cell lymphoma in a HCV carrier.

  14. Identification of uniquely expressed transcription factors in highly purified B-cell lymphoma samples

    DEFF Research Database (Denmark)

    Andréasson, Ulrika; Edén, Patrik; Peterson, Carsten; Högerkorp, Carl-Magnus; Jerkeman, Mats; Andersen, Niels Smedegaard; Berglund, Mattias; Sundström, Christer; Rosenquist, Richard; Borrebaeck, Carl A K; Ek, Sara

    2010-01-01

    Transcription factors (TFs) are critical for B-cell differentiation, affecting gene expression both by repression and transcriptional activation. Still, this information is not used for classification of B-cell lymphomas (BCLs). Traditionally, BCLs are diagnosed based on a phenotypic resemblance ...

  15. B-cell lymphoma of the appendix: A case report and review of literature

    OpenAIRE

    Jagannath Dev Sharma; C. Chonzik; Tonmoy Das; Manigreeva Krishnatreya

    2014-01-01

    Appendicular tumors are rare, and lymphoma of the appendix is rarer. A 50 - year - old female patient presented with vague abdominal discomfort and lump in the right iliac fossa. The diagnosis of diffuse large B - cell lymphoma was made after laparotomy and histopathological examination (HPE) supported by immunohistochemistry study. For appendicular neoplasms diagnosed postoperatively, including lymphoma, a meticulous grossing and HPE cannot be over emph...

  16. Primary lymphoblastic B-cell lymphoma of the stomach: A case report

    Institute of Scientific and Technical Information of China (English)

    Miao-Xia He; Ming-Hua Zhu; Wei-Qiang Liu; Li-Li Wu; Xiong-Zeng Zhu

    2008-01-01

    Primary stomach lymphoblastic B-cell lymphoma (B-LBL) is a rare tumor. We describe a primary stomach B-LBL in a 38 years old female who presented with nonspecific complaints of fatigue and vomiting for 2 mo.Gastrofiberscopy revealed a large gastric ulcer, which was successfully resected. Pathology showed a lymphoblastic cell lymphoma arising from the stomach, and there was no evidence of disease at any extrastomach site.Immunohistochemical staining and gene rearrangement studies supported that the stomach tumor was a clonal B-cell lymphoma. Therefore, the diagnosis of B-LBL was made based on the stomach specimen.

  17. Radiotherapy dose–response analysis for diffuse large B-cell lymphoma with a complete response to chemotherapy

    International Nuclear Information System (INIS)

    To examine the efficacy of different radiation doses after achievement of a complete response to chemotherapy in diffuse large B-cell lymphoma (DLBCL). Patients with stage I-IV DLBCL treated from 1995–2009 at Duke Cancer Institute who achieved a complete response to chemotherapy were reviewed. In-field control, event-free survival, and overall survival were calculated using the Kaplan-Meier method. Dose response was evaluated by grouping treated sites by delivered radiation dose. 105 patients were treated with RT to 214 disease sites. Chemotherapy (median 6 cycles) was R-CHOP (65%), CHOP (26%), R-CNOP (2%), or other (7%). Post-chemotherapy imaging was PET/CT (88%), gallium with CT (1%), or CT only (11%). The median RT dose was 30 Gy (range, 12–40 Gy). The median radiation dose was higher for patients with stage I-II disease compared with patients with stage III-IV disease (30 versus 24.5 Gy, p < 0.001). Five-year in-field control, event-free survival, and overall survival for all patients was 94% (95% CI: 89-99%), 84% (95% CI: 77-92%), and 91% (95% CI: 85-97%), respectively. Six patients developed an in-field recurrence at 10 sites, without a clear dose response. In-field failure was higher at sites ≥ 10 cm (14% versus 4%, p = 0.06). In-field control was excellent with a combined modality approach when a complete response was achieved after chemotherapy without a clear radiation dose response

  18. Pediatric B-Cell Lymphoma With Lymphoblastic Morphology, TdT Expression, MYC Rearrangement, and Features Overlapping With Burkitt Lymphoma.

    Science.gov (United States)

    Meznarich, Jessica; Miles, Rodney; Paxton, Christian N; Afify, Zeinab

    2016-05-01

    Burkitt lymphoma (BL) and B-lymphoblastic lymphoma are subtypes of pediatric non-Hodgkin lymphoma with different presenting features, treatment, and outcomes. This case report documents a 5-year-old female who presented with B-cell lymphoma with lymphoblastic morphology, terminal deoxynucleotidyl transferase expression, MYC rearrangement, and features overlapping with BL. Genomic microarray analysis identified a gain on the long arm of chromosome 1 without other definitive changes. She was treated according to a BL protocol and remains in remission 16-months after initial diagnosis. PMID:26785246

  19. Array-based comparative genomic hybridization analysis reveals chromosomal copy number aberrations associated with clinical outcome in canine diffuse large B-cell lymphoma.

    Directory of Open Access Journals (Sweden)

    Arianna Aricò

    Full Text Available Canine Diffuse Large B-cell Lymphoma (cDLBCL is an aggressive cancer with variable clinical response. Despite recent attempts by gene expression profiling to identify the dog as a potential animal model for human DLBCL, this tumor remains biologically heterogeneous with no prognostic biomarkers to predict prognosis. The aim of this work was to identify copy number aberrations (CNAs by high-resolution array comparative genomic hybridization (aCGH in 12 dogs with newly diagnosed DLBCL. In a subset of these dogs, the genetic profiles at the end of therapy and at relapse were also assessed. In primary DLBCLs, 90 different genomic imbalances were counted, consisting of 46 gains and 44 losses. Two gains in chr13 were significantly correlated with clinical stage. In addition, specific regions of gains and losses were significantly associated to duration of remission. In primary DLBCLs, individual variability was found, however 14 recurrent CNAs (>30% were identified. Losses involving IGK, IGL and IGH were always found, and gains along the length of chr13 and chr31 were often observed (>41%. In these segments, MYC, LDHB, HSF1, KIT and PDGFRα are annotated. At the end of therapy, dogs in remission showed four new CNAs, whereas three new CNAs were observed in dogs at relapse compared with the previous profiles. One ex novo CNA, involving TCR, was present in dogs in remission after therapy, possibly induced by the autologous vaccine. Overall, aCGH identified small CNAs associated with outcome, which, along with future expression studies, may reveal target genes relevant to cDLBCL.

  20. Impact of Consolidation Radiation Therapy in Stage III-IV Diffuse Large B-cell Lymphoma With Negative Post-Chemotherapy Radiologic Imaging

    International Nuclear Information System (INIS)

    Purpose: While consolidation radiation therapy (i.e., RT administered after chemotherapy) is routine treatment for patients with early-stage diffuse large B-cell lymphoma (DLBCL), the role of consolidation RT in stage III-IV DLBCL is controversial. Methods and Materials: Cases of patients with stage III-IV DLBCL treated from 1991 to 2009 at Duke University, who achieved a complete response to chemotherapy were reviewed. Clinical outcomes were calculated using the Kaplan-Meier method and were compared between patients who did and did not receive RT, using the log-rank test. A multivariate analysis was performed using Cox proportional hazards model. Results: Seventy-nine patients were identified. Chemotherapy (median, 6 cycles) consisted of anti-CD20 antibody rituximab combined with cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP; 65%); cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP; 22%); or other (13%). Post-chemotherapy imaging consisted of positron emission tomography (PET)/computed tomography (CT) (73%); gallium with CT (14%); or CT only (13%). Consolidation RT (median, 25 Gy) was given to involved sites of disease in 38 (48%) patients. Receipt of consolidation RT was associated with improved in-field control (92% vs. 69%, respectively, p = 0.028) and event-free survival (85% vs. 65%, respectively, p = 0.014) but no difference in overall survival (85% vs. 78%, respectively, p = 0.15) when compared to patients who did not receive consolidation RT. On multivariate analysis, no RT was predictive of increased risk of in-field failure (hazard ratio [HR], 8.01, p = 0.014) and worse event-free survival (HR, 4.3, p = 0.014). Conclusions: Patients with stage III-IV DLBCL who achieve negative post-chemotherapy imaging have improved in-field control and event-free survival with low-dose consolidation RT.

  1. Impact of Consolidation Radiation Therapy in Stage III-IV Diffuse Large B-cell Lymphoma With Negative Post-Chemotherapy Radiologic Imaging

    Energy Technology Data Exchange (ETDEWEB)

    Dorth, Jennifer A., E-mail: jennifer.dorth@duke.edu [Department of Radiation Oncology, Duke University Medical Center, Durham, North Carolina (United States); Prosnitz, Leonard R. [Department of Radiation Oncology, Duke University Medical Center, Durham, North Carolina (United States); Broadwater, Gloria [Cancer Statistical Center, Duke University Medical Center, Durham, North Carolina (United States); Diehl, Louis F.; Beaven, Anne W. [Department of Medicine, Division of Medical Oncology, Duke University Medical Center, Durham, North Carolina (United States); Coleman, R. Edward [Department of Radiology, Division of Nuclear Medicine, Duke University Medical Center, Durham, North Carolina (United States); Kelsey, Chris R. [Department of Radiation Oncology, Duke University Medical Center, Durham, North Carolina (United States)

    2012-11-01

    Purpose: While consolidation radiation therapy (i.e., RT administered after chemotherapy) is routine treatment for patients with early-stage diffuse large B-cell lymphoma (DLBCL), the role of consolidation RT in stage III-IV DLBCL is controversial. Methods and Materials: Cases of patients with stage III-IV DLBCL treated from 1991 to 2009 at Duke University, who achieved a complete response to chemotherapy were reviewed. Clinical outcomes were calculated using the Kaplan-Meier method and were compared between patients who did and did not receive RT, using the log-rank test. A multivariate analysis was performed using Cox proportional hazards model. Results: Seventy-nine patients were identified. Chemotherapy (median, 6 cycles) consisted of anti-CD20 antibody rituximab combined with cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP; 65%); cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP; 22%); or other (13%). Post-chemotherapy imaging consisted of positron emission tomography (PET)/computed tomography (CT) (73%); gallium with CT (14%); or CT only (13%). Consolidation RT (median, 25 Gy) was given to involved sites of disease in 38 (48%) patients. Receipt of consolidation RT was associated with improved in-field control (92% vs. 69%, respectively, p = 0.028) and event-free survival (85% vs. 65%, respectively, p = 0.014) but no difference in overall survival (85% vs. 78%, respectively, p = 0.15) when compared to patients who did not receive consolidation RT. On multivariate analysis, no RT was predictive of increased risk of in-field failure (hazard ratio [HR], 8.01, p = 0.014) and worse event-free survival (HR, 4.3, p = 0.014). Conclusions: Patients with stage III-IV DLBCL who achieve negative post-chemotherapy imaging have improved in-field control and event-free survival with low-dose consolidation RT.

  2. Central nervous system relapse in patients with diffuse large B cell lymphoma: analysis of the risk factors and proposal of a new prognostic model.

    Science.gov (United States)

    Kanemasa, Yusuke; Shimoyama, Tatsu; Sasaki, Yuki; Tamura, Miho; Sawada, Takeshi; Omuro, Yasushi; Hishima, Tsunekazu; Maeda, Yoshiharu

    2016-10-01

    Central nervous system (CNS) relapse in patients with diffuse large B cell lymphoma (DLBCL) is an uncommon event, and the outcome of patients with CNS relapse is poor. However, no reliable prediction models for CNS relapse have been developed. We retrospectively analyzed consecutive de novo DLBCL patients referred to our department between September 2004 and August 2015 and treated with R-CHOP or R-CHOP-like regimens. Of 413 patients analyzed in this study, a total of 27 patients (6.5 %) eventually developed CNS relapse. The 5-year probability of CNS relapse was 8.4 %. The median time from diagnosis of DLBCL to CNS relapse was 15 months, and the median survival after CNS relapse was 7 months. In univariate analysis, the risk factors significantly associated with CNS relapse were Ann Arbor stage 3 or 4, albumin level 1, and involvement of retroperitoneal lymph node. We developed a new prognostic model consisting of these four factors. The 5-year probability of CNS relapse was significantly higher in patients with at least three of these four factors than in those with two or fewer factors (26.4 vs. 3.0 %, P < 0.001). Using this model, we evaluated the incidence and the risk factors of CNS relapse in DLBCL patients. The new risk model consisting of the four factors demonstrated good risk stratification for CNS relapse, and could help to identify high-risk patients for whom CNS prophylaxis is warranted. PMID:27370993

  3. Advance in research of B-cell lymphoma stem cells%B细胞淋巴瘤干细胞的研究进展

    Institute of Scientific and Technical Information of China (English)

    丁晶

    2011-01-01

    淋巴瘤干细胞的发生机制十分复杂多样.对于滤泡淋巴瘤(FL)和套细胞淋巴瘤( NCL)来说,有观点认为在骨髓中经V-D-J重排过的淋巴祖细胞(CLP)是其肿瘤干细胞(TSC)的来源;而在弥漫性大B细胞淋巴瘤( DLBCL)和散发性Burkitt淋巴瘤(BL)中,生发中心B细胞是TSC的来源.另一种观点是,表观遗传学改变一次打击使正常造血细胞重新获得干细胞功能,然后经过进一步的染色体易位使这些“前-淋巴瘤干细胞”最终成为淋巴瘤干细胞.分离与鉴定非霍奇金淋巴瘤(NHL)的TSC能够为NHL的发病机制和治疗研究提供新的认识.%Origin of lymphoma stem cells is very complicated,it is proposed that committed lymphoid progenitor/precursor cells (CLP) with V-D-J recombination are stem cells of follicular lymphoma (FL) and mantle cell lymphoma (MCL).Conversely,B lymphocytes within the germinal center as the diffuse large B-cell lymphoma (DLBCL) and sporadic Burkitt lymphoma (BL) stem cells.An alternative model supports an epigenetic modification of genes as the first occurring hit,which leads to retaining stem-cell features in hematopoietic cells, followed by secondary chromosomal translocations that eventually transformed into lymphoma.Isolation and characterization of the different B-cell non-Hodgkin lymphomas will provide critical insights into the disease pathogenesis and will represent a step towards the development of more effective therapies.

  4. B-cell lymphoma of the appendix: A case report and review of literature

    Directory of Open Access Journals (Sweden)

    Jagannath Dev Sharma

    2014-08-01

    Full Text Available Appendicular tumors are rare, and lymphoma of the appendix is rarer. A 50 - year - old female patient presented with vague abdominal discomfort and lump in the right iliac fossa. The diagnosis of diffuse large B - cell lymphoma was made after laparotomy and histopathological examination (HPE supported by immunohistochemistry study. For appendicular neoplasms diagnosed postoperatively, including lymphoma, a meticulous grossing and HPE cannot be over emphasized. In case of wall thickening of >2.50- 3 cm detected by the computed tomogram scan, the possibility of a neoplasm or lymphoma in particular should be included as the differential diagnosis irrespective of the clinical presentation

  5. [Results of immuno-chemotherapeutic treatment of patients with diffuse large B-cell lymphoma].

    Science.gov (United States)

    Schneider, Tamás; Molnár, Zsuzsanna; Deák, Beáta; Várady, Erika; Tóth, Erika; Csomor, Judit; Matolcsy, András; Lovey, József; Lengyel, Zsolt; Petri, Klára; Gaudi, István; Rosta, András

    2009-11-01

    Treatment with cyclophosphamide, doxorubicin, vincristine and prednisolone (CHOP) has been considered as the standard therapy for diffuse large B-cell lymphoma (DLBCL) for more than 20 years. CHOP treatment in combination with targeted immunotherapy, rituximab (R-CHOP), resulted in significant improvements in the treatment of this group of patients. In this study, efficacy of R-CHOP and R-CHOP-like treatments was analysed. Results were compared to the data of historical patients only receiving CHOP treatment or CHOP-like treatment. Between September 2002 and April 2005, 140 newly diagnosed, untreated DLBCL patients started to receive R-CHOP treatment in a single centre. The eligibility criteria included advanced stage (clinical stages III-IV), or large tumour size (>7 cm) and/or symptom B or extranodal manifestation in the case of clinical stages I-II. The results were compared to the data of 130 patients only receiving CHOP treatment in the past. In the patients receiving R-CHOP, the therapeutic outcomes were superior for all parameters. During an average follow-up period of 44 or 52 months, the overall remission rate was 73.6% in the R-CHOP group in comparison with 47.7% in the CHOP group. The 5-year overall survival was 68.6% vs. 41.0% (RR: 0.4293, CI: 0.2963-0.6221; p < 0.0001), the event-free survival was 59.8% vs. 33.5% (RR: 0.5038, CI: 0.3606-0.7038; p < 0.0001) and the progression-free survival was 64.4% vs. 37.6% (RR: 0.4915, CI: 0.3442-0.7019; p < 0.0001). Since prognostic parameters were more favourable in the R-CHOP group, patient groups were also compared using the International Prognostic Index score. Again, significant differences were revealed by the subgroup analyses. The 5-year overall survival was 74.4% vs. 47.9% (RR: 0.4475, CI: 0.2418-0.8285; p = 0.0084) and 52.0% vs. 28.8% (RR: 0.4989, CI: 0.3098-0.8035; p = 0.003) in the group with good prognosis and in the group with poor prognosis, respectively. In the group with very good prognosis, the

  6. ALK+弥漫大B细胞淋巴瘤患者临床决策探讨%Clinical decision on a patient with ALK+diffuse large B cell lymphoma

    Institute of Scientific and Technical Information of China (English)

    董玲; 王先火; 王华庆; 付凯; 张会来; 孟斌; 张新伟; 宋秀宇; 张希梅; 翟琼莉; 刘霞; 侯芸; 李维

    2016-01-01

    Anaplastic lymphoma kinase (ALK)-positive diffuse large B-cell lymphoma (DLBCL) is a rare and distinct variant of DLBCL. It is classified as a unique subtype of DLBCL in the 2008 WHO classification of lymphomas. No standard and effective therapeutic regi-men is available for ALK+DLBCL because it shows a more aggressive clinical course and frequent relapse. Therefore, a standardized and individualized treatment is needed to benefit more patients diagnosed with ALK+DLBCL through a multiple disciplinary team. This arti-cle presents a case of an ALK+DLBCL patient who relapsed after transplantation and was successfully treated with the ALK kinase inhibi-tor Crizotinib.%ALK+弥漫大B细胞淋巴瘤(anaplastic lymphoma kinase-positive diffuse large B-cell lymphoma,ALK+DLBCL)是淋巴瘤中一种罕见的和具有明显差异性的病理类型,2008年WHO将其归类为DLBCL一个独特的亚型,该病侵袭性高,容易复发,目前尚无规范有效的治疗方案。采取多学科协作体系(multidisciplinary treatment,MDT)有利于制定规范化、个体化的治疗方案,探索针对ALK+DLBCL患者更有效的治疗方法,从而让更多的患者获益。本研究分享1例2012年1月天津医科大学肿瘤医院收治的ALK+DLBCL高剂量化疗联合自体造血干细胞移植(autologous hematopoietic stem cell transplantation,AHSCT)后复发,采用ALK激酶抑制剂克唑替尼(Crizotinib)治疗成功的案例。

  7. MYC expression in concert with BCL2 and BCL6 expression predicts outcome in Chinese patients with diffuse large B-cell lymphoma, not otherwise specified.

    Directory of Open Access Journals (Sweden)

    Li-Xu Yan

    Full Text Available Recent studies provide convincing evidence that a combined immunohistochemical or fluorescence in situ hybridization (FISH score of MYC, BCL2, BCL6 proteins and MYC translocations predicted outcome in diffuse large B-cell lymphoma (DLBCL patients treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP. However, by far, all these researches are based on Western populations. Therefore, we investigate the prognostic relevance of MYC-, BCL2- and BCL6-rearrangements and protein expression by immunohistochemistry and FISH from 336 de novo DLBCL, NOS treated with CHOP or R-CHOP. Breaks in MYC and BCL6, and fusion in IGH/BCL2 were detected in 9.7%, 20.0%, and 11.1% of the cases, respectively, and were not significantly associated with clinical outcomes. Protein overexpression of MYC (≥40%, BCL2 (≥70% and BCL6 (≥50% was encountered in 51%, 51% and 36% of the tumors, respectively. On the basis of MYC, BCL2 and BCL6 expression, double-hit scores (DHSs and triple-hit score (THS were assigned to all patients with DLBCL. Patients with high MYC/BCL2 DHS, high MYC/BCL6 DHS and high THS had multiple adverse prognostic factors including high LDH level, poor performance status, advanced clinical stage, high International Prognostic Index (IPI score, and non-germinal center B-cell. In univariate analysis, high MYC/BCL2 DHS, high MYC/BCL6 DHS and high THS were associated with inferior OS and PFS in both CHOP and R-CHOP cohorts (P0.05. These data together suggest that the immunohistochemical DHSs and THS defined a large subset of DLBCLs with double-hit biology and was strongly associated with poor outcome in patients treated with R-CHOP or CHOP.

  8. Two cases of uveitis masquerade syndrome caused by bilateral intraocular large B-cell lymphoma

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    Jovanović Svetlana

    2013-01-01

    Full Text Available Introduction. Sometimes it is not easy to clinically recognize subtle differences between intraocular lymphoma and noninfectious uveitis. The most common lymphoma subtype involving the eye is B-cell lymphoma. Case report. We presented two patients aged 59 and 58 years with infiltration of the subretinal space with a large B-cell non-Hodgkin intraocular lymphoma. The patients originally had clinically masked syndrome in the form of intermediate uveitis. As it was a corticosteroid-resistant uveitis, we focused on the possible diagnosis of neoplastic causes of this syndrome. During hospitalization, the neurological symptoms emerged and multiple subretinal changes accompanied by yellowish white patches of retinal pigment epithelium with signs of vitritis, which made us suspect the intraocular lymphoma. Endocranial magnetic resonance imaging established tumorous infiltration in the region of the left hemisphere of the cerebellum. The histopathological finding confirmed the diagnosis of large B-cell non-Hodgkin lymphoma of risk moderate degree, immunoblast - centroblast cytological type. The other patient had clinical chronic uveitis accompanied by yellowish shaped white echographic changes of the retina and localized changes in the level of the subretina. The diagnosis of lymphoma was made by brain biopsy. Conclusion. Uveitis masquerade syndrome should be considered in all patients over 40 years with idiopathic steroid-resistant uveitis. Treatment begun on time can affect the course and improve the prognosis of uveitis masquerade syndrome (UMS and systemic disease.

  9. A positive feedback regulation of ISL-1 in DLBCL but not in pancreatic β-cells

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Qiao, E-mail: zhangqiao200824@126.com [Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Key Laboratory of Molecular Cardiovascular Sciences (Ministry of Education), Peking University, 38 Xueyuan Road, 100191 Beijing (China); Yang, Zhe, E-mail: zheyang@bjmu.edu.cn [Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Key Laboratory of Molecular Cardiovascular Sciences (Ministry of Education), Peking University, 38 Xueyuan Road, 100191 Beijing (China); Wang, Weiping, E-mail: wwp@bjmu.edu.cn [Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Key Laboratory of Molecular Cardiovascular Sciences (Ministry of Education), Peking University, 38 Xueyuan Road, 100191 Beijing (China); Guo, Ting, E-mail: luckyguoting@bjmu.edu.cn [Department of Gastrointestinal Translation Research, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital, 52 Fucheng Road, 100142 Beijing (China); Jia, Zhuqing, E-mail: zhuqingjia@126.com [Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Key Laboratory of Molecular Cardiovascular Sciences (Ministry of Education), Peking University, 38 Xueyuan Road, 100191 Beijing (China); Ma, Kangtao, E-mail: makangtao11@126.com [Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Key Laboratory of Molecular Cardiovascular Sciences (Ministry of Education), Peking University, 38 Xueyuan Road, 100191 Beijing (China); Zhou, Chunyan, E-mail: chunyanzhou@bjmu.edu.cn [Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Key Laboratory of Molecular Cardiovascular Sciences (Ministry of Education), Peking University, 38 Xueyuan Road, 100191 Beijing (China)

    2014-07-04

    Highlights: • ISL-1 is highly expressed in human pancreatic β-cells and DLBCL. • ISL-1 accelerates the tumorigenesis of DLBCL in vivo. • c-Myc positively regulates ISL-1 expression in DLBCL but not in pancreatic β-cells. • ISL-1 and c-Myc forms an ISL-1/c-Myc transcriptional complex only in DLBCL. • Positive feedback regulation of ISL-1 does not exist in normal pancreatic β-cell. - Abstract: Insulin enhancer binding protein-1 (ISL-1), a LIM-homeodomain transcription factor, has been reported to play essential roles in promoting adult pancreatic β-cells proliferation. Recent studies indicate that ISL-1 may also involve in the occurrence of a variety of tumors. However, whether ISL-1 has any functional effect on tumorigenesis, and what are the differences on ISL-1 function in distinct conditions, are completely unknown. In this study, we found that ISL-1 was highly expressed in human pancreatic β-cells, as well as in diffuse large B cell lymphoma (DLBCL), but to a much less extent in other normal tissues or tumor specimens. Further study revealed that ISL-1 promoted the proliferation of pancreatic β-cells and DLBCL cells, and also accelerated the tumorigenesis of DLBCL in vivo. We also found that ISL-1 could activate c-Myc transcription not only in pancreatic β-cells but also in DLBCL cells. However, a cell-specific feedback regulation was detectable only in DLBCL cells. This auto-regulatory loop was established by the interaction of ISL-1 and c-Myc to form an ISL-1/c-Myc transcriptional complex, and synergistically to promote ISL-1 transcription through binding on the ISL-1 promoter. Taken together, our results demonstrate a positive feedback regulation of ISL-1 in DLBCL but not in pancreatic β-cells, which might result in the functional diversities of ISL-1 in different physiological and pathological processes.

  10. A positive feedback regulation of ISL-1 in DLBCL but not in pancreatic β-cells

    International Nuclear Information System (INIS)

    Highlights: • ISL-1 is highly expressed in human pancreatic β-cells and DLBCL. • ISL-1 accelerates the tumorigenesis of DLBCL in vivo. • c-Myc positively regulates ISL-1 expression in DLBCL but not in pancreatic β-cells. • ISL-1 and c-Myc forms an ISL-1/c-Myc transcriptional complex only in DLBCL. • Positive feedback regulation of ISL-1 does not exist in normal pancreatic β-cell. - Abstract: Insulin enhancer binding protein-1 (ISL-1), a LIM-homeodomain transcription factor, has been reported to play essential roles in promoting adult pancreatic β-cells proliferation. Recent studies indicate that ISL-1 may also involve in the occurrence of a variety of tumors. However, whether ISL-1 has any functional effect on tumorigenesis, and what are the differences on ISL-1 function in distinct conditions, are completely unknown. In this study, we found that ISL-1 was highly expressed in human pancreatic β-cells, as well as in diffuse large B cell lymphoma (DLBCL), but to a much less extent in other normal tissues or tumor specimens. Further study revealed that ISL-1 promoted the proliferation of pancreatic β-cells and DLBCL cells, and also accelerated the tumorigenesis of DLBCL in vivo. We also found that ISL-1 could activate c-Myc transcription not only in pancreatic β-cells but also in DLBCL cells. However, a cell-specific feedback regulation was detectable only in DLBCL cells. This auto-regulatory loop was established by the interaction of ISL-1 and c-Myc to form an ISL-1/c-Myc transcriptional complex, and synergistically to promote ISL-1 transcription through binding on the ISL-1 promoter. Taken together, our results demonstrate a positive feedback regulation of ISL-1 in DLBCL but not in pancreatic β-cells, which might result in the functional diversities of ISL-1 in different physiological and pathological processes

  11. A phase II study of belinostat (PXD101) in relapsed and refractory aggressive B-cell lymphomas: SWOG S0520.

    Science.gov (United States)

    Puvvada, Soham D; Li, Hongli; Rimsza, Lisa M; Bernstein, Steven H; Fisher, Richard I; LeBlanc, Michael; Schmelz, Monika; Glinsmann-Gibson, Betty; Miller, Thomas P; Maddox, Anne-Marie; Friedberg, Jonathan W; Smith, Sonali M; Persky, Daniel O

    2016-10-01

    Recent advances in diffuse large B-cell lymphomas (DLBCL) have underscored the importance of tumor microenvironment in escaping host anti-tumor responses. One mechanism is loss of major histocompatibility Class II antigens (MHCII) associated with decreased tumor infiltrating T lymphocytes (TIL) and poor survival. Transcription of MHCII is controlled by CIITA which in turn is regulated by histone acetylation. In this study, we hypothesized that HDAC inhibition with belinostat increases MHCII, CIITA expression, TIL and improves patient outcomes. Primary objective was evaluation of toxicity and response. Twenty-two patients were enrolled for the study. Belinostat was well tolerated with mild toxicity. Two partial responses were observed at 5, 13 months after registration for an overall response rate (ORR) (95% CI) of 10.5% (1.3-33.1%), and three patients had stable disease for 4.7, 42.3+, and 68.4 + months with minimum 3-year follow-up. Included correlative studies support the hypothesis and serve as the basis for SWOG S0806 combining vorinostat with R-CHOP. PMID:26758422

  12. High levels of nuclear MYC protein predict the presence of MYC rearrangement in diffuse large B-cell lymphoma

    DEFF Research Database (Denmark)

    Green, Tina Marie; Nielsen, Ole; de Stricker, Karin;

    2012-01-01

    with poor prognosis in DLBCL. Fluorescence in situ hybridization and karyotyping are standard tests for detecting MYC aberrations, but these techniques are laborious and expensive. Here, we studied MYC status of 219 DLBCLs and Burkitt lymphomas using fluorescence in situ hybridization, immunohistochemistry...

  13. Treatment and prognosis of primary gastric B-cell lymphoma. Special Reference to therapeutic strategy of MALT lymphoma

    International Nuclear Information System (INIS)

    To evaluate the influence of therapeutic methods on the prognosis of primary gastric B-cell lymphoma, we analyzed the prognostic factors for 322 patients, comprised of 186 with low-grade mucosa-associated lymphoid tissue (MALT) lymphoma, 54 with diffuse large B-cell lymphoma (DLBL) plus MALT lymphoma, and 82 with DLBL without MALT lymphoma. Among them, the clinical course of 96 patients who were treated by Helicobacter pylori eradication was also evaluated. Patients who underwent stomach-conserving treatment (H. pylori eradication, chemotherapy or radiation; n=100) showed a better overall survival probability than those treated by surgery (n=222), but the progression-free probability did not differ between the two groups. After H. pylori eradication, complete remission was achieved in 55 patients, of whom histologic relapse was observed in 4 patients (7%). Second line treatment for 34 patients, who failed to respond to eradication therapy, including oral monochemotherapy with cyclophosphamide, radiation, CHOP (CHOP; cyclophosphamide, doxorubicin, vincristine, prednisolone) chemotherapy, and gastrectomy resulted in complete remission in 29 patients (85%). These results suggest stomach- conserving treatment to be an optimal therapeutic modality for primary gastric B-cell lymphoma. (author)

  14. Breast schwannoma in a patient with diffuse large B-cell lymphoma: a case report

    Directory of Open Access Journals (Sweden)

    Salihoglu Ayse

    2012-12-01

    Full Text Available Abstract Introduction Schwannomas are mostly benign tumors arising from Schwann cells of the nerve sheaths. Breast schwannomas are very rare and account for only 2.6% of cases. As far as we know this is the first reported case of breast schwannoma discovered in a patient with diffuse large B-cell lymphoma. The breast schwannoma was evaluated with positron emission tomography and it exhibited moderate 18F-fluorodeoxyglucose uptake. Case presentation We present the case of a breast schwannoma in a 63-year-old Caucasian woman who was diagnosed with diffuse large B-cell lymphoma. Conclusion Imaging modalities including positron emission tomography-computed tomography failed to distinguish breast schwannoma from diffuse large B-cell lymphoma involvement of the breast.

  15. Hemophagocytic lymphohistiocytosis secondary to T-cell/histiocyte-rich large B-cell lymphoma

    Directory of Open Access Journals (Sweden)

    Katherine Devitt

    2014-01-01

    Full Text Available Hemophagocytic lymphohistiocytosis (HLH is a life-threatening clinical syndrome characterized by dysregulation of the immune system. Impaired function of cytotoxic T cells and natural killer cells is often seen, and T-cell malignancies represent most cases of lymphoma-associated HLH. HLH associated with B-cell lymphoma is rare. We describe a case of a 30-year-old man who presented with fever, splenomegaly, and hyperferritinemia. Bone marrow biopsy revealed T-cell/histiocyte-rich large B-cell lymphoma, a rare, aggressive B-cell malignancy. This case highlights the interplay between a pro-inflammatory cytokine microenvironment and tumor-mediated immune suppression, and addresses the importance of accurately diagnosing these entities for appropriate clinical management.

  16. B-cell Lymphoma in retrieved femoral heads: a long term follow up

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    van Kemenade Folkert J

    2009-05-01

    Full Text Available Abstract Background A relatively high incidence of pathological conditions in retrieved femoral heads, including a group of patients having low grade B-cell lymphoma, has been described before. At short term follow up none of these patients with low-grade B-cell lymphoma showed evidence of systemic disease. However, the long term follow up of these patients is not known. Methods From November 1994 up to and including December 2005 we screened all femoral heads removed at the time of primary total hip replacement histopathologically and included them in the bone banking protocol according to the guidelines of the American Associations of Tissue Banks (AATB and the European Association of Musculo-Skeletal Transplantation (EAMST. We determined the percentage of B-cell lymphoma in all femoral heads and in the group that fulfilled all criteria of the bone banking protocol and report on the long-term follow-up. Results Of 852 femoral heads fourteen (1.6% were highly suspicious for low-grade B-cell lymphoma. Of these 852 femoral heads, 504 were eligible for bone transplantation according to the guidelines of the AATB and the EAMST. Six femoral heads of this group of 504 were highly suspicious for low-grade B-cell lymphoma (1.2%. At long term follow up two (0.2% of all patients developed systemic malignant disease and one of them needed medical treatment for her condition. Conclusion In routine histopathological screening we found variable numbers of low-grade B-cell lymphoma throughout the years, even in a group of femoral heads that were eligible for bone transplantation. Allogenic transmission of malignancy has not yet been reported on, but surviving viruses are proven to be transmissible. Therefore, we recommend the routine histopathological evaluation of all femoral heads removed at primary total hip arthroplasty as a tool for quality control, whether the femoral head is used for bone banking or not.

  17. Frequent biclonality and Ig gene alterations among B cell lymphomas that show multiple histologic forms

    OpenAIRE

    1985-01-01

    Configurations of Ig gene DNA were examined in multiple biopsy specimens from seven cases of human B cell lymphoma that showed histologic differences among the specimens within each case. Analysis by Southern blot hybridizations with DNA probes for each of the three Ig loci revealed that the configurations of DNA within these loci were identical among the specimens in two of the cases. This result indicated the monoclonality of these lymphomas, despite differences in histology between biopsy ...

  18. Zosteriform Secondary Cutaneous Diffuse Large B-Cell Lymphoma on FDG PET/CT.

    Science.gov (United States)

    Liao, Chiung-Wei; Yen, Kuo-Yang; Hsieh, Te-Chun; Kao, Chia-Hung

    2016-09-01

    We present a case of a woman who had erythematous papules on the abdomen accompanied with numbness and local heat sensation. She had received chemotherapy for advanced follicular lymphoma. F-FDG PET/CT demonstrated band-like hypermetabolic lesions seemingly involving dermatomes of lower abdominal wall, which was confirmed as secondary cutaneous diffuse large B-cell lymphoma via skin biopsy. PMID:27405036

  19. Cyclophosphamide pharmacokinetics and pharmacogenetics in children with B-cell non-Hodgkin's lymphoma

    OpenAIRE

    Veal, Gareth J.; Cole, Michael; Chinnaswamy, Girish; Sludden, Julieann; Jamieson, David; Errington, Julie; Malik, Ghada; Hill, Christopher R.; Chamberlain, Thomas; Boddy, Alan V.

    2016-01-01

    Introduction Variation in cyclophosphamide pharmacokinetics and metabolism has been highlighted as a factor that may impact on clinical outcome in various tumour types. The current study in children with B-cell non-Hodgkin's lymphoma (NHL) was designed to corroborate previous findings in a large prospective study incorporating genotype for common polymorphisms known to influence cyclophosphamide pharmacology. Methods A total of 644 plasma samples collected over a 5 year period, from 49 B-cell...

  20. A comparison between protein profiles of B cell subpopulations and mantle cell lymphoma cells

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    Lehtiö Janne

    2009-11-01

    Full Text Available Abstract Background B-cell lymphomas are thought to reflect different stages of B-cell maturation. Based on cytogenetics and molecular markers, mantle cell lymphoma (MCL is presumed to derive predominantly from naïve, pre-germinal centre (pre-GC B lymphocytes. The aim of this study was to develop a method to investigate the similarity between MCL cells and different B-cell compartments on a protein expression level. Methods Subpopulations of B cells representing the germinal centre (GC, the pre-GC mantle zone and the post-GC marginal zone were isolated from tonsils using automated magnetic cell sorting (AutoMACS of cells based on their expression of CD27 and IgD. Protein profiling of the B cell subsets, of cell lines representing different lymphomas and of primary MCL samples was performed using top-down proteomics profiling by surface-enhanced laser detection/ionization time-of-flight mass spectrometry (SELDI-TOF-MS. Results Quantitative MS data of significant protein peaks (p-value Conclusion AutoMACS sorting generates sufficient purity to enable a comparison between protein profiles of B cell subpopulations and malignant B lymphocytes applying SELDI-TOF-MS. Further validation with an increased number of patient samples and identification of differentially expressed proteins would enable a search for possible treatment targets that are expressed during the early development of MCL.

  1. Phospho-specific flow cytometry identifies aberrant signaling in indolent B-cell lymphoma

    Directory of Open Access Journals (Sweden)

    Blix Egil S

    2012-10-01

    Full Text Available Abstract Background Knowledge about signaling pathways in malignant cells may provide prognostic and diagnostic information in addition to identify potential molecular targets for therapy. B-cell receptor (BCR and co-receptor CD40 signaling is essential for normal B cells, and there is increasing evidence that signaling via BCR and CD40 plays an important role in the pathogenesis of B-cell lymphoma. The aim of this study was to investigate basal and induced signaling in lymphoma B cells and infiltrating T cells in single-cell suspensions of biopsies from small cell lymphocytic lymphoma/chronic lymphocytic leukemia (SLL/CLL and marginal zone lymphoma (MZL patients. Methods Samples from untreated SLL/CLL and MZL patients were examined for basal and activation induced signaling by phospho-specific flow cytometry. A panel of 9 stimulation conditions targeting B and T cells, including crosslinking of the B cell receptor (BCR, CD40 ligand and interleukins in combination with 12 matching phospho-protein readouts was used to study signaling. Results Malignant B cells from SLL/CLL patients had higher basal levels of phosphorylated (p-SFKs, p-PLCγ, p-ERK, p-p38, p-p65 (NF-κB, p-STAT5 and p-STAT6, compared to healthy donor B cells. In contrast, anti-BCR induced signaling was highly impaired in SLL/CLL and MZL B cells as determined by low p-SFK, p-SYK and p-PLCγ levels. Impaired anti-BCR-induced p-PLCγ was associated with reduced surface expression of IgM and CD79b. Similarly, CD40L-induced p-ERK and p-p38 were also significantly reduced in lymphoma B cells, whereas p-p65 (NF-κB was equal to that of normal B cells. In contrast, IL-2, IL-7 and IL-15 induced p-STAT5 in tumor-infiltrating T cells were not different from normal T cells. Conclusions BCR signaling and CD40L-induced p-p38 was suppressed in malignant B cells from SLL/CLL and MZL patients. Single-cell phospho-specific flow cytometry for detection of basal as well as activation

  2. MDM2 gene SNP309 T/G and p53 gene SNP72 G/C do not influence diffuse large B-cell non-Hodgkin lymphoma onset or survival in central European Caucasians

    International Nuclear Information System (INIS)

    SNP309 T/G (rs2279744) causes higher levels of MDM2, the most important negative regulator of the p53 tumor suppressor. SNP72 G/C (rs1042522) gives rise to a p53 protein with a greatly reduced capacity to induce apoptosis. Both polymorphisms have been implicated in cancer. The SNP309 G-allele has recently been reported to accelerate diffuse large B-cell lymphoma (DLBCL) formation in pre-menopausal women and suggested to constitute a genetic basis for estrogen affecting human tumorigenesis. Here we asked whether SNP309 and SNP72 are associated with DLBCL in women and are correlated with age of onset, diagnosis, or patient's survival. SNP309 and SNP72 were PCR-genotyped in a case-control study that included 512 controls and 311 patients diagnosed with aggressive NHL. Of these, 205 were diagnosed with DLBCL. The age of onset was similar in men and women. The control and patients group showed similar SNP309 and SNP72 genotype frequencies. Importantly and in contrast to the previous findings, similar genotype frequencies were observed in female patients diagnosed by 51 years of age and those diagnosed later. Specifically, 3/20 female DLBCL patients diagnosed by 51 years of age were homozygous for SNP309 G and 2/20 DLBCL females in that age group were homozygous for SNP72 C. Neither SNP309 nor SNP72 had a significant influence on event-free and overall survival in multivariate analyses. In contrast to the previous study on Ashkenazi Jewish Caucasians, DLBCL in pre-menopausal women of central European Caucasian ethnicity was not associated with SNP309 G. Neither SNP309 nor SNP72 seem to be correlated with age of onset, diagnosis, or survival of patients

  3. A Novel Non-Immunoglobulin (non-Ig)/BCL6 Translocation in Diffuse Large B-Cell Lymphoma Involving Chromosome 10q11.21 Loci and Review on Clinical Consequences of BCL6 Rearrangements.

    Science.gov (United States)

    Jarosova, Marie; Kriegova, Eva; Schneiderova, Petra; Fillerova, Regina; Prochazka, Vit; Mikesova, Michaela; Flodr, Patrik; Indrak, Karel; Papajik, Tomas

    2016-04-01

    BCL6 rearrangements (3q27) are the most common chromosomal abnormalities in diffuse large B-cell lymphoma (DLBCL), with numerous immunoglobulin (Ig) and non-Ig genes as partners. In DLBCL, the translocations occur predominantly in the "major breakpoint region" encompassing the first noncoding exon and a part of the first intron of BCL6; few cases with "alternative breakpoint cluster" located 245-285 kb 5' BCL6 were also described. The regulatory sequences of known Ig and non-Ig partners replace the 5' untranslated region of the BCL6 in the same transcriptional orientation. Contrary to Ig/BCL6 fusions typical by high BCL6 gene expression, in non-Ig/BCL6 translocations were observed unexpectedly low BCL6 mRNA levels. From the clinical point of view, the survival rate of DLBCL patients with non-Ig partners is inferior to those with Ig/BCL6 translocations, suggesting that non-Ig/BCL6 fusion is a poor prognostic indicator. Hereby we provide comprehensive information about known non-Ig translocation partners and clinical consequences of BCL6 rearrangements in DLBCL. Moreover, we describe a novel reciprocal translocation t(3;10) in refractory patient with DLBCL with the breaking points at 5' untranslated region of BCL6 and 5' untranslated region of the RASGEF1A gene on chromosome 10q11.21 loci; this rearrangement was associated with low BCL6 and RASGEF1A gene expressions. Our patient harbouring dual chromosomal rearrangement involving BCL2 and BCL6 genes relapsed three-times and died soon; thus, further supporting the notion that non-Ig/BCL6 fusion is a poor prognostic indicator of DLBCL. There is evidence of prognostic value of BCL6 rearrangements also in rituximab era. PMID:26319027

  4. Cystatin C in sera of patients with aggressive non-Hodgkin B-cell lymphoma

    OpenAIRE

    Adaleta Softić; Lejla Begić; Alma Halilbašić; Janko Kos

    2015-01-01

    Aim To investigate the cystatin C levels in sera of patients with aggressive non-Hodgkin B-cell lymphoma. Methods The levels of cystatin C in sera of lymphoma patients and control group consisted of healthy individuals, were measured by using speciic sandwich-type ELISA. For each patient the clinical stage of disease was determined according to Ann Arbor staging system for lymphomas. Results Our study shows that mean cystatin C serum level in the patients group (1056 ± 65 ng/mL) was signiican...

  5. Diffuse large B-cell lymphoma of the kidney: A rare neoplasm

    Directory of Open Access Journals (Sweden)

    Ram Narayan Das

    2013-01-01

    Full Text Available Primary renal lymphoma is a rare neoplasm, but it should be kept in mind in the differential diagnosis of renal neoplasms. A middle aged man presented with symptoms of weight loss, anorexia and fullness of the abdomen after meals. On clinical and radiological examination, a renal mass was revealed and operated upon. A diagnosis of primary high grade renal lymphoma was made on histopathological examination and immunohistochemically it was further classified as diffuse large B-cell lymphoma. Unfortunately, the patient died after 5 months of diagnosis in spite of three cycles of chemotherapy following surgery. The pathological details of rare tumor are presented here.

  6. B-Cell Activation and Non-Hodgkin Lymphoma Risk in an HIV Positive Population

    OpenAIRE

    Chang, Po-Yin

    2013-01-01

    Background: B-cell non-Hodgkin lymphoma (NHL) in HIV populations (AIDS-NHL) has become the leading cause of AIDS-defining cancers. Studies suggested that genetic or serum markers of B-cell activation are related to AIDS-NHL. However, associations between HIV viral load and AIDS-NHL risk have not been explicitly explored with consideration of B-cell activation markers. Furthermore, associations of hepatitis C virus (HCV) infection to AIDS-NHL risk are inconclusive. Methods: We used two nested ...

  7. Value of Surveillance Studies for Patients With Stage I to II Diffuse Large B-Cell Lymphoma in the Rituximab Era

    International Nuclear Information System (INIS)

    Background: The role of surveillance studies in limited-stage diffuse large B-cell lymphoma (DLBCL) in the rituximab era has not been well defined. We sought to evaluate the use of imaging (computed tomography [CT] and positron emission tomography [PET]-CT) scans and lactate dehydrogenase (LDH) in surveillance of patients with stage I to II DLBCL. Methods: A retrospective analysis was performed of patients who received definitive treatment between 2000 and 2013. Results: One hundred sixty-two consecutive patients with stage I to II DLBCL were treated with chemotherapy +/− rituximab, radiation, or combined modality therapy. The 5-year rates of overall survival (OS) and freedom from progression (FFP) were 81.2% and 80.8%, respectively. Of the 162 patients, 124 (77%) were followed up with at least 1 surveillance PET scan beyond end-of-treatment scans; of those, 94 of 124 (76%) achieved a complete metabolic response on PET scan after completion of chemotherapy, and this was associated with superior FFP (P=.01, HR=0.3) and OS (P=.01, HR 0.3). Eighteen patients experienced relapse after initial response to therapy. Nine relapses were initially suspected by surveillance imaging studies (8 PET, 1 CT), and 9 were suspected clinically (5 by patient-reported symptoms and 4 by symptoms and physical examination). No relapses were detected by surveillance LDH. The median duration from initiation of treatment to relapse was 14.3 months among patients with relapses suspected by imaging, and 59.8 months among patients with relapses suspected clinically (P=.077). There was no significant difference in OS from date of first therapy or OS after relapse between patients whose relapse was suspected by imaging versus clinically. Thirteen of 18 patients underwent successful salvage therapy after relapse. Conclusions: A complete response on PET scan immediately after initial chemotherapy is associated with superior FFP and OS in stage I to II DLBCL. The use of PET scans as

  8. Rituximab Treatment Strategy for Patients with Diffuse Large B-Cell Lymphoma after First-Line Therapy: A Systematic Review and Meta-Analysis

    Directory of Open Access Journals (Sweden)

    Yuan-Rong Ren

    2015-01-01

    Full Text Available Background: Rituximab in combination with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP significantly prolonged event-free survival in first-line chemotherapy for patients with diffuse large B-cell lymphoma (DLBCL. But relapse and refractory DLBCL occur frequently. Although rituximab is effective, its role in salvage therapy after autologous transplant remains unclear. Maintenance therapy with rituximab in responding patients after first line chemotherapy may be a useful novel approach capable of eradicating minimal residual disease and to bring survival benefit. This systematic review and meta-analysis evaluated the effects of rituximab maintenance treatment and salvage therapy of patients with DLBCL. Methods: We performed a systematic review and meta-analysis of randomized controlled trials and compared rituximab maintenance or salvage therapy at relapse with observation. We searched the Cochrane Library, PubMed, EMBASE, conference proceedings, databases of ongoing trials, and references of published trials. Two reviewers independently assessed the quality of the trials and extracted data. Hazard ratios for time-to-event data were estimated and pooled. Results: Seven trials including 1470 DLBCL patients were included in this systematic review and meta-analysis. Patients treated with maintenance rituximab have better overall survival (OS and event-free survival (EFS than patients in the observation arm, but there was no statistical significance. Patients who received rituximab salvage therapy for relapse or refractory DLBCL have statistically significantly better OS [HR of death = 0.72, 95% CI (0.55-0.94, P = 0.02], progression-free survival (PFS [HR = 0.61, 95% CI (0.52-0.72, P < 0.05], odds ratio (OR [RR = 1.26, 95% CI (1.07-1.47, P = 0.004] than patients in the observation arm. The rate of infection-related adverse events was higher with rituximab treatment [RR = 1.37, 95% CI = (1.14 - 1.65 P =0.001]. Conclusions: After

  9. Value of Surveillance Studies for Patients With Stage I to II Diffuse Large B-Cell Lymphoma in the Rituximab Era

    Energy Technology Data Exchange (ETDEWEB)

    Hiniker, Susan M.; Pollom, Erqi L. [Department of Radiation Oncology, Stanford Cancer Institute, Stanford, California (United States); Khodadoust, Michael S. [Division of Oncology, Department of Medicine, Stanford Cancer Institute, Stanford, California (United States); Kozak, Margaret M. [Department of Radiation Oncology, Stanford Cancer Institute, Stanford, California (United States); Xu, Guofan; Quon, Andrew [Division of Nuclear Medicine, Department of Radiology, Stanford Cancer Institute, Stanford, California (United States); Advani, Ranjana H. [Division of Oncology, Department of Medicine, Stanford Cancer Institute, Stanford, California (United States); Hoppe, Richard T., E-mail: rhoppe@stanford.edu [Department of Radiation Oncology, Stanford Cancer Institute, Stanford, California (United States)

    2015-05-01

    Background: The role of surveillance studies in limited-stage diffuse large B-cell lymphoma (DLBCL) in the rituximab era has not been well defined. We sought to evaluate the use of imaging (computed tomography [CT] and positron emission tomography [PET]-CT) scans and lactate dehydrogenase (LDH) in surveillance of patients with stage I to II DLBCL. Methods: A retrospective analysis was performed of patients who received definitive treatment between 2000 and 2013. Results: One hundred sixty-two consecutive patients with stage I to II DLBCL were treated with chemotherapy +/− rituximab, radiation, or combined modality therapy. The 5-year rates of overall survival (OS) and freedom from progression (FFP) were 81.2% and 80.8%, respectively. Of the 162 patients, 124 (77%) were followed up with at least 1 surveillance PET scan beyond end-of-treatment scans; of those, 94 of 124 (76%) achieved a complete metabolic response on PET scan after completion of chemotherapy, and this was associated with superior FFP (P=.01, HR=0.3) and OS (P=.01, HR 0.3). Eighteen patients experienced relapse after initial response to therapy. Nine relapses were initially suspected by surveillance imaging studies (8 PET, 1 CT), and 9 were suspected clinically (5 by patient-reported symptoms and 4 by symptoms and physical examination). No relapses were detected by surveillance LDH. The median duration from initiation of treatment to relapse was 14.3 months among patients with relapses suspected by imaging, and 59.8 months among patients with relapses suspected clinically (P=.077). There was no significant difference in OS from date of first therapy or OS after relapse between patients whose relapse was suspected by imaging versus clinically. Thirteen of 18 patients underwent successful salvage therapy after relapse. Conclusions: A complete response on PET scan immediately after initial chemotherapy is associated with superior FFP and OS in stage I to II DLBCL. The use of PET scans as

  10. Rituximab Treatment Strategy for Patients with Diffuse Large B-Cell Lymphoma after First-Line Therapy: A Systematic Review and Meta-Analysis

    Institute of Scientific and Technical Information of China (English)

    Yuan-Rong Ren; Yong-Dong Jin; Zhi-Hui Zhang; Li Li; Ping Wu

    2015-01-01

    Background:Rituximab in combination with cyclophosphamide,doxorubicin,vincristine,and prednisone (CHOP) significantly prolonged event-free survival in first-line chemotherapy for patients with diffuse large B-cell lymphoma (DLBCL).But relapse and refractory DLBCL occur frequently.Although rituximab is effective,its role in salvage therapy after autologous transplant remains unclear.Maintenance therapy with rituximab in responding patients after first line chemotherapy may be a useful novel approach capable of eradicating minimal residual disease and to bring survival benefit.This systematic review and meta-analysis evaluated the effects of rituximab maintenance treatment and salvage therapy of patients with DLBCL.Methods:We performed a systematic review and meta-analysis of randomized controlled trials and compared rituximab maintenance or salvage therapy at relapse with observation.We searched the Cochrane Library,PubMed,EMBASE,conference proceedings,databases of ongoing trials,and references of published trials.Two reviewers independently assessed the quality of the trials and extracted data.Hazard ratios for time-to-event data were estimated and pooled.Results:Seven trials including 1470 DLBCL patients were included in this systematic review and meta-analysis.Patients treated with maintenance rituximab have better overall survival (OS) and event-free survival (EFS) than patients in the observation arm,but there was no statistical significance.Patients who received rituximab salvage therapy for relapse or refractory DLBCL have statistically significantly better OS [HR of death =0.72,95% CI (0.55-0.94),P=0.02],progression-free survival (PFS) [HR =0.61,95% CI (0.52-0.72),P< 0.05],odds ratio (OR) [RR =1.26,95% CI (1.07-1.47),P =0.004] than patients in the observation arm.The rate of infection-related adverse events was higher with rituximab treatment [RR =1.37,95% CI =(1.14-1.65) P =0.001].Conclusions:After first-line chemotherapy,the two rituximab

  11. BiovaxID, a personalized therapeutic vaccine against B-cell lymphomas

    Czech Academy of Sciences Publication Activity Database

    Reiniš, Milan

    2008-01-01

    Roč. 10, č. 5 (2008), s. 526-534. ISSN 1464-8431 Institutional research plan: CEZ:AV0Z50520514 Keywords : B-cell lymphomas * tumor antigen * therapeutic vaccine Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 2.913, year: 2008

  12. Cytomegalovirus enterocolitis in a patient with diffuse large B-cell lymphoma after chemotherapy with rituximab

    Institute of Scientific and Technical Information of China (English)

    Jason Seewoodhary

    2006-01-01

    Rituximab has been associated with the development of cytomegalovirus enterocolitis in immunosuppressed patients. A 51-year-old patient with diffuse large B-cell lymphoma who received a conditioning chemotherapy regimen (RCVP and RICE) consisting of rituximab before bone marrow transplantation went on to develop cytomegalovirus enterocolitis. This supports evidence from previously described cases that rituximab may be associated with cytomegalovirus enterocolitis.

  13. Comparison of Three Chemotherapy Regimens in Elderly Patients with Diffuse Large B Cell Lymphoma: Experience at a Single National Reference Center in Mexico

    Directory of Open Access Journals (Sweden)

    Diana Nolasco-Medina

    2016-01-01

    Full Text Available Background. Although chemotherapy added to rituximab is a standard of care for diffuse large B cell lymphoma (DLBCL, treatment of patients ≥65 years of age remains controversial due to comorbidities. Methods. This is a retrospective, comparative, nonrandomized study of patients ≥65 years of age, who were diagnosed with DLBCL but not previously treated. Demographic characteristics and comorbidities were analyzed. Three rituximab-containing treatment regimens (standard RCHOP, anthracycline dose-reduced RChOP, and RCOP were compared. Descriptive analyses were conducted. Survival was calculated with the Kaplan-Meier method, and differences were compared with the log-rank test. Results. In total, 141 patients with a median age of 73.9 years were studied. The three treatment groups had comparable demographic characteristics. The overall response was 77%, 72.5%, and 59% in groups treated with RCHOP, RChOP, and RCOP, respectively. After multivariate analysis, the factors influencing the overall survival were the presence of B symptoms, poor performance status (ECOG ≥ 3, and febrile neutropenia. Factors influencing disease-free survival were febrile neutropenia, high-intermediate and high-risk IPI scores, and treatment without anthracycline. Conclusion. A higher ORR (overall response rate was achieved with standard RCHOP, which influenced DFS and OS, although it was not statistically significant compared with the other groups. Interventional phase 3 trials testing new molecules in patients aged 70 to 80 years and older are required to improve the prognosis within this growing population.

  14. Comparison of Three Chemotherapy Regimens in Elderly Patients with Diffuse Large B Cell Lymphoma: Experience at a Single National Reference Center in Mexico.

    Science.gov (United States)

    Nolasco-Medina, Diana; Reynoso-Noveron, Nancy; Mohar-Betancourt, Alejandro; Aviles-Salas, Alejandro; García-Perez, Osvaldo; Candelaria, Myrna

    2016-01-01

    Background. Although chemotherapy added to rituximab is a standard of care for diffuse large B cell lymphoma (DLBCL), treatment of patients ≥65 years of age remains controversial due to comorbidities. Methods. This is a retrospective, comparative, nonrandomized study of patients ≥65 years of age, who were diagnosed with DLBCL but not previously treated. Demographic characteristics and comorbidities were analyzed. Three rituximab-containing treatment regimens (standard RCHOP, anthracycline dose-reduced RChOP, and RCOP) were compared. Descriptive analyses were conducted. Survival was calculated with the Kaplan-Meier method, and differences were compared with the log-rank test. Results. In total, 141 patients with a median age of 73.9 years were studied. The three treatment groups had comparable demographic characteristics. The overall response was 77%, 72.5%, and 59% in groups treated with RCHOP, RChOP, and RCOP, respectively. After multivariate analysis, the factors influencing the overall survival were the presence of B symptoms, poor performance status (ECOG ≥ 3), and febrile neutropenia. Factors influencing disease-free survival were febrile neutropenia, high-intermediate and high-risk IPI scores, and treatment without anthracycline. Conclusion. A higher ORR (overall response rate) was achieved with standard RCHOP, which influenced DFS and OS, although it was not statistically significant compared with the other groups. Interventional phase 3 trials testing new molecules in patients aged 70 to 80 years and older are required to improve the prognosis within this growing population. PMID:27478844

  15. Comparison of Three Chemotherapy Regimens in Elderly Patients with Diffuse Large B Cell Lymphoma: Experience at a Single National Reference Center in Mexico

    Science.gov (United States)

    Nolasco-Medina, Diana; Reynoso-Noveron, Nancy; Mohar-Betancourt, Alejandro; Aviles-Salas, Alejandro; García-Perez, Osvaldo

    2016-01-01

    Background. Although chemotherapy added to rituximab is a standard of care for diffuse large B cell lymphoma (DLBCL), treatment of patients ≥65 years of age remains controversial due to comorbidities. Methods. This is a retrospective, comparative, nonrandomized study of patients ≥65 years of age, who were diagnosed with DLBCL but not previously treated. Demographic characteristics and comorbidities were analyzed. Three rituximab-containing treatment regimens (standard RCHOP, anthracycline dose-reduced RChOP, and RCOP) were compared. Descriptive analyses were conducted. Survival was calculated with the Kaplan-Meier method, and differences were compared with the log-rank test. Results. In total, 141 patients with a median age of 73.9 years were studied. The three treatment groups had comparable demographic characteristics. The overall response was 77%, 72.5%, and 59% in groups treated with RCHOP, RChOP, and RCOP, respectively. After multivariate analysis, the factors influencing the overall survival were the presence of B symptoms, poor performance status (ECOG ≥ 3), and febrile neutropenia. Factors influencing disease-free survival were febrile neutropenia, high-intermediate and high-risk IPI scores, and treatment without anthracycline. Conclusion. A higher ORR (overall response rate) was achieved with standard RCHOP, which influenced DFS and OS, although it was not statistically significant compared with the other groups. Interventional phase 3 trials testing new molecules in patients aged 70 to 80 years and older are required to improve the prognosis within this growing population. PMID:27478844

  16. Central nervous system prophylaxis in patients with aggressive diffuse large B cell lymphoma: an analysis of 3,258 patients in a single center.

    Science.gov (United States)

    Avilés, Agustin; Jesús Nambo, M; Neri, Natividad

    2013-06-01

    Central nervous system (CNS) relapse continues to be a frequent and usually fatal complication in patients with diffuse large B cell lymphoma (DLBCL). Multiple factors identify the possibility of relapse and justify neurological prophylaxis; however, most of these have not been confirmed. Thus, the use of prophylaxis has not been defined. From 1988 to 2008, 3,258 patients with DLBCL with higher clinical risks and multiple extranodal involvement that have been treated with standard anthracycline-based chemotherapy: CHOP (cyclophosphamide, doxorubicin, vincristine and prednisone) or CHOP-R (CHOP plus rituximab) and that achieve complete response were retrospectively analyzed to assess the efficacy of CNS prophylaxis. One thousand five patients received different schedules for CNS prophylaxis, and 2,253 patients did not receive CNS prophylaxis. CNS relapse was similar in patients who receive prophylaxis (6 %) compared to patients who did not receive prophylaxis (5.9 %). Overall survival of patients who either receive or did not receive prophylaxis was not statistically significant: 49 % versus 53 % (p = 0.802). Thus, it seems that CNS prophylaxis did not improve outcome in this special setting of patients, and no prognostic factors to predict the presence of CNS relapse were identified. It is evident that multicentric studies are necessary to define the role of prophylaxis in order to prevent CNS relapse and that the therapeutic procedure will be carefully revised. PMID:23456620

  17. A comparison of HLA-identical sibling allogeneic versus autologous transplantation for diffuse large B cell lymphoma: a report from the CIBMTR.

    Science.gov (United States)

    Lazarus, Hillard M; Zhang, Mei-Jie; Carreras, Jeanette; Hayes-Lattin, Brandon M; Ataergin, Asli Selmin; Bitran, Jacob D; Bolwell, Brian J; Freytes, César O; Gale, Robert Peter; Goldstein, Steven C; Hale, Gregory A; Inwards, David J; Klumpp, Thomas R; Marks, David I; Maziarz, Richard T; McCarthy, Philip L; Pavlovsky, Santiago; Rizzo, J Douglas; Shea, Thomas C; Schouten, Harry C; Slavin, Shimon; Winter, Jane N; van Besien, Koen; Vose, Julie M; Hari, Parameswaran N

    2010-01-01

    We compared outcomes of 916 diffuse large B cell lymphoma (DLBCL) patients aged >or=18 years undergoing first autologous (n = 837) or myeloablative (MA) allogeneic hematopoietic cell transplant (HCT) (n = 79) between 1995 and 2003 reported to the Center for International Blood and Marrow Transplant Research (CIBMTR). Median follow-up was 81 months for allogeneic HCT versus 60 months for autologous HCT. Allogeneic HCT recipients were more likely to have high-risk disease features including higher stage, more prior chemotherapy regimens, and resistant disease. Allogeneic HCT was associated with a higher 1 year treatment-related mortality (TRM) (relative risk [RR] 4.88, 95% confidence interval [CI], 3.21-7.40, P 50 years), lower performance score, chemoresistance, and earlier year of transplant. In a cohort of mainly high-risk DLBCL patients, upfront MA allogeneic HCT, although associated with increased early mortality, was associated with a similar risk of disease progression compared to lower risk patients receiving autologous HCT. PMID:20053330

  18. Intravascular large B-cell lymphoma complicated by invasive pulmonary aspergillosis: a rare presentation

    Science.gov (United States)

    Mahasneh, Tamadur; Harrington, Zinta; Williamson, Jonathan; Alkhawaja, Darweesh; Duflou, Jo; Shin, Joo-Shik

    2014-01-01

    We describe a patient with persisting fevers, a progressive pulmonary infiltrate, and high levels of serum lactate dehydrogenase. No underlying cause for these changes was found prior to her death despite extensive investigations. Postmortem tissue revealed invasive pulmonary aspergillosis and subsequent brain examination revealed vascular changes in keeping with intravascular large B-cell lymphoma (IVLBCL). On review, subtle yet extensive lymphomatous infiltrates involved the vasculature of multiple other organs, including the lungs. Aspergillosis is a relatively rare presenting feature of lymphoproliferative disorders, and IVLBCL is a rare subtype of diffuse large B-cell non-Hodgkin's lymphoma with, to our knowledge, very few case reports to date. Lymphoma should be considered in patients presenting with pneumonitis with bilateral lung infiltrates on imaging, with a high serum level of lactate dehydrogenase. PMID:25473570

  19. An Oncogenic Role for Alternative NF-κB Signaling in DLBCL Revealed upon Deregulated BCL6 Expression

    Directory of Open Access Journals (Sweden)

    Baochun Zhang

    2015-05-01

    Full Text Available Diffuse large B cell lymphoma (DLBCL is a complex disease comprising diverse subtypes and genetic profiles. Possibly because of the prevalence of genetic alterations activating canonical NF-κB activity, a role for oncogenic lesions that activate the alternative NF-κB pathway in DLBCL has remained elusive. Here, we show that deletion/mutation of TRAF3, a negative regulator of the alternative NF-κB pathway, occurs in ∼15% of DLBCLs and that it often coexists with BCL6 translocation, which prevents terminal B cell differentiation. Accordingly, in a mouse model constitutive activation of the alternative NF-κB pathway cooperates with BCL6 deregulation in DLBCL development. This work demonstrates a key oncogenic role for the alternative NF-κB pathway in DLBCL development.

  20. Additional Survival Benefit of Involved-Lesion Radiation Therapy After R-CHOP Chemotherapy in Limited Stage Diffuse Large B-Cell Lymphoma

    Energy Technology Data Exchange (ETDEWEB)

    Kwon, Jeanny [Department of Radiation Oncology, Seoul National University College of Medicine, Seoul (Korea, Republic of); Kim, Il Han, E-mail: ihkim@snu.ac.kr [Department of Radiation Oncology, Seoul National University College of Medicine, Seoul (Korea, Republic of); Cancer Research Institute, Seoul National University College of Medicine, Seoul (Korea, Republic of); Institute of Radiation Medicine, Medical Research Center, Seoul National University, Seoul (Korea, Republic of); Kim, Byoung Hyuck [Department of Radiation Oncology, Seoul National University College of Medicine, Seoul (Korea, Republic of); Kim, Tae Min; Heo, Dae Seog [Department of Internal Medicine, Seoul National University Hospital, Seoul (Korea, Republic of)

    2015-05-01

    Purpose: The purpose of this study was to evaluate the role of involved-lesion radiation therapy (ILRT) after rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) chemotherapy in limited stage diffuse large B-cell lymphoma (DLBCL) by comparing outcomes of R-CHOP therapy alone with R-CHOP followed by ILRT. Methods and Materials: We identified 198 patients treated with R-CHOP (median, 6 cycles) for pathologically confirmed DLBCL of limited stage from July 2004 to December 2012. Clinical characteristics of these patients were 33% with stage I and 66.7% with stage II; 79.8% were in the low or low-intermediate risk group; 13.6% had B symptoms; 29.8% had bulky tumors (≥7 cm); and 75.3% underwent ≥6 cycles of R-CHOP therapy. RT was given to 43 patients (21.7%) using ILRT technique, which included the prechemotherapy tumor volume with a median margin of 2 cm (median RT dose: 36 Gy). Results: After a median follow-up of 40 months, 3-year progression-free survival (PFS) and overall survival (OS) were 85.8% and 88.9%, respectively. Multivariate analysis showed ≥6 cycles of R-CHOP (PFS, P=.004; OS, P=.004) and ILRT (PFS, P=.021; OS, P=.014) were favorable prognosticators of PFS and OS. A bulky tumor (P=.027) and response to R-CHOP (P=.012) were also found to be independent factors of OS. In subgroup analysis, the effect of ILRT was prominent in patients with a bulky tumor (PFS, P=.014; OS, P=.030) or an elevated level of serum lactate dehydrogenase (LDH; PFS, P=.004; OS, P=.012). Conclusions: Our results suggest that ILRT after R-CHOP therapy improves PFS and OS in patients with limited stage DLBCL, especially in those with bulky disease or an elevated serum LDH level.

  1. Prognostic significance of interim 18F-FDG PET/CT SUV reduction associated with Ki67 in patients with diffuse large B-cell lymphoma

    International Nuclear Information System (INIS)

    To detect the prognostic significance of interim 18F-FDG PET/CT SUV (standard uptake value) reduction (ΔSUVmax) associated with Ki67 in patients with diffuse large B cell lymphoma (DLBCL). 47 DLBCL patients underwent PET/CT before initiation and after 2-4 cycles of chemotherapy were included. The SUVmax of the dominant lesions were calculated. Ki67 positive indices were provided by enzyme-labeled immunohistochemistry. SPSS17.0 was used for statistical analysis. ΔSUVmax of different groups were compared by t test. Receiver-operator characteristic analysis was performed to determine the optimal cutoff values. Kaplan- Meier analyses of PFS (Progression-free survival) were compared using log-rank test. The average of ΔSUVmax and ΔSUVmax% were 11.53 and 69.10%, respectively. The optimal cutoff values of ΔSUVmax and ΔSUVmax% were 11.45 and 82.92%, respectively. Higher ΔSUVmax and ΔSUVmax% indicated longer PFS (p<0.001). The optimal cutoff value of Ki67 was 55%. Ki67 ≥55% was revealed to be an indicator of shorter PFS (p=0.019). Either ΔSUVmax<11.45 or Ki67>55% was defined as an indicator to poor outcome and scored 1 point. The PFS rate was 100% in patients scored 0 point, yet 0% in patients scored 2 points. PFS tended to be shorter along with the score getting higher (p=0.006). ΔSUVmax and Ki67 positive index were both of significance in DLBCL prognosis. The prognostic value may be confirmed when ΔSUVmax was accordant with Ki67. (authors)

  2. Additional Survival Benefit of Involved-Lesion Radiation Therapy After R-CHOP Chemotherapy in Limited Stage Diffuse Large B-Cell Lymphoma

    International Nuclear Information System (INIS)

    Purpose: The purpose of this study was to evaluate the role of involved-lesion radiation therapy (ILRT) after rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) chemotherapy in limited stage diffuse large B-cell lymphoma (DLBCL) by comparing outcomes of R-CHOP therapy alone with R-CHOP followed by ILRT. Methods and Materials: We identified 198 patients treated with R-CHOP (median, 6 cycles) for pathologically confirmed DLBCL of limited stage from July 2004 to December 2012. Clinical characteristics of these patients were 33% with stage I and 66.7% with stage II; 79.8% were in the low or low-intermediate risk group; 13.6% had B symptoms; 29.8% had bulky tumors (≥7 cm); and 75.3% underwent ≥6 cycles of R-CHOP therapy. RT was given to 43 patients (21.7%) using ILRT technique, which included the prechemotherapy tumor volume with a median margin of 2 cm (median RT dose: 36 Gy). Results: After a median follow-up of 40 months, 3-year progression-free survival (PFS) and overall survival (OS) were 85.8% and 88.9%, respectively. Multivariate analysis showed ≥6 cycles of R-CHOP (PFS, P=.004; OS, P=.004) and ILRT (PFS, P=.021; OS, P=.014) were favorable prognosticators of PFS and OS. A bulky tumor (P=.027) and response to R-CHOP (P=.012) were also found to be independent factors of OS. In subgroup analysis, the effect of ILRT was prominent in patients with a bulky tumor (PFS, P=.014; OS, P=.030) or an elevated level of serum lactate dehydrogenase (LDH; PFS, P=.004; OS, P=.012). Conclusions: Our results suggest that ILRT after R-CHOP therapy improves PFS and OS in patients with limited stage DLBCL, especially in those with bulky disease or an elevated serum LDH level

  3. Treatment of a Frail Older Patient with Diffuse Large B-Cell Lymphoma on Maintenance Dialysis: Attenuated Immunochemotherapy and Adapted Care Plan

    Directory of Open Access Journals (Sweden)

    Luciola de Barros Pontes

    2013-04-01

    Full Text Available Purpose of the Study: Diffuse large B-cell lymphoma (DLBCL is the most common lymphoid malignancy worldwide. Its incidence increases with age and about 40% of cases occur in patients over 70 years. Herein, we describe a case of a frail elderly patient with renal insufficiency and DLBCL treated with R-mini-CHOP. Case Report: A 77-year-old man on maintenance hemodialysis started experiencing persistent fatigue. He was diagnosed with a large mass on the left lobe of the lung. Biopsy demonstrated a DLBCL, CD20 positive. The patient was assigned clinical stage IIBX, with a high age-adjusted international prognosis index. A proper geriatric assessment revealed a frail patient. Thus, an adapted chemotherapy regimen was proposed which consisted of R-mini-CHOP every 21 days, with a reduction of 10% in the doses of doxorubicin and cyclophosphamide. During the treatment, the patient went through regular dialysis sessions, 3 times per week, with an extra session performed 12 h after each chemotherapy administration. The patient experienced no adverse events or grade 3/4 toxicities. After 6 cycles of R-mini-CHOP, the patient achieved unconfirmed complete remission, and consolidation radiotherapy was performed. At the last follow-up, he was still in unconfirmed complete remission, with a progression-free survival of 11.3 months. Conclusions: R-mini-CHOP represented a reasonable treatment option for this patient with renal failure. The oncogeriatric approach led to a successful management of this frail patient, highlighting that an adapted plan of care is a key issue to improve the outcomes of elderly cancer patients.

  4. Predictors of Local Recurrence After Rituximab-Based Chemotherapy Alone in Stage III and IV Diffuse Large B-Cell Lymphoma: Guiding Decisions for Consolidative Radiation

    Energy Technology Data Exchange (ETDEWEB)

    Jegadeesh, Naresh; Rajpara, Raj; Esiashvili, Natia; Shi, Zheng [Department of Radiation Oncology, Emory University, Atlanta, Georgia (United States); Winship Cancer Institute, Emory University, Atlanta, Georgia (United States); Liu, Yuan [Winship Cancer Institute, Emory University, Atlanta, Georgia (United States); Department of Biostatistics and Bioinformatics Shared Resource, Emory University, Atlanta, Georgia (United States); Okwan-Duodu, Derrick [Department of Radiation Oncology, Emory University, Atlanta, Georgia (United States); Winship Cancer Institute, Emory University, Atlanta, Georgia (United States); Flowers, Christopher R. [Winship Cancer Institute, Emory University, Atlanta, Georgia (United States); Department of Medical Oncology, Emory University, Atlanta, Georgia (United States); Khan, Mohammad K., E-mail: drkhurram2000@gmail.com [Department of Radiation Oncology, Emory University, Atlanta, Georgia (United States); Winship Cancer Institute, Emory University, Atlanta, Georgia (United States)

    2015-05-01

    Purpose: The role of consolidative radiation therapy (RT) for stage III and IV diffuse large B-cell lymphoma (DLBCL) in the era of rituximab is not well defined. There is evidence that some patients with bulky disease may benefit, but patient selection criteria are not well established. We sought to identify a subset of patients who experienced a high local failure rate after receiving rituximab-based chemotherapy alone and hence may benefit from the addition of consolidative RT. Methods and Materials: Two hundred eleven patients with stage III and IV DLBCL treated between August 1999 and January 2012 were reviewed. Of these, 89 had a complete response to systemic therapy including rituximab and received no initial RT. Kaplan-Meier analysis and Cox proportional hazards regression were performed, with local recurrence (LR) as the primary outcome. Results: The median follow-up time was 43.9 months. Fifty percent of patients experienced LR at 5 years. In multivariate analysis, tumor ≥5 cm and stage III disease were associated with increased risk of LR. The 5-year LR-free survival was 47.4% for patients with ≥5-cm lesions versus 74.7% for patients with <5-cm lesions (P=.01). In patients with <5-cm tumors, the maximum standardized uptake value (SUVmax) was ≥15 in all patients with LR. The 5-year LR-free survival was 100% in SUV<15 versus 68.8% in SUV≥15 (P=.10). Conclusions: Advanced-stage DLBCL patients with stage III disease or with disease ≥5 cm appear to be at an increased risk for LR. Patients with <5-cm disease and SUVmax ≥15 may be at higher risk for LR. These patients may benefit from consolidative RT after chemoimmunotherapy.

  5. Predictors of Local Recurrence After Rituximab-Based Chemotherapy Alone in Stage III and IV Diffuse Large B-Cell Lymphoma: Guiding Decisions for Consolidative Radiation

    International Nuclear Information System (INIS)

    Purpose: The role of consolidative radiation therapy (RT) for stage III and IV diffuse large B-cell lymphoma (DLBCL) in the era of rituximab is not well defined. There is evidence that some patients with bulky disease may benefit, but patient selection criteria are not well established. We sought to identify a subset of patients who experienced a high local failure rate after receiving rituximab-based chemotherapy alone and hence may benefit from the addition of consolidative RT. Methods and Materials: Two hundred eleven patients with stage III and IV DLBCL treated between August 1999 and January 2012 were reviewed. Of these, 89 had a complete response to systemic therapy including rituximab and received no initial RT. Kaplan-Meier analysis and Cox proportional hazards regression were performed, with local recurrence (LR) as the primary outcome. Results: The median follow-up time was 43.9 months. Fifty percent of patients experienced LR at 5 years. In multivariate analysis, tumor ≥5 cm and stage III disease were associated with increased risk of LR. The 5-year LR-free survival was 47.4% for patients with ≥5-cm lesions versus 74.7% for patients with <5-cm lesions (P=.01). In patients with <5-cm tumors, the maximum standardized uptake value (SUVmax) was ≥15 in all patients with LR. The 5-year LR-free survival was 100% in SUV<15 versus 68.8% in SUV≥15 (P=.10). Conclusions: Advanced-stage DLBCL patients with stage III disease or with disease ≥5 cm appear to be at an increased risk for LR. Patients with <5-cm disease and SUVmax ≥15 may be at higher risk for LR. These patients may benefit from consolidative RT after chemoimmunotherapy

  6. Development and blind clinical validation of a microRNA based predictor of response to treatment with R-CHO(E)P in DLBCL

    DEFF Research Database (Denmark)

    Knudsen, Steen; Hother, Christoffer; Grønbæk, Kirsten;

    2015-01-01

    MicroRNAs (miRNA) are a group of short noncoding RNAs that regulate gene expression at the posttranscriptional level. It has been shown that microRNAs are independent predictors of outcome in patients with diffuse large B-cell lymphoma (DLBCL) treated with the drug combination R-CHOP. Based on the...

  7. EBV-positive B cell cerebral lymphoma 12 years after sex-mismatched kidney transplantation: post-transplant lymphoproliferative disorder or donor-derived lymphoma?

    LENUS (Irish Health Repository)

    Phelan, Paul J

    2010-06-01

    We present a follow-up case report of possible transmission of lymphoma 12 years after deceased-donor renal transplantation from a male donor who was found at autopsy to have had an occult lymphoma. The female recipient underwent prompt transplant nephrectomy. However, 12 years later, she presented with cerebral B cell lymphoma. A donor origin for the cerebral lymphoma was supported by in situ hybridization demonstration of a Y chromosome in the lymphoma. There was a dramatic resolution of the cerebral lesions with tapering of immunosuppression and introduction of rituximab treatment. The finding of a Y chromosome in the cerebral lymphoma does not exclude a host contribution to lymphoma development.

  8. Generation and selection of immunized Fab phage display library against human B cell lymphoma

    Institute of Scientific and Technical Information of China (English)

    Yongmei Shen; Xiaochun Yang; Ningzheng Dong; Xiaofang Xie; Xia Bai; Yizhen Shi

    2007-01-01

    The approval of using monoclonal antibodies as a targeted therapy in the management of patients with B cell lymphoma has led to new treatment options for this group of patients. Production of monoclonal antibodies by the traditional hybridoma technology is costly, and the resulting murine antibodies often have the disadvantage of triggering human anti-mouse antibody (HAMA) response. Therefore recombinant Fab antibodies generated by the phage display technology can be a suitable alternative in managing B cell lymphoma. In this study, we extracted total RNA from spleen cells of BALB/c mice immunized with human B lymphoma cells, and used RT-PCR to amplify cDNAs coding for the K light chains and Fd fragments of heavy chains. After appropriate restriction digests, these cDNA fragments were successively inserted into the phagemid vector pComb3H-SS to construct an immunized Fab phage display library. The diversity of the constructed library was approximately 1.94×107. Following five rounds of biopanning, soluble Fab antibodies were produced from positive clones identified by ELISA. From eight positive clones, FabC06, FabC21, FabC43 and FabC59 were selected for sequence analysis. At the level of amino acid sequences, the variable heavy domains (VH) and variable light domains (VL) were found to share 88-92% and 89-94% homology with sequences coded by the corresponding murine germline genes respectively. Furthermore, reactivity with membrane proteins of the B cell lymphoma was demonstrated by immunohistochemistry and western blotting. These immunized Fab antibodies may provide a valuable tool for further study of B cell lymphoma and could also contribute to the improvement of disease therapy.

  9. Diffuse large B cell lymphoma presenting as a peri-anal abscess.

    Science.gov (United States)

    Jayasekera, Hasanga; Gorissen, Kym; Francis, Leo; Chow, Carina

    2014-01-01

    A non-healing peri-anal abscess can be difficult to manage and is often attributed to chronic disease. This case documents a male in his seventh decade who presented with multiple peri-anal collections. The abscess cavity had caused necrosis of the internal sphincter muscles resulting in faecal incontinence. Biopsies were conclusive for diffuse large B-cell lymphoma. A de-functioning colostomy was performed and the patient was initiated on CHOP-R chemotherapy. Anal lymphoma masquerading as a peri-anal abscess is rare. A high degree of suspicion must be maintained for an anal abscess which does not resolve with conservative management. PMID:24898408

  10. Diffuse large B cell lymphoma presenting as a peri-anal abscess

    OpenAIRE

    Jayasekera, Hasanga; Gorissen, Kym; Francis, Leo; Chow, Carina

    2014-01-01

    A non-healing peri-anal abscess can be difficult to manage and is often attributed to chronic disease. This case documents a male in his seventh decade who presented with multiple peri-anal collections. The abscess cavity had caused necrosis of the internal sphincter muscles resulting in faecal incontinence. Biopsies were conclusive for diffuse large B-cell lymphoma. A de-functioning colostomy was performed and the patient was initiated on CHOP-R chemotherapy. Anal lymphoma masquerading as a ...

  11. Primary diffuse large B-cell non-Hodgkin lymphoma of the cranial vault

    Directory of Open Access Journals (Sweden)

    Shantanu Ghosh

    2014-09-01

    Full Text Available Primary non-Hodgkin lymphoma of the cranial vault with extra and intracranial extension in a nonimmunocompromised patient is extremely uncommon. Until date, only limited number of such cases has been reported in the literature and none was the lesion located as a diffuse swelling in the forehead. Imaging of the present case showed in a homogenous contrast enhancement mass involving the scalp of bifrontal supraorbital compartment and intracranial extra axial extension through the frontal bone with extension to the right orbit and right ethmoidal sinus. The intracranial mass was excised along with involved dura. Histopathology of the mass showed diffuse large B-cell non-Hodgkin lymphoma.

  12. Central nervous system prophylaxis with intrathecal liposomal cytarabine in a subset of high-risk patients with diffuse large B-cell lymphoma receiving first line systemic therapy in a prospective trial.

    Science.gov (United States)

    González-Barca, E; Canales, M; Salar, A; Ferreiro-Martínez, J J; Ferrer-Bordes, S; García-Marco, J A; Sánchez-Blanco, J J; García-Frade, J; Peñalver, J; Bello-López, J L; Sancho, J M; Caballero, D

    2016-05-01

    The dissemination in the central nervous system (CNS) is an uncommon but fatal complication occurring in patients with diffuse large B-cell lymphoma (DLBCL). Standard prophylaxis has been demonstrated to reduce CNS relapse and improve survival rates. Intrathecal (IT) liposomal cytarabine allows maintaining elevated drug levels in the cerebrospinal fluid for an extended period of time. Data on the efficacy and safety of liposomal cytarabine as CNS prophylaxis in patients with DLBCL are still insufficient. The objective of the present study was to evaluate the effectiveness and safety of the prophylaxis with IT liposomal cytarabine in prevention of CNS relapse in high-risk patients with DLBCL who were included in a trial of first line systemic therapy with 6 cycles of dose-dense R-CHOP every 14 days. Twenty-four (18.6 %) out of 129 patients were identified to have risk factors for CNS involvement, defined as follows: >30 % bone marrow infiltration, testes infiltration, retroperitoneal mass ≥10 cm, Waldeyer ring, or bulky cervical nodes involvement. Liposomal cytarabine (50 mg) was administered by lumbar puncture the first day of the 1st, 2nd, and 6th cycle of R-CHOP14 scheme. Among 70 IT infusions, grade 3-4 adverse events reported were headache (one patient) and nausea/vomiting (one patient). With a median follow-up of 40.1 months, no CNS involvement by DLBCL was observed in any patient. In conclusion, IT liposomal cytarabine is safe, feasible, and effective for CNS prophylaxis, causing few associated risks and little discomfort to patients with DLBCL. PMID:27025508

  13. Homozygous A polymorphism of the complement C1qA276 correlates with prolonged overall survival in patients with diffuse large B cell lymphoma treated with R-CHOP

    Directory of Open Access Journals (Sweden)

    Jin Xuan

    2012-08-01

    Full Text Available Abstract Background The precise mechanism of action for rituximab (R is not fully elucidated. Besides antibody-dependent cellular cytotoxicity (ADCC, complements may also play an important role in the clinical response to rituximab-based therapy in diffuse large B cell lymphoma (DLBCL. The purpose of this study was to explore the relationship between C1qA[276] polymorphism and the clinical response to standard frontline treatment with R-CHOP in DLBCL patients. Methods Genotyping for C1qA[276A/G] was done in 164 patients with DLBCL. 129 patients treated with R-CHOP as frontline therapy (R ≥ 4 cycles were assessable for the efficacy. Results Patients with homozygous A were found to have a higher overall response rate than those with heterozygous or homozygous G alleles (97.3% vs. 83.7%,P = 0.068. The complete response rate in patients with homozygous A was statistically higher than that in AG and GG allele carriers (89.2% vs. 51.1%,P = 0.0001. The overall survival of patients with homozygous A was longer than that of the G allele carriers (676 days vs. 497 days, P = 0.023. Multivariate Cox regression analysis showed that C1qA A/A allele was an independent favorable prognostic factor for DLBCL patients treated with R-CHOP as first-line therapy. Conclusion These results suggest that C1qA polymorphism may be a biomarker to predict response to R-CHOP as frontline therapy for DLBCL patients.

  14. 胃弥漫大B细胞淋巴瘤与黏膜相关淋巴组织淋巴瘤CT比较研究%Diffuse Large B-cell Lymphoma and Mucosa-Associated Lymphoid Tissue Lymphoma: A CT Comparison Study

    Institute of Scientific and Technical Information of China (English)

    唐磊; 张晓鹏; 孙应实; 曹崑; 汪宁; 齐丽萍; 崔湧

    2009-01-01

    目的 探讨胃淋巴瘤两种主要类型:弥漫性大B细胞淋巴瘤(Diffuse large B-cell lymphoma,DLBCL)和黏膜相关淋巴组织淋巴瘤(Mucosa-associated lymphoid tissue lymphoma,MALToma)CT征象的异同,为胃淋巴瘤的生物学行为评价和影像学鉴别诊断提供依据.方法 回顾分析我院规范CT检查胃淋巴瘤病例42例,均经胃镜或手术病理证实.根据病理结果将全部病例分为DLBCL和MALToma.分析两种类型淋巴瘤CT影像学征象特征,包括病变所处胃的分部、范围、形态、厚度、强化、黏膜及浆膜面情况、淋巴结转移、腹腔大血管及脏器侵犯情况、腹腔转移及有无腹水等.统计学分析比较两种类型淋巴瘤的CT征象差异.结果 DLBCL多累及胃的多个部分,且以近端胃受累为主,MALToma以胃的单一部分受累更为多见,且以胃远端分布为主,差异有显著性.DLBCL癌肿平均厚度(2.75±1.52)cm,大于MALToma癌肿平均厚度(1.23±0.64)cm,差异存在显著性(P<0.01).DLBCL胃壁以弥漫性、不均匀增厚为主,MALToma以局限性、均匀增厚为主;DLBCL较MALToma更易侵犯浆膜,淋巴结转移率较MALToma高,转移淋巴结体积大、分布更为广泛,侵犯腹腔干分支大血管及腹腔脏器的比例均高于MALToma.DLBCL静脉期强化CT值(69.09±13.49)HU,低于 MALToma静脉期强化CT值(81.79±25.82)HU.MALToma黏膜面"白线征"显示率高于 DLBCL;DLBCL浆膜侧"血管穿行征"显示率高于MALToma.结论 CT影像学征象可反映DLBCL和MALToma的生物学行为,显示两种胃淋巴瘤侵袭性的差异,可作为两者鉴别的重要手段.MALToma黏膜面"白线征"、DLBCL浆膜侧"血管穿行征"丰富了胃淋巴瘤的CT征象,为鉴别诊断及生物学行为评价提供了新的指标.%Objective To explore the differences of CT signs in two kinds of gastric lymphomas, diffuse large B-cell lymphoma, DLBCL and mucosa-associated lymphoid tissue lymphoma, MALToma, to provide the evidence for the

  15. Treatment progress of young patients with high-risk diffuse large B-cell lymphoma%年轻高危弥漫大B细胞淋巴瘤患者治疗研究进展

    Institute of Scientific and Technical Information of China (English)

    陈溢

    2015-01-01

    弥漫大B细胞淋巴瘤(DLBCL)是成年人淋巴瘤中最常见的一种类型,约占非霍奇金淋巴瘤(NHL)的30%~ 40%.年轻高危DLBCL患者是临床预后不良的一组特殊人群,目前在临床实践中尚无标准治疗方案,常规化疗、联合利妥昔单抗的R-CHOP、R-CHOP样方案、大剂量化疗及自体造血干细胞移植并未完全扭转其预后不良的现实.文章就年轻高危DLBCL患者的治疗现状及未来的治疗方向进行综述.%Diffuse large B-cell lymphoma (DLBCL) is the most common adult lymphoid malignancy accounting for 30 %-40 % of all non-Hodgkin lymphoma (NHL).Young patients with high-risk DLBCL as a special group with poor clinical prognosis still can not receive standard treatment protocols in clinical practice at present.Conventional chemotherapy, combination of rituximab (R) to conventional CHOP chemotherapy, R-CHOP-like protocol, high-dose chemotherapy and autologous hematopoietic stem cell transplantation have not fully reversed the poor prognosis.This review focuses on the recent advances and future direction in the treatment of the young patients with high-risk DLBCL.

  16. Extranodal large B cell lymphoma of the anterior maxilla. Case report and review of literature.

    Science.gov (United States)

    Webber, Brian; Webber, Mariel; Keinan, David

    2015-01-01

    In the oral cavity, lymphoproliferative disorders can manifest in various ways, often as an extranodal externalization. In the case presented here, it was a B cell lymphoma originating in the periapical bone of the anterior maxilla. X-ray revealed a periapical radiolucency associated with an intact tooth with no decay, fillings or history of trauma. The tooth tested non-vital. After root canal treatment, an apicoectomy was performed with a biopsy. The most common diagnosis would be of dental etiology. The pathology report revealed a non-Hodgkin's B cell lymphoma. Most often, this disease appears as localized dental or oral pathology. Non-specific signs and symptoms present in association with lymphoproliferative disorders include lymphadenopathy, trismus, pain, swelling, sinusitis, fever, sepsis, prosthetic instability and paresthesia. Early detection results in decreased morbidity and a better prognosis for the patient. PMID:25707167

  17. Intravascular Large B-Cell Lymphoma Presenting as Interstitial Lung Disease

    Directory of Open Access Journals (Sweden)

    Elham Vali Khojeini

    2014-01-01

    Full Text Available Intravascular large B-cell lymphoma (IVLBL is a rare subtype of diffuse large B-cell lymphoma that resides in the lumen of blood vessels. Patients typically present with nonspecific findings, particularly bizarre neurologic symptoms, fever, and skin lesions. A woman presented with shortness of breath and a chest CT scan showed diffuse interstitial thickening and ground glass opacities suggestive of an interstitial lung disease. On physical exam she was noted to have splenomegaly. The patient died and at autopsy was found to have an IVLBL in her lungs as well as nearly all her organs that were sampled. Although rare, IVLBL should be included in the differential diagnosis of interstitial lung disease and this case underscores the importance of the continuation of autopsies.

  18. P11.09A NEUROLOGIC PRESENTATION OF INTRAVASCULAR LARGE B-CELL LYMPHOMA

    OpenAIRE

    Matas, A.F.M.R.; Veiga, A.S.B.T.; Gabriel, J.P.M.S.; Silva, M. R.

    2014-01-01

    INTRODUCTION: Intravascular large B-cell lymphoma is a rare and fatal disease that can have central nervous system manifestations. Given its rarity and the multiplicity of presentations, diagnosis is extremely difficult. We report a case that presented with neurological manifestations and which diagnosis was made ante mortem. CASE REPORT: A 74-year-old man, with a background of hypertension and dyslipidemia was referred to our neurology department with a history of speech difficulties and wal...

  19. Role of ATM in Suppressing Oncogenic Translocations and Mature B Cell Lymphomas

    OpenAIRE

    Tepsuporn, Suprawee

    2013-01-01

    The ATM protein senses DNA double-stranded breaks (DSBs) and facilitates proper repair. B and T lymphocytes of ATM-deficient patients have increased antigen receptor locus translocations associated with aberrant V(D)J recombination. Correspondingly, ATM-deficient humans are predisposed to both T and B cell malignancies. However, ATM-deficiency in mice only leads to T cell lymphomas, all of which harbor T cell receptor locus translocations resulting from aberrant V(D)J recombination. The first...

  20. Clear cell variant of diffuse large B-cell lymphoma: a case report

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    Sahatciu-Meka Vjollca

    2011-05-01

    Full Text Available Abstract Introduction Diffuse large B-cell lymphoma is a diffuse proliferation of large neoplastic B lymphoid cells with a nuclear size equal to or exceeding the normal macrophage nuclei. We report a case of a clear cell variant of diffuse large B-cell lymphoma involving a lymph node in the neck, which was clinically suspected of being metastatic carcinoma. Case presentation A 39-year-old Caucasian ethnic Albanian man from Kosovo presented with a rapidly enlarging lymph node in his neck, but he also disclosed B symptoms and fatigue. A cytological aspirate of the lymph node revealed pleomorphic features. Our patient underwent a cervical lymph node biopsy (large excision. The mass was homogeneously fish-flesh, pale white tissue replacing almost the whole structure of the lymph node. The lymph node biopsy showed a partial alveolar growth pattern, which raised clinical suspicion that it was an epithelial neoplasm. With regard to morphological and phenotypic features, we discovered large nodules in diffuse areas, comprising large cells with slightly irregular nuclei and clear cytoplasm admixed with a few mononuclear cells. In these areas, there was high mitotic activity, and in some areas there were macrophages with tangible bodies. Staining for cytokeratins was negative. These areas had the following phenotypes: cluster designation marker 20 (CD20 positive, B-cell lymphoma (Bcl-2-positive, Bcl-6-, CD5-, CD3-, CD21+ (in alveolar patterns, prostate-specific antigen-negative, human melanoma black marker 45-negative, melanoma marker-negative, cytokeratin-7-negative and multiple myeloma marker 1-positive in about 30% of cells, and exhibited a high proliferation index marker (Ki-67, 80%. Conclusion According to the immunohistochemical findings, we concluded that this patient has a clear cell variant of diffuse large B-cell lymphoma of activated cell type, post-germinal center cell origin. Our patient is undergoing R-CHOP chemotherapy treatment.

  1. Intravascular large B-cell lymphoma complicated by invasive pulmonary aspergillosis: a rare presentation

    OpenAIRE

    Mahasneh, Tamadur; Harrington, Zinta; Williamson, Jonathan; Alkhawaja, Darweesh; Duflou, Jo; Shin, Joo-Shik

    2014-01-01

    We describe a patient with persisting fevers, a progressive pulmonary infiltrate, and high levels of serum lactate dehydrogenase. No underlying cause for these changes was found prior to her death despite extensive investigations. Postmortem tissue revealed invasive pulmonary aspergillosis and subsequent brain examination revealed vascular changes in keeping with intravascular large B-cell lymphoma (IVLBCL). On review, subtle yet extensive lymphomatous infiltrates involved the vasculature of ...

  2. Elevated serum IL-10 levels in diffuse large B-cell lymphoma: a mechanism of aberrant JAK2 activation

    OpenAIRE

    Gupta, Mamta; Han, Jing Jing; Stenson, Mary; Maurer, Matthew; Wellik, Linda; Hu, Guangzhen; Ziesmer, Steve; Dogan, Ahmet; Witzig, Thomas E.

    2012-01-01

    Cytokines are deregulated in cancers and can contribute to tumor growth. In patients with diffuse large-cell lymphoma (DLBCL), we observed higher levels of JAK/STAT pathway-related serum cytokines (ie, IL-6, IL-10, epidermal growth factor, and IL-2) compared with controls. Of these, only IL-10 activated the JAK2 pathway in lymphoma cells in vitro. Patients with high serum IL-10 had shorter event-free survival (EFS) than patients with low levels (P > .01) and high IL-10 was correlated with hig...

  3. Synthetic Lethal Screen Demonstrates That a JAK2 Inhibitor Suppresses a BCL6-dependent IL10RA/JAK2/STAT3 Pathway in High Grade B-cell Lymphoma.

    Science.gov (United States)

    Beck, Daniel; Zobel, Jenny; Barber, Ruth; Evans, Sian; Lezina, Larissa; Allchin, Rebecca L; Blades, Matthew; Elliott, Richard; Lord, Christopher J; Ashworth, Alan; Porter, Andrew C G; Wagner, Simon D

    2016-08-01

    We demonstrate the usefulness of synthetic lethal screening of a conditionally BCL6-deficient Burkitt lymphoma cell line, DG75-AB7, with a library of small molecules to determine survival pathways suppressed by BCL6 and suggest mechanism-based treatments for lymphoma. Lestaurtinib, a JAK2 inhibitor and one of the hits from the screen, repressed survival of BCL6-deficient cells in vitro and reduced growth and proliferation of xenografts in vivo BCL6 deficiency in DG75-AB7 induced JAK2 mRNA and protein expression and STAT3 phosphorylation. Surface IL10RA was elevated by BCL6 deficiency, and blockade of IL10RA repressed STAT3 phosphorylation. Therefore, we define an IL10RA/JAK2/STAT3 pathway each component of which is repressed by BCL6. We also show for the first time that JAK2 is a direct BCL6 target gene; BCL6 bound to the JAK2 promoter in vitro and was enriched by ChIP-seq. The place of JAK2 inhibitors in the treatment of diffuse large B-cell lymphoma has not been defined; we suggest that JAK2 inhibitors might be most effective in poor prognosis ABC-DLBCL, which shows higher levels of IL10RA, JAK2, and STAT3 but lower levels of BCL6 than GC-DLBCL and might be usefully combined with novel approaches such as inhibition of IL10RA. PMID:27268052

  4. Qualitative visual trichotomous assessment improves the value of fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography in predicting the prognosis of diffuse large B-cell lymphoma

    Institute of Scientific and Technical Information of China (English)

    Xu Zhang; Wei Fan; Ying-Ying Hu; Zhi-Ming Li; Zhong-Jun Xia; Xiao-Ping Lin; Ya-Rui Zhang; Pei-Yan Liang; Yuan-Hua Li

    2015-01-01

    Introduction:Fluorine-18 fluorodeoxyglucose (18 F-FDG) positron emission tomography/computed tomography (PET/CT) is a powerful tool for monitoring the response of diffuse large B-cell lymphoma (DLBCL) to therapy, but the criteria to interpret PET/CT results remain under debate. We investigated the value of post-treatment PET/CT in predicting the prognosis of DLBCL patients when interpreted according to qualitative visual trichotomous assessment (QVTA) criteria compared with the Deauvil e criteria. Methods:In this retrospective study, final PET/CT scans of DLBCL patients treated with rituximab-based regimens between October 2005 and November 2010 were interpreted using the Deauvil e and QVTA criteria. Survival curves were estimated using Kaplan-Meier analysis and compared using the log-rank test. Results:A total of 253 patients were enrol ed. The interpretation according to the Deauvil e criteria revealed that 181 patients had negative PET/CT scan results and 72 had positive results. The 3 year overal survival (OS) rate was significantly higher in patients with negative scan results than in those with positive results (91.6%vs. 57.5%, P<0.001). The 72 patients with positive scan results according to the Deauville criteria were divided into two groups by the interpretation according to the QVTA criteria:29 had indeterminate results, and 43 had positive results. The 3 year OS rate was significantly higher in patients with indeterminate scan results than in those with positive results (91.2%vs. 33.5%, P<0.001) but was similar between patients with negative and indeterminate scan results (91.6%vs. 91.2%, P=0.921). Conclusions:Compared with the Deauvil e criteria, using the QVTA criteria for interpreting post-treatment PET/CT scans of DLBCL patients is likely to reduce the number of false positive results. The QVTA criteria are feasible for therapeutic outcome evaluation and can be used to guide risk-adapted therapy.

  5. Genetically Engineered Lymphocyte Therapy in Treating Patients With B-Cell Leukemia or Lymphoma That is Resistant or Refractory to Chemotherapy

    Science.gov (United States)

    2015-07-31

    Hematopoietic/Lymphoid Cancer; Adult Acute Lymphoblastic Leukemia in Remission; B-cell Adult Acute Lymphoblastic Leukemia; B-cell Chronic Lymphocytic Leukemia; Prolymphocytic Leukemia; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Refractory Chronic Lymphocytic Leukemia; Stage III Adult Diffuse Large Cell Lymphoma; Stage III Chronic Lymphocytic Leukemia; Stage III Grade 1 Follicular Lymphoma; Stage III Grade 2 Follicular Lymphoma; Stage III Grade 3 Follicular Lymphoma; Stage III Mantle Cell Lymphoma; Stage IV Adult Diffuse Large Cell Lymphoma; Stage IV Chronic Lymphocytic Leukemia; Stage IV Grade 1 Follicular Lymphoma; Stage IV Grade 2 Follicular Lymphoma; Stage IV Grade 3 Follicular Lymphoma; Stage IV Mantle Cell Lymphoma

  6. Unusual case of B cell lymphoma after immunosuppressive treatment for psoriasis.

    Science.gov (United States)

    Nosotti, Lorenzo; Baiocchini, Andrea; Bonifati, Claudio; Visco-Comandini, Ubaldo; Mirisola, Concetta; Del Nonno, Franca

    2015-04-18

    Lymphomas may be induced by the systemic immunosuppressive therapies used to treat psoriasis, such as ciclosporin, methotrexate and tumour necrosis factor (TNF)-α blockers. The biologic agents currently used in psoriasis include alefacept, efalizumab, and the TNF-α antagonists etanercept, infliximab, and adalimumab. Infections and cancer are the main possible consequences of intended or unexpected immunosuppression. We report a 59-year-old man with a history of severe psoriasis vulgaris treated with traditional immunosuppressant drugs followed by anti-TNF-α therapy; the patient was firstly hospitalized for an acute cholestatic toxic hepatitis, which we supposed to be related to adalimumab. The first liver biopsy showed active disease with severe hepatocellular damage caused by heavy lymphocytes infiltrate in portal tracts at in the interface with a not conclusive diagnosis of lymphoproliferative disease. The correct diagnosis of T cell/histiocyte- rich large B cell lymphoma (T/HRBCL) was only reached through a gastric biopsy and a second liver biopsy. T/HRBCL is an uncommon morphologic variant of diffuse large B-cell lymphoma not described until now in psoriatic patients receiving immunosuppressive biologic agents. In psoriatic patients, treated with biologic immunosuppressive agents, the suspect of abdominal lymphoma should always be included as differential diagnosis. Abdominal ultrasound evaluation need therefore to be included in the pre-treatment screening as in the follow-up surveillance. PMID:25914782

  7. Diverse hematological malignancies including hodgkin-like lymphomas develop in chimeric MHC class II transgenic mice.

    Directory of Open Access Journals (Sweden)

    Silke H Raffegerst

    Full Text Available A chimeric HLA-DR4-H2-E (DR4 homozygous transgenic mouse line spontaneously develops diverse hematological malignancies with high frequency (70%. The majority of malignancies were distributed equally between T and B cell neoplasms and included lymphoblastic T cell lymphoma (LTCL, lymphoblastic B cell lymphoma (LBCL, diffuse large B cell lymphoma (DLBCL, the histiocyte/T cell rich variant of DLBCL (DLBCL-HA/T cell rich DLBCL, splenic marginal zone lymphoma (SMZL, follicular B cell lymphoma (FBL and plasmacytoma (PCT. Most of these neoplasms were highly similar to human diseases. Also, some non-lymphoid malignancies such as acute myeloid leukemia (AML and histiocytic sarcoma were found. Interestingly, composite lymphomas, including Hodgkin-like lymphomas, were also detected that had CD30(+ Hodgkin/Reed-Sternberg (H/RS-like cells, representing a tumor type not previously described in mice. Analysis of microdissected H/RS-like cells revealed their origin as germinal center B cells bearing somatic hypermutations and, in some instances, crippled mutations, as described for human Hodgkin lymphoma (HL. Transgene integration in an oncogene was excluded as an exclusive driving force of tumorigenesis and age-related lymphoma development suggests a multi-step process. Thus, this DR4 line is a useful model to investigate common molecular mechanisms that may contribute to important neoplastic diseases in man.

  8. Selective loss of B-cell phenotype in lymphocyte predominant Hodgkin lymphoma.

    Science.gov (United States)

    Tedoldi, S; Mottok, A; Ying, J; Paterson, J C; Cui, Y; Facchetti, F; van Krieken, J H J M; Ponzoni, M; Ozkal, S; Masir, N; Natkunam, Y; Pileri, Sa; Hansmann, M-L; Mason, Dy; Tao, Q; Marafioti, T

    2007-12-01

    The neoplastic Reed-Sternberg cells characteristic of classical Hodgkin's lymphoma (cHL) are of B-cell origin but they almost always show striking loss of a range of B-cell-associated molecules. In contrast, the neoplastic cells found in lymphocyte predominant Hodgkin's lymphoma (LPHL) (L&H cells) are traditionally thought of as possessing the full repertoire of features associated with germinal centre B cells (eg BCL-6 expression, 'ongoing' Ig gene mutation). In the present paper, we report an extensive phenotypic analysis of L&H cells which revealed down-regulation of a number of markers associated with the B-cell lineage (eg CD19, CD37) and with the germinal centre maturation stage (eg PAG, LCK). The promoter methylation status of three of these down-regulated genes (CD10, CD19, and LCK) was further studied in microdissected L&H cells, and this revealed that their promoters were unmethylated. In contrast, these genes showed promoter methylation in cell lines derived from CHL. Further investigation of the mechanisms responsible for the deregulation of these molecules in L&H cells may provide new insights into the genetic abnormalities underlying LPHL. PMID:17935142

  9. Expression of programmed cell death 1 ligand 2 (PD-L2) is a distinguishing feature of primary mediastinal (thymic) large B-cell lymphoma and associated with PDCD1LG2 copy gain.

    Science.gov (United States)

    Shi, Min; Roemer, Margaretha G M; Chapuy, Bjoern; Liao, Xiaoyun; Sun, Heather; Pinkus, Geraldine S; Shipp, Margaret A; Freeman, Gordon J; Rodig, Scott J

    2014-12-01

    Primary mediastinal (thymic) large B-cell lymphoma (PMBL) and diffuse large B-cell lymphoma (DLBCL) are tumors with distinct clinical and molecular characteristics that are difficult to distinguish by histopathologic and phenotypic analyses alone. Programmed cell death 1 ligand 2 (PD-L2) is a cell surface protein expressed by activated macrophages and dendritic cells that binds PD-1 on T cells to inhibit immune responses. Amplification and/or translocations involving chromosome 9p24.1, a region that includes PDCD1LG2-encoding PD-L2, is a common event in PMBL but not DLBCL and suggests that PD-L2 expression might be a distinguishing feature of PMBL. We developed an assay for the immunohistochemical detection of PD-L2 protein in fixed biopsy specimens (PD-L2 IHC), which we applied to a cohort of PMBLs and DLBCLs. For a subset of cases, we correlated the results of PD-L2 IHC with PDCD1LG2 copy number (CN) as determined by quantitative polymerase chain reaction. Twenty-three of 32 (72%) PMBLs but only 1 of 37 (3%) DLBCLs were positive by PD-L2 IHC. Among PMBLs with PDCD1LG2 CN gain, all were positive by PD-L2 IHC. One PMBL without CN gain was positive by PD-L2 IHC. When expressed in PMBL, PD-L2 was restricted to tumor cells and not detected on intratumoral macrophages. We conclude that PD-L2 protein is robustly expressed by the majority of PMBLs but only rare DLBCLs and often associated with PDCD1LG2 copy gain. PD-L2 IHC may serve as a useful ancillary test for distinguishing PMBL from DLBCL and for the rational selection of patients for therapeutic antibodies that inhibit PD-1 signaling. PMID:25025450

  10. Pediatric mature B-cell non Hodgkin lymphoma treatment with LMB-96 protocol. The Children Cancer Hospital Egypt experience

    OpenAIRE

    Hany Abdel Rahman; Emad Moussa; Mohamed Sedky; Iman Gouda; Madiha El Wakeel; Omneya Hassanein

    2015-01-01

    Purpose: Burkitt lymphoma (BL) is a highly aggressive mature B-cell non-Hodgkin lymphoma (NHL) and is the fastest growing human tumor. The outcome of childhood NHL has improved steadily over the past decades through the use of intensive sequential multi-agent chemotherapy regimens.Methods: A retrospective study having all patients 18 years old or younger diagnosed with mature B cell NHL and treated at Children Cancer Hospital Egypt (CCHE). All children were treated according to the modified (...

  11. Absence of missense mutations in activated c-myc genes in avian leukosis virus-induced B-cell lymphomas

    International Nuclear Information System (INIS)

    The authors determined the nucleotide sequences of two independent DNA clones which contained the activated c-myc genes from avian leukosis virus-induced B-cell lymphomas. Neither of these c-myce genes contained missense mutations. This strongly supports the notion that the c-myc photo-oncogene in avian leukosis virus-induced B-cell lymphomas can be oncogenically activated by altered expression of the gene without a change in the primary structure of the gene product

  12. Absence of missense mutations in activated c-myc genes in avian leukosis virus-induced B-cell lymphomas.

    OpenAIRE

    Hahn, M; Hayward, W S

    1988-01-01

    We have determined the nucleotide sequences of two independent DNA clones which contained the activated c-myc genes from avian leukosis virus-induced B-cell lymphomas. Neither of these c-myc genes contained missense mutations. This strongly supports the notion that the c-myc proto-oncogene in avian leukosis virus-induced B-cell lymphomas can be oncogenically activated by altered expression of the gene without a change in the primary structure of the gene product.

  13. Absence of missense mutations in activated c-myc genes in avian leukosis virus-induced B-cell lymphomas

    Energy Technology Data Exchange (ETDEWEB)

    Hahn, M.; Hayward, W.S.

    1988-06-01

    The authors determined the nucleotide sequences of two independent DNA clones which contained the activated c-myc genes from avian leukosis virus-induced B-cell lymphomas. Neither of these c-myce genes contained missense mutations. This strongly supports the notion that the c-myc photo-oncogene in avian leukosis virus-induced B-cell lymphomas can be oncogenically activated by altered expression of the gene without a change in the primary structure of the gene product.

  14. R-CHOP with dose-attenuated radiation therapy could induce good prognosis in gastric diffuse large B cell lymphoma

    Directory of Open Access Journals (Sweden)

    Mishima Yuko

    2012-09-01

    Full Text Available Abstract Background The treatment strategy for gastric diffuse large cell lymphoma (DLBCL has not been standardized in such as to the cycles of chemotherapy, dose of radiation, or necessity for the surgery. Although the results of CHOP or R-CHOP treatments have demonstrated the good prognosis, the treatments have been controversial in many cases. Methods We retrospectively analyzed 40 gastric DLBCL patients receiving chemotherapy with or without radiation in our institute. Those in stages II-IV were treated with six cycles of R-CHOP without radiation; for those in stage I, we administered three cycles of R-CHOP with radiation. Results The three-year overall survival (OS and progression-free survival (PFS rates were 95.2 and 91.8%, respectively. Those in stage I obtained 100% of OS. The radiation dose prescribed was 30.6 Gy for CR cases and 39.6 to 40 Gy for PR after chemotherapy. Although survival rates tended to correlate with staging groups or age-adjusted IPI classifications, multivariate statistical analysis did not show clear differences. All 14 patients with initial bleeding were successfully managed without surgery during treatment. Conclusion R-CHOP therapy was very effective for gastric DLBCL. It may be not necessary to use more than 30.6 Gy of radiotherapy in the highly chemo-sensitive cases. Less toxic treatments should be made available to gastric DLBCL patients.

  15. p63 expression confers significantly better survival outcomes in high-risk diffuse large B-cell lymphoma and demonstrates p53-like and p53-independent tumor suppressor function

    DEFF Research Database (Denmark)

    Xu-Monette, Zijun Y; Zhang, Shanxiang; Li, Xin;

    2016-01-01

    The role of p53 family member p63 in oncogenesis is the subject of controversy. Limited research has been done on the clinical implications of p63 expression in diffuse large B-cell lymphoma (DLBCL). In this study, we assessed p63 expression in de novo DLBCL samples (n=795) by immunohistochemistry...... with a pan-p63-monoclonal antibody and correlated it with other clinicopathologic factors and clinical outcomes. p63 expression was observed in 42.5% of DLBCL, did not correlate with p53 levels, but correlated with p21, MDM2, p16INK4A, Ki-67, Bcl-6, IRF4/MUM-1 and CD30 expression, REL gains, and BCL6...... was likely due to the association of p63 expression with high-risk IPI, and potential presence of ∆Np63 isoform in TP63 rearranged patients (a mere speculation). Gene expression profiling suggested that p63 has both overlapping and distinct functions compared with p53, and that p63 and mutated p53...

  16. Induction of B-cell lymphoma by UVB Radiation in p53 Haploinsufficient Mice

    Directory of Open Access Journals (Sweden)

    Ullrich Stephen E

    2011-01-01

    Full Text Available Abstract Background The incidence of non-Hodgkin's lymphoma has increased over recent years. The exact etiology of lymphoma remains unknown. Ultraviolet light exposure has been associated with the development of internal lymphoid malignancies and some reports suggest that it may play a role in the development of lymphoma in humans. Here we describe the characterization and progression of lymphoma in p53 heterozygous mice exposed to UVB irradiation. Methods UVB-irradiated p53+/- mice developed enlargement of the spleen. Isolated spleen cells were transplanted into Rag deficient hosts. The UV-induced tumor cells were analyzed by flow cytometry. The tumor cells were tagged with GFP to study their metastatic potential. SKY and karyotypic analysis were carried out for the detection of chromosomal abnormalities. Functional assays included in vitro class switch recombination assay, immunoglobulin rearrangement assay, as well as cytokine profiling. Results UVB-exposed mice showed enlargement of the spleen and lymph nodes. Cells transplanted into Rag deficient mice developed aggressive tumors that infiltrated the lymph nodes, the spleen and the bone marrow. The tumor cells did not grow in immune competent syngeneic C57Bl/6 mice yet showed a modest growth in UV-irradiated B6 mice. Phenotypic analysis of these tumor cells revealed these cells are positive for B cell markers CD19+, CD5+, B220+, IgM+ and negative for T cell, NK or dendritic cell markers. The UV-induced tumor cells underwent robust in vitro immunoglobulin class switch recombination in response to lipopolysaccharide. Cytogenetic analysis revealed a t(14;19 translocation and trisomy of chromosome 6. These tumor cells secret IL-10, which can promote tumor growth and cause systemic immunosuppression. Conclusion UV-irradiated p53+/- mice developed lymphoid tumors that corresponded to a mature B cell lymphoma. Our results suggest that an indirect mechanism is involved in the development of internal

  17. Induction of B-cell lymphoma by UVB Radiation in p53 Haploinsufficient Mice

    International Nuclear Information System (INIS)

    The incidence of non-Hodgkin's lymphoma has increased over recent years. The exact etiology of lymphoma remains unknown. Ultraviolet light exposure has been associated with the development of internal lymphoid malignancies and some reports suggest that it may play a role in the development of lymphoma in humans. Here we describe the characterization and progression of lymphoma in p53 heterozygous mice exposed to UVB irradiation. UVB-irradiated p53+/- mice developed enlargement of the spleen. Isolated spleen cells were transplanted into Rag deficient hosts. The UV-induced tumor cells were analyzed by flow cytometry. The tumor cells were tagged with GFP to study their metastatic potential. SKY and karyotypic analysis were carried out for the detection of chromosomal abnormalities. Functional assays included in vitro class switch recombination assay, immunoglobulin rearrangement assay, as well as cytokine profiling. UVB-exposed mice showed enlargement of the spleen and lymph nodes. Cells transplanted into Rag deficient mice developed aggressive tumors that infiltrated the lymph nodes, the spleen and the bone marrow. The tumor cells did not grow in immune competent syngeneic C57Bl/6 mice yet showed a modest growth in UV-irradiated B6 mice. Phenotypic analysis of these tumor cells revealed these cells are positive for B cell markers CD19+, CD5+, B220+, IgM+ and negative for T cell, NK or dendritic cell markers. The UV-induced tumor cells underwent robust in vitro immunoglobulin class switch recombination in response to lipopolysaccharide. Cytogenetic analysis revealed a t(14;19) translocation and trisomy of chromosome 6. These tumor cells secret IL-10, which can promote tumor growth and cause systemic immunosuppression. UV-irradiated p53+/- mice developed lymphoid tumors that corresponded to a mature B cell lymphoma. Our results suggest that an indirect mechanism is involved in the development of internal tumors after chronic exposure to UV light. The induction of

  18. Stereotyped patterns of B-cell receptor in splenic marginal zone lymphoma

    KAUST Repository

    Zibellini, S.

    2010-05-29

    Antigen stimulation may be important for splenic marginal zone lymphoma pathogenesis. To address this hypothesis, the occurrence of stereotyped B-cell receptors was investigated in 133 SMZL (26 HCV+) compared with 4,414 HCDR3 sequences from public databases. Sixteen SMZL (12%) showed stereotyped BCR; 7 of 86 (8%) SMZL sequences retrieved from public databases also belonged to stereotyped HCDR3 subsets. Three categories of subsets were identified: i) SMZL-specific subsets (n=5), composed only of 12 SMZL (9 HCV- from our series); ii) Non-Hodgkin\\'s lymphoma-like subsets (n=5), comprising 5 SMZL (4 from our series) clustering with other indolent lymphomas; iii) "CLL-like subsets" (n=6), comprising 6 SMZL (3 from our series) that belonged to known CLL subsets (n=4) or clustered with public CLL sequences. Immunoglobulin 3D modeling of 3 subsets revealed similarities in antigen binding regions not limited to HCDR3. Overall, data suggest that the pathogenesis of splenic marginal zone lymphoma may involve also HCV unrelated epitopes or an antigenic trigger common to other indolent lymphomas. ©2010 Ferrata Storti Foundation.

  19. Efficacy and Tolerability of Anthracycline-Based Therapy in Elderly Patients With Diffuse Large B-Cell Lymphoma

    OpenAIRE

    Davis, Christine C.; Cohen, Jonathon B.; Shah, Katherine S.; Hutcherson, Don A.; Surati, Minal J.; Valla, Kelly; Panjic, Elyse H.; Handler, Caitlin E.; Switchenko, Jeffrey M.; Flowers, Christopher R.

    2014-01-01

    We examined treatment with or without anthracyclines in 72 eldery diffuse large B-cell lymphoma patients (age ≥ 65 years) in a retrospective cohort analysis. Factors leading to treatment without an anthracycline included age and ejection fraction, whereas markers of tolerability were similar between groups. This study highlights the details of anthracycline tolerability in elderly lymphoma patients.

  20. Transient Global Amnesia as the First Clinical Symptom for Malignant B-Cell Lymphoma with Central Nervous System Involvement

    Directory of Open Access Journals (Sweden)

    Atif Zafar

    2015-01-01

    be diagnosed with B-cell lymphoma with central nervous system involvement a few weeks later. This is the first ever case reported in literature with lymphoma presenting as TGA. Literature review and pertinent points regarding high-yield imaging protocol for presumed TGA patients are discussed.

  1. Narcolepsy associated with primary temporal lobe B-cells lymphoma in a HLA DR2 negative subject.

    OpenAIRE

    Onofrj, M; Curatola, L; Ferracci, F; Fulgente, T

    1992-01-01

    Narcolepsy and cataplexy began one year before treatment of a left mid-temporal primary B-cells lymphoma in a HLA DR2 negative man. Treatment with radio therapy and immunosuppression induced regression of the lymphoma and disappearance of narcolepsy and cataplexy.

  2. Combination of cyclophosphamide, rituximab, and intratumoral CpG oligodeoxynucleotide successfully eradicates established B cell lymphoma.

    Science.gov (United States)

    Betting, David J; Hurvitz, Sara A; Steward, Kristopher K; Yamada, Reiko E; Kafi, Kamran; van Rooijen, Nico; Timmerman, John M

    2012-09-01

    Rituximab plus chemotherapy is standard therapy for patients with non-Hodgkin B cell lymphoma, but often complete response or cure is not achieved. Toll-like receptor 9 agonist CpG oligodeoxynucleotides (CpG) can improve antibody-dependent cellular cytotoxicity and adaptive antitumor immune responses. Using a syngeneic murine B cell lymphoma expressing human CD20 (38C13-huCD20), we previously demonstrated that rituximab plus intratumoral CpG, but not systemic CpG, could eradicate up to half of 7-day established 38C13-huCD20 tumors. However, larger 10-day established tumors could not be cured with this regimen. We thus hypothesized that cytoreduction with cyclophosphamide (Cy) before immunotherapy might permit eradication of these more advanced tumor burdens. Pretreatment with Cy resulted in tumor eradication from 83% of animals treated with rituximab/CpG, whereas Cy/CpG or Cy/rituximab treatments only cured 30% or 17%, respectively (P<0.005). Tumor eradication depended on natural killer cells, but not T cells, macrophages, or complement. Only mice treated with Cy/rituximab/CpG partially resisted rechallenge with tumor cells. Foxp3 Treg and CD11bGr1 myeloid suppressor cells persisted within lymphoid organs after therapy, possibly influencing the ability to establish adaptive tumor immunity. In conclusion, cytoreduction with Cy permitted the cure of large, established lymphomas not otherwise responsive to rituximab plus intratumoral CpG immunotherapy. PMID:22892450

  3. The Role of mTOR Inhibitors for the Treatment of B-Cell Lymphomas

    Directory of Open Access Journals (Sweden)

    Pinelopi Argyriou

    2012-01-01

    Full Text Available Despite the fact that the majority of lymphomas initially respond to treatment, many patients relapse and die from disease that is refractory to current regimens. The need for new treatment strategies in lymphomas has led to the investigation and evaluation of novel agents that target cellular pathways. The mammalian target of rapamycin (mTOR is a representative pathway that may be implicated in lymphomagenesis. Rapamycin and especially its derivatives (temsirolimus, everolimus, and deforolimus represent the first described mTOR inhibitors. These agents have shown promising results in the treatment of lymphoid malignancies. On the other hand, new ATP-competitive mTOR inhibitors that provoke a broader inhibition of mTOR activity are in early stages of clinical development. The purpose of this paper is to summarize the existing knowledge about mTOR inhibitors and their use in the treatment of B-cell lymphomas. Relevant issues regarding mTOR biology in general as well as in B-cell lymphoid neoplasms are also discussed in short.

  4. Cutaneous diffuse large B-cell lymphoma of the leg associated with chronic lymphedema.

    Science.gov (United States)

    González-Vela, M Carmen; González-López, Marcos A; Val-Bernal, J Fernando; Fernández-Llaca, Héctor

    2008-02-01

    Development of malignant tumors is a rare but well known complication in chronic lymphedema (CL). We report herein a cutaneous diffuse large B-cell lymphoma of the leg associated with CL. An 89-year-old man presented with multiple cutaneous lesions on his right limb that showed a CL. Dermatological examination disclosed multiple violaceous, firm, slightly infiltrated nodules on the anterior aspect of the leg and the dorsum and sole of the foot. A biopsy of one nodule of the leg disclosed a diffuse large B-cell lymphoma, type of the legs. There was no evidence of lymphadenopathy on computed tomography (CT) scans of the chest, abdomen, and pelvis. A bone marrow aspiration and biopsy showed normal results. The patient was treated with local radiotherapy at a dose of 40 Gy, obtaining a highly significant, almost complete, clinical remission. A literature search identified 11 additional cases of primary cutaneous lymphoma associated with CL. An inadequate lymphatic drainage may make the lymphedematous region an immunologically vulnerable area, predisposing to neoplasia. PMID:18211492

  5. Characterization of genetic lesions in apoptosis-regulating and proliferation control genes in diffuse large B-cell non-Hodgkin′s lymphoma

    Directory of Open Access Journals (Sweden)

    Pervez Shahid

    2009-01-01

    Full Text Available Background : This study was conducted to analyze the frequency, expression patterns, and the impact of individual proteins BCL2, BCL6, and p53 on overall survival (OS in adult, diffuse large B-cell lymphoma (DLBCL patients. BCL2 gene was further investigated for potential alterations at the DNA level and correlated with OS. Materials and Methods : A total of 117 adult well-characterized DLBCL cases were included. The panel of antibodies comprised CD45, CD20, CD79a, CD3, BCL2, BCL6, and p53. PCR was also employed to correlate the events at the DNA level in BCL2. Results : The mean and median ages were 47.74 and 49 with a M:F ratio of 2.07:1. The incidence of BCL2, BCL6, and p53 expression was observed in 64.10%, 37.60%, and 52.13% of cases, respectively. Amplifiable quality DNA was available from 90 cases. BCL2/IGH translocation was found in 35/90 patients (38.88% with 24 cases showing BCL2 (MBR/IGH and 11 cases BCL2 (mcr/IGH translocation. No association between BCL2 overexpression and BCL2 /IGH translocation was seen. Clinical data were available for 52 patients treated by CHOP therapy. It was found that patients with p53 overexpression had decreased overall survival (P = 0.0004 whereas BCL2, BCL6 expression, and BCL2/IGH translocation had no impact on overall survival. Conclusion : Our data suggest that simple p53 protein expression by IHC at the time of diagnosis may help to identify high-risk patients, who may benefit with more aggressive and newer treatments in addition to standard CHOP.

  6. A Primary Testicular Diffuse Large B-cell Lymphoma Belonging to the Germinal Center B-cell-like Group

    OpenAIRE

    Mlika, Mona; Chelly, Ines; Benrhouma, Mohamed; Haouet, Slim; Horchani, Ali; Zitouna, Mohamed Moncef; Kchir, Nidham

    2010-01-01

    Testicular lymphoma was first reported by Malassez and Curling in 1866. Primary testicular lymphoma constitutes only 1 - 7% of all testicular neoplasms and less than 1% of all non Hodgkin lymphoma. The authors report a new case of primary testicular lymphoma and highlight its diagnostic and therapeutic challenge. We report the case of a 26-year old man without a particular past medical history, who presented with a painful right testicular swelling that he has noticed for several weeks. Radio...

  7. A rare cytological diagnosis of primary non-Hodgkin lymphoma of the parotid gland

    Directory of Open Access Journals (Sweden)

    Biswajit Dey

    2016-01-01

    Full Text Available Primary lymphoma of the parotid gland is relatively rare and constitutes about 4-5% of extranodal lymphomas. The majority of them is non-Hodgkin lymphoma (NHL and is B cell in nature. We report a case of primary diffuse large B-cell lymphoma (DLBCL of the parotid gland in an elderly male. The case was diagnosed on fine needle aspiration cytology (FNAC of the right parotid gland as high grade B-cell NHL and confirmed on histopathology as DLBCL. In correlation with the clinicoradiological findings, the case was diagnosed as primary parotid DLBCL. The case highlights the role of FNAC as a timely and useful diagnostic tool.

  8. Absence of annexin I expression in B-cell non-Hodgkin's lymphomas and cell lines

    International Nuclear Information System (INIS)

    Annexin I, one of the 20 members of the annexin family of calcium and phospholipid-binding proteins, has been implicated in diverse biological processes including signal transduction, mediation of apoptosis and immunosuppression. Previous studies have shown increased annexin I expression in pancreatic and breast cancers, while it is absent in prostate and esophageal cancers. Data presented here show that annexin I mRNA and protein are undetectable in 10 out of 12 B-cell lymphoma cell lines examined. Southern blot analysis indicates that the annexin I gene is intact in B-cell lymphoma cell lines. Aberrant methylation was examined as a cause for lack of annexin I expression by treating cells 5-Aza-2-deoxycytidine. Reexpression of annexin I was observed after prolonged treatment with the demethylating agent indicating methylation may be one of the mechanisms of annexin I silencing. Treatment of Raji and OMA-BL-1 cells with lipopolysaccharide, an inflammation inducer, and with hydrogen peroxide, a promoter of oxidative stress, also failed to induce annexin I expression. Annexin I expression was examined in primary lymphoma tissues by immunohistochemistry and presence of annexin I in a subset of normal B-cells and absence of annexin I expression in the lymphoma tissues were observed. These results show that annexin I is expressed in normal B-cells, and its expression is lost in all primary B-cell lymphomas and 10 of 12 B-cell lymphoma cell lines. Our results suggest that, similar to prostate and esophageal cancers, annexin I may be an endogenous suppressor of cancer development, and loss of annexin I may contribute to B-cell lymphoma development

  9. Targeting CD19 in B-cell lymphoma: emerging role of SAR3419

    International Nuclear Information System (INIS)

    Non-Hodgkin lymphoma symbolizes a heterogeneous group of diseases resulting from malignant transformation of lymphocytes with differing patterns of behavior and responses to treatment. The potential curability of non-Hodgkin lymphoma differs among the various histologic subtypes and is associated in part with the stage at presentation. CD19 antigen is a type I transmembrane glycoprotein belonging to the immunoglobulin Ig superfamily. CD19 is specifically expressed in normal and neoplastic B-cells. Recent study showed that in a mouse model, CD19 and c-Myc synergize functionally to accelerate B-cell lymphomagenesis, which is associated with increased disease severity. Specificity is the most important challenge in cancer therapeutics. Antibody–drug conjugates have the prospect of enhancing the therapeutic efficacy over unconjugated monoclonal antibodies through the selective delivery of cytotoxic agents to cancer cells. The ubiquitous expression of CD19 in these tumors, especially at an earlier stage and the property of efficient internalization, makes CD19 an attractive and affective target for antibody–drug conjugate therapy as compared to CD20. SAR3419 (huB4-DM4) is a novel antibody–drug conjugate that is composed of a humanized monoclonal IgG1 anti-CD19 antibody (huB4) attached to the potent cytotoxic drug, a maytansine derivative (DM4), through a cleavable disulfide cross-linking agent N-Succinimidyl-4-2-pyridyldithio butanoic acid (SPDB). The preclinical efficacy of maytansine derivative–anti-CD19 conjugate was demonstrated in our laboratory, and SAR3419 was found to be more effective than CHOP in a xenograft model. Phase I trials have also been conducted on the basis of preclinical studies that demonstrated promising antitumor activity with acceptable safety results in human B-cell lymphoma models. Additional trials are ongoing and will provide additional insight into the full potential of this novel drug

  10. Memory-enriched CAR-T Cells Immunotherapy for B Cell Lymphoma

    Science.gov (United States)

    2016-04-25

    Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Stage III Adult Diffuse Large Cell Lymphoma; Stage III Follicular Lymphoma; Stage III Mantle Cell Lymphoma; Stage IV Adult Diffuse Large Cell Lymphoma; Stage IV Follicular Lymphoma; Stage IV Mantle Cell Lymphoma

  11. Numb Chin Syndrome as First Symptom of Diffuse Large B-Cell Lymphoma

    Directory of Open Access Journals (Sweden)

    Mario Carbone

    2014-01-01

    Full Text Available Numb chin syndrome is a rare sensory neuropathy of the mental nerve characterized by numbness, hypoesthesia, paraesthesia, and very rarely pain. Dental causes, especially iatrogenic ones, maxillofacial trauma, or malignant neoplasm are etiologic factors for this rare syndrome. Many malignant and metastatic neoplasms are causing this syndrome, like primary osteosarcoma, squamous cell carcinoma, and mandibular metastasis of primary carcinoma of breast, lung, thyroid, kidney, prostate, and nasopharynx. Haematological malignancies like acute lymphocytic leukaemia, Hodgkin and non-Hodgkin lymphoma, and myeloma can cause this neuropathy. The authors report a case of a 71-year-old woman in which the numb chin syndrome was the first symptom of the diffuse large B-cell lymphoma, which caused infiltration and reabsorption of the alveolar ridge and lower mandibular cortex. A biopsy of the mass was performed on fragments of tissue collected from the mandibular periosteum, medullary and cortical mandibular bone, and inferior alveolar nerve.

  12. Recent molecular and therapeutic advances in B-cell non-Hodgkin lymphoma in children.

    Science.gov (United States)

    Giulino-Roth, Lisa; Goldman, Stanton

    2016-05-01

    Paediatric B-cell non-Hodgkin lymphoma (B-NHL) compromises a heterogeneous group of histological entities of which Burkitt lymphoma is the most common. In resource-rich countries, the expected cure rate is in excess of 85% with application of risk-adapted short intensive chemotherapy. In recent years, large paediatric cooperative group trials have sought to improve upon outcomes by decreasing the intensity of cytotoxic treatment as well as introducing targeted therapies, such as rituximab. These efforts have resulted in excellent outcomes, however there remains a group of high-risk patients for whom novel treatment approaches are needed. In this review, we will summarize the recent paediatric clinical trials in B-NHL as well as compare treatment approaches across the major cooperative groups. We will also highlight our current understanding of the molecular biology of paediatric B-NHL with a focus on how this may help guide future rational targeted therapy. PMID:26996160

  13. Jaw1/LRMP, a germinal centre-associated marker for the immunohistological study of B-cell lymphomas.

    Science.gov (United States)

    Tedoldi, S; Paterson, J C; Cordell, J; Tan, S-Y; Jones, M; Manek, S; Dei Tos, A P; Roberton, H; Masir, N; Natkunam, Y; Pileri, S A; Facchetti, F; Hansmann, M-L; Mason, D Y; Marafioti, T

    2006-08-01

    Jaw1, also known as lymphoid-restricted membrane protein (LRMP), is an endoplasmic reticulum-associated protein. High levels of Jaw1/LRMP mRNA have been found in germinal centre B-cells and in diffuse large B-cell lymphomas of 'germinal centre' subtype. This paper documents Jaw1/LRMP expression at the protein level in human tissues by immunohistochemical and western blotting analysis using an antibody reactive with paraffin-embedded tissues. Jaw1/LRMP was highly expressed in germinal centre B-cells (in keeping with gene expression data), in 'monocytoid B-cells', and in splenic marginal zone B-cells. It was absent, or present at only low levels, in mature T-cells, although cortical thymocytes were weakly positive. Among lymphoid neoplasms, Jaw1/LRMP was found in germinal centre-derived lymphomas (follicle centre lymphoma, Burkitt's lymphoma, lymphocyte-predominant Hodgkin's disease) but not in T-cell neoplasms (with the exception of a single T lymphoblastic lymphoma). Classical Hodgkin's disease and myeloma lacked Jaw1/LRMP but many cases of chronic lymphocytic leukaemia (but not mantle zone lymphoma) were Jaw1/LRMP-positive. Approximately half of the marginal zone lymphomas were Jaw1/LRMP-positive. In diffuse large B-cell lymphomas, Jaw1/LRMP was found in three-quarters (24/32) of the cases classified phenotypically as being of 'germinal centre' type, but it was also expressed in almost half (13/28) of the 'non-germinal centre' cases. A similar proportion of 'non-germinal centre' cases were positive for the protein products of two other genes expressed highly in germinal centre cells (HGAL/GCET2 and PAG). The fact that all three of these proteins are expressed in a significant proportion of diffuse large B-cell lymphomas assigned to the 'non-germinal centre' category indicates that the immunophenotypic categorization of diffuse large B-cell lymphoma according to cellular origin may be more complicated than currently understood. Finally, the expression of Jaw1/LRMP

  14. Piperlongumine selectively suppresses ABC-DLBCL through inhibition of NF-κB p65 subunit nuclear import

    International Nuclear Information System (INIS)

    Constitutive NF-κB activation is required for survival of activated B cell-like subtype of diffuse large B cell lymphoma (ABC-DLBCL). However, current NF-κB targeting strategies lack cancer cell specificity. Here, we identified a novel inhibitor, piperlongumine, features direct binding to NF-κB p65 subunit and suppression of p65 nuclear import. This was accompanied by NF-κB reporter activity suppression and NF-κB target gene downregulation. Moreover, mutation of Cys38 to Ser in p65 abolished this effect of piperlongumine on inhibition of p65 nuclear import. Furthermore, we show that piperlongumine selectively inhibited proliferation and induced apoptosis of ABC-DLBCL cells. Most notably, it has been reported that piperlongumine did not affect normal cells even at high doses and was nontoxic to animals. Hence, our current study provides new insight into piperlongumine's mechanism of action and novel approach to ABC-DLBCL target therapy. - Highlights: • Current NF-κB targeting strategies lack cancer cell specificity. • Piperlongumine inhibits NF-κB p65 subunit nuclear import via directly binding to p65. • Piperlongumine selectively inhibits proliferation of ABC-DLBCL cells. • This study provides a novel approach to ABC-DLBCL target therapy

  15. Piperlongumine selectively suppresses ABC-DLBCL through inhibition of NF-κB p65 subunit nuclear import

    Energy Technology Data Exchange (ETDEWEB)

    Niu, Mingshan [Blood Diseases Institute, Xuzhou Medical College, Xuzhou, Jiangsu (China); Jiangsu Key Laboratory of Bone Marrow Stem Cell, Xuzhou Medical College, Xuzhou, Jiangsu (China); Department of Hematology, Affiliated Hospital of Xuzhou Medical College, Xuzhou, Jiangsu (China); Shen, Yangling; Xu, Xiaoyu [Blood Diseases Institute, Xuzhou Medical College, Xuzhou, Jiangsu (China); Jiangsu Key Laboratory of Bone Marrow Stem Cell, Xuzhou Medical College, Xuzhou, Jiangsu (China); Yao, Yao; Fu, Chunling [Blood Diseases Institute, Xuzhou Medical College, Xuzhou, Jiangsu (China); Jiangsu Key Laboratory of Bone Marrow Stem Cell, Xuzhou Medical College, Xuzhou, Jiangsu (China); Department of Hematology, Affiliated Hospital of Xuzhou Medical College, Xuzhou, Jiangsu (China); Yan, Zhiling [Department of Hematology, Affiliated Hospital of Xuzhou Medical College, Xuzhou, Jiangsu (China); Wu, Qingyun [Blood Diseases Institute, Xuzhou Medical College, Xuzhou, Jiangsu (China); Jiangsu Key Laboratory of Bone Marrow Stem Cell, Xuzhou Medical College, Xuzhou, Jiangsu (China); Department of Hematology, Affiliated Hospital of Xuzhou Medical College, Xuzhou, Jiangsu (China); Cao, Jiang; Sang, Wei [Department of Hematology, Affiliated Hospital of Xuzhou Medical College, Xuzhou, Jiangsu (China); Zeng, Lingyu [Blood Diseases Institute, Xuzhou Medical College, Xuzhou, Jiangsu (China); Jiangsu Key Laboratory of Bone Marrow Stem Cell, Xuzhou Medical College, Xuzhou, Jiangsu (China); Department of Hematology, Affiliated Hospital of Xuzhou Medical College, Xuzhou, Jiangsu (China); Li, Zhenyu [Department of Hematology, Affiliated Hospital of Xuzhou Medical College, Xuzhou, Jiangsu (China); Liu, Xuejiao, E-mail: liuxuejiao0923@126.com [Insititute of Nervous System Diseases, Xuzhou Medical College, Xuzhou, Jiangsu (China); and others

    2015-07-10

    Constitutive NF-κB activation is required for survival of activated B cell-like subtype of diffuse large B cell lymphoma (ABC-DLBCL). However, current NF-κB targeting strategies lack cancer cell specificity. Here, we identified a novel inhibitor, piperlongumine, features direct binding to NF-κB p65 subunit and suppression of p65 nuclear import. This was accompanied by NF-κB reporter activity suppression and NF-κB target gene downregulation. Moreover, mutation of Cys{sup 38} to Ser in p65 abolished this effect of piperlongumine on inhibition of p65 nuclear import. Furthermore, we show that piperlongumine selectively inhibited proliferation and induced apoptosis of ABC-DLBCL cells. Most notably, it has been reported that piperlongumine did not affect normal cells even at high doses and was nontoxic to animals. Hence, our current study provides new insight into piperlongumine's mechanism of action and novel approach to ABC-DLBCL target therapy. - Highlights: • Current NF-κB targeting strategies lack cancer cell specificity. • Piperlongumine inhibits NF-κB p65 subunit nuclear import via directly binding to p65. • Piperlongumine selectively inhibits proliferation of ABC-DLBCL cells. • This study provides a novel approach to ABC-DLBCL target therapy.

  16. Cystatin C in sera of patients with aggressive non-Hodgkin B-cell lymphoma

    Directory of Open Access Journals (Sweden)

    Adaleta Softić

    2011-02-01

    Full Text Available Aim To investigate the cystatin C levels in sera of patients with aggressive non-Hodgkin B-cell lymphoma. Methods The levels of cystatin C in sera of lymphoma patients and control group consisted of healthy individuals, were measured by using speciic sandwich-type ELISA. For each patient the clinical stage of disease was determined according to Ann Arbor staging system for lymphomas. Results Our study shows that mean cystatin C serum level in the patients group (1056 ± 65 ng/mL was signiicantly higher when compared with the mean level of the healthy control group (819 ± 28 ng/mL (P=0,001. Mean cystatin C level of the group with clinical stages III and IV (1255 ± 109 ng/mL was signiicantly elevated when compared with the mean level of the group with clinical stages I and II (896 ± 51 ng/mL (P=0,03. Conclusion This inding points out a connection between inhibitor level and aggressive behaviour of lymphoma and could be considered for further strategies of prognosis of the disease.

  17. Mda-7/IL-24 enhances sensitivity of B cell lymphoma to chemotherapy drugs.

    Science.gov (United States)

    Ma, Ming; Zhao, Lianmei; Sun, Guogui; Zhang, Chao; Liu, Lihua; Du, Yanyan; Yang, Xingxiao; Shan, Baoen

    2016-05-01

    Interleukin-24 (IL-24) is a cytokine encoded by a tumor suppressor gene of the IL-10 family, also known as the melanoma differentiation associated gene-7 (Mda-7) and first discovered in human melanoma cells. Mda-7/IL-24 has been shown to inhibit the proliferation of various human tumor cell lines, but its effect on the sensitivity of B cell lymphoma to chemotherapy agents is not yet clear. The present study investigated the effects of Mda-7/IL-24 overexpression on the sensitivity of human B cell lymphoma cells to chemotherapy, as well as its mechanism of action. The sensitivity of stable Mda-7/IL-24 overexpressing Raji and Daudi cells to cis-diamminedichloroplatinum (CDDP), epirubicin and vinblastine (VCR) were assessed by the MTS method, and the IC50 value calculated. Cell apoptosis and the intracellular accumulation of Rhodamine-123 were assayed by flow cytometry. The expression of multidrug resistance gene 1 (MDR1), B-cell-specific Moloney murine leukemia virus insertion site 1 (BMI1), topoisomerase II (Topo II) and multidrug resistance-related protein 1 (MRP1) mRNA and protein were analyzed by reverse transcription quantitative polymerase chain reaction (RT-qPCR) and western blotting, respectively. In addition, western blot analysis was also used to investigate the effect of Mda-7/IL-24 on activity of GTP-RhoA-ERK signaling pathway in Raji and Daudi cells. Growth inhibition and apoptosis rates of Mda-7/IL-24 overexpressing Raji and Daudi cells were higher than those of non-transfected cells and cells transfected with vector alone when treated with CDDP, epirubicin and VCR. The IC50 values of CDDP, epirubicin and VCR were lower for Mda-7/IL-24-overexpressing Raji and Daudi cells than for non-transfected cells and cells transfected with empty vector. Intracellular accumulation of Rhodamine-123 and the expression of Topo II were higher, while the levels of MDR1, BMI and MRP1 mRNA and protein were lower, in Mda-7/IL-24 overexpressing Raji and Daudi cells

  18. Ocular adnexal marginal zone B cell lymphoma infiltrated by IgG4-positive plasma cells

    OpenAIRE

    KUBOTA, TOSHINOBU; Moritani, Suzuko; Yoshino, Tadashi; Nagai, Hirokazu; Terasaki, Hiroko

    2010-01-01

    Aims To report the clinicopathological characteristics of patients with ocular adnexal marginal zone B cell lymphoma (MZBL) with IgG4-positive plasma cells. Methods 114 biopsy samples of ocular adnexal MZBLs were analysed. MZBLs with IgG4-positive plasma cells were included when the IgG4:IgG ratio was >40% (IgG4-related group). The serum levels of each subclass of immunoglobulins and soluble interleukin-2 receptor in the IgG4-related group were compared with those in 61 consecutive patients h...

  19. CCR 20th anniversary commentary: Radioactive Drones for B-cell lymphoma.

    Science.gov (United States)

    Knox, Susan J; Levy, Ronald

    2015-02-01

    In a study published in the March 1, 1996, issue of Clinical Cancer Research, Knox and colleagues (1) demonstrated the safety and efficacy of Yttirium-90 ((90)Y)-anti-CD20 monoclonal antibody therapy, as well as the benefit of preinfusion of unlabeled antibody on radiolabeled antibody biodistribution. Subsequent clinical trials with this radiolabeled antibody led to regulatory approval of this treatment for B-cell lymphoma. See related article by Knox et al., Clin Cancer Res 1996;2(3) Mar 1996; 457-70. PMID:25646179

  20. Implementation and importance of fluorescence in situ hybridization (fish) in paraffin tissues for categorization of B-cell lymphoma unclassifiable, with features intermediate between Burkitt lymphoma and diffuse large B-cell lymphoma

    International Nuclear Information System (INIS)

    The diagnostic criteria have been defined based on the tools that the country has acquired and international guidelines for pure entities: the LB, LDCGB, and the new entity of B lymphoma unclassifiable with features intermediate LDCGB and LB. The fluorescence in situ hybridization for the translocation (8;14) has been implemented in paraffin tissues for proper categorization. A total of 21 cases have been studied: the characteristics of patients, morphology, immunohistochemistry and the presence or absence of the translocation (8;14). Twelve of the cases have been classified as B-cell lymphoma unclassifiable with features intermediate between LDCGB and LB. Furthermore, nine of the cases were classified in LB. Fluorescence in situ hybridization (FISH) has been negative in 5 of the 21 cases. The diagnosis of lymphoma with features bordering between the LB and the LDCGB has been imperative for the survival of the patient and the corresponding treatment

  1. The Effect of FcγRIIIA Gene Polymorphism on the Treatment of Diffuse Large B-cell Non-Hodgkin Lymphoma: A Multicenter Prospective Observational Study

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    Nurhilal Büyükkurt

    2015-06-01

    Full Text Available INTRODUCTION: The curative treatment approach for diffuse large B-cell lymphoma (DLBCL is controversial even in the rituximab (R era. The aim of this study was to examine the FcγRIIIA gene polymorphism distribution of DLBCL patients who had been treated with R-CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone chemotherapy. Furthermore, we investigated the impact of FcγRIIIA gene polymorphism on the overall response rate (ORR and overall survival (OS. METHODS: Patients from 3 centers in the Aegean region of Turkey who had newly diagnosed CD20-positive DLBCL were enrolled in the study. The single nucleotide polymorphisms of the FcγRIIIA gene were analyzed by real time-PCR. The response to treatment was determined in the middle and at the end of the protocol. During 2 years of follow-up, the patients were clinically and radiologically evaluated for disease status every 3 months. RESULTS: Thirty-six patients were included in the study and the distributions of F/F, V/F, and V/V types of alleles of FcγRIIIA were 25%, 50%, and 25%, respectively. Twenty-seven patients were considered as evaluable according to ORR and OS. The patients’ ORR was 87.5%, 100%, and 50% in the F/F, V/F, and V/V allele groups, respectively. We did not establish any statistically significant differences among the 3 alleles groups in respect to ORR (p=0.93. The OS within 2 years in the F/F, V/F, and V/V allele groups was 62.5%, 100%, and 100%, respectively. The OS in the F/F allele group was found to be lower than in the other 2 allele groups (p=0.01. DISCUSSION AND CONCLUSION: The distribution of gene polymorphisms in our study group was similar to those of previous studies. While ORR was similar between the groups, our results highlight a lower OS in F/F patients ompared to other allele groups of FcγRIIIA.

  2. FDG PET/CT for the detection of bone marrow involvement in diffuse large B-cell lymphoma: systematic review and meta-analysis

    International Nuclear Information System (INIS)

    To systematically review and meta-analyse published data on the diagnostic performance of 18F-FDG PET/CT in detecting bone marrow involvement in patients with newly diagnosed diffuse large B-cell lymphoma (DLBCL). PubMed/MEDLINE and Embase were systematically searched for relevant studies. The methodological quality of each study was assessed. Sensitivities and specificities of FDG PET/CT in individual studies were calculated and meta-analysed with a random effects model. A summary receiver operating characteristic curve (sROC) was constructed with the Moses-Shapiro-Littenberg method. Weighted summary proportions of discrepancies between the FDG PET/CT and (blind) bone marrow biopsy (BMB) results among all patients were calculated. Seven studies, with a total of 654 patients with newly diagnosed DLBCL, were included. Overall, the quality of the included studies was moderate. The sensitivity and specificity of FDG PET/CT for detecting bone marrow involvement ranged from 70.8 % to 95.8 % and from 99.0 % to 100 %, with pooled estimates of 88.7 % (95 % confidence interval, CI, 82.5 - 93.3 %) and 99.8 % (95 % CI 98.8 - 100 %), respectively. The area under the sROC curve was 0.9983. The weighted summary proportion of FDG PET/CT-negative patients with positive BMB findings among all patients was 3.1 % (95 % CI 1.8 - 5.0 %) and the weighted summary proportion of FDG PET/CT-positive patients with negative BMB findings among all patients was 12.5 % (95 % CI 8.4 - 17.3 %). FDG PET/CT is accurate and complementary to BMB for detecting bone marrow involvement in patients with newly diagnosed DLBCL. A negative FDG PET/CT scan cannot rule out the presence of bone marrow involvement, but positive FDG PET/CT findings obviate the need for BMB for the detection of bone marrow involvement in these patients. (orig.)

  3. Epstein-Barr virus positive B-cell lymphoproliferative disorder/polymorphous B-cell lymphoma of the urinary bladder: A case report with review of literature

    OpenAIRE

    Sundaram, Sandhya; Zhang, Kai

    2009-01-01

    We report an unusual case of a localized Epstein-Barr virus (EBV)-positive B cell lymphoproliferative disorder (LPD)/polymorphous B cell lymphoma of the urinary bladder in a 67 years old female patient. She had no known predisposing immunodeficiencies and presented with recent onset of hematuria. The CT and cystoscopic examination revealed a localized 2.5 cm polypoid or plaque-like mucosal mass on the right posterior and lateral wall of the bladder. The biopsy sample showed a diffuse and dens...

  4. Pediatric Burkitt’s Lymphoma and Diffuse B cell Lymphoma: Are Surveillance Scans Required?

    OpenAIRE

    Eissa, HM; Allen, CE; Kamdar, K; Simko, S; Dreyer, Z.; Steuber, P; McClain, KL; Guillerman, RP; Bollard, Catherine M.

    2013-01-01

    Outcomes in pediatric B-Non-Hodgkin Lymphoma have improved with intensive chemotherapy protocols, with long-term survival now over 80%. However, long-term adverse effects of therapy and poor outcomes for patients who relapse remain challenges. In this study, we aimed to evaluate the potential risks and benefits of routine relapse surveillance imaging after the completion of therapy. We reviewed 44 B NHL patients diagnosed and treated at Texas Children’s Cancer Center in the period between 200...

  5. Glomerulonephritis associated with marginal zone B-cell lymphoma: clinical, pathological characteristics of renal injury and treatment (clinical cases

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    B. T. Dzhumabaeva

    2015-12-01

    Full Text Available Glomerulonephritis associated with marginal zone B-cell lymphoma at the onset of disease is rarely diagnosed. In this article we reported two patient of the extranodal marginal zone B-cell lymphoma with kidney damage. The first patient with the extranodal marginal zone B-cell lymphoma involved the stomach, lymph nodes, bone marrow and associated with mesangioproliferative glomerulonephritis and renal failure. The second patient with the splenic form of marginal zone B-cell lymphoma associated with fibrillary glomerulonephritis and hepatitis C and involve the lymph nodes, liver, bone marrow, and synthesis monoclonal immunoglobulin (IgMκ, cryoglobulin type II. Glomerulonephritis of the both cases were established on the renal biopsies by the morphological investigation, immunofluorescence, and electron microscopy.Both patients received therapy with bendamustine and rituximab, which has resulted in complete remission for lymphatic tumors and improve of kidney function. Overall and event-free survival in the first case corresponds to 21 and 16 months, the second 29 and 20, respectively.These cases illustrates that the kidney may be initially involved by extranodal marginal zone B-cell lymphoma, and the need for expanded investigation of the possible dissemination. Combination of bendamustine and rituximab were effective and safety treatment in these cases.

  6. GNA13 loss in germinal center B cells leads to impaired apoptosis and promotes lymphoma in vivo.

    Science.gov (United States)

    Healy, Jane A; Nugent, Adrienne; Rempel, Rachel E; Moffitt, Andrea B; Davis, Nicholas S; Jiang, Xiaoyu; Shingleton, Jennifer R; Zhang, Jenny; Love, Cassandra; Datta, Jyotishka; McKinney, Matthew E; Tzeng, Tiffany J; Wettschureck, Nina; Offermanns, Stefan; Walzer, Katelyn A; Chi, Jen-Tsan; Rasheed, Suhail A K; Casey, Patrick J; Lossos, Izidore S; Dave, Sandeep S

    2016-06-01

    GNA13 is the most frequently mutated gene in germinal center (GC)-derived B-cell lymphomas, including nearly a quarter of Burkitt lymphoma and GC-derived diffuse large B-cell lymphoma. These mutations occur in a pattern consistent with loss of function. We have modeled the GNA13-deficient state exclusively in GC B cells by crossing the Gna13 conditional knockout mouse strain with the GC-specific AID-Cre transgenic strain. AID-Cre(+) GNA13-deficient mice demonstrate disordered GC architecture and dark zone/light zone distribution in vivo, and demonstrate altered migration behavior, decreased levels of filamentous actin, and attenuated RhoA activity in vitro. We also found that GNA13-deficient mice have increased numbers of GC B cells that display impaired caspase-mediated cell death and increased frequency of somatic hypermutation in the immunoglobulin VH locus. Lastly, GNA13 deficiency, combined with conditional MYC transgene expression in mouse GC B cells, promotes lymphomagenesis. Thus, GNA13 loss is associated with GC B-cell persistence, in which impaired apoptosis and ongoing somatic hypermutation may lead to an increased risk of lymphoma development. PMID:26989201

  7. Immunotherapy for B-cell lymphoma: current status and prospective advances.

    Science.gov (United States)

    Hollander, Nurit

    2012-01-01

    Therapy for non-Hodgkin's lymphoma has progressed significantly over the last decades. However, the majority of patients remain incurable, and novel therapies are needed. Because immunotherapy ideally offers target selectivity, an ever increasing number of immunotherapies, both passive and active, are undergoing development. The champion of passive immunotherapy to date is the anti-CD20 monoclonal antibody rituximab that revolutionized the standard of care for lymphoma. The great success of rituximab catalyzed the development of new passive immunotherapy strategies that are currently undergoing clinical evaluation. These include improvement of rituximab efficacy, newer generation anti-CD20 antibodies, drug-conjugated and radio labeled anti-CD20 antibodies, monoclonal antibodies targeting non-CD20 lymphoma antigens, and bispecific antibodies. Active immunotherapy aims at inducing long-lasting antitumor immunity, thereby limiting the likelihood of relapse. Current clinical studies of active immunotherapy for lymphoma consist largely of vaccination and immune checkpoint blockade. A variety of protein- and cell-based vaccines are being tested in ongoing clinical studies. Recently completed phase III clinical trials of an idiotype protein vaccine suggest that the vaccine may have clinical activity in a subset of patients. Efforts to enhance the efficacy of active immunotherapy are ongoing with an emphasis on optimization of antigen delivery and presentation of vaccines and modulation of the immune system toward counteracting immunosuppression, using antibodies against immune regulatory checkpoints. This article discusses results of the various immunotherapy approaches applied to date for B-cell lymphoma and the ongoing trials to improve their effect. PMID:22566889

  8. Immunotherapy for B-cell lymphoma: current status and prospective advances

    Directory of Open Access Journals (Sweden)

    Nurit eHollander

    2012-01-01

    Full Text Available Therapy for non-Hodgkin's lymphoma has progressed significantly over the last decades. However, the majority of patients remain incurable, and novel therapies are needed. Because immunotherapy ideally offers target selectivity, an ever increasing number of immunotherapies, both passive and active, are undergoing development. The champion of passive immunotherapy to date is the anti-CD20 monoclonal antibody rituximab that revolutionized the standard of care for lymphoma. The great success of rituximab catalyzed the development of new passive immunotherapy strategies that are currently undergoing clinical evaluation. These include improvement of rituximab efficacy, newer generation anti-CD20 antibodies, drug-conjugated and radiolabelled anti-CD20 antibodies, monoclonal antibodies targeting non-CD20 lymphoma antigens, and bispecific antibodies. Active immunotherapy aims at inducing long-lasting antitumor immunity, thereby limiting the likelihood of relapse. Current clinical studies of active immunotherapy for lymphoma consist largely of vaccination and immune checkpoint blockade. A variety of protein- and cell-based vaccines are being tested in ongoing clinical studies. Recently completed phase III clinical trials of an idiotype protein vaccine suggest that the vaccine may have clinical activity in a subset of patients. Efforts to enhance the efficacy of active immunotherapy are ongoing with an emphasis on optimization of antigen delivery and presentation of vaccines and modulation of the immune system toward counteracting immunosuppression, using antibodies against immune regulatory checkpoints. This article discusses results of the various immunotherapy approaches applied to date for B-cell lymphoma and the ongoing trials to improve their effect.

  9. Intravascular Large B Cell Lymphoma as a Rare Cause of Reversed Halo Sign: A Case Report.

    Science.gov (United States)

    Peng, Min; Shi, Juhong; Liu, Hongrui; Li, Guangxi

    2016-03-01

    Intravascular large B cell lymphoma (IVLBCL) is a rare type of extranodal diffused large B-cell lymphoma. IVLBCL with primary lung lesion is very rare and it is very difficult to diagnose. Radiographic findings of pulmonary IVLBCL are nonspecific and resembling interstitial lung diseases. Reversed halo sign (RHS) was initially reported in patients diagnosed with cryptogenic organizing pneumonia and then described in a variety of diseases with inflammatory, infectious, autoimmune, and malignant causes. This is the first case of IVLBCL that has presented with RHSs on CT scan.A 59-year-old Chinese man presented with a 4-month history of a nonproductive cough and a weight loss of 5 kg. Physical examination was unremarkable. High-resolution computed tomography scan of the chest showed bilateral patchy ground glass opacities (GGOs) and RHSs. Laboratory tests were unremarkable except elevated serum lactate dehydrogenase (LDH). Surgical lung biopsy was performed. Light microscopic examination of the specimen disclosed diffuse alveolar septal widening caused by neoplastic lymphocytes, which were positive for CD20 and infiltrated in the alveolar capillaries. The patient was diagnosed with IVLBCL and underwent chemotherapy and autologous blood stem cell transplantation. The patient is still alive 5 years after diagnosis.IVLBCL is a rare cause of RHS and should be considered in differential diagnosis of RHS. An increased serum LDH concentration is another important clue. PMID:27015192

  10. Carfilzomib, Rituximab, and Combination Chemotherapy in Treating Patients With Diffuse Large B-Cell Lymphoma

    Science.gov (United States)

    2016-05-10

    Contiguous Stage II Adult Diffuse Large Cell Lymphoma; Noncontiguous Stage II Adult Diffuse Large Cell Lymphoma; Stage I Adult Diffuse Large Cell Lymphoma; Stage III Adult Diffuse Large Cell Lymphoma; Stage IV Adult Diffuse Large Cell Lymphoma

  11. Whole-Body Diffusion-weighted Imaging in Hodgkin Lymphoma and Diffuse Large B-Cell Lymphoma.

    Science.gov (United States)

    Toledano-Massiah, Sarah; Luciani, Alain; Itti, Emmanuel; Zerbib, Pierre; Vignaud, Alexandre; Belhadj, Karim; Baranes, Laurence; Haioun, Corinne; Lin, Chieh; Rahmouni, Alain

    2015-01-01

    Whole-body imaging, in particular molecular imaging with fluorine 18 ((18)F)-fluorodeoxyglucose (FDG) positron emission tomography (PET), is essential to management of lymphoma. The assessment of disease extent provided by use of whole-body imaging is mandatory for planning appropriate treatment and determining patient prognosis. Assessment of treatment response allows clinicians to tailor the treatment strategy during therapy if necessary and to document complete remission at the end of treatment. Because of rapid technical developments, such as echo-planar sequences, parallel imaging, multichannel phased-array surface coils, respiratory gating, and moving examination tables, whole-body diffusion-weighted (DW) magnetic resonance (MR) imaging that reflects cell density is now feasible in routine clinical practice. Whole-body DW MR imaging allows anatomic assessment as well as functional and quantitative evaluation of tumor sites by calculation of the apparent diffusion coefficient (ADC). Because of their high cellularity and high nucleus-to-cytoplasm ratio, lymphomatous lesions have low ADC values and appear hypointense on ADC maps. As a result, whole-body DW MR imaging with ADC mapping has become a promising tool for lymphoma staging and treatment response assessment. The authors review their 4 years of experience with 1.5-T and 3-T whole-body DW MR imaging used with (18)F-FDG PET/computed tomography at baseline, interim, and end of treatment in patients with Hodgkin lymphoma and diffuse large B-cell lymphoma and discuss the spectrum of imaging findings and potential pitfalls, limitations, and challenges associated with whole-body DW MR imaging in these patients. PMID:25815803

  12. Bone marrow infiltration of CD20-negative follicular lymphoma after rituximab therapy: a histological mimicker of hematogones and B-cell acute lymphoblastic leukemia/lymphoma

    Science.gov (United States)

    Matsuda, Ikuo; Hirota, Seiichi

    2015-01-01

    Rituximab is a monoclonal antibody against CD20. Rituximab combined with CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) chemotherapy, termed R-CHOP, have improved the overall survival of patients with B-cell lymphoma in comparison with that of CHOP therapy. However, as with other molecularly-targeted therapies, resistance to rituximab could emerge sooner or later after rituximab administration. A number of mechanisms for rituximab resistance have been proposed, including downregulation of CD20 protein expression. Differential diagnosis of B-cell proliferation with reduced or lost CD20 expression includes not only B-cell lymphomas with CD20 downregulation, but also other tumorous and non-tumorous lesions. These include precursor B-cell neoplasms such as B acute lymphoblastic leukemia/lymphoblastic lymphoma (B-ALL/LBL) and hematogones, a normal precursor B-cell proliferation during regeneration of hematopoiesis, typically observed following bone marrow suppression by chemotherapy. It is important to distinguish these possibilities because distinct therapies are required for each. In this paper, we report a case where bone marrow infiltration of follicular lymphoma histopathologically mimicked hematogones or B-ALL/LBL when CD20 expression was downregulated in follicular lymphoma after R-CHOP therapy. PMID:26464748

  13. Regulation of normal B-cell differentiation and malignant B-cell survival by OCT2.

    Science.gov (United States)

    Hodson, Daniel J; Shaffer, Arthur L; Xiao, Wenming; Wright, George W; Schmitz, Roland; Phelan, James D; Yang, Yandan; Webster, Daniel E; Rui, Lixin; Kohlhammer, Holger; Nakagawa, Masao; Waldmann, Thomas A; Staudt, Louis M

    2016-04-01

    The requirement for the B-cell transcription factor OCT2 (octamer-binding protein 2, encoded by Pou2f2) in germinal center B cells has proved controversial. Here, we report that germinal center B cells are formed normally after depletion of OCT2 in a conditional knockout mouse, but their proliferation is reduced and in vivo differentiation to antibody-secreting plasma cells is blocked. This finding led us to examine the role of OCT2 in germinal center-derived lymphomas. shRNA knockdown showed that almost all diffuse large B-cell lymphoma (DLBCL) cell lines are addicted to the expression of OCT2 and its coactivator OCA-B. Genome-wide chromatin immunoprecipitation (ChIP) analysis and gene-expression profiling revealed the broad transcriptional program regulated by OCT2 that includes the expression of STAT3, IL-10, ELL2, XBP1, MYC, TERT, and ADA. Importantly, genetic alteration of OCT2 is not a requirement for cellular addiction in DLBCL. However, we detected amplifications of the POU2F2 locus in DLBCL tumor biopsies and a recurrent mutation of threonine 223 in the DNA-binding domain of OCT2. This neomorphic mutation subtly alters the DNA-binding preference of OCT2, leading to the transactivation of noncanonical target genes including HIF1a and FCRL3 Finally, by introducing mutations designed to disrupt the OCT2-OCA-B interface, we reveal a requirement for this protein-protein interface that ultimately might be exploited therapeutically. Our findings, combined with the predominantly B-cell-restricted expression of OCT2 and the absence of a systemic phenotype in our knockout mice, suggest that an OCT2-targeted therapeutic strategy would be efficacious in both major subtypes of DLBCL while avoiding systemic toxicity. PMID:26993806

  14. Hypernatremia associated with intracranial B-cell lymphoma in a cat.

    Science.gov (United States)

    Morrison, Jo Ann; Fales-Williams, Amanda

    2006-09-01

    An 8-year-old, spayed female, domestic shorthair cat with a history of hyperthyroidism, anorexia, dehydration, cervical ventroflexion, and behavioral changes was referred to the Iowa State University College of Veterinary Medicine. The cat was obtunded, with severe dehydration (15%) and hypothermia (86 degrees F), and severe muscle atrophy and fasciculations. Serum biochemical abnormalities included severe hypernatremia (195 mmol/L, reference interval 155-165 mmol/L), hyperchloridemia (161 mmol/L, reference interval 123-131 mmol/L), and hypokalemia (3.6 mmol/L, reference interval 4.0-5.7 mmol/L). Calculated osmolality was 418 mOsm/kg (reference interval 280-305 mOsm/kg), attributable to the hypernatremia. The cat was kept warm and given fluid and glucocorticoid therapy and supportive measures but remained unresponsive. Hypernatremia and hyperosmolality improved through day 3, when the cat died suddenly. At necropsy, a 1.25-cm mass was found in the area of the thalamus and interthalamic adhesion that extended to the ventral aspect of the cerebrum. The histologic and immunohistochemical diagnosis was B-cell lymphoma. Hypernatremia and hyperosmolality in this cat were attributed to primary adipsia and hypothalamic dysfunction secondary to effacement of central nervous system tissue by neoplastic lymphocytes. To the authors' knowledge, this is the first reported case of central nervous system lymphoma, confirmed by use of immunohistochemical analysis as a B-cell phenotype, associated with hypernatremia. It also is the first reported case of lymphoma in animals limited to the thalamus, hypothalamus, and cerebrum, with no involvement of the spinal cord. PMID:16967428

  15. Secondary infiltration of the central nervous system in patients with diffuse large B-cell lymphoma

    Directory of Open Access Journals (Sweden)

    Talita Maira Bueno da Silveira da Rocha

    2013-01-01

    Full Text Available OBJECTIVE: To investigate the incidence and risk factors of infiltration of the central nervous system after the initial treatment of diffuse large B-cell lymphoma in patients treated at Santa Casa de Misericórdia de São Paulo. METHODS: A total of 133 patients treated for diffuse large B-cell lymphoma from January 2001 to April 2008 were retrospectively analyzed in respect to the incidence and risk factors of secondary central nervous system involvement of lymphoma. Intrathecal prophylaxis was not a standard procedure for patients considered to be at risk. This analysis includes patients whether they received rituximab as first-line treatment or not. RESULTS: Nine of 133 (6.7% patients developed central nervous system disease after a mean observation time of 29 months. The median time to relapse or progression was 7.9 months after diagnosis and all but one patient died despite the treatment administered. Twenty-six (19.5% patients of this cohort received rituximab as first-line treatment and nine (7.1% received intrathecal chemoprophylaxis. Of the nine patients that relapsed, seven (77.7% had parenchymal central nervous system involvement; seven (77.7% had stage III or IV disease; one (11.1% had bone marrow involvement; two (22.2% had received intrathecal chemoprophylaxis; and 3 (33.3% had taken rituximab. In a multivariate analysis, the risk factors for this infiltration were being male, previous use of intrathecal chemotherapy and patients that were refractory to initial treatment. CONCLUSION: Central nervous system infiltration in this cohort is similar to that of previous reports in the literature. As this was a small cohort with a rare event, only three risk factors were important for this infiltration

  16. Functional role of regulatory T cells in B cell lymphoma and related mechanisms.

    Science.gov (United States)

    Wu, Wei; Wan, Jun; Xia, Ruixiang; Huang, Zhenqi; Ni, Jing; Yang, Mingzhen

    2015-01-01

    B cell lymphoma (BCL) has a higher degree of malignancy and complicated pathogenic mechanism. Regulatory T cells (Treg cells) are known to exert certain immune suppression functions, in addition to immune mediating effects. Recent studies have revealed the role of Treg cells in pathogenesis and progression of multiple malignant tumors. This study therefore investigated the functional role and related mechanism of Treg cells in BCL. A cohort of thirty patients who were diagnosed with BCL in our hospital between January 2013 and December 2014. Another thirty healthy individuals were recruited. Peripheral blood mononuclear cells (PBMCs) were separated and analyzed for the ratio of CD4+/CD25+ Treg cells. The mRNA expression levels of Foxp3, transforming growth factor (TGF)-β1 and interleukin (IL)-10 genes were quantified by real-time PCR, while their serum levels were determined by enzyme-linked immunosorbent assay (ELISA). Meanwhile all laboratory indexes for patients were monitored during the complete remission (CR) stage. BCL patients significantly elevated ratio of CD4+/CD25+ Treg cells, which were decreased at CR stage. mRNA levels of Foxp3, TGF-β1 and IL-10, in addition to protein levels of TGF-β1 and IL-10 were potentiated in lymphoma patients but decreased in CR patients (Pregulating cytokines, thereby facilitating the pathogenesis and progression of lymphoma. PMID:26464657

  17. Primary pediatric gastrointestinal lymphoma

    Directory of Open Access Journals (Sweden)

    Ranjana Bandyopadhyay

    2011-01-01

    Full Text Available Background: Primary non-Hodgkin′s lymphoma (NHL of the gastrointestinal (GI tract is the most common extranodal lymphoma in pediatric age group. Yet, the overall incidence is very low. The rarity of the disease as well as variable clinical presentation prevents early detection when the possibility of cure exists. Materials and Methods: We studied six cases of primary GI NHL in pediatric age group with reference to their clinical presentation, anatomic distribution and histopathologic characteristics. Results: All were males except one. Intestinal obstruction was the presenting feature in 50%. Half the cases showed ileocaecal involvement, while large bowel was involved in 16%. Histology showed four cases of diffuse large B-cell lymphoma (DLBCL, one case of Burkitt lymphoma, and one Burkitt-like lymphoma. Immunohistochemistry for Tdt, CD20, CD3, CD30, bcl2, bcl6 confirmed the morphological diagnosis. Conclusion: Pediatric GI lymphoma commonly involves the ileocaecal region and presents with intestinal obstruction. A higher prevalence of DLBCL is found compared to other series. A high proliferative index is useful in differentiating Burkitt-like lymphoma from DLBCL.

  18. Gemcitabine and treatment of diffuse large B-cell lymphoma in relapsed or refractory elderly patients: A prospective randomized trial in Algeria

    Directory of Open Access Journals (Sweden)

    Aribi Mourad

    2010-01-01

    Full Text Available Context: Support for non-Hodgkin′s lymphoma (NHL with large cells that is refractory or relapsed after first-line chemotherapy poses a greater therapeutic problem with bone marrow transplant therapy or when old age is a contra-indication for high-dose chemotherapy, especially among developing countries such as Algeria. Aim: To show that the regimen, including gemcitabine, could be more effective in treating elderly patients with diffuse large B-cell lymphoma (DLBCL in relapse / refractory, without complete remission, when compared with the ESHAP (etoposide, cisplatine, solumedrol, aracytine regimen. Materials and Methods: Ninety-six patients in the age group of 60-70 years were volunteers for a prospective randomized single-blind study, carried out for three years. Patients were divided into two groups by the drawing of lots. The first group (GA, n = 48, relapse; n = 27 [56.3%], refractory; n = 21 [43.7%] received treatment with ESHAP protocol and the second one (GB, n = 48, relapse; n = 28 [58%], refractory; n = 20 [42%] with GPD (gemcitabine, dexamethasone, cisplatine protocol. Results: The overall response rates and mean survival at three years were significantly higher among patients subjected to GPD treatment compared with those subjected to ESHAP treatment (63% vs. 55%, P = 0.01 and 20.5% [95% CI 16.5-24.5] vs. 11.8% [8.9-14.6], respectively. Additionally, three-year progression-free and event-free survival rates were 20.5% (16.3-24 and 19.7% (15.9-23.5, respectively, for the GPD regimen and 10.9% (8.2-13.7 and 11.1% (95% CI 8.5-13.7, respectively, for the ESHAP regimen. Moreover, the GPD regimen was associated with improving overall survival (RR=2.02, 95% CI 1.59-2.56; P = 0.000, event-free survival (2.03, 1.64-2.52; P < 0.001 and progression-free survival (1.86, 1.46-2.37; P < 0.001. Conclusion: In cases of contra-indication for high-dose chemotherapy for elderly patients with DLBCL, without complete remission, the Gemcitabine

  19. MYC protein expression and genetic alterations have prognostic impact in diffuse large B-cell lymphoma treated with immunochemotherapy

    OpenAIRE

    Valera Barros, Alexandra; López Guillermo, Armando; Cardesa Salzmann, Antonio; Climent, Fina; González Barca, Eva; Mercadal, Santiago; Espinosa, Iñigo; Novelli, Silvana; Briones, Javier; Mate, José L.; Salamero, Olga; Sancho, Juan M.; Arenillas, Leonor; Serrano, Sergi; Erill, Nadina

    2013-01-01

    MYC alterations influence the survival of patients with diffuse large B-cell lymphoma. Most studies have focused on MYC translocations but there is little information regarding the impact of numerical alterations and protein expression. We analyzed the genetic alterations and protein expression of MYC, BCL2, BCL6, and MALT1 in 219 cases of diffuse large B-cell lymphoma. MYC rearrangement occurred as the sole abnormality (MYC single-hit) in 3% of cases, MYC and concurrent BCL2 and/or BCL6 rear...

  20. Primary cutaneous large B-cell lymphoma, leg type: Report of two cases and review of literature

    Directory of Open Access Journals (Sweden)

    Santosh Kumar Mondal

    2012-01-01

    Full Text Available Primary cutaneous large B-cell lymphoma, leg type (PCLBCL-LT, is very rare neoplasm presenting on and confined to leg(s. PCLBCL-LT is distinguished from other type of primary cutaneous B-cell lymphoma (PCBCL by its frequent relapses and poorer prognosis. We report, two cases of PCLBCL-LT, occurring in two younger patients compared to published cases in literature. Both the patients were treated with chemotherapy and local radiotherapy. During the 1-year follow-up period one patient presented with extracutaneous dissemination and succumbed. The other patient is symptom free and follow-up period was uneventful.

  1. RAV-1 insertional mutagenesis: disruption of the c-myb locus and development of avian B-cell lymphomas.

    OpenAIRE

    Pizer, E; Humphries, E H

    1989-01-01

    Infection of young chickens with RAV-1, a subgroup A isolate of avian leukosis virus, results in the development of lymphoid leukosis, a B-cell lymphoma characterized by provirus insertion into the c-myc locus. We report here that when 12- to 13-day-old embryos rather than 1-day-old chickens were infected with RAV-1, a novel B-cell lymphoma developed in which proviral insertions had activated expression of the c-myb gene. These tumors expressed elevated levels of a 4.5-kilobase myb-containing...

  2. Spontaneous Remission of Epstein-Barr Virus-Positive Diffuse Large B-Cell Lymphoma of the Elderly

    OpenAIRE

    Mizuno, T; Ishigaki, M.; K. Nakajima; Matsue, T; Fukushima, M.; Minato, H.; Nojima, N.; Atsushi, Saito; Ishigami, K; Atsumi, H.; Ito, T.; Iguchi, M.; Usuda, D.; Okamura, H; Urashima, S.

    2013-01-01

    A 94-year-old female patient presented with anorexia and left axillar lymphadenopathy on admission. Her past history was angina pectoris at 83 years of age and total gastrectomy due to gastric cancer at 87 years. The family history revealed that her son had had a malignant lymphoma, the histopathological diagnosis of which was diffuse large B-cell lymphoma. A physical examination showed both cervical, axillar, and inguinal lymphadenopathy without tenderness. She had elevated lactate dehydroge...

  3. Expression of MHC class II antigens in human B-cell leukaemia and non-Hodgkin's lymphoma.

    OpenAIRE

    Guy, K.; Krajewski, A S; Dewar, A E

    1986-01-01

    In this review we have summarized our experiences of serological analysis of MHC class II antigen expression in human B cell malignant disease. Cells from a large number of cases of B-cell chronic lymphocytic leukaemia (CLL) and non-Hodgkin's lymphoma (NHL) have been examined for expression of class II antigens. Using a number of monoclonal antibodies which in some cases are specific for class II subregion products (DP, DQ and DR), MHC class II antigens were detected by indirect immunofluores...

  4. A novel missense (M206K STAT3 mutation in diffuse large B cell lymphoma deregulates STAT3 signaling.

    Directory of Open Access Journals (Sweden)

    Guangzhen Hu

    Full Text Available Persistent STAT3 activation has been found in activated B-cell like diffuse large B cell tumors (DLBCL. To investigate whether genetic mutations play a role in aberrant STAT3 signaling in DLBCL, we bi-directionally sequenced all 24 exons of the STAT3 gene in DLBCL tumors (n = 40. We identified 2 novel point mutations in 2 separate (2/40; 5% patients at exon 7 and 24. Point mutation 2552G>A was a silent mutation in the stop codon. Another heterozygous mutation 857T>A encoded a methionine substitution by lysine at codon 206 (M206K in the coiled-coil domain of STAT3. We performed site directed mutagenesis to mutate wild type (WT STAT3α and STAT3β at codon 206 and constructed stable cell lines by lentiviral transfection of STAT3α(WT, STAT3α(M206K, STAT3β(WT and STAT3β(M206K plasmids. The mutation was found to increase STAT3 phosphorylation in STAT3α mutant cell lines with no effect on the STAT3β mutant cell line. Transcriptional activation was also increased in the STAT3α mutant cells compared with STAT3α WT cells as detected by a luciferase reporter assay. Moreover, STAT3α(M206K mutant cells were resistant to JAK2 pathway inhibition compared to STAT3α WT cells. These results indicate that missense mutations in STAT3 increase signaling through the JAK/STAT pathway. JAK2 inhibitors may be useful in the patient with this STAT3 mutation as well as those with pathway activation by other mechanisms.

  5. Lymphocyte cytosolic protein 1 regulates proliferation of diffuse large B-cell lymphoma cells%淋巴细胞溶质蛋白1调控弥漫性大B细胞淋巴瘤细胞的增殖初探

    Institute of Scientific and Technical Information of China (English)

    张竹红; 田亚平

    2013-01-01

    Objective To study the biological significance of lymphocyte cytosolic protein 1 (LCP1) expression in diffuse large B-cell lymphoma (DLBCL) cells and its effect on proliferation of DLBCL cells. Methods Expression of LCP1 in healthy human B lymphoblastoid cells and various DLBCL cells was detected by Western blot. Over-expressed LCP1 was silenced in DLBCL cell line OCI-LY19. Vitality of the cells was tested with a CCK8 kit. Effect of LCP1 on cell cycle of OCI-LY19 cells was observed with PI staining. Results The expression level of LCP1 was significantly higher in DLBCL cells than in healthy human B lymphoblastoid cells. The vitality of OCI-LY19 cells decreased and the progressive cell sycle of OCI-LY19 cells was inhibited after LCP1 was silenced. Conclusion LCP1 is closely related with the proliferation of DLBCL cells and is an important biological marker for DLBCL.%目的:探索弥漫性大B细胞淋巴瘤中淋巴细胞溶质蛋白1(lymphocyte cytosolic protein 1,LCP1)表达的生物学意义及对细胞增殖的影响。方法用Wstern Blot的方法观察LCP1在正常人B淋巴母细胞系和多种弥漫性大B细胞淋巴瘤细胞系中的表达情况;进而在高表达LCP1的弥漫性大B细胞淋巴瘤(diffuse large B-cell lymphom,DLBCL)细胞系OCI-LY19中将其沉默,使用CCK8试剂盒检测其对细胞活力的影响;并用PI染色的方法检测LCP1对OCI-LY19细胞的细胞周期的影响。结果 LCP1在DLBCL细胞中的表达量明显高于正常人B淋巴母细胞系,沉默LCP1后发现OCI-LY19细胞活力下降,且细胞周期进展明显被抑制。结论 LCP1与DLBCL细胞增殖密切相关,提示其是一个重要DLBCL生物标记。

  6. 儿童散发性伯基特淋巴瘤的研究进展%Research evolution of children with sporadic Burkitt' s lymphoma

    Institute of Scientific and Technical Information of China (English)

    徐红艳

    2012-01-01

    Children with sporadic Burkitt's lymphoma (BL) is a highly aggressive lymphoma.It partly overlaps with diffuse large B cell lymphoma (DLBCL) and unclassified B cell lymphoma (DLBCL/BL) which is between DLBCL and BL in the morphological,immunophenotypic and molecular genetic aspects,but it has its unique.characterization. Enhancing awareness of the disease based on the BL pathology, pathogenesis and prognosis of understanding,at the time of diagnosis and identificate with DLBCL and DLBCL/BL at the tine of diagnosis will be beneficial to clinical correct treatment and prognosis.%儿童散发性伯基特淋巴瘤(BL)属于高度侵袭性淋巴瘤,在形态学、免疫表型和分子遗传学等方面与弥漫性大B细胞淋巴瘤( DLBCL)及介于DLBCL和BL之间的未分类B细胞淋巴瘤( DLBCL/BL)有部分重叠,但亦有其独特的表征.通过对BL病理、发病机制及预后的了解,增强对该病的认识,并在诊断时与DLBCL、DLBCL/BL进行鉴别,有利于临床正确的治疗及预后判断.

  7. SEOM clinical guidelines for the treatment of diffuse large B-cell lymphoma.

    Science.gov (United States)

    Gómez Codina, José; Sabín Domínguez, Pilar; Provencio Pulla, Mariano; Rueda Domínguez, Antonio; Isla Casado, Dolores

    2010-11-01

    Diffuse large B-cell non-Hodgkin's lymphoma (LDCGB) is one of the best examples of chemotherapy curable malignant diseases. This "Oncoguía SEOM" summarizes the basic directions of staging and recommended treatment options. The staging study should be thorough and includes clinical, laboratory, diagnostic imaging and nuclear medicine. Treatment depends on patient characteristics and comorbidity and on disease extension and prognostic factors. In localized cases, chemoimmunotherapy (CHOP-R) of short duration, followed by involved-field irradiation is the preferred option. In advanced stages, the association of CHOP-like chemotherapy and Rituximab has been a major breakthrough in terms of cure rate. It is important do not forget the supportive treatment in these patients. PMID:20974570

  8. Inhibition of geranylgeranylation mediates sensitivity to CHOP-induced cell death of DLBCL cell lines

    International Nuclear Information System (INIS)

    Prenylation is a post-translational hydrophobic modification of proteins, important for their membrane localization and biological function. The use of inhibitors of prenylation has proven to be a useful tool in the activation of apoptotic pathways in tumor cell lines. Rab geranylgeranyl transferase (Rab GGT) is responsible for the prenylation of the Rab family. Overexpression of Rab GGTbeta has been identified in CHOP refractory diffuse large B cell lymphoma (DLBCL). Using a cell line-based model for CHOP resistant DLBCL, we show that treatment with simvastatin, which inhibits protein farnesylation and geranylgeranylation, sensitizes DLBCL cells to cytotoxic treatment. Treatment with the farnesyl transferase inhibitor FTI-277 or the geranylgeranyl transferase I inhibitor GGTI-298 indicates that the reduction in cell viability was restricted to inhibition of geranylgeranylation. In addition, treatment with BMS1, a combined inhibitor of farnesyl transferase and Rab GGT, resulted in a high cytostatic effect in WSU-NHL cells, demonstrated by reduced cell viability and decreased proliferation. Co-treatment of BMS1 or GGTI-298 with CHOP showed synergistic effects with regard to markers of apoptosis. We propose that inhibition of protein geranylgeranylation together with conventional cytostatic therapy is a potential novel strategy for treating patients with CHOP refractory DLBCL.

  9. Inhibition of geranylgeranylation mediates sensitivity to CHOP-induced cell death of DLBCL cell lines

    Energy Technology Data Exchange (ETDEWEB)

    Ageberg, Malin, E-mail: Malin.Ageberg@med.lu.se [Division of Hematology and Transfusion Medicine, Lund University, BMC C14, 221 84 Lund (Sweden); Rydstroem, Karin, E-mail: Karin.Rydstom@skane.se [Department of Oncology, Skanes University Hospital, Allmaenmott, Onkologiska kliniken i Lund, 221 85 Lund (Sweden); Linden, Ola, E-mail: Ola.Linden@skane.se [Department of Oncology, Skanes University Hospital, Allmaenmott, Onkologiska kliniken i Lund, 221 85 Lund (Sweden); Linderoth, Johan, E-mail: Johan.Linderoth@skane.se [Department of Oncology, Skanes University Hospital, Allmaenmott, Onkologiska kliniken i Lund, 221 85 Lund (Sweden); Jerkeman, Mats, E-mail: Mats.Jerkeman@skane.se [Department of Oncology, Skanes University Hospital, Allmaenmott, Onkologiska kliniken i Lund, 221 85 Lund (Sweden); Drott, Kristina, E-mail: Kristina.Drott@med.lu.se [Division of Hematology and Transfusion Medicine, Lund University, BMC C14, 221 84 Lund (Sweden)

    2011-05-01

    Prenylation is a post-translational hydrophobic modification of proteins, important for their membrane localization and biological function. The use of inhibitors of prenylation has proven to be a useful tool in the activation of apoptotic pathways in tumor cell lines. Rab geranylgeranyl transferase (Rab GGT) is responsible for the prenylation of the Rab family. Overexpression of Rab GGTbeta has been identified in CHOP refractory diffuse large B cell lymphoma (DLBCL). Using a cell line-based model for CHOP resistant DLBCL, we show that treatment with simvastatin, which inhibits protein farnesylation and geranylgeranylation, sensitizes DLBCL cells to cytotoxic treatment. Treatment with the farnesyl transferase inhibitor FTI-277 or the geranylgeranyl transferase I inhibitor GGTI-298 indicates that the reduction in cell viability was restricted to inhibition of geranylgeranylation. In addition, treatment with BMS1, a combined inhibitor of farnesyl transferase and Rab GGT, resulted in a high cytostatic effect in WSU-NHL cells, demonstrated by reduced cell viability and decreased proliferation. Co-treatment of BMS1 or GGTI-298 with CHOP showed synergistic effects with regard to markers of apoptosis. We propose that inhibition of protein geranylgeranylation together with conventional cytostatic therapy is a potential novel strategy for treating patients with CHOP refractory DLBCL.

  10. Analysis of local control in patients with non-Hodgkin's lymphoma according to the WHO classification

    Energy Technology Data Exchange (ETDEWEB)

    Sakata, K.; Someya, M.; Nagakura, H.; Oouchi, A.; Nakata, K.; Koito, K.; Hareyama, M. [Dept. of Radiology, Sapporo Medical Univ., School of Medicine, Sapporo (Japan); Satoh, M. [Dept. of Clinical Pathology, Sapporo Medical Univ., School of Medicine, Sapporo (Japan); Kogawa, K. [Dept. of Fourth Internal Medicine, Sapporo Medical Univ., School of Medicine, Sapporo (Japan); Himi, T. [Dept. of Otorhinolaryngology, Sapporo Medical Univ., School of Medicine, Sapporo (Japan)

    2005-06-01

    Purpose: to analyze the influence of radiotherapy doses, chemotherapy doses, and clinical parameters on in-field disease control to assess the optimal radiation doses for treatment of non-Hodgkin's lymphoma according to the newly proposed WHO classification. Patients and methods: subjects consisted of 35 extranodal marginal-zone B-cell lymphomas of mucosa-associated lymphoid tissue (MALT) type, 75 diffuse large B-cell lymphomas (DLBCL), 14 follicular lymphomas, 17 extranodal natural killer (NK)/T-cell lymphomas, nasal type, eight unclassified peripheral T-cell lymphomas, four anaplastic large-cell lymphomas, T/null cell type, and five others. 59 patients received radiotherapy alone. 98 patients received CHOP, modified CHOP, or more intensive chemotherapy, and six patients were treated with other combination. Results: no patients with MALT lymphoma had in-field local recurrence. There were no recurrences in DLBCL patients who received chemotherapy in which the doses of adriamycin were > 200 mg/m{sup 2}, nor in DLBCL patients who were treated with > 45 Gy. Only nine of 15 patients with T-cell lymphoma treated with {<=} 50 Gy and three of five patients treated with > 50 Gy had local control. The dose of adriamycin had no influence on local control of T-cell lymphoma. Conclusion: T/NK-cell lymphomas were more radioresistant than B-cell lymphomas. The prognosis for peripheral T/NK-cell lymphomas is poor even when treated by irradiation combined with chemotherapy. (orig.)

  11. Intravascular large B-cell lymphoma of the kidney: A case report

    Directory of Open Access Journals (Sweden)

    Jia Nan

    2011-09-01

    Full Text Available Abstract We report a 41-year-old Chinese woman with intravascular large B-cell lymphoma diagnosed by percutaneous renal biopsy. The patient was admitted to Nanfang Hospital of Southern Medical University, Guangzhou, China with complaints of high spiking fever for a month and bilateral lower limb fatigue with difficulty ambulating for the past 5 months. She had renal dysfunction with a total urinary protein of 5.61 g/dL (56.1 g/L, serum albumin of 2.89 g/dL (28.9 g/L, urea nitrogen of 2.24 mg/dL (1.6 mmol/L, and serum creatinine of 0.54 mg/dL (48 μmol/L. Bone marrow biopsy revealed myeloproliferative disorder without abnormal myeloid or lymphocytic proliferation. Positron Emission Tomography-Computed Tomography (PET-CT showed marked bilateral swelling and enlargement of the renal parenchyma with splenic enlargement and involvement of multiple vertebrae. Percutaneous renal biopsy showed island-like accumulations of medium to large lymphoid cells in many areas of the interstitium, with round vesicular nuclei containing distinct basophilic nucleoli. Immunohistochemical analysis together with other supportive investigation confirmed the diagnosis of intravascular large B-cell lymphoma. Ten days later, she was started on chemotherapy with CHOP (cyclophosphamide, doxorubicin, leurocristime and prednisone for a week. Palliative radiotherapy DT 40Gy/20F with other supportive treatment was provided for metastatic foci in the medullary cavity of the sternum, T1-T7. The patient regained muscle strength in both lower limbs and was able to walk again after three weeks. The patient was discharged after hepatic and renal function and proteinuria values had returned to normal. Follow-up data shows the patient to be alive nine months after discharge.

  12. Specific expression of miR-17-5p and miR-127 in testicular and central nervous system diffuse large B-cell lymphoma

    NARCIS (Netherlands)

    Robertus, Jan-Lukas; Harms, Geert; Blokzijl, Tjasso; Booman, Marije; de Jong, Daphne; van Imhoff, Gustaaf; Rosati, Stefano; Schuuring, Ed; Kluin, Philip; van den Berg, Anke

    2009-01-01

    Recent studies have shown that certain non-coding short RNAs, called miRNAs, play an important role in diffuse large B-cell lymphomas. Patients with diffuse large B-cell lymphoma have great diversity in both clinical characteristics, site of presentation and outcome. The aim of our study is to valid

  13. Diffuse Large B-cell Lymphoma in Adults (Beyond the Basics)

    Science.gov (United States)

    ... DLBCL is fatal if left untreated, but with timely and appropriate treatment, approximately 70 percent of all ... 8.0 Print Options: Text References Graphics Contributor Disclosures All topics are updated as new information becomes ...

  14. Pediatric Burkitt's lymphoma and diffuse B-cell lymphoma: are surveillance scans required?

    Science.gov (United States)

    Eissa, H M; Allen, C E; Kamdar, K; Simko, S; Goradia, P; Dreyer, Z; Steuber, P; McClain, K L; Guillerman, R P; Bollard, Catherine M

    2014-04-01

    Outcomes in pediatric B-Non-Hodgkin Lymphoma (B NHL) have improved with intensive chemotherapy protocols, with long-term survival now over 80%. However, long-term adverse effects of therapy and poor outcomes for patients who relapse remain challenges. In this study, we aimed to evaluate the potential risks and benefits of routine relapse surveillance imaging after the completion of therapy. We reviewed 44 B NHL patients diagnosed and treated at Texas Children's Cancer Center in the period between 2000 to 2011. All cross-sectional diagnostic imaging examinations performed for disease assessment after completion of chemotherapy were reviewed and cumulative radiation dosage from these examinations and the frequency of relapse detection by these examinations were recorded. Only 3 patients of the 44 relapsed (6.8%), though none of the relapses were initially diagnosed by computed tomography (CT) or fludeoxyglucose positron emission tomography (FDG-PET) scans. Median effective dose of ionizing radiation per patient was 40.3 mSv with an average of 49.1 mSv (range 0-276 mSv). This single-institution study highlights the low relapse rate in pediatric B-NHL with complete response at the end of therapy, the low sensitivity of early detection of relapse with surveillance CT or FDG-PET imaging, and the costs and potential increased risk of secondary malignancies from cumulative radiation exposure from surveillance imaging. We propose that routine surveillance CT or FDG-PET scans for these patients may not be necessary. PMID:24087880

  15. TNF Polymorphisms Independently Predict Outcome in Patients with B-Cell Non-Hodgkin’s Lymphoma

    Directory of Open Access Journals (Sweden)

    Osman NF

    2009-02-01

    Full Text Available Objectives: Tumour Necrosis Factor α (TNFα and Lymphotoxin α (LTα have been implicated in the pathogenesis of lymphoproliferative disorders. Patients with B-cell non-Hodgkin’s lymphoma (NHL often have high serum levels of TNF which may be associated with a poor outcome. TNFα and LTα polymorphisms are known to influence expression of these cytokines and may explain the variable response to therapy. Patients and Methods: In patients with NHL, serum levels of TNFα and LTα were measured. DNA was typed using allele specific PCR and restriction fragment length polymorphism for the –308 TNFα and +252 LTα polymorphisms and comparison was made with clinical outcome. Results: The presence of high producing alleles was significantly associated with high serum levels of TNFα and LTα. The presence of 2 or more high producing alleles was significantly associated with more advanced disease at presentation (stage III and IV, p=0.024, a higher International Prognostic Index (IPI score, p=0.038, failure to achieve a complete remission (CR after 1st line therapy (88% vs 33%, p=0.01 and shorter progression free survival (PFS (median 24 months compared with 78 months, p=0.001. Multivariate analysis confirmed that TNF highrisk haplotype (HRH was an independent prognostic factor for PFS. Conclusions: These results demonstrate that TNF polymorphisms are independent prognostic factors in NHL. Further study is required to further define the importance of TNF polymorphisms within different lymphoma subtypes and with different therapeutic approaches.

  16. [Recent advances in the understanding and treatment of diffuse large B-cell lymphoma].

    Science.gov (United States)

    Gergely, Lajos; Illés, Árpád

    2016-07-01

    Diffuse large B-cell lymphoma is the most common type of non-Hodgkin's lymphoma. Using the conventional cyclophosphamide adriablastin vincristin prednisolon polychemotherapy about 50% of the patients were cured. The addition of rituximab to the regimen increased the cure rate to 60%. This is a major improvement, however, further advance is still needed to increase the cure rate. The extensive genetic testing performed recently revealed several important pathognomic mutations as potential targets in this disease. Routine diagnosis of patients now includes the use of (18)Fluor-deoxy-glucose positron emission computer tomography, according to the recent Lugano classification system. With all these data we can better predict the prognosis of patients, and we can select candidates for novel targeted therapies as well. Answering these questions, and utilizing novel therapies possibly will further increase the cure rate in the near future. This paper summarizes current diagnostic and therapeutic approaches and describes recent understanding in the mutations and pathognomic changes resulting in the disease. The authors also summarize the data available on experimental therapies possibly entering clinical pratice in the forthcoming years. Orv. Hetil., 2016, 157(31), 1232-1241. PMID:27476519

  17. Peritoneal fluid immunocytochemistry used for the diagnosis of a possible case of equine gastrointestinal B-cell lymphoma.

    Science.gov (United States)

    Duran, Maria Carolina; Starrak, Gregory; Dickinson, Ryan; Montgomery, Julia

    2016-06-01

    After physical examination, ultrasonographic evaluation of thorax and abdomen, and peritoneal fluid analysis, gastrointestinal neoplasia with suspected diffuse peritoneal metastasis was diagnosed in a 17-year-old Arabian gelding. The owner elected euthanasia and declined postmortem examination. Immunocytochemistry analysis of the peritoneal fluid resulted in a diagnosis of B-cell lymphoma. PMID:27247458

  18. Data Mining on Survival Prediction after Chemotherapy for Diffuse Large-B-Cell Lymphoma and Genomics of Metastasis Cancer

    Directory of Open Access Journals (Sweden)

    Shen Lu

    2014-12-01

    Full Text Available This research pertains to the applications of data mining of microarray databases for large-B-cell Lymphoma and metastasis cancer, the latter of which little has been known about the genomic events that regulate the transformation of a tumor into a metastatic phenotype.

  19. Biotherapy of relapsed/refractory diffuse large B-cell lymphoma%难治性/复发性弥漫大B细胞淋巴瘤的生物治疗

    Institute of Scientific and Technical Information of China (English)

    史丽君

    2013-01-01

    尽管弥漫大B细胞淋巴瘤(diffuse large B-cell lymphoma,DLBCL)患者的总体预后有所改善,但仍有大约三分之一患者属于难治性/复发性DLBCL,这是导致其发病率和病死率增加的主要原因.临床上治疗难治性/复发性DLBCL的方法仍以大剂量化疗以及对无并发症的患者进行大剂量化疗-自体干细胞移植(high-dose chemotherapy-autologous stem cell transplant,HD-ASCT)为主.但对于给予利妥昔单抗联合CHOP化疗(rituximab-CHOP,R-CHOP)治疗后无反应的难治性DLBCL患者进行HD-ASCT,预后极差.因此,如何提高难治性/复发性DLBCL患者总生存期成了新的研究热点.本文主要从治疗方面对难治性/复发性DLBCL进行综述.

  20. Double-hit and double-protein-expression lymphomas: aggressive and refractory lymphomas.

    Science.gov (United States)

    Sarkozy, Clémentine; Traverse-Glehen, Alexandra; Coiffier, Bertrand

    2015-11-01

    Double-hit lymphoma (DHL) is a subgroup of aggressive lymphomas with both MYC and BCL2 gene rearrangements, characterised by a rapidly progressing clinical course that is refractory to aggressive treatment and short survival. Over time, the definition was modified and now includes diffuse large B-cell lymphoma (DLBCL) with MYC translocation combined with an additional translocation involving BCL2 or BCL6. Some cases that have a similar clinical course with concomitant overexpression of MYC or BCL2 proteins were recently characterised as immunohistochemical double-hit lymphomas (ie, double-protein-expression lymphomas [DPLs]). The clinical course of these DPLs is worse than so-called standard DLBCL but suggested by some studies to be slightly better than DHL, although there is overlap between the two categories. Present treatment does not allow cure or long-term survival in patients with genetic or immunohistochemical double-hit lymphomas, but several new drugs are being developed. PMID:26545844

  1. Chronic Inflammation-Related Diffuse Large B-Cell Lymphoma Around the Area of Thoracotomy After Decortication

    Directory of Open Access Journals (Sweden)

    Bayram Metin

    2014-06-01

    Full Text Available Chest wall tumors consist 5% of all tumors in the thorax. Lymphomas compose of less than 5% of all primary chest wall malignancy.Sixty three years old patient who had an operation for pleural thickness two years ago admitted with complaint of left-sided chest pain.Following the detection of mass lesion radiologically at the place of previous operation area, the patient was operated based on needle biopsy result suggesting Ewing /PNET or pulmonary originated tumor. After the operation, pathological examination confirmed chronic inflammation-related diffuse large B-cell lymphoma. Since it has been rarely reported in the literature, we aimed to present the case of chronic inflammation-related diffuse large B-cell lymphoma developed within such a short time as two years on the ground of surgical incision scar tissue together with our radiologic, surgical, and pathological findings.

  2. Double-Hit Lymphoma Presenting as Primary Renal Lymphoma: A Case Report

    Directory of Open Access Journals (Sweden)

    Vikas Mehta

    2013-04-01

    Full Text Available B-cell lymphomas with concurrent IGH-BCL2 and MYC rearrangements, also known as “double hit” lymphomas (DHL, are rare neoplasms characterized by highly aggressive clinical behavior, complex karyotypes, and a spectrum of pathological features overlapping with Burkitt lymphoma (BL and diffuse large B-cell lymphoma (DLBCL. Primary renal lymphoma (PRL by definition is a renal lymphoma without evidence of systemic involvement. PRL is extremely rare with less than 100 cases of both Hodgkin disease and non-Hodgkin lymphoma reported in literature. Double hit lymphomas have extremely poor prognosis, and high resistance to intensive chemotherapy, including high-dose chemotherapy. We describe a very rare case of DHL arising in kidney as PRL in whom concurrent IGH-BCL2 and MYC rearrangements were detected. [J Interdiscipl Histopathol 2013; 1(2.000: 93-97

  3. Results of bone marrow examination in 275 patients with histological features that suggest an indolent type of cutaneous B-cell lymphoma

    NARCIS (Netherlands)

    Senff, Nancy J.; Kluin-Nelemans, Hanneke C.; Willemze, Rein

    2008-01-01

    Whether or not bone marrow biopsies should be performed routinely in patients with skin lesions that show histological features consistent with an indolent B-cell lymphoma [marginal zone lymphoma (MZL) or follicle centre lymphoma (FCL)] has been debated. As no studies have addressed this question fo

  4. Precursor B-Cell Lymphoblastic Lymphoma (PBLL) in Children: Pattern of Presentation and Outcome

    International Nuclear Information System (INIS)

    B-cell lymphoblastic lymphoma (PBLL) is a rare subtype of NHL seen primarily in children or young adults. There are approximately 100 immunophenotyped cases of PBLL; reported in the literature; most as single case reports or very small series. In this report, we describe patterns of presentation, and results of a retrospective study looking at patients with PBLL treated at KFSH and RC between 1993 and 2000. Patients and Methods: We present results of a retrospective study looking at patients with PBLL treated at KFSHRC between 1993 and 2000, younger than 14 years of age (cut-off age for pediatric department). Six cases of PBLL were lacking evidence of blood and bone marrow involvement. Histologic sections were available for review in all cases. Twenty one patients were treated for lymphoblastic lymphoma, of which six had a precursor B cell phenotype. There were three boys and the median age at diagnosis was 6 years (range 3-13). In four of the patients the primary involved were oro-nasopharynx or the paranasal sinuses. One patient had a soft tissue mass in the upper thigh while one patient had a solitary bone lesion in the distal tibia. Four of the patients had limited stage disease (2 stage I and stage 11), while 2 were stage IV. Both patients with stage IV disease had CNS involvement with blasts in the CSF. Both had paranasal primaries and had bone infiltration involving the base of the skull, with radiological documentation of intracranial extension in one patient. Median LDH level was 542 lU/L (range 463-5000). Five patients were treated according to B-cell NHL type protocols. Because of the specific diagnosis of PBLL, two of these patients were switched to an ALL-type protocol following post induction intensification; one died in remission due to encephalitis, while the other remained in CR almost 2 years after diagnosis. A third patient suffered a loco-regional relapse 17 months after completing first line therapy, and was re-treated on an ALL-type protocol

  5. Monoclonal B-cell hyperplasia and leukocyte imbalance precede development of B-cell malignancies in uracil-DNA glycosylase deficient mice

    DEFF Research Database (Denmark)

    Andersen, Sonja; Ericsson, Madelene; Dai, Hong Yan;

    2005-01-01

    Ung-deficient mice have reduced class switch recombination, skewed somatic hypermutation, lymphatic hyperplasia and a 22-fold increased risk of developing B-cell lymphomas. We find that lymphomas are of follicular (FL) and diffuse large B-cell type (DLBCL). All FLs and 75% of the DLBCLs were...... interleukin 2 is clearly different in wild type and in Ung-deficient mice. This suggests that Ung-proteins, directly or indirectly, have important functions in the immune system, not only in the process of antibody maturation, but also for production and functions of immunologically important cell types. The...

  6. The NF-κB subunit c-Rel regulates Bach2 tumour suppressor expression in B-cell lymphoma.

    Science.gov (United States)

    Hunter, J E; Butterworth, J A; Zhao, B; Sellier, H; Campbell, K J; Thomas, H D; Bacon, C M; Cockell, S J; Gewurz, B E; Perkins, N D

    2016-06-30

    The REL gene, encoding the NF-κB subunit c-Rel, is frequently amplified in B-cell lymphoma and functions as a tumour-promoting transcription factor. Here we report the surprising result that c-rel-/- mice display significantly earlier lymphomagenesis in the c-Myc driven, Eμ-Myc model of B-cell lymphoma. c-Rel loss also led to earlier onset of disease in a separate TCL1-Tg-driven lymphoma model. Tumour reimplantation experiments indicated that this is an effect intrinsic to the Eμ-Myc lymphoma cells but, counterintuitively, c-rel-/- Eμ-Myc lymphoma cells were more sensitive to apoptotic stimuli. To learn more about why loss of c-Rel led to earlier onset of disease, microarray gene expression analysis was performed on B cells from 4-week-old, wild-type and c-rel-/- Eμ-Myc mice. Extensive changes in gene expression were not seen at this age, but among those transcripts significantly downregulated by the loss of c-Rel was the B-cell tumour suppressor BTB and CNC homology 2 (Bach2). Quantitative PCR and western blot analysis confirmed loss of Bach2 in c-Rel mutant Eμ-Myc tumours at both 4 weeks and the terminal stages of disease. Moreover, Bach2 expression was also downregulated in c-rel-/- TCL1-Tg mice and RelA Thr505Ala mutant Eμ-Myc mice. Analysis of wild-type Eμ-Myc mice demonstrated that the population expressing low levels of Bach2 exhibited the earlier onset of lymphoma seen in c-rel-/- mice. Confirming the relevance of these findings to human disease, analysis of chromatin immunoprecipitation sequencing data revealed that Bach2 is a c-Rel and NF-κB target gene in transformed human B cells, whereas treatment of Burkitt's lymphoma cells with inhibitors of the NF-κB/IκB kinase pathway or deletion of c-Rel or RelA resulted in loss of Bach2 expression. These data reveal a surprising tumour suppressor role for c-Rel in lymphoma development explained by regulation of Bach2 expression, underlining the context-dependent complexity of NF-κB signalling in

  7. Radioimmunotherapy in refractory b-cell nonhodgkins lymphoma with I-131-labeled chimeric anti cd-20 c2b8 (I-131 rituximab): preliminary result

    Energy Technology Data Exchange (ETDEWEB)

    Kang, Hye Jin; Park, Yeon Hee; Kim, Sung Eun and others [Korea University Medical School, Seoul (Korea, Republic of)

    2005-07-01

    Recently, the native chimeric human-mouse anti CD-20 antibody IDEC-C2B8 (Rituximab) has been widely applied in NHL. This ongoing phase study was to evaluate whether radioimmunotherapy (RIT) with I-131 rituximab is effective in refractory B-cell NHL. Inclusion criteria were as follows: B-cell NHL with relapsed or refractory to primary standard therapy, measurable disease, adequate hematologic, renal, and hepatic function, informed consent. The rituximab (Mabthera, Roach) was radiolabeled with iodine-131(I-131) using a modified chloramine T method with high radiochemical purity (95%) and preservation of immuno-reactivity. All patients received loading doses of unlabeled rituximab (median, 40 mg: range, 20{approx}70 mg) immediately prior to administration of therapeutic dose (51.4{approx}152.2 MBq/kg), and then underwent gamma camera scan. 11 patients were enrolled (4 low-grade B-cell NHL, 7 DLBCL, median age 63 years). Patients had received a median of three prior chemotherapy regimens. The objective response rate was 36.4% (1 CR, 3 PRs). These all responses were observed in low-grade B-cell NHL, except one with DLBCL. Adverse events were primarily hematologic toxicities; the incidence of grade 3/4 neutropenia, thrombocytopenia, and anemia was 27.3%, 45.5%, and 18.2%, respectively. The treatment-related mortality was observed in one patient, who had been previously treated with high-dose chemotherapy plus TBI with autologous stem cell transplantation. RIT with I-131 rituximab seems to be effective tolerable in refractory low-grade B-cell NHL, although modest activity in refractory DLBCL. Further studies to define the efficacy of I-131 rituximab in DLBCL are warranted.

  8. Nanoscale mapping and organization analysis of target proteins on cancer cells from B-cell lymphoma patients

    Energy Technology Data Exchange (ETDEWEB)

    Li, Mi [State Key Laboratory of Robotics, Shenyang Institute of Automation, Chinese Academy of Sciences, Shenyang 110016 (China); University of Chinese Academy of Sciences, Beijing 100049 (China); Xiao, Xiubin [Department of Lymphoma, Affiliated Hospital of Military Medical Academy of Sciences, Beijing 100071 (China); Liu, Lianqing, E-mail: lqliu@sia.cn [State Key Laboratory of Robotics, Shenyang Institute of Automation, Chinese Academy of Sciences, Shenyang 110016 (China); Xi, Ning, E-mail: xin@egr.msu.edu [State Key Laboratory of Robotics, Shenyang Institute of Automation, Chinese Academy of Sciences, Shenyang 110016 (China); Department of Mechanical and Biomedical Engineering, City University of Hong Kong, Hong Kong (China); Wang, Yuechao; Dong, Zaili [State Key Laboratory of Robotics, Shenyang Institute of Automation, Chinese Academy of Sciences, Shenyang 110016 (China); Zhang, Weijing, E-mail: zhangwj3072@163.com [Department of Lymphoma, Affiliated Hospital of Military Medical Academy of Sciences, Beijing 100071 (China)

    2013-11-01

    CD20, a membrane protein highly expressed on most B-cell lymphomas, is an effective target demonstrated in clinical practice for treating B-cell non-Hodgkin's lymphoma (NHL). Rituximab is a monoclonal antibody against CD20. In this work, we applied atomic force microscopy (AFM) to map the nanoscale distribution of CD20 molecules on the surface of cancer cells from clinical B-cell NHL patients under the assistance of ROR1 fluorescence recognition (ROR1 is a specific cell surface marker exclusively expressed on cancer cells). First, the ROR1 fluorescence labeling experiments showed that ROR1 was expressed on cancer cells from B-cell lymphoma patients, but not on normal cells from healthy volunteers. Next, under the guidance of ROR1 fluorescence, the rituximab-conjugated AFM tips were moved to cancer cells to image the cellular morphologies and detect the CD20-rituximab interactions on the cell surfaces. The distribution maps of CD20 on cancer cells were constructed by obtaining arrays of (16×16) force curves in local areas (500×500 nm{sup 2}) on the cell surfaces. The experimental results provide a new approach to directly investigate the nanoscale distribution of target protein on single clinical cancer cells. - Highlights: • Cancer cells were recognized from healthy cells by ROR1 fluorescence labeling. • The nanoscale distribution of CD20 on cancer cells was characterized. • The distribution of CD20 was non-uniform on the surface of cancer cells.

  9. Nanoscale mapping and organization analysis of target proteins on cancer cells from B-cell lymphoma patients

    International Nuclear Information System (INIS)

    CD20, a membrane protein highly expressed on most B-cell lymphomas, is an effective target demonstrated in clinical practice for treating B-cell non-Hodgkin's lymphoma (NHL). Rituximab is a monoclonal antibody against CD20. In this work, we applied atomic force microscopy (AFM) to map the nanoscale distribution of CD20 molecules on the surface of cancer cells from clinical B-cell NHL patients under the assistance of ROR1 fluorescence recognition (ROR1 is a specific cell surface marker exclusively expressed on cancer cells). First, the ROR1 fluorescence labeling experiments showed that ROR1 was expressed on cancer cells from B-cell lymphoma patients, but not on normal cells from healthy volunteers. Next, under the guidance of ROR1 fluorescence, the rituximab-conjugated AFM tips were moved to cancer cells to image the cellular morphologies and detect the CD20-rituximab interactions on the cell surfaces. The distribution maps of CD20 on cancer cells were constructed by obtaining arrays of (16×16) force curves in local areas (500×500 nm2) on the cell surfaces. The experimental results provide a new approach to directly investigate the nanoscale distribution of target protein on single clinical cancer cells. - Highlights: • Cancer cells were recognized from healthy cells by ROR1 fluorescence labeling. • The nanoscale distribution of CD20 on cancer cells was characterized. • The distribution of CD20 was non-uniform on the surface of cancer cells

  10. Idelalisib therapy of indolent B-cell malignancies: chronic lymphocytic leukemia and small lymphocytic or follicular lymphomas

    Directory of Open Access Journals (Sweden)

    Madanat YF

    2016-03-01

    Full Text Available Yazan F Madanat,1 Mitchell R Smith,2 Alexandru Almasan,3 Brian T Hill2 1Department of Internal Medicine, 2Department of Hematology and Medical Oncology, Taussig Cancer Institute, 3Department of Cancer Biology, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA Abstract: Chronic lymphocytic leukemia, small lymphocytic lymphoma, and follicular lymphoma are indolent B-cell lymphoproliferative disorders that mainly affect an older population. Although the majority of patients in need of treatment derive significant benefit from conventional chemotherapeutic agents as well as monoclonal antibodies, less toxic and more effective treatments are needed. Novel agents that inhibit the B-cell receptor signaling pathway have shown promising outcomes in these disorders. Idelalisib is a potent selective oral inhibitor of phosphatidylinositol 3-kinase delta and has shown significant clinical activity in B-cell malignancies. In this review, we summarize the clinical trial data using idelalisib as monotherapy or in combination with rituximab for the treatment of relapsed/refractory disease. The adverse effect profile includes autoimmune disorders such as transaminitis, colitis, and pneumonitis. Given the efficacy and manageable toxicity profile of idelalisib, it is being increasingly incorporated into the management of indolent B-cell malignancies. Keywords: idelalisib, PI3Kδ inhibitors, chronic lymphocytic leukemia, follicular lymphoma

  11. Impact of dual expression of MYC and BCL2 by immunohistochemistry on the risk of CNS relapse in DLBCL.

    Science.gov (United States)

    Savage, Kerry J; Slack, Graham W; Mottok, Anja; Sehn, Laurie H; Villa, Diego; Kansara, Roopesh; Kridel, Robert; Steidl, Christian; Ennishi, Daisuke; Tan, King L; Ben-Neriah, Susana; Johnson, Nathalie A; Connors, Joseph M; Farinha, Pedro; Scott, David W; Gascoyne, Randy D

    2016-05-01

    Dual expression of MYC and BCL2 by immunohistochemistry (IHC) is associated with poor outcome in diffuse large B-cell lymphoma (DLBCL). Dual translocation of MYC and BCL2, so-called "double-hit lymphoma," has been associated with a high risk of central nervous system (CNS) relapse; however, the impact of dual expression of MYC and BCL2 (dual expressers) on the risk of CNS relapse remains unknown. Pretreatment formalin-fixed paraffin-embedded DLBCL biopsies derived from patients subsequently treated with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) were assembled on tissue microarrays from 2 studies and were evaluated for expression of MYC and BCL2 by IHC. In addition, cell of origin was determined by IHC and the Lymph2Cx gene expression assay in a subset of patients. We identified 428 patients who met the inclusion criteria. By the recently described CNS risk score (CNS-International Prognostic Index [CNS-IPI]), 34% were low risk (0 to 1), 45% were intermediate risk (2 to 3), and 21% were high risk (4 or greater). With a median follow-up of 6.8 years, the risk of CNS relapse was higher in dual expressers compared with non-dual expressers (2-year risk, 9.7% vs 2.2%; P = .001). Patients with activated B-cell or non-germinal center B-cell type DLBCL also had an increased risk of CNS relapse. However, in multivariate analysis, only dual expresser status and CNS-IPI were associated with CNS relapse. Dual expresser MYC(+) BCL2(+) DLBCL defines a group at high risk of CNS relapse, independent of CNS-IPI score and cell of origin. Dual expresser status may help to identify a high-risk group who should undergo CNS-directed evaluation and consideration of prophylactic strategies. PMID:26834242

  12. (18)FDG PET/CT appearance in primary cutaneous diffuse large B-cell lymphoma, leg type.

    Science.gov (United States)

    Samarghandi, Amin; Gru, Alejandro Ariel; Natwa, Mona; Barker, David W

    2015-06-01

    We report the case of a 70-year-old woman who presented with a small and painless red skin nodule in the right lower leg, which rapidly and significantly increased in size over few weeks and developed a central eschar. Skin biopsy was consistent with primary cutaneous diffuse large B-cell lymphoma, leg type (PCDBCL-LT), an aggressive and rare cutaneous lymphoma. F-FDG PET/CT showed a hypermetabolic soft tissue mass in the right leg with no evidence of systemic involvement of disease. PMID:25742229

  13. Definition of MYC genetic heteroclonality in diffuse large B-cell lymphoma with 8q24 rearrangement and its impact on protein expression.

    Science.gov (United States)

    Valera, Alexandra; Epistolio, Samantha; Colomo, Lluis; Riva, Alice; Balagué, Olga; Dlouhy, Ivan; Tzankov, Alexandar; Bühler, Marco; Haralambieva, Eugenia; Campo, Elias; Soldini, Davide; Mazzucchelli, Luca; Martin, Vittoria

    2016-08-01

    MYC rearrangement can be detected in a subgroup of diffuse large B-cell lymphoma characterized by unfavorable prognosis. In contrast to Burkitt lymphoma, the correlation between MYC rearrangement and MYC protein expression in diffuse large B-cell lymphoma is less clear, as approximately one-third of rearranged cases show negative or low expression by immunohistochemistry. To better understand whether specific characteristics of the MYC rearrangement may influence its protein expression, we investigated 43 de novo diffuse large B-cell lymphoma positive for 8q24 rearrangement by FISH, using 14 Burkitt lymphoma for comparison. Different cell populations (clones), breakpoints (classical vs non-classical FISH patterns), partner genes (IGH vs non-IGH) and immunostaining were detected and analyzed using computerized image systems. In a subgroup of diffuse large B-cell lymphoma, we observed different clones within the same tumor distinguishing the founder clone with MYC rearrangement alone from other subclones, carrying MYC rearrangement coupled with loss/extra copies of derivatives/normal alleles. This picture, which we defined MYC genetic heteroclonality, was found in 42% of cases and correlated to negative MYC expression (P=0.026). Non-classical FISH breakpoints were detected in 16% of diffuse large B-cell lymphoma without affecting expression (P=0.040). Non-IGH gene was the preferential partner of rearrangement in those diffuse large B-cell lymphoma showing MYC heteroclonality (P=0.016) and/or non-classical FISH breakpoints (P=0.058). MYC heteroclonality was not observed in Burkitt lymphoma and all cases had positive MYC expression. Non-classical FISH MYC breakpoint and non-IGH partner were found in 29 and 20% of Burkitt lymphoma, respectively. In conclusion, MYC genetic heteroclonality is a frequent event in diffuse large B-cell lymphoma and may have a relevant role in modulating MYC expression. PMID:27125356

  14. Application of the protein chip technology in pathology classification and prognosis of B-cell non-Hodgkin lymphoma%蛋白质芯片技术在B细胞淋巴瘤病理分型及预后方面的应用

    Institute of Scientific and Technical Information of China (English)

    王军; 张巧花; 郭素堂; 郑玉萍; 侯淑玲; 贺建霞; 王列样; 杨斌

    2009-01-01

    目的 应用表面增强激光解吸/离子化-飞行时间-质谱(SELDI-TOF-MS)蛋白质芯片技术检测B细胞非霍奇金淋巴瘤(B-cell NHL)及其弥漫大B细胞淋巴瘤(DLBCL)和滤泡性淋巴瘤(FL)患者血清中的差异表达蛋白.探讨其临床意义.方法 弱阳离子交换蛋白芯片检测54例初治B-cell NHL和27名健康人血清中的差异表达蛋白,并筛选DLBCL与FL之间病理类型的差异表达蛋白及影响DLBCL预后的差异表达蛋白.结果 B-cellNHL患者血清中有5个特异性标志蛋白.高表达蛋白质的相对分子质量为7974和15938,低表达的为3398、8564和8692.DLBCL与FL之间有3个差异表达蛋白,为3379、3976和4302,在DLBCL低表达,在FL高表达.影响DLBCL患者预后的差异表达蛋白有2个,为4795和4998,其高表达者预后好.结论 SELDI-TOF-MS蛋白质芯片技术可以直接筛选B-cell NHL血清中相对特异的标志蛋白作为诊断的指标,并用于病理分型、判断预后.%Objective To test different expression protein markers of the serum from B-cell non-Hodgkin lymphoma(B-cell NHL) between diffuse large B-cell lymphoma(DLBCL) and follicular lymphoma(FL)patients using sudace enhanced laser desorption/ionization-time of flight-mass spectrometry(SELDI-TOF-MS)protein chip technology. Further, to test different expression of the protein markers of B-eell NHL patients after chemical therapy in order to discuss clinical significance. Methods Different expression of protein markers were analysed in serum between 54 B-cell NHL patients and 27 healthy volunteers by using SELDI-TOF-MS WCX-2 pertein chip. Meanwhile different expression of protein markers relative to pathology classification between 23 DLBCL patients and 12 FL patients were screened; and protein markers which affected prognosis of 23 DLBCL patients were screened. Results There were five specific marker proteins in 54 B-cell NHL patients and 27 healthy volunteers. Their relative molecular weights were 7974, 15 938

  15. Chronic lymphocytic leukemia/small lymphocytic lymphoma: another neoplasm related to the B-cell follicle?

    Science.gov (United States)

    Tandon, Bevan; Swerdlow, Steven H; Hasserjian, Robert P; Surti, Urvashi; Gibson, Sarah E

    2015-01-01

    Although there has been increased attention paid to the critical nature of nodal involvement in chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), the B-cell compartment it is most closely related to and its relationship to the follicle remain uncertain. A clinicopathologic investigation of 60 extramedullary biopsies of LEF1+ CLL/SLL, including 29 cases with perifollicular/follicular (PF/F) growth, was therefore performed. A subset of PF/F cases demonstrated inner mantle zone preservation or intra-mantle zone growth. All PF/F and 16/31 other cases contained CD21+ follicular dendritic cells. No cytogenetic, IGHV mutational or gene usage differences were seen between PF/F and diffuse cases. PF/F cases were more often kappa positive (pa subset of bona fide CLL/SLL is related to the follicle, most likely the outer mantle zone, and that at least a subset of the diffuse cases may represent "later" disease. PMID:25860247

  16. Therapy-related AML/MDS after treatment of low-grade B-cell lymphoma

    International Nuclear Information System (INIS)

    Described is the therapy-related AML (acute myelogenetic leukemia)/MDS (myelo-dysplasia syndrome), which is manifested after various treatments of low-grade B-cell lymphoma and has strongly attracted attention because of the markedly improved prognosis due to recent advantages of the therapy for the disease. AML/MDS occurs several years after chemotherapy and/or radiation therapy which cause DNA damage in hematopoietic cells, and the AML/MDS risk is known increased in patients undergone especially with autologous transplantation of those cells. AML/MDS has the feature similar to that caused either by alkylating agent or by topoisomerase-2 inhibitor, and the disease by radiation belong to the former. Yet unclear is the problem whether malignant cells causing the disease after therapy are derived from the remaining cells in the graft or in the body. Although irradiations of total body and total lymphaden as well as chemotherapy are said to be related to AML/MDS and local irradiation does not contribute to its risk, the most important factor for the disease is considered to be the autotransplantation as the recurrence occurs in 50% after it. Thus the treatment history should be taken into consideration for suppressing AML/MDS, for which follow up with consideration for the disease is required particularly after autotransplantation. (R.T.)

  17. The anti-lymphoma activity of antiviral therapy in HCV-associated B-cell non-Hodgkin lymphomas: a meta-analysis.

    Science.gov (United States)

    Peveling-Oberhag, J; Arcaini, L; Bankov, K; Zeuzem, S; Herrmann, E

    2016-07-01

    Many epidemiological studies provide solid evidence for an association of chronic hepatitis C virus (HCV) infection with B-cell non-Hodgkin's lymphoma (B-NHL). However, the most convincing evidence for a causal relationship between HCV infection and lymphoma development is the observation of B-NHL regression after HCV eradication by antiviral therapy (AVT). We conducted a literature search to identify studies that included patients with HCV-associated B-NHL (HCV-NHL) who received AVT, with the intention to treat lymphoma and viral disease at the same time. The primary end point was the correlation of sustained virological response (SVR) under AVT with lymphoma response. Secondary end points were overall lymphoma response rates and HCV-NHL response in correlation with lymphoma subtypes. We included 20 studies that evaluated the efficacy of AVT in HCV-NHL (n = 254 patients). Overall lymphoma response rate through AVT was 73% [95%>confidence interval, (CI) 67-78%]. Throughout studies there was a strong association between SVR and lymphoma response (83% response rate, 95%>CI, 76-88%) compared to a failure in achieving SVR (53% response rate, 95%>CI, 39-67%, P = 0.0002). There was a trend towards favourable response for AVT in HCV-associated marginal zone lymphomas (response rate 81%, 95%>CI, 74-87%) compared to nonmarginal zone origin (response rate 71%, 95%>CI, 61-79%, P = 0.07). In conclusion, in the current meta-analysis, the overall response rate of HCV-NHL under AVT justifies the recommendation for AVT as first-line treatment in patients who do not need immediate conventional treatment. The strong correlation of SVR and lymphoma regression supports the hypothesis of a causal relationship of HCV and lymphomagenesis. PMID:26924533

  18. Lenalidomide and Ibrutinib in Treating Patients With Relapsed or Refractory B-cell Non-Hodgkin Lymphoma

    Science.gov (United States)

    2016-08-31

    Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Follicular Lymphoma; Recurrent Lymphoplasmacytic Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Refractory Follicular Lymphoma; Refractory Lymphoplasmacytic Lymphoma; Refractory Mantle Cell Lymphoma

  19. Prognostic Value of P53 Aberrations in Diffuse Large B-cell Lymphoma%P53异常在弥漫大B细胞淋巴瘤中的预后价值

    Institute of Scientific and Technical Information of China (English)

    陆静涛; 岑岭; 周民

    2012-01-01

    本研究旨在分析P53异常在弥漫大B细胞淋巴瘤(DLBCL)中的预后价值.采用荧光原位杂交法(FISH)对50例DLBCL患者的扁桃体组织进行P53基因检测,同时采集患者外周血用酶联免疫吸附(ELISA)法进行血清P53蛋白含量的检测,了解DLBCL患者P53基因及P53蛋白表达与淋巴瘤预后的关系.结果表明,50例患者中P53缺失者21例,阳性率42.0%,患者血清P53蛋白含量为(176.25±61.25) pg/ml,高于正常对照.经Cox模型似然比检验结果筛选,DLBCL患者的P53异常可作为独立的预后因素.P53基因检测阳性患者的死亡风险高于P53检测阴性者.经FISH检测,组织学P53基因缺失的患者同时有相对较高的血清突变型P53蛋白水平.结论:P53异常可作为DLBCL患者独立的预后因素,在疾病诊断初期即对DLBCL患者的P53表达进行检测有利于准确判断预后.%The aim of this study was to analyze the P53 aberrations in diffuse large B-cell lymphoma (DLBCL) and its prognostic value. Using fluorescence in situ hybridization (FISH) , the P53 gene was detected in paraffin-embedded tonsil tissues from 50 cases of DLBCL, while all the peripheral blood of patients was collected for detecting P53 protein in serum by using enzyme-linked immunosorbent assay (ELISA). The relationships between P53 gene and protein expression and the prognosis of patients with DLBCL were analyzed. The results showed that 21 out of 50 cases had P53 gene deletion, serum P53 protein content was (176. 25 ±61. 25) pg/ml, which was higher than that in normal controls. The Cox model likelihood ratio test found that abnormal P53 could be used as independent prognostic factor in DLBCL patients. The risk of death in patients with P53 gene deletion were more than that in patients with P53 gene normal. The patients with histology P53 gene deletion detected by FISH also had relatively high level of mutant P53 protein in serum. It is concluded that P53 aberrations in patients with DLBCL can

  20. 21例原发乳腺弥漫大B细胞淋巴瘤患者临床分析%Primary breast diffuse large B-cell lymphoma-report of 21 cases from China with literatures review

    Institute of Scientific and Technical Information of China (English)

    孙星; 徐斌; 李玉富; 杜建伟; 董丽华; 高雪; 李钢苹; 魏旭东; 宋永平

    2015-01-01

    Objective To evaluateclinical features, treatment and outcomes of patients diagnosed with primary breast diffuse large B-cell lymphoma(DLBCL). Methods Clinical data were analyzed for all patients diagnosed with primary breast DLBCL(n=21). Kaplan-Meier method was used to estimate 5-year overall survival(OS)rate, and the difference was compared by Log-rank test. Results The 21 cases of patients with primary breast DLBCL were all female with median age at diagnosis as 48 years (range 21-64 years). 13 patients had International Prognostic Index(IPI)of 0, 6 IPI 1, and 2 IPI 2. The 5-year OS rates of CHOP/R-CHOP and R ± DICE after R ± EPOCH groups were 40.0% and 72.2%, respectively(P=0.035). The central nervous system relapse rate of CHOP/R-CHOP and R±DICE after R± EPOCH groups were 16.7% and 6.7%(P=0.500), respectively. The 5-year OS rates of patients with primary breast DLBCL staging ⅡE-ⅢE and ⅠE were 21.4% and 83.3%, respectively (P=0.025). Conclusions Primary breast DLBCL was rare. The patients of primary breast DLBCL with chemotherapy regimen of R ± DICE after R ± EPOCH might have a better prognosis and lower relapse rate of central nervous system;the primary breast DLBCL patients stagingⅡE-ⅢE might have a poor prognosis.%目的:探讨原发乳腺弥漫大B细胞淋巴瘤(DLBCL)患者的临床特征、治疗及预后。方法回顾性分析21例原发乳腺DLBCL患者的临床资料,用Kaplan-Meier法分析5年总生存(OS)率,采用Log-rank检验法进行亚组间差异性分析。结果21例患者均为女性,中位年龄48(21~64)岁,其中国际预后指数(IPI)评分0分者13例,1分者6例,2分者2例。21例患者中R-CHOP/CHOP方案治疗组(6例)和EPOCH±R序贯DICE±R方案治疗组(15例)患者的5年OS率分别为40.0%和72.2%,差异有统计学意义(P=0.035);中枢神经系统复发率分别为16.7%和6.7%(P=0.500);ⅡE~ⅢE期组(9例)和ⅠE期(12例)患者5

  1. FDG PET-CT Finding in Bilateral Renal and Bone Involvement of Diffuse Large B-Cell Lymphoma

    Directory of Open Access Journals (Sweden)

    Yusuf Ziya Tan

    2014-10-01

    Full Text Available Thirty-six year old male patient with pathological fracture of the left tibia underwent intramedullary and soft tissue curettage. The histopathological examination revealed diffuse large B cell lymphoma. The patient underwent F18-FDG PET-CT scanning for initial staging. FDG PET-CT scan revealed hypermetabolic lesions at the left tibia and in bilateral kidneys. After the systemic chemotherapy and local radiotherapy to the tibia, repeated FDG PET/CT scan showed improvement of the previous hypermetabolic lesions, suggesting good response to therapy. Bone and renal involvement is an uncommon variant of diffuse large B-cell lymphoma and FDG PET-CT is an useful whole body imaging modality in these cases.

  2. Portraying the Expression Landscapes of B-CellLymphoma-Intuitive Detection of Outlier Samples and of Molecular Subtypes

    Directory of Open Access Journals (Sweden)

    Lydia Hopp

    2013-12-01

    Full Text Available We present an analytic framework based on Self-Organizing Map (SOM machine learning to study large scale patient data sets. The potency of the approach is demonstrated in a case study using gene expression data of more than 200 mature aggressive B-cell lymphoma patients. The method portrays each sample with individual resolution, characterizes the subtypes, disentangles the expression patterns into distinct modules, extracts their functional context using enrichment techniques and enables investigation of the similarity relations between the samples. The method also allows to detect and to correct outliers caused by contaminations. Based on our analysis, we propose a refined classification of B-cell Lymphoma into four molecular subtypes which are characterized by differential functional and clinical characteristics.

  3. Effect of Combination of Rituximab and CHOP Chemotherapy Regimen for Patients with Diffuse Large B Cell Lymphoma in Long - Term Survival%利妥昔单抗联合CHOP方案对弥漫大B细胞淋巴瘤患者长期生存率的影响

    Institute of Scientific and Technical Information of China (English)

    汪淑英

    2015-01-01

    Objective To investigate the therapeutic effect of diffuse large B cell lymphoma(DLBCL) in patients with long - term sur-vival rate of rituximab combined with COPD scheme. Methods 84 cases of untreated diffuse large B cell lymphoma patients were ran-domly divided into control group and observation group, 42 cases in each group. The control group was treated by traditional CHOP chemotherapy, the observation group were treated by chemotherapy of R - CHOP regimen. Results Patients in the observation group the rate of CR was significantly higher than the control group ( P 0. 05) . Comparing the total effective rate, patients in the observation group was significantly higher than the control group ( P 0. 05), while the patients in the observation group 3 year PFS rate and OS rate were increased significantly compared with control group( P 0. 05). Conclusion Rituximab combined with CHOP regimen in the treatment of diffuse large B cell lymphoma, effective process safety. Compared with the traditional scheme, the combination scheme can significantly improve the long - term survival of patients.%目的:探讨利妥昔单抗联合 CHOP 方案治疗弥漫大 B 细胞淋巴瘤(DLBCL)对患者远期生存率的影响。方法将84例初治 DLBCL 患者随机分为对照组和观察组,各42例。对照组患者采用传统 CHOP 方案化疗,观察组患者采用利妥昔单抗联合 CHOP(R - CHOP)方案化疗,观察疗效指标,比较两组患者不良反应发生率间差异。结果观察组患者完全缓解(CR)率较对照组显著提高( P 0.05)。观察组患者总有效率较对照组显著提高( P 0.05),而观察组患者3年 PFS 率及 OS 率均较对照组明显增高( P 0.05)。结论 R - CHOP 方案治疗 DLBCL 过程安全、有效,较传统方案联合方案能显著改善患者长期生存率。

  4. FDG PET-CT Finding in Bilateral Renal and Bone Involvement of Diffuse Large B-Cell Lymphoma

    OpenAIRE

    Yusuf Ziya Tan; Sabire Yılmaz; Meftune Özhan

    2014-01-01

    Thirty-six year old male patient with pathological fracture of the left tibia underwent intramedullary and soft tissue curettage. The histopathological examination revealed diffuse large B cell lymphoma. The patient underwent F18-FDG PET-CT scanning for initial staging. FDG PET-CT scan revealed hypermetabolic lesions at the left tibia and in bilateral kidneys. After the systemic chemotherapy and local radiotherapy to the tibia, repeated FDG PET/CT scan showed improvement of the previous hyper...

  5. Bowel perforation from occult ileal involvement after diagnosis in a case of primary mediastinal large B-cell lymphoma.

    Science.gov (United States)

    De Philippis, Chiara; Di Chio, Maria Chiara; Sabattini, Elena; Bolli, Niccolo

    2016-01-01

    Primary mediastinal large B-cell lymphoma (PMBCL) is confined to the mediastinum or contiguous nodal areas in most cases. Extramediastinal and abdominal involvement, especially at diagnosis, is extremely rare. Our case describes the first case of histologically proven ileal involvement of PMBCL at diagnosis that led to ileal perforation. Positron emission tomography CT could increase the sensitivity of staging by detecting unusual sites of disease localisation, and could impact clinical management. PMID:27417993

  6. Elevated RNA expression of long non‑coding HOTAIR promotes cell proliferation and predicts a poor prognosis in patients with diffuse large B cell lymphoma.

    Science.gov (United States)

    Yan, Yuling; Han, Jingyin; Li, Zhenqing; Yang, Honglan; Sui, Yanmin; Wang, Minglin

    2016-06-01

    Diffuse large B cell lymphoma (DLBCL) is one of the most common types of malignancy worldwide. The lack of clear symptoms and early detection make it difficult to diagnose at an early stage, leading to poor prognosis of the patients. Long non‑coding RNAs (lncRNAs) have come into focus for their important regulatory roles in fundamental biological processes, particularly in cancer initiation, development and progression. The aim of the present study was to investigate the expression of lncRNA Hox transcript antisense intergenic RNA (HOTAIR) in a cohort of patients with DLBCL to assess its clinical value and biological function in DLBCL. The reverse transcription‑polymerase chain reaction was used to detect HOTAIR expression levels and cells were transfected with small interfering RNA to compare cell proliferation, cell cycle progression and apoptosis. Western blotting was also conducted to detect possible signaling pathways. It was first found that the expression levels of HOTAIR were upregulated in DLBCL tumor tissues and cell lines, compared with normal tissues and cells. In addition, HOTAIR was significantly correlated with tumor size, clinical stage, B symptoms and International Prognostic Index scores; and higher expression levels of HOTAIR were correlated with improved prognosis. Univariate and multivariate analyses verified that HOTAIR was a key independent predictive factor for DLBCL prognosis. Furthermore, it was revealed that the knockdown of the expression of HOTAIR led to growth inhibition, cell cycle arrest and apoptosis in vitro, possibly through the phosphoinositide 3‑kinase/AKT/nuclear factor‑κB pathway. These results suggested that HOTAIR may be regarded as a novel indicator of poor prognosis, and may serve as a potential target for gene therapy in the treatment of DLBCL. PMID:27122348

  7. Primary bone lymphoma: A report of two cases and review of the literature

    Directory of Open Access Journals (Sweden)

    Singh Tejinder

    2010-01-01

    Full Text Available Primary bone lymphoma (PBL is an uncommon tumor accounting for approximately 4-5% of extra nodal lymphoma and less than 1% of all non-Hodgkin′s lymphoma. Disease may be complicated at presentation by pathological fracture or spinal cord compression. Diffuse large-B-cell lymphoma (DLBCL accounts for the majority of cases of PBL. Owing to its rarity, only a few retrospective studies have been published addressing the prognosis and treatment of primary bone lymphoma. In this paper, we report our experience with two cases of PBL treated with chemotherapy and radiotherapy and review literature to elucidate the optimal treatment of primary bone lymphoma.

  8. Competitive Transfer of αCD19-TCRz-CD28 and αCD19-TCRz-CD137 CAR-T Cells for B-cell Leukemia/Lymphoma

    Science.gov (United States)

    2016-04-25

    Hematopoietic/Lymphoid Cancer; Adult Acute Lymphoblastic Leukemia in Remission; B-cell Adult Acute Lymphoblastic Leukemia; B-cell Chronic Lymphocytic Leukemia; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Refractory Chronic Lymphocytic Leukemia; Stage III Adult Diffuse Large Cell Lymphoma; Stage III Chronic Lymphocytic Leukemia; Stage III Grade 1 Follicular Lymphoma; Stage III Grade 2 Follicular Lymphoma; Stage III Grade 3 Follicular Lymphoma; Stage III Mantle Cell Lymphoma; Stage IV Adult Diffuse Large Cell Lymphoma; Stage IV Chronic Lymphocytic Leukemia; Stage IV Grade 1 Follicular Lymphoma; Stage IV Grade 2 Follicular Lymphoma; Stage IV Grade 3 Follicular Lymphoma; Stage IV Mantle Cell Lymphoma

  9. MYC-IG rearrangements are negative predictors of survival in DLBCL patients treated with immunochemotherapy: a GELA/LYSA study.

    Science.gov (United States)

    Copie-Bergman, Christiane; Cuillière-Dartigues, Peggy; Baia, Maryse; Briere, Josette; Delarue, Richard; Canioni, Danielle; Salles, Gilles; Parrens, Marie; Belhadj, Karim; Fabiani, Bettina; Recher, Christian; Petrella, Tony; Ketterer, Nicolas; Peyrade, Frederic; Haioun, Corinne; Nagel, Inga; Siebert, Reiner; Jardin, Fabrice; Leroy, Karen; Jais, Jean-Philippe; Tilly, Herve; Molina, Thierry Jo; Gaulard, Philippe

    2015-11-26

    Diffuse large B-cell lymphoma (DLBCL) with MYC rearrangement (MYC-R) carries an unfavorable outcome. We explored the prognostic value of the MYC translocation partner gene in a series of MYC-R de novo DLBCL patients enrolled in first-line prospective clinical trials (Groupe d'Etudes des Lymphomes de l'Adulte/Lymphoma Study Association) and treated with rituximab-anthracycline-based chemotherapy. A total of 774 DLBCL cases characterized for cell of origin by the Hans classifier were analyzed using fluorescence in situ hybridization with BCL2, BCL6, MYC, immunoglobulin (IG)K, and IGL break-apart and IGH/MYC, IGK/MYC, and IGL/MYC fusion probes. MYC-R was observed in 51/574 (8.9%) evaluable DLBCL cases. MYC-R cases were predominantly of the germinal center B-cell-like subtype 37/51 (74%) with no distinctive morphologic and phenotypic features. Nineteen cases were MYC single-hit and 32 cases were MYC double-hit (MYC plus BCL2 and/or BCL6) DLBCL. MYC translocation partner was an IG gene in 24 cases (MYC-IG) and a non-IG gene (MYC-non-IG) in 26 of 50 evaluable cases. Noteworthy, MYC-IG patients had shorter overall survival (OS) (P = .0002) compared with MYC-negative patients, whereas no survival difference was observed between MYC-non-IG and MYC-negative patients. In multivariate analyses, MYC-IG predicted poor progression-free survival (P = .0051) and OS (P = .0006) independently from the International Prognostic Index and the Hans classifier. In conclusion, we show in this prospective randomized trial that the adverse prognostic impact of MYC-R is correlated to the MYC-IG translocation partner gene in DLBCL patients treated with immunochemotherapy. These results may have an important impact on the clinical management of DLBCL patients with MYC-R who should be routinely characterized according to MYC partner gene. These trials are individually registered at www.clinicaltrials.gov as #NCT00144807, #NCT01087424, #NCT00169143, #NCT00144755, #NCT00140660, #NCT00140595, and

  10. CD20 mutations involving the rituximab epitope are rare in diffuse large B-cell lymphomas and are not a significant cause of R-CHOP failure

    OpenAIRE

    Johnson, Nathalie A.; Leach, Stephen; Woolcock, Bruce; deLeeuw, Ronald J; Bashashati, Ali; Sehn, Laurie H.; Connors, Joseph M; Chhanabhai, Mukesh; Brooks-Wilson, Angela; Gascoyne, Randy D.

    2009-01-01

    The findings of this study indicate that CD20 mutations nvolving the rituximab epitope are rare in both de novo and relapsed diffuse large B-cell lymphoma, and do not represent a significant cause of R-CHOP resistance.

  11. Metallothionein-I plus II and receptor megalin are altered in relation to oxidative stress in cerebral lymphomas

    DEFF Research Database (Denmark)

    Pedersen, M.O.; Hansen, P.B.; Nielsen, Signe Ledou;

    2010-01-01

    Primary central nervous system lymphoma (PCNSL) in immunocompetent patients is highly malignant and has a poor prognosis. The PCNSL molecular features are reminiscent to some degree of diffuse large B-cell lymphoma (DLBCL), yet PCNSL shows unique molecular profiles and a distinct clinical behavior....... This article characterizes the histopathology and expression profiles of metallothionein-I + II (MT-I + II) and their receptor megalin along with proliferation, oxidative stress, and apoptosis in PCNSL and in central nervous system (CNS) lymphomas due to relapse from DLBCL (collectively referred to as...

  12. Rhesus Lymphocryptovirus Type 1-associated B-cell Nasal Lymphoma in SIV-infected Rhesus Macaques

    OpenAIRE

    Marr-Belvin, A. K.; Carville, A. K.; Fahey, M. A.; Boisvert, K.; Klumpp, S. A.; Ohashi, M.; Wang, F.; O’Neil, S. P.; Westmoreland, S. V.

    2008-01-01

    Epstein-Barr virus (EBV) is a worldwide endemic gamma herpesvirus of the genus Lymphocryptovirus (LCV) that infects more than 90% of the world’s population. EBV has been associated with a variety of malignancies, but it has a demonstrated role in lymphomas, especially in immunosuppressed individuals. Lymphomas of the nasal cavity, paranasal sinuses, and nasopharynx are uncommon and constitute less than 5% of all extranodal lymphomas. Sinonasal non-Hodgkin’s lymphomas have been reported in pat...

  13. A longitudinal study of non-medical determinants of adherence to R-CHOP therapy for diffuse large B-cell lymphoma: implication for survival

    OpenAIRE

    Borel, Cécile; Lamy, Sébastien; Compaci, Gisèle; Récher, Christian; Jeanneau, Pauline; Nogaro, Jean Claude; Bauvin, Eric; Despas, Fabien; Delpierre, Cyrille; LAURENT, GUY

    2015-01-01

    AbstractBackgroundAdherence to therapy has been established for years as a critical parameter for clinical benefit in medical oncology. This study aimed to assess, in the current practice, the influence of the socio-demographical characteristics and the place of treatment on treatment adherence and overall survival among diffuse large B-cell lymphoma patients.MethodsWe analysed data from 380 patients enrolled in a French multi-centre regional cohort, with diffuse large B-cell lymphoma receivi...

  14. B-cell lymphoma 6 protein stimulates oncogenicity of human breast cancer cells

    International Nuclear Information System (INIS)

    B-cell lymphoma 6 (BCL6) protein, an evolutionarily conserved zinc finger transcription factor, showed to be highly expressed in various human cancers in addition to malignancies in the lymphoid system. This study investigated the role of BCL6 expression in breast cancer and its clinical significance in breast cancer patients. Expression of BCL6 protein was assessed using in situ hybridization and immunohistochemistry in 127 breast cancer patients and 50 patients with breast benign disease as well as in breast cell lines. Expression of BCL6 was restored or knocked down in two breast cancer cell lines (MCF-7 and T47D) using BCL6 cDNA and siRNA, respectively. The phenotypic change of these breast cancer cell lines was assessed using cell viability MTT, Transwell invasion, colony formation, and flow cytometry assays and in a xenograft mice model. Luciferase reporter gene, immunoblot, and qRT-PCR were used to investigate the molecular events after manipulated BCL6 expression in breast cancer cells. BCL6 protein was highly expressed in breast cancer cell lines and tissue specimens and expression of BCL6 protein was associated with disease progression and poor survival of breast cancer patients. In vitro, the forced expression of BCL6 results in increased proliferation, anchorage-independent growth, migration, invasion and survival of breast cancer cell lines, whereas knockdown of BCL6 expression reduced these oncogenic properties of breast cancer cells. Moreover, forced expression of BCL6 increased tumor growth and invasiveness in a nude mouse xenograft model. At the gene level, BCL6 was a target gene of miR-339-5p. Expression of BCL6 induced expression of CXCR4 and cyclinD1 proteins. The current study demonstrated the oncogenic property of BCL6 in breast cancer and further study could target BCL6 as a novel potential therapeutic strategy for breast cancer

  15. Targeting early B-cell receptor signaling induces apoptosis in leukemic mantle cell lymphoma

    Directory of Open Access Journals (Sweden)

    Boukhiar Mohand-Akli

    2013-02-01

    Full Text Available Abstract Background We previously showed that B-cell receptor (BCR signaling pathways are important for in vitro survival of mantle cell lymphoma (MCL cells. To further identify early BCR-activated signaling pathways involved in MCL cell survival, we focused our study on BCR-proximal kinases such as LYN whose dysregulations could contribute to the aggressive course of MCL. Methods Primary MCL cells were isolated from 14 leukemic patients. Early BCR-induced genes were identified by qRT-PCR array. The basal and BCR-induced phosphorylation of LYN and JNK were evaluated by immunoblottting. Cell survival signals were evaluated by apoptosis using flow cytometry. Results We showed that LYN was constitutively phosphorylated in MCL cell lines and in 9/10 leukemic MCL cases. Treatment with dasatinib or with a specific inhibitor of Src kinases such as PP2 suppressed constitutive LYN activation and increased in vitro spontaneous apoptosis of primary MCL cells. BCR engagement resulted in an increase of LYN phosphorylation leading to activation of c-JUN NH2-terminal kinase (JNK and over-expression of the early growth response gene-1 (EGR-1. Inhibition of JNK with SP600125 induced apoptosis and reduced level of basal and BCR-induced expression of EGR-1. Furthermore, decreasing EGR1 expression by siRNA reduced BCR-induced cell survival. Treatment with PP2 or with dasatinib suppressed BCR-induced LYN and JNK phosphorylation as well as EGR-1 upregulation and is associated with a decrease of cell survival in all cases analysed. Conclusions This study highlights the importance of BCR signaling in MCL cell survival and points out to the efficiency of kinase inhibitors in suppressing proximal BCR signaling events and in inducing apoptosis.

  16. Determination of apoptosis, proliferation status and O6-methylguanine DNA methyltransferase methylation profiles in different immunophenotypic profiles of diffuse large B-cell lymphoma

    Directory of Open Access Journals (Sweden)

    Nilay Şen Türk

    2011-03-01

    Full Text Available Objective: Our aim was to investigate the expression of apoptosis-associated proteins (bcl-2, bcl-xl, bax, bak, bid, apoptotic index (AI and proliferation index (PI in germinal center B-cell-like immunophenotypic profile (GCB and non-GCB of diffuse large B-cell lymphoma (DLBCL. Materials and Methods: The methylation status of the promoter region of O6-methylguanine-DNA yerine O6-methylguanine-DNA methyltransferase (MGMT gene and its relation with immunophenotypic differentiation of DLBCLs were also investigated. 101 cases were classified as GCB (29 cases or non-GCB (72 cases. Apoptosis-associated proteins and PI were determined by IHC, and TUNEL method was used to determine AI. MGMT methylation analysis was performed by real-time PCR. Results: The PI was significantly higher in GCB compared with non-GCB (p=0.011. Percentage of cells stained with bcl-6 was positively correlated with the percentage of cells expressing bcl-2 (p=0.023, AI (p=0.006 and PI (p<0.001, while a significant negative correlation was observed with the percentage of cells expressing bax (p=0.027. The percentage of cells stained with MUM1 showed a significantly positive correlation with the percentage of cells expressing bcl-xl (p=0.003, bid (p=0.002, AI (p<0.001, and PI (p=0.001. MGMT methylation analysis was performed in 95 samples, and methylated profile was found in 31 cases (32.6%. GCB was found in 6 cases (22.2% and non-GCB was determined in 25 cases (36.8% out of 31 with MGMT methylated samples. There was no significant association between MGMT methylation status and immunophenotypic profiles (p=0.173. Conclusion: These results suggest that bcl-6 protein expression may be responsible for the high PI in GCB. Additionally, we found that apoptosis-associated proteins were not significantly associated with immunophenotypic profiles.

  17. Expression of DNA mismatch repair proteins in transformed non-Hodgkin's lymphoma: relationship to smoking

    DEFF Research Database (Denmark)

    Nandi, S; Yu, J; Reinert, Line;

    2006-01-01

    It has been hypothesized that defects in DNA-mismatch repair are associated with smoking in certain types of transformed non-Hodgkin lymphoma (NHL). We have analyzed biopsy samples from two indolent B-cell lymphomas, follicular lymphoma (FL) and chronic lymphocytic leukemia/small lymphocytic...... leukemia (CLL/SLL), that have transformed to diffuse-large B-cell lymphoma (DLBCL). We correlated the presence or absence of DNA-mismatch repair enzymes by immunostaining as well as the p53 status to smoking history. Of all patients (n = 30), 37% showed negative immunostaining of MLH1, 16% showed negative...... immunostaining of MSH2 and 63% had p53 mutations and/or protein expression. Eighteen out of 20 transformed follicular lymphomas and seven out of 10 CLL/SLL that have transformed to DLBCL (Richter's syndrome) were informative for smoking histories. We found that the relative risk of negative immunostaining for...

  18. Diagnosing lymphoma in a setting with a high burden of infection: a pediatric case of Epstein-Barr virus-associated aggressive B-cell lymphoma with t(8;14 (q23;q32 and extensive necrosis mimicking tuberculosis

    Directory of Open Access Journals (Sweden)

    Mário Henrique Magalhães Barros

    2015-02-01

    Full Text Available The association of lymphoma with necrotic granuloma can pose diagnostic challenges and delay treatment, especially in settings with a high burden of infection. In these settings, the timely use of cytogenetic and molecular methods is most relevant. Here, we report a case of B-cell lymphoma with t (8;14 in a 5-year-old male child. The lymphoma was associated with necrotic granuloma and was initially misdiagnosed as tuberculosis. Polymerase chain reaction was used to detect clonal lymphoproliferation and to rule out Mycobacterium tuberculosis infection. Tumor cells harbored Epstein-Barr virus and expressed CD20, CD10, BCL6, and Ki67 (30%, leading to the diagnosis of B-cell lymphoma with features intermediate between diffuse large B-cell lymphoma and Burkitt lymphoma.

  19. RNA-binding protein VICKZ is expressed in a germinal center associated pattern among lymphoma subtypes

    DEFF Research Database (Denmark)

    Natkunam, Y.; Vainer, G.; Zhao, S.C.;

    2005-01-01

    Recent effort in the molecular characterization of diffuse large B-cell lymphoma (DLBCL) has led to the recognition that patients with DLBCL of germinal center origin exhibit a better overall survival. Thus, identification and characterization of markers of germinal center derivation are of...... tumorigenesis/metastasis. We generated an antibody that recognizes all three isoforms of VICKZ protein and characterized its expression in normal lymphoid tissue and in lymphoma subtypes. In normal tonsils, VICKZ protein showed a germinal center-specific pattern of expression with staining localized to the....... Among T cell lymphoma, anaplastic large cell lymphoma were positive (75%, 6/9). Additional work is in progress to correlate VICKZ protein expression with other germinal center markers such as HGAL, BCL6 and CD10 as well as with prognostic subclasses of DLBCL. The differential expression pattern of VICKZ...

  20. Clinical implication of genome-wide profiling in diffuse large B-cell lymphoma and other subtypes of B-cell lymphoma

    DEFF Research Database (Denmark)

    Iqbal, Javeed; Joshi, Shantaram; Patel, Kavita N;

    2007-01-01

    of Lymphoid Neoplasms (REAL) and World Health Organization (WHO) classifications. These classification methods were based on histological, immunophenotypic and cytogenetic markers and widely accepted by pathologists and oncologists worldwide. During last several decades, great progress has been made...... is DNA microarray technology. The genome-wide transcriptional measurement, also called gene expression profile (GEP) can accurately define the biological phenotype of the tumor. In this review, important discoveries made by genome-wide GEP in understanding the biology of lymphoma and additionally the...

  1. Renal small B-cell lymphoma with plasmacytic differentiation presenting with monoclonal gammopathy and disseminated intravascular coagulation syndrome

    Directory of Open Access Journals (Sweden)

    Paula de Oliveira Pádua Prestes

    2013-10-01

    Full Text Available Primary renal lymphomas are very rare. However, the kidney may be a site of metastasis, usually from a disseminated aggressive lymphoma. A 58-year-old woman was brought to the medical facility due to acute mental confusion, severe hypotension, septic shock, and signs of disseminated intravascular coagulation. Laboratory tests showed severe leukopenia, renal failure, altered liver function, and elevated serum lactate dehydrogenase levels. Protein electrophoresis revealed hypergammaglobulinemia with a monoclonal peak of IgG lambda. The clinical outcome was fulminant and the patient died less than 24 hours after admission. Autopsy revealed an indolent B-cell lymphoma with extensive plasmacytic differentiation infiltrating the right renal sinus and involving the submandibular and sublingual glands, cervical and peri-aortic lymph nodes, multiple microscopic foci in pituitary and adrenal glands, lung, breast, liver, thyroid, and bone marrow. Numerous IgG4-positive plasma cells were detected by immunohistochemistry although other histological features of IgG4-related disease were missing. There was also extensive hemorrhagic necrosis of the adrenal glands and purulent cystitis, which was probably responsible for the septic shock. The authors concluded that the kidney was most likely the primary site of the indolent lymphoma, as that was the site with the largest tumor mass. Infiltration of other organs was considered as dissemination of the disease. The differential diagnosis with mucosa-associated lymphoid tissue and lymphoplasmacytic lymphoma is discussed.

  2. Non-Hodgkin Lymphoma in Children.

    Science.gov (United States)

    Sandlund, John T

    2015-09-01

    The non-Hodgkin lymphomas (NHLs) of childhood include high-grade mature B cell lymphoma [Burkitt lymphoma (BL), diffuse large B cell lymphoma (DLBCL), and primary mediastinal large B cell lymphoma (PMLBCL)], anaplastic large cell lymphoma (ALCL), and lymphoblastic lymphoma (LL). The prognosis for children with NHL is generally excellent, although there are some higher risk groups. In this regard, PMLBCL is generally associated with a poorer outcome than BL or DLBCL of comparable stage. The long-term event-free survival for children with ALCL is approximately 70 %. Novel biological agents, including those that target CD-30 or ALK, may hold promise for improving treatment results. Children with LL are treated with regimens derived from those used to treat acute lymphoblastic leukemia (ALL). Recent biological study of LL may provide insights into revising treatment stratification. The challenge in pediatric NHL, a group that already has a relatively good prognosis, is to improve treatment outcome without increasing concerning late effects. PMID:26174528

  3. Prognostic value of Ki-67 protein in patients with diffuse large B-cell lymphoma%Ki-67对弥漫大B细胞淋巴瘤预后评估的意义

    Institute of Scientific and Technical Information of China (English)

    尚晋; 陈志忠; 魏天南; 陈为民

    2012-01-01

    Objective:To evaluate the expression of Ki-67 protein in patients with diffuse large B-cell lymphoma (DL-BCL) so as to analyze the clinical utility of Ki-67 for predicting prognosis. Method:The expression of Ki-67 was measured in 85 patients with DLBCL by Eli Vision plus method. Its relationship to clinical feature and prognosis was studied. Result: High-level expression of Ki-67 was found in 36(42.4%) of the 85 DLBCL patients. The high Ki-67 expression rate in non-GCB group was higher than that in GCB group(56.1% vs 29. 5%, P <0.05). The median of 24-months follow-up research revealed that progression-free survival (PFS) was significantly lower ( P <0.05) in the high Ki-67 expression group than in the low Ki-67 expression group (median,18 vs 31 months). Patients with high Ki-67 expression had lower PFS( P <0.05) when they were treated with R-CHOP regiment compared with standard CHOP regiment. On the other hand,PFS was similar between R-CHOP and CHOP groups in patients with low Ki-67 expression ( P >0. 05). Conclusion: Ki-67 can be used for predicting prognosis in patients with DLBCL. High Ki-67 expression is associated with non-GCB immunology type of DLBCL and poor survival . R-CHOP might be preferable to CHOP in patients with high Ki-67 expression.%目的:探讨Ki67蛋白在弥漫大B细胞淋巴瘤(DLBCL)组织中的表达情况及其对患者预后的意义.方法:采用EliVision plus免疫组织化学二步法测定85例DLBCL患者肿瘤组织中Ki-67蛋白的表达,前瞻性调查分析其与临床特征及疗效的关系.结果:85例DLBCL患者中36例(42.4%)肿瘤组织呈Ki-67蛋白高表达.Non-GCB组Ki-67高表达率为56.1%,GCB组Ki-67高表达率为29.5%,差异有统计学意义(P<0.05).中位随访24个月后,生存分析显示Ki-67高表达组中位疾病无进展生存时间(PFS)为18个月,短于Ki-67低表达组31个月,两组PFS差异有统计学意义(P<0.05).Ki-67高表达组接受R-CHOP方案化疗PFS长于CHOP方案

  4. Irreversible dual inhibitory mode: the novel Btk inhibitor PLS-123 demonstrates promising anti-tumor activity in human B-cell lymphoma

    OpenAIRE

    Ding, Ning; Li, Xitao; Shi, Yunfei; Ping, Lingyan; Wu, Lina; Fu, Kai; Feng, Lixia; Zheng, Xiaohui; Song, Yuqin; Pan, Zhengying; Zhu, Jun

    2015-01-01

    The B-cell receptor (BCR) signaling pathway has gained significant attention as a therapeutic target in B-cell malignancies. Recently, several drugs that target the BCR signaling pathway, especially the Btk inhibitor ibrutinib, have demonstrated notable therapeutic effects in relapsed/refractory patients, which indicates that pharmacological inhibition of BCR pathway holds promise in B-cell lymphoma treatment. Here we present a novel covalent irreversible Btk inhibitor PLS-123 with more poten...

  5. Hypercalcemia and huge splenomegaly presenting in an elderly patient with B-cell non-Hodgkin's lymphoma: a case report

    Directory of Open Access Journals (Sweden)

    Tirgari Farrokh

    2010-10-01

    Full Text Available Abstract Introduction Hypercalcemia is the major electrolyte abnormality in patients with malignant tumors. It can be due to localized osteolytic hypercalcemia or elaboration of humoral substances such as parathyroid hormone-related protein from tumoral cells. In hematological malignancies, a third mechanism of uncontrolled synthesis and secretion of 1-25(OH2D3 from tumoral cells or neighboring macrophages may contribute to the problem. However, hypercalcemia is quite unusual in patients with B-cell non-Hodgkin's lymphoma. Case presentation An 85-year-old Caucasian woman presented with low grade fever, anorexia, abdominal discomfort and fullness in her left abdomen for the last six months. She was mildly anemic and complained of fatigability. She had huge splenomegaly and was hypercalcemic. After correction of her hypercalcemia, she had a splenectomy. Microscopic evaluation revealed a malignant lymphoma. Her immunohistochemistry was positive for leukocyte common antigen, CD20 and parathyroid hormone-related peptide. Conclusion Immunopositivity for parathyroid hormone-related peptide clearly demonstrates that hypersecretion of a parathyroid hormone-like substance from the tumor had led to hypercalcemia in this case. High serum calcium is seen in only seven to eight percent of patients with B-cell non-Hodgkin's lymphoma, apparently due to different mechanisms. Evaluation of serum parathyroid hormone-related protein and 1-25(OH2D3 can be helpful in diagnosis and management. It should be noted that presentation with hypercalcemia has a serious impact on prognosis and survival.

  6. A Case Presenting with Splenic Infarct Diagnosed as Primary Bone Marrow CD5 Positive DLBCL: A Clinicopathological Correlation.

    Science.gov (United States)

    Bansal, Anupriya; Mittal, Suchi; Dass, Jasmita; Gupta, Nitin; Agarwal, P K; Kotwal, Jyoti

    2016-06-01

    De novo CD5+ Diffuse large B cell lymphoma (DLBCL) is a rare and aggressive subtype of DLBCL. It is a distinct clinicopathologic entity with complex molecular profile and poor prognosis. A 59 year old female presented with pyrexia of unknown origin since 1 month. On examination, there was severe pallor, hepatosplenomegaly and no palpable lymphadenopathy. Complete blood count revealed bicytopenia with normal total leucocyte count. Liver and renal function tests were normal. Ultrasonography abdomen revealed splenic enlargement with two focal lesions attributed to either splenic abscess or infarcts. Patient was being managed as splenic infarct but continued to have bicytopenia. Further investigation showed elevated serum ferritin, triglycerides and LDH. With a clinical suspicion of infection and haemophagocytic lymphohistiocytosis bone marrow aspiration (BMA) and biopsy (BMBx) was done. BMA showed extensive haemophagocytosis and ~7.4 % large lymphoma-like cells. On this basis PET-CT was suggested which showed enlarged spleen with diffuse uptake. BMBx showed nodular and intrasinusoidal collection of abnormal lymphoid cells. On immunohistochemistry, these cells were positive for CD20, CD5, MUM1, BCL-2, BCL-6 and negative for CD3, CD10 and CD23. CD34 highlighted focal intrasinusoidal pattern. The complete clinicopathological profile suggested the diagnosis of de novo CD5+ DLBCL, with primary hepatosplenic pattern of involvement. CD5+ DLBCL presenting as splenic infarct is very rare. This case was unusual as the diagnosis of a primary aggressive lymphoma with haemophagocytosis was established in a patient who presented with fever and splenic infarct without lymphadenopathy. This indicates the importance of good morphological assessment of a bone marrow aspirate and biopsy to make a correct diagnosis. PMID:27408381

  7. Excellent Outcome of Immunomodulation or Bruton’s Tyrosine Kinase Inhibition in Highly Refractory Primary Cutaneous Diffuse Large B-Cell Lymphoma, Leg Type

    OpenAIRE

    Eva Gupta; Joseph Accurso; Jason Sluzevich; Menke, David M.; Tun, Han W

    2015-01-01

    Primary cutaneous diffuse large B-cell lymphoma, leg type (PCDLBCL-LT) is a rare diffuse large B-cell lymphoma confined to the skin of the legs. The typical presentation is characterized by solitary or multiple growing plaques, usually confined to one leg. We report a case of PCDLBCL-LT of activated B-cell subtype characterized by multiple local relapses in the legs, initially, and systemic relapses about seven years after the diagnosis. Local relapses were sensitive to radiation therapy. Cut...

  8. Piperlongumine selectively suppresses ABC-DLBCL through inhibition of NF-κB p65 subunit nuclear import.

    Science.gov (United States)

    Niu, Mingshan; Shen, Yangling; Xu, Xiaoyu; Yao, Yao; Fu, Chunling; Yan, Zhiling; Wu, Qingyun; Cao, Jiang; Sang, Wei; Zeng, Lingyu; Li, Zhenyu; Liu, Xuejiao; Xu, Kailin

    2015-07-10

    Constitutive NF-κB activation is required for survival of activated B cell-like subtype of diffuse large B cell lymphoma (ABC-DLBCL). However, current NF-κB targeting strategies lack cancer cell specificity. Here, we identified a novel inhibitor, piperlongumine, features direct binding to NF-κB p65 subunit and suppression of p65 nuclear import. This was accompanied by NF-κB reporter activity suppression and NF-κB target gene downregulation. Moreover, mutation of Cys(38) to Ser in p65 abolished this effect of piperlongumine on inhibition of p65 nuclear import. Furthermore, we show that piperlongumine selectively inhibited proliferation and induced apoptosis of ABC-DLBCL cells. Most notably, it has been reported that piperlongumine did not affect normal cells even at high doses and was nontoxic to animals. Hence, our current study provides new insight into piperlongumine's mechanism of action and novel approach to ABC-DLBCL target therapy. PMID:25979358

  9. Bruton tyrosine kinase inhibitors: a promising novel targeted treatment for B cell lymphomas

    OpenAIRE

    Aalipour, Amin; Advani, Ranjana H.

    2013-01-01

    Constitutive or aberrant signalling of the B cell receptor signalling cascade has been implicated in the propagation and maintenance of a variety of B cell malignancies. Small molecule inhibitors of Bruton tyrosine kinase (BTK), a protein early in this cascade and specifically expressed in B cells, have emerged as a new class of targeted agents. There are several BTK inhibitors, including ONO-WG-307, LFM-A13, dasatinib, CC-292, and PCI-32765 (ibrutinib), in preclinical and/or clinical develop...

  10. Prevalence and chemotherapy-induced reactivation of occult hepatitis B virus among hepatitis B surface antigen negative patients with diffuse large B-cell lymphoma: Significance of hepatitis B core antibodies screening

    International Nuclear Information System (INIS)

    Background: Occult hepatitis B infection (OBI) is characterized by negative hepatitis B surface antigen (HBsAg) and detectable hepatitis B virus (HBV)-DNA in the liver and/or serum, with or without hepatitis B core antibody (anti-HBc). Anti-HBc is the most sensitive marker of previous HBV. HBV reactivation in patients under immunosuppressive treatment is life-threatening, occurring in both overt and occult HBV especially in hematological malignancies. Aim of the work: To evaluate the prevalence and chemotherapy-induced reactivation of OBI among hepatitis B surface antigen negative patients with diffuse large B-cell lymphoma (DLBCL) patients and to determine the significance of anti-HBc screening among this group of patients before receiving chemotherapy. Patients and methods: This cross-sectional study included 72 DLBCL patients negative for HBsAg, HBsAb and hepatitis C virus antibodies (anti-HCV). Patients were subjected to investigations including anti-HBc. All patients underwent alanine transaminase (ALT) monitoring before each cycle of chemotherapy and monthly for 12 months after the end of chemotherapy. Patients with suspected OBI were tested for HBV-DNA using real-time polymerase chain reaction (PCR). Results: Anti-HBc was detected in 10 of 72 HBsAg negative sera (13.89%) (95% confidence interval 6.9-22.2%). Five of the 10 anti-HBc positive patients in this study had OBI reactivation. Conclusion: The study concluded that anti-HBc screening is mandatory before chemotherapy. HBsAg-negative/anti-HBc-positive patients should be closely observed for signs of HBV reactivation through the regular monitoring of ALT. Prophylaxis lamivudine is recommended for anti-HBc positive patients before chemotherapy.

  11. Enhancer mutations of Akv murine leukemia virus inhibit the induction of mature B-cell lymphomas and shift disease specificity towards the more differentiated plasma cell stage

    DEFF Research Database (Denmark)

    Sørensen, Karina Dalsgaard; Kunder, Sandra; Quintanilla-Martinez, Leticia; Jonna, Sorensen; Jörg, Schmidt; Pedersen, Finn Skou

    2007-01-01

    , 25% follicular B-cell lymphomas and few splenic marginal zone and small B-cell lymphomas. Deleting one copy of the 99-bp proviral enhancer sequence still allowed induction of multiple B-cell tumor types, although PCPs dominated (77%). Additional mutation of binding sites for the glucocorticoid...... receptor, Ets, Runx, or basic helix-loop-helix transcription factors in the proviral U3 region, however, shifted disease induction to almost exclusively PCPs, but had no major influence on tumor latency periods. Southern analysis of immunoglobulin rearrangements and ecotropic provirus integration patterns...... showed that many of the tumors/cell proliferations induced by each virus were polyclonal. Our results indicate that enhancer mutations weaken the ability of Akv to induce mature B-cell lymphomas prior to the plasma cell stage, whereas development of plasma cell proliferations is less dependent of viral...

  12. Primary endobronchial marginal zone B-cell lymphoma of bronchus-associated lymphoid tissue: CT findings 7 patients

    Energy Technology Data Exchange (ETDEWEB)

    Yoon, Ra Gyoung; Kim, Mi Young; Song, Jae Woo; Chae, Eun Jin; Choi, Chang Min; Jang, Se Jin [University of Ulsan College of Medicine, Seoul (Korea, Republic of)

    2013-04-15

    To investigate CT and 1{sup 8F}-fluorodeoxyglucose (1{sup 8F}-FDG) positron-emission tomography/CT findings of primary endobronchial marginal zone B-cell lymphoma of the bronchus-associated lymphoid tissue (BALT). From June 2006 through April 2012, seven patients (six female, one male; age range, 21-61 years; mean age, 49 years) were examined who were pathologically diagnosed with the primary endobronchial marginal zone B-cell lymphoma of BALT. We evaluated the locations and characteristics of the lesions on CT and 1{sup 8F}-FDG-PET/CT scans. The lesions were classified into the following three patterns: 1) solitary intraluminal nodule; 2) several tiny nodular protrusions; and 3) diffuse wall thickening. A solitary intraluminal nodule was observed in four patients (57.1%), several tiny nodular protrusion in two patients (28.6%), and diffuse wall thickening in one patient (14.3%). The lesions were categorized into 3 major locations: confined to the trachea (n 3), confined to the lobar bronchus (n = 2), and diffuse involvement of the trachea and both main bronchi (n = 2). All lesions demonstrated homogeneous iso-attenuation as compared with muscle on pre- and post-enhancement scans. Secondary findings in the lungs (n = 3; 42.9%) included postobstructive lobar atelectasis (n = 1), air trapping (n = 1), and pneumonia (n = 1). On 1{sup 8F}-FDG-PET/CT (n = 5), 4 lesions showed homogeneous uptake with maximum standardized uptake values (mSUV), ranging 2.3-5.7 (mean mSUV: 3.3). One lesion showed little FDG uptake. Primary endobronchial marginal zone B-cell lymphoma of the BALT manifests as three distinct patterns on CT, with the solitary intraluminal nodule presenting as the main pattern. Most lesions demonstrate homogeneous but weak FDG uptake on 1{sup 8F}-FDG-PET/CT.

  13. Genetic aberrations in small B-cell lymphomas and leukemias: molecular pathology, clinical relevance and therapeutic targets.

    Science.gov (United States)

    Bogusz, Agata M; Bagg, Adam

    2016-09-01

    Small B-cell lymphomas and leukemias (SBCLs) are a clinically, morphologically, immunophenotypically and genetically heterogeneous group of clonal lymphoid neoplasms, including entities such as chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), mantle cell lymphoma (MCL), follicular lymphoma (FL), lymphoplasmacytic lymphoma (LPL), marginal zone lymphoma (MZL) and hairy cell leukemia (HCL). The pathogenesis of some of these lymphoid malignancies is characterized by distinct translocations, for example t(11;14) in the majority of cases of MCL and t(14;18) in most cases of FL, whereas other entities are associated with a variety of recurrent but nonspecific numeric chromosomal abnormalities, as exemplified by del(13q14), del(11q22), and +12 in CLL, and yet others such as LPL and HCL that lack recurrent or specific cytogenetic aberrations. The recent surge in next generation sequencing (NGS) technology has shed more light on the genetic landscape of SBCLs through characterization of numerous driver mutations including SF3B1 and NOTCH1 in CLL, ATM and CCND1 in MCL, KMT2D and EPHA7 in FL, MYD88 (L265P) in LPL, KLF2 and NOTCH2 in splenic MZL (SMZL) and BRAF (V600E) in HCL. The identification of distinct genetic lesions not only provides greater insight into the molecular pathogenesis of these disorders but also identifies potential valuable biomarkers for prognostic stratification, as well as specific targets for directed therapy. This review discusses the well-established and recently identified molecular lesions underlying the pathogenesis of SBCLs, highlights their clinical relevance and summarizes novel targeted therapies. PMID:27121112

  14. Experimental therapy of disseminated B-Cell lymphoma xenografts with 213Bi-labeled anti-CD74

    International Nuclear Information System (INIS)

    A 213Bi-labeled antibody to CD74 was evaluated as a therapeutic agent for B-cell lymphoma. The α-particle emission, with a half-life of 46 min, is appropriate for therapy of micrometastases. The labeled Ab retained full immunoreactivity, and was potent at single-cell kill of the Raji B-lymphoma cell line. Approximately 30 decays of cell-bound 213Bi was required for a cell kill of 99%, and dosimetry calculations suggested that the cGy dose delivered was sufficient to produce the level of toxicity observed. A non-reactive control Ab, labeled similarly, also produced toxicity, due to decays occurring in the medium, but was approximately 3-fold less potent than the reactive Ab. In a SCID mouse xenograft micrometastatic model, Ab injection at day 2 or day 5 after tumor inoculation resulted in strong, specific suppression of tumor growth, with some apparent cures

  15. Sporadic Burkitt's lymphoma/acute B-cell leukaemia presenting with progressive proptosis and orbital mass in a child.

    Science.gov (United States)

    Grasso, Daniela; Borreggine, Carmela; Ladogana, Saverio; De Santis, Raffaela; Delle Noci, Nicola; Grilli, Gianpaolo; Macarini, Luca

    2016-06-01

    Burkitt's lymphoma (BL) is an aggressive B-cell non-Hodgkin lymphoma that is found predominantly in children, with the highest incidence occurring in Africa. The sporadic form occurs in non-endemic areas and typically involves the ileo-caecum and the bowel, whereas orbital and paranasal sinus involvement is rare. Here, we present an unusual case of sporadic BL in a Caucasian male child with rapidly progressive painful proptosis of the right eye. Magnetic resonance imaging showed an oval-shaped, extraconal mass in the supero-lateral part of the right orbit that deformed and dislocated the eyeball antero-inferiorly. The patient underwent anterior orbitotomy, and a biopsy of the excised tissue revealed a starry-sky appearance characteristic of BL. Postoperative aggressive chemotherapy was initiated with a good response after one week. PMID:27006106

  16. B cell non-Hodgkin's lymphoma in a girl with the DiGeorge anomaly

    OpenAIRE

    J. Ramos; Lopez-Laso, E.; Ruiz-Contreras, J.; Giancaspro, E.; Madero, S.

    1999-01-01

    The DiGeorge anomaly (DGA) is occasionally associated with cellular immunodeficiency. We report a female infant diagnosed with complete DGA, who developed fatal, high grade, non-Hodgkin's lymphoma that expressed Epstein-Barr virus (EBV). Non-Hodgkin's lymphoma should be considered in children with DGA.



  17. Clinical experience with lenalidomide alone or in combination with rituximab in indolent B-cell and mantle cell lymphomas.

    Science.gov (United States)

    Ruan, J; Shah, B; Martin, P; Schuster, S J

    2016-07-01

    Lenalidomide is an oral immunomodulatory drug with significant activity in indolent B-cell and mantle cell lymphomas. Lenalidomide has a manageable safety profile whether administered as a single agent or in combination with rituximab. The combination of lenalidomide with rituximab, known as the 'R(2)' regimen, enhances efficacy over what has been shown with monotherapy and has demonstrated activity in patients considered resistant to rituximab. Tolerability of these regimens has been consistent among studies. Asymptomatic neutropenia is the most common grade 3/4 adverse event, typically managed by dose interruption, followed by dose reduction once neutrophils have recovered. Nonhematologic toxicities (e.g. fatigue) are generally low-grade, manageable with concomitant treatment, and/or lenalidomide dose modification. More frequent with R(2), immune-related symptoms such as rash and tumor flare are important to recognize as lenalidomide-associated treatment effects in patients with lymphoma who require supportive care and potential dose modifications. Severe tumor flare reactions with painful lymphadenopathy are not typically observed outside of chronic lymphocytic leukemia/small lymphocytic lymphoma. Venous thromboembolism is uncommon in lymphomas, though prophylaxis is recommended. The general safety profile, differences between lenalidomide monotherapy and R(2) treatment, and optimal strategies for managing adverse events are discussed here. PMID:27052651

  18. Clinicopathological Analysis of Ocular Adnexal Extranodal Marginal Zone B-Cell Lymphoma with IgG4-Positive Cells

    OpenAIRE

    Lee, Min Joung; Kim, Namju; Choe, Ji-Young; Khwarg, Sang In; Jeon, Yoon Kyung; Choung, Ho-Kyung; Kim, Ji Eun

    2015-01-01

    This study aims to analyze clinical and pathological characteristics of ocular adnexal extranodal marginal zone B-cell lymphoma (EMZL) accompanying IgG4-positive cells. Fifty patients with a diagnosis of primary non-conjunctival ocular adnexal EMZL were enrolled in this study. The number of IgG4-positive cells and the ratio of IgG/IgG4 were evaluated by immunohistochemistry in the biopsy specimens. The patients were divided into two groups based on the absolute number and the ratio of IgG4-po...

  19. Synthetic Peptide Ligands of the Antigen Binding Receptor Induce Programmed Cell Death in a Human B-Cell Lymphoma

    Science.gov (United States)

    Renschler, Markus F.; Bhatt, Ramesh R.; Dower, William J.; Levy, Ronald

    1994-04-01

    Peptide ligands for the antigen binding site of the surface immunoglobulin receptor of a human B-cell lymphoma cell line were identified with the use of filamentous phage libraries displaying random 8- and 12-amino acid peptides. Corresponding synthetic peptides bound specifically to the antigen binding site of this immunoglobulin receptor and blocked the binding of an anti-idiotype antibody. The ligands, when conjugated to form dimers or tetramers, induced cell death by apoptosis in vitro with an IC50 between 40 and 200 nM. This effect was associated with specific stimulation of intracellular protein tyrosine phosphorylation.

  20. The utility of lactate dehydrogenase in the follow up of patients with diffuse large B-cell lymphoma

    Directory of Open Access Journals (Sweden)

    Basem Magdy William

    2013-06-01

    Full Text Available Background: Serum lactate dehydrogenase is a non-specific marker for lymphoma whose prognostic significance is well established for both indolent and aggressive lymphomas at the time of diagnosis. The performance characteristics of this enzyme in predicting relapse in patients with diffuse large B-cell lymphoma has not been well studied. Methods: This study compared serum lactate dehydrogenase levels in 27 patients with diffuse large B-cell lymphoma who relapsed after sustaining a complete response versus 87 patients who did not relapse. For relapsed patients, the serum lactate dehydrogenase level at relapse was compared with the level three months before (considered baseline. For non-relapsed patients, the last two levels during follow-up were compared. For statistical analysis the T-test was used to compare differences in mean values between groups. The sensitivity, specificity, positive and negative predictive values for serum lactate dehydrogenase in detecting relapse compared to confirmatory imaging were calculated. Results: At relapse, only 33% patients had increases in serum lactate dehydrogenase above the upper limit of normal. The mean increase was 1.2-fold above the upper limit of normal for relapsed vs. 0.83 for those who did not relapse (p-value = 0.59. The mean increase in serum lactate dehydrogenase, from baseline, was 1.1-fold in non-relapsed vs. 1.3 in relapsed patients (p-value = 0.3. The likelihood ratio of relapse was 4.65 for patients who had 1.5-fold increases in serum lactate dehydrogenase above baseline (p-value = 0.03. The sensitivity, specificity, positive and negative predictive values of 1.5-fold increases for detecting relapse, compared to clinical and imaging findings were 0.18, 0.95, 0.55, and 0.79, respectively. Conclusion: A 1.5-fold increase in serum lactate dehydrogenase, over a period of 3 months, is associated with increased likelihood of relapse from diffuse large B-cell lymphoma.

  1. Downregulation of B-cell lymphoma/leukemia-2 by overexpressed microRNA 34a enhanced titanium dioxide nanoparticle-induced autophagy in BEAS-2B cells

    Science.gov (United States)

    Bai, Wenlin; Chen, Yujiao; Sun, Pengling; Gao, Ai

    2016-01-01

    Titanium dioxide (TiO2) nanoparticles (TNPs) are manufactured worldwide for a wide range of applications and the toxic effect of TNPs on biological systems is gaining attention. Autophagy is recognized as an emerging toxicity mechanism triggered by nanomaterials. MicroRNA 34a (miR34a) acts as a tumor suppressor gene by targeting many oncogenes, but how it affects autophagy induced by TNPs is not completely understood. Here, we observed the activation of TNP-induced autophagy through monodansylcadaverine staining and LC3-I/LC3-II conversion. Meanwhile, the transmission electron microscope ultrastructural analysis showed typical morphological characteristics in autophagy process. We detected the expression of miR34a and B-cell lymphoma/leukemia-2 (Bcl-2). In addition, the underlying mechanism of TNP-induced autophagy was performed using overexpression of miR34a by lentivirus vector transfection. Results showed that TNPs induced autophagy generation evidently. Typical morphological changes in the process of autophagy were observed by the transmission electron microscope ultrastructural analysis and LC3-I/LC3-II conversion increased significantly in TNP-treated cells. Meanwhile, TNPs induced the downregulation of miR34a and increased the expression of Bcl-2. Furthermore, overexpressed miR34a decreased the expression of Bcl-2 both in messenger RNA and protein level, following which the level of autophagy and cell death rate increased after the transfected cells were incubated with TNPs for 24 hours. These findings provide the first evidence that overexpressed miR34a enhanced TNP-induced autophagy and cell death through targeted downregulation of Bcl-2 in BEAS-2B cells.

  2. Primary breast lymphoma: A single-institute experience in Taiwan

    Directory of Open Access Journals (Sweden)

    Che-Wei Ou

    2014-10-01

    Full Text Available Background: Breast is an uncommon location of lymphoma involvement. The most common type of primary breast lymphoma (PBL is diffuse large B-cell lymphoma (DLBCL. Rituximab is the widely used monoclonal antibody against CD20+ B-cell lymphoma, especially DLBCL. We aimed to analyze the clinical features, prognostic factors, and treatment outcome with or without rituximab in primary breast DLBCL. Methods: We retrospectively analyzed patients diagnosed with PBL from October 1987 to March 2012 in our hospital, excluding metastasis by whole-body computed tomography and bone marrow study. Results: Twenty-three patients were diagnosed with PBL. All were females. Eighteen patients were stage IE and five were stage IIE according to the Ann Arbor staging system. Two patients had lymphoma other than DLBCL. The median age of primary breast DLBCL patients was 48 years (range 27-79. Two were excluded from the analysis due to refusal or ineligibility for chemotherapy. No significant prognostic factor was found. Patients receiving chemotherapy with (RC or without (C rituximab were not significantly different in the 5-year overall survival (RC: 57.1%; C: 58.3%; p = 0.457 or progression-free survival (RC: 57.1%; C: 50.0%; p = 0.456. A high incidence of relapse in the central nervous system (CNS (17.6% was observed. Conclusions: In accordance with prior literature reports, our Taiwanese cohort of primary breast DLBCL seemed younger than those reported in Japan, Korea, and Western societies. Relapse in the CNS was not uncommon. The benefit of rituximab in addition to chemotherapy was not statistically significant. Treatment modality remained to be defined by further large-scale studies.

  3. Diffuse Large B-Cell Lymphoma Transformed from Mucosa-Associated Lymphoid Tissue Lymphoma Arising in a Female Urethra Treated with Rituximab for the First Time

    OpenAIRE

    Zahrani, A. Al; Abdelsalam, M.; Fiaar, A. Al; Ibrahim, N.; Al-Elawi, A.; Muhammad, B

    2012-01-01

    A 30-year-old female patient presented to the gynecology clinic with a small (painless) swelling at the urethral orifice. She underwent surgical excision of the lesion. Pathological examination revealed non-Hodgkin's lymphoma of diffuse large B-cell type and mucosa-associated lymphoid tissue type, stage IE. The patient refused radiotherapy. Accordingly, we started CHOP-R chemotherapy. She received a total of 6 cycles of CHOP and 8 cycles of rituximab. Patient follow-up was done 3 months later...

  4. Patterns of Failure in Advanced Stage Diffuse Large B-Cell Lymphoma Patients After Complete Response to R-CHOP Immunochemotherapy and the Emerging Role of Consolidative Radiation Therapy

    Energy Technology Data Exchange (ETDEWEB)

    Shi, Zheng [Department of Radiation Oncology, Emory University, Atlanta, Georgia (United States); Winship Cancer Institute, Emory University, Atlanta, Georgia (United States); Das, Satya; Okwan-Duodu, Derick [Emory University School of Medicine, Atlanta, Georgia (United States); Esiashvili, Natia [Department of Radiation Oncology, Emory University, Atlanta, Georgia (United States); Winship Cancer Institute, Emory University, Atlanta, Georgia (United States); Flowers, Christopher [Winship Cancer Institute, Emory University, Atlanta, Georgia (United States); Department of Medical Oncology, Emory University, Atlanta, Georgia (United States); Chen, Zhengjia; Wang, Xiaojing [Winship Cancer Institute, Emory University, Atlanta, Georgia (United States); Department of Biostatistics and Bioinformatics, Emory University, Atlanta, Georgia (United States); Jiang, Kun [Department of Pathology, Emory University, Atlanta, Georgia (United States); Nastoupil, Loretta J. [Winship Cancer Institute, Emory University, Atlanta, Georgia (United States); Department of Medical Oncology, Emory University, Atlanta, Georgia (United States); Khan, Mohammad K., E-mail: drkhurram2000@gmail.com [Department of Radiation Oncology, Emory University, Atlanta, Georgia (United States); Winship Cancer Institute, Emory University, Atlanta, Georgia (United States)

    2013-07-01

    Purpose: The role of consolidative radiation therapy (RT) after complete response (CR) to rituximab combined with cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) for stage III-IV diffuse large B-cell lymphoma (DLBCL) patients is unclear. We aimed to evaluate our institutional experience when consolidative RT is delivered to initial presenting sites or bulky sites in these patients. Methods and Materials: We identified 211 histologically confirmed stage III-IV DLBCL patients who received R-CHOP from January 2000 to May 2012 at our institution. Patterns of failure for patients who achieved CR to R-CHOP were analyzed. Local control (LC), distant control (DC), progression-free survival (PFS), and overall survival (OS) were estimated using Kaplan-Meier method and compared between patients who received R-CHOP alone versus R-CHOP plus consolidative RT using the log–rank test. Multivariate analyses were also performed using Cox proportional hazards model. Results: Detailed treatment records were available for 163 patients. After a median 6 cycles of R-CHOP, 110 patients (67.5%) achieved CR and were entered for analysis. Fourteen patients (12.7%) received consolidative RT. After median follow-up of 32.9 months, 43.8% of patients who received R-CHOP alone failed at the initial sites with or without distant recurrence (DR), whereas isolated DR only occurred in 3.7% of these patients. Consolidative RT was associated with significantly improved LC (91.7% vs 48.8%), DC (92.9% vs 71.9%), PFS (85.1% vs 44.2%), and OS (92.3% vs 68.5%; all Ps<.0001) at 5 years compared with patients with R-CHOP alone. On multivariate analysis, consolidative RT and nonbulky disease were predictive of increased LC and PFS, whereas bone marrow involvement was associated with increased risk of DR and worse OS. Consolidative RT was also associated with marginal improved OS. Conclusions: Forty-four percent of patients with advanced stage DLBCL failed at initial presenting sites after

  5. Enhancer mutations of Akv murine leukemia virus inhibit the induction of mature B-cell lymphomas and shift disease specificity towards the more differentiated plasma cell stage

    International Nuclear Information System (INIS)

    This study investigates the role of the proviral transcriptional enhancer for B-lymphoma induction by exogenous Akv murine leukemia virus. Infection of newborn inbred NMRI mice with Akv induced 35% plasma cell proliferations (PCPs) (consistent with plasmacytoma), 33% diffuse large B-cell lymphomas, 25% follicular B-cell lymphomas and few splenic marginal zone and small B-cell lymphomas. Deleting one copy of the 99-bp proviral enhancer sequence still allowed induction of multiple B-cell tumor types, although PCPs dominated (77%). Additional mutation of binding sites for the glucocorticoid receptor, Ets, Runx, or basic helix-loop-helix transcription factors in the proviral U3 region, however, shifted disease induction to almost exclusively PCPs, but had no major influence on tumor latency periods. Southern analysis of immunoglobulin rearrangements and ecotropic provirus integration patterns showed that many of the tumors/cell proliferations induced by each virus were polyclonal. Our results indicate that enhancer mutations weaken the ability of Akv to induce mature B-cell lymphomas prior to the plasma cell stage, whereas development of plasma cell proliferations is less dependent of viral enhancer strength

  6. An Unusual Case of Marginal Zone B-Cell Lymphoma Arising in the Breast - Its Diagnosis and the Role of Radiotherapy in its Management.

    LENUS (Irish Health Repository)

    Rock, Kathy

    2011-10-01

    BACKGROUND: Primary lymphoma of the breast accounts for 0.04-0.5% of all breast malignancies and approximately 1% of all extranodal lymphomas. For stage IE node-negative disease, involved field radiotherapy is recommended except for very young women in whom the risk of breast cancer is a concern. The rate of complete response for limited stage extranodal marginal B-cell lymphoma is in excess of 90%. CASE REPORT: We report the case of a 62-year-old lady who presented with a unilateral painless palpable right breast lump. She subsequently underwent a trucut biopsy of the lesion. The histology revealed a low-grade B-cell non-Hodgkin\\'s lymphoma (NHL). Immunohistochemistry showed that more than 95% of the cells were B cells which were CD 20+\\/CD 45+ and BC L6+. This confirmed the diagnosis of marginal zone lymphoma. Staging work-up was negative for distant metastases. Serum alkaline phosphatase and lactate dehydrogenase were normal. The patient had no \\'B\\' symptoms. Her final diagnosis was clinical stage IAE NHL, and she was referred for curative radiotherapy. CONCLUSION: Radiation treatment is a safe and extremely effective modality of treatment for early stage I marginal zone B-cell lymphomas of the breast.

  7. Immunotherapy for B-Cell Lymphoma: Current Status and Prospective Advances

    OpenAIRE

    Hollander, Nurit

    2012-01-01

    Therapy for non-Hodgkin’s lymphoma has progressed significantly over the last decades. However, the majority of patients remain incurable, and novel therapies are needed. Because immunotherapy ideally offers target selectivity, an ever increasing number of immunotherapies, both passive and active, are undergoing development. The champion of passive immunotherapy to date is the anti-CD20 monoclonal antibody rituximab that revolutionized the standard of care for lymphoma. The great success of r...

  8. Histological analysis on adhesive molecules of renal intravascular large B cell lymphoma treated with CHOP chemotherapy and rituximab.

    Science.gov (United States)

    Kusaba, T; Hatta, T; Tanda, S; Kameyama, H; Tamagaki, K; Okigaki, M; Inaba, T; Shimazaki, C; Sasaki, S

    2006-03-01

    A 48-year-old man was admitted to our hospital for investigation of mild renal dysfunction. A blood examination revealed mild elevation of creatinine level (1.77 mg/dl). Urinary examination revealed mild protein excretion (0.54 g/day) and microhematuria; renal biopsy revealed the focal proliferation of large mononuclear cells with mitosis in glomerular capillaries. According to immunohistochemical analysis, the intravascular lymphomatous cells stained positively with anti-leukocyte common antigen (LCA: CD45) and CD20, indicating a B lymphocyte lineage. In electron microscopy, the glomerular capillary was filled with lymphoma cells and epithelial foot process fusion was noted. Immunohistochemical analysis on adhesive molecules revealed a lack of CD11a expression on lymphoma cells, but positive CD54 expression on endothelial cells. Systemic 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) revealed no abnormal uptake of isotopes. On the basis of these findings, we diagnosed intravascular diffuse large B cell lymphoma localized in the kidney. Despite treatment with rituximab and CHOP (prednisolone, doxorubicin, vincristine, cyclophosphamide) for 3 cycles at 1-month intervals, the renal dysfunction did not change. In histopathological analysis of the second biopsy, lymphoma cells disappeared, but focal segmental glomerulosclerosis and moderate interstitial fibrosis were noted. Electron microscopic findings revealed severe subendothelial edema with mesangial interposition, indicating severe endothelial damage. Epithelial foot process fusion was improved. These pathological analyses let us conclude that a lack of CD11a could be a candidate factor for prevention of the extravasation of lymphoma cells from blood vessels in our patient. We also presumed that the intraglomerular endothelial damage occurred due to chemotherapy-associated cell injury. PMID:16550755

  9. In vivo biotinylation of the vasculature in B-cell lymphoma identifies BST-2 as a target for antibody-based therapy.

    Science.gov (United States)

    Schliemann, Christoph; Roesli, Christoph; Kamada, Haruhiko; Borgia, Beatrice; Fugmann, Tim; Klapper, Wolfram; Neri, Dario

    2010-01-21

    The discovery of accessible markers of lymphoma may facilitate the development of antibody-based therapeutic strategies. Here, we describe the results of a chemical proteomic study, based on the in vivo biotinylation of vascular proteins in lymphoma-bearing mice followed by mass spectrometric and bioinformatic analysis, to discover proteins expressed at the tissue-blood border of disseminated B-cell lymphoma. From a list of 58 proteins, which were more than 10-fold up-regulated in nodal and extranodal lymphoma lesions compared with their levels in the corresponding normal host organs, we validated BST-2 as a novel vascular marker of B-cell lymphoma, using immunochemical techniques and in vivo biodistribution studies. Furthermore, targeting BST-2 with 2 independent monoclonal antibodies delayed lymphoma growth in a syngeneic mouse model of the disease. The results of this study delineate a strategy for the treatment of systemic B-cell lymphoma in humans and suggest that anti-BST-2 antibodies may facilitate pharmacodelivery approaches that target the tumor-stroma interface. PMID:19903902

  10. Hepatitis B virus reactivation and hepatitis in diffuse large B-cell lymphoma patients with resolved hepatitis B receiving rituximab-containing chemotherapy:risk factors and survival

    Institute of Scientific and Technical Information of China (English)

    Kai-Lin Chen; De-Hui Zou; Li-Yang Hu; Michael Lucas Wirian; Qing-Qing Cai; Jie Chen; Hui-Lan Rao; Ying Guo; Hui-Qiang Huang; Liang Zhang; Jian-Yong Shao; Tong-Yu Lin; Wen-Qi Jiang

    2015-01-01

    Introduction:Hepatitis B virus (HBV) reactivation has been reported in B-cel lymphoma patients with resolved hepatitis B (hepatitis B surface antigen [HBsAg]-negative and hepatitis B core antibody [HBcAb]-positive). This study aimed to assess HBV reactivation and hepatitis occurrence in diffuse large B-cel lymphoma (DLBCL) patients with resolved hepatitis B receiving rituximab-containing chemotherapy compared with HBsAg-negative/HBcAb-negative patients to identify risk factors for HBV reactivation and hepatitis occurrence and to analyze whether HBV reactivation and hepatitis affect the survival of DLBCL patients with resolved hepatitis B. Methods:We reviewed the clinical data of 278 patients with DLBCL treated with rituximab-containing therapy between January 2004 and May 2008 at Sun Yat-sen University Cancer Center, China. Predictive factors for HBV reactivation, hepatitis development, and survival were examined by univariate analysis using the chi-square or Fisher’s exact test and by multivariate analysis using the Cox regression model. Results:Among the 278 patients, 165 were HBsAg-negative. Among these 165 patients, 6 (10.9%) of 55 HBcAb-positive (resolved HBV infection) patients experienced HBV reactivation compared with none (0%) of 110 HBcAb-negative patients (P=0.001). Patients with resolved hepatitis B had a higher hepatitis occurrence rate than HBsAg-negative/HBcAb-negative patients (21.8%vs. 8.2%, P=0.013). HBcAb positivity and elevated baseline alanine aminotransferase (ALT) levels were independent risk factors for hepatitis. Among the 55 patients with resolved hepatitis B, patients with elevated baseline serum ALT or aspartate aminotransferase (AST) levels were more likely to develop hepatitis than those with normal serum ALT or AST levels (P=0.037, P=0.005, respectively). An elevated baseline AST level was an independent risk factor for hepatitis in these patients. Six patients with HBV reactivation recovered after immediate antiviral therapy, and

  11. From the radiologic pathology archives: gastrointestinal lymphoma: radiologic and pathologic findings.

    Science.gov (United States)

    Lewis, Rachel B; Mehrotra, Anupamjit K; Rodríguez, Pablo; Manning, Maria A; Levine, Marc S

    2014-01-01

    Gastrointestinal (GI) lymphoma encompasses a heterogeneous group of neoplasms that have a common lymphoid origin but variable pathologic and imaging features. Extranodal marginal zone B-cell lymphoma (ENMZL) and diffuse large B-cell lymphoma (DLBCL) are the most common. ENMZL usually occurs in the stomach, where it is associated with chronic infection by Helicobacter pylori, and is typically a superficial spreading lesion that causes mucosal nodularity or ulceration and mild wall thickening. DLBCL may arise de novo or from transformation of ENMZL or other low-grade lymphomas. This form of lymphoma produces extensive wall thickening or a bulky mass, but obstruction is uncommon. Mantle cell lymphoma is the classic cause of lymphomatous polyposis, but multiple polyps or nodules can also be seen with ENMZL and follicular lymphoma. Burkitt lymphoma is usually characterized by an ileocecal mass or wall thickening in the terminal ileum in young children, often in the setting of widespread disease. Primary GI Hodgkin lymphoma, which is rare, may be manifested by a variety of findings, though stenosis is more common than with non-Hodgkin lymphoma. Enteropathy-associated T-cell lymphoma is frequently associated with celiac disease and is characterized by wall thickening, ulceration, and even perforation of the jejunum. Accurate radiologic diagnosis of GI lymphoma requires a multifactorial approach based on the clinical findings, site of involvement, imaging findings, and associated complications. PMID:25384294

  12. Non-Hodgkin’s lymphoma with bone involvement: a single center experience with 18 patients

    OpenAIRE

    Filiz Vural; Nur Akad Soyer; Pınar Özen; Ayhan Dönmez; Serkan Ocakçı; Güray Saydam; Seçkin Çağırgan; Murat Tombuloğlu

    2010-01-01

    Objective: Non-Hodgkin’s lymphoma (NHL) of bone is a rare entity. The most common histological subtype is diffuse large B cell lymphoma (DLBCL). The major presenting symptoms are soft tissue swelling, bone pain and pathological fracture. Treatment options are chemotherapy, radiotherapy, surgery, or a combination of these modalities. Materials and Methods: We retrospectively analyzed the 18 patients (11 females, 7 males) with NHL of bone who were diagnosed and treated between 1995-2005. The me...

  13. CD5-positive marginal zone B-cell lymphoma of the mucosa-associated lymphoid tissue (MALT of the lung

    Directory of Open Access Journals (Sweden)

    Terada Tadashi

    2012-02-01

    Full Text Available Abstract CD5-positive marginal zone B-cell lymphoma of the mucosa-associated lymphoid tissue (MALT of the lung is very rare. An 82-year-old Japanese woman was found to have an abnormal lung shadow on chest X-ray photography, and was admitted to our hospital. Imaging modalities including X-ray photography, computed tomography, and magnetic resonance imaging showed a small (2 × 1 × 1 cm opacity of the right upper lobe. Transbronchial lung biopsy was performed. It showed severe proliferation of small lymphocytes. The small lymphocytes were centrocytes-like, and minor plasma cell differentiation was recognized. Lymphoepithelial lesions were scattered. Immunohistochemically, the tumor cells were positive for CD5, CD20, CD43, CD45, CD79α, bcl-2, and κ-chain, but negative for CD2, CD3, CD10, CD21, CD23, CD35, CD45RO, CD56, IgA, IgG, IgM, IgD, λ-chain, TdT, and cyclin D1. The Ki-67 labeling was 10%. CD3-positive and CD45RO-positive inflammatory T-cells were scattered in small amount. The pathological diagnosis was CD5-positive marginal zone B-cell lymphoma of the mucosa-associated lymphoid tissue (MALT of the lung. The patient was treated with chemotherapy (CHOP: cyclophosphamide, hydroxydaunorbicin, vincristine, and predonisone, and the lung tumor disappeared. The patient is now free of the lymphoma 10 years after the first manifestation. Virtual slides The virtual slide(s for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1541653085652296

  14. Elucidation of tonic and activated B-cell receptor signaling in Burkitt's lymphoma provides insights into regulation of cell survival.

    Science.gov (United States)

    Corso, Jasmin; Pan, Kuan-Ting; Walter, Roland; Doebele, Carmen; Mohr, Sebastian; Bohnenberger, Hanibal; Ströbel, Philipp; Lenz, Christof; Slabicki, Mikolaj; Hüllein, Jennifer; Comoglio, Federico; Rieger, Michael A; Zenz, Thorsten; Wienands, Jürgen; Engelke, Michael; Serve, Hubert; Urlaub, Henning; Oellerich, Thomas

    2016-05-17

    Burkitt's lymphoma (BL) is a highly proliferative B-cell neoplasm and is treated with intensive chemotherapy that, because of its toxicity, is often not suitable for the elderly or for patients with endemic BL in developing countries. BL cell survival relies on signals transduced by B-cell antigen receptors (BCRs). However, tonic as well as activated BCR signaling networks and their relevance for targeted therapies in BL remain elusive. We have systematically characterized and compared tonic and activated BCR signaling in BL by quantitative phosphoproteomics to identify novel BCR effectors and potential drug targets. We identified and quantified ∼16,000 phospho-sites in BL cells. Among these sites, 909 were related to tonic BCR signaling, whereas 984 phospho-sites were regulated upon BCR engagement. The majority of the identified BCR signaling effectors have not been described in the context of B cells or lymphomas yet. Most of these newly identified BCR effectors are predicted to be involved in the regulation of kinases, transcription, and cytoskeleton dynamics. Although tonic and activated BCR signaling shared a considerable number of effector proteins, we identified distinct phosphorylation events in tonic BCR signaling. We investigated the functional relevance of some newly identified BCR effectors and show that ACTN4 and ARFGEF2, which have been described as regulators of membrane-trafficking and cytoskeleton-related processes, respectively, are crucial for BL cell survival. Thus, this study provides a comprehensive dataset for tonic and activated BCR signaling and identifies effector proteins that may be relevant for BL cell survival and thus may help to develop new BL treatments. PMID:27155012

  15. Primary Diffuse Large B-Cell Lymphoma of Central Nervous System: Is Still Surgery an Unorthodox Treatment?

    Science.gov (United States)

    Siasios, Ioannis; Fotiadou, Aggeliki; Fotakopoulos, George; Ioannou, Maria; Anagnostopoulos, Vassilios; Fountas, Konstantinos

    2015-12-01

    Primary central nervous system lymphoma (PCNSL) is characterized as an extra-nodal non-Hodgkin lymphoma which develops from the neuraxis. The purpose was to report a case of a patient with a supra-tentorial tumor who underwent subtotal resection of his tumor as his biopsy was not indicative of a PCNSL tumor and had uneventful recovery until his last follow-up. A 42-year-old man was admitted to our department for generalized epileptic seizures. CT and MRI examinations revealed a tumor in his right parietal-occipital lobe that was surrounded by edema and was enhancing after gadolinium administration. The patient underwent a navigation-assisted parieto-occipital craniotomy and posterior parietal transcortical approach for tumor biopsy which was not indicative of PCNSL tumor. The surgical team decided to remove the tumor on site. Histological analysis of the resected specimen showed primary diffuse large B-cell lymphoma. Combined chemotherapy and radiation therapy was applied to the patient, and at his last follow-up (16 months), he is tumor free. In our case as in several other studies during the last decade, the outcome after the surgical resection of a PCNSL tumor in combination to radiation and chemotherapy was unexpectedly good. The role of surgery probably should be reconsidered for single lesion PCNSL tumors. PMID:26566417

  16. Improvement of recurrent urticaria in a patient with Schnitzler syndrome associated with B-cell lymphoma with combination rituximab and radiotherapy.

    Science.gov (United States)

    Murota, Hiroyuki; Shoda, Yukiko; Ishibashi, Tomohiko; Sugahara, Hiroyuki; Matsumura, Itaru; Katayama, Ichiro

    2009-12-01

    Schnitzler syndrome is a rare condition defined by chronic urticaria, osteosclerotic bone lesions, and monoclonal IgM gammopathy. Schnitzler syndrome can precede the onset of a true lymphoproliferative disorder including Waldenström macroglobulinemia and rarely systemic marginal zone B-cell lymphoma. We describe a case of intractable chronic urticaria accompanied by a retroperitoneal neoplasm. IgM monoclonal gammopathy, lumber pain, intermittent fever, and elevation of C-reactive protein were the clues for the diagnosis of Schnitzler syndrome. An evaluation for malignancy using systemic computed tomography scan and fluorodeoxyglucose positron emission tomography revealed the retroperitoneal tumor, and a subsequent bone-marrow aspirate confirmed the diagnosis of B-cell lymphoma. Combined rituximab and radiotherapy ameliorated the skin symptoms. This case indicates that a detailed search for malignant neoplasms might be required for the long-term management of Schnitzler syndrome, and that B-cell lymphomas may contribute to the pathogenesis of this condition. PMID:19632739

  17. A Clinical Analysis of 194 Cases of Diffuse Large B-cell Lymphoma%弥漫大B细胞淋巴瘤194例临床分析

    Institute of Scientific and Technical Information of China (English)

    敬小梅; 吴萍; 李力; 熊竹娟; 任苑蓉; 魏雯; 张智慧

    2015-01-01

    Objective:To analyze the clinical chracteristics,therapeutic approach of diffuse large B-cell lymphoma (DLBCL),and to explore the influence factors on the therapeutic effect and prognosis of DLBCL.Methods:A total of 194 DLBCL patients treated in Sichuan Cancer Hospital from 2009 to 2014 were selected,the general clinical characteristics were analyzed to determine the relationship of relevant factors with therapeutic effect and prognosis.The patients were trea-ted with chemotherapy or chemoradiotherapy.The chemotherapy regimens included CHOP and R-CHOP.Results:The me-dian age of the 194 patients was 53 years.The ratio of male:female was 1.66:1.Among 184 patients who accepted treat-ment,68 cases(37.0%)got complete remission (CR)and 72 cases(39.1%)got partial remission (PR)after treatment with an effective rate of 76.1% in all.Univariate analysis showed that the complications of patients、extranodal involve-ment、the serum level of LDH、B symptom、bulky disease、the level of hemoglobin、the clinical stage and cell origins were im-portant influence factors for curative effect.The extranodal involvement、bulky disease and the clinical stage had significant influence on the survival rate of patients (P <0.05).In Cox multivariable analysis,the clinical factors including clinical stage and bulky disease were independent predicting factors for overall survival(OS)(P <0.05).R-CHOP can extend the OS of patients remarkably(P <0.05).Conclusion:DLBCL commonly occurs in male patients at middle ages.The clinical stage and bulky disease are independent factors for the OS of DLBCL.R-CHOP may be the best effective approach for treat-ment of this disease.%目的:分析弥漫大 B 细胞淋巴瘤(DLBCL)的临床特征和治疗方法,探讨 DLBCL 的疗效及预后影响因素。方法:对我院2009~2014年收治的194例 DLBCL 的临床资料进行回顾性分析,以确定相关因素与疗效及预后的关系。治疗方法包括单纯化疗及

  18. Characterization of intratumoral follicular helper T cells in follicular lymphoma: role in the survival of malignant B cells

    Science.gov (United States)

    Amé-Thomas, Patricia; Le Priol, Jérôme; Yssel, Hans; Caron, Gersende; Pangault, Céline; Jean, Rachel; Martin, Nadine; Marafioti, Teresa; Gaulard, Philippe; Lamy, Thierry; Fest, Thierry; Semana, Gilbert; Tarte, Karin

    2012-01-01

    Accumulating evidences indicate that the cellular and molecular microenvironment of follicular lymphoma (FL) plays a key role in both lymphomagenesis and patient outcome. Malignant FL B cells are found admixed to specific stromal and immune cell subsets, in particular CD4pos T cells displaying phenotypic features of follicular helper T cells (TFH). The goal of our study was to functionally characterize intratumoral CD4pos T cells. We showed that CXCR5hiICOShiCD4pos T cells sorted from FL biopsies comprise at least two separate cell populations with distinct genetic and functional features: i) CD25pos follicular regulatory T cells (TFR), and ii) CD25neg TFH displaying a FL-B cell supportive activity without regulatory functions. Furthermore, despite their strong similarities with tonsil-derived TFH, purified FL-derived TFH displayed a specific gene expression profile including an overexpression of several genes potentially involved directly or indirectly in lymphomagenesis, in particular TNF, LTA, IL4, or CD40LG. Interestingly, we further demonstrated that these two last signals efficiently rescued malignant B cells from spontaneous and Rituximab-induced apoptosis. Altogether, our study demonstrates that tumor-infiltrating CD4pos T cells are more heterogeneous than previously presumed, and underlines for the first time the crucial role of TFH in the complex set of cellular interactions within FL microenvironment. PMID:22015774

  19. Array-based DNA methylation profiling of primary lymphomas of the central nervous system

    International Nuclear Information System (INIS)

    Although primary lymphomas of the central nervous system (PCNSL) and extracerebral diffuse large B-cell lymphoma (DLBCL) cannot be distinguished histologically, it is still a matter of debate whether PCNSL differ from systemic DLBCL with respect to their molecular features and pathogenesis. Analysis of the DNA methylation pattern might provide further data distinguishing these entities at a molecular level. Using an array-based technology we have assessed the DNA methylation status of 1,505 individual CpG loci in five PCNSL and compared the results to DNA methylation profiles of 49 DLBCL and ten hematopoietic controls. We identified 194 genes differentially methylated between PCNSL and normal controls. Interestingly, Polycomb target genes and genes with promoters showing a high CpG content were significantly enriched in the group of genes hypermethylated in PCNSL. However, PCNSL and systemic DLBCL did not differ in their methylation pattern. Based on the data presented here, PCNSL and DLBCL do not differ in their DNA methylation pattern. Thus, DNA methylation analysis does not support a separation of PCNSL and DLBCL into individual entities. However, PCNSL and DLBCL differ in their DNA methylation pattern from non- malignant controls

  20. MYC protein expression and genetic alterations have prognostic impact in patients with diffuse large B-cell lymphoma treated with immunochemotherapy

    OpenAIRE

    Valera, Alexandra; López-Guillermo, Armando; Cardesa-Salzmann, Teresa; Climent, Fina; González-Barca, Eva; Mercadal, Santiago; Espinosa, Íñigo; Novelli, Silvana; Briones, Javier; Mate, José L.; Salamero, Olga; Sancho, Juan M.; Arenillas, Leonor; Serrano, Sergi; Erill, Nadina

    2013-01-01

    MYC alterations influence the survival of patients with diffuse large B-cell lymphoma. Most studies have focused on MYC translocations but there is little information regarding the impact of numerical alterations and protein expression. We analyzed the genetic alterations and protein expression of MYC, BCL2, BCL6, and MALT1 in 219 cases of diffuse large B-cell lymphoma. MYC rearrangement occurred as the sole abnormality (MYC single-hit) in 3% of cases, MYC and concurrent BCL2 and/or BCL6 rear...

  1. Genome-wide profiling identifies a DNA methylation signature that associates with TET2 mutations in diffuse large B-cell lymphoma

    DEFF Research Database (Denmark)

    Asmar, Fazila; Punj, Vasu; Christensen, Jesper Aagaard; Pedersen, Marianne T; Pedersen, Anja; Nielsen, Anders B; Hother, Christoffer; Ralfkiaer, Ulrik; Brown, Peter; Ralfkiaer, Elisabeth; Helin, Kristian; Grønbæk, Kirsten

    2013-01-01

    The discovery that the Ten-Eleven Translocation (TET) hydroxylases cause DNA demethylation has fundamentally changed the notion of how DNA methylation is regulated. Clonal analysis of the hematopoetic stem cell compartment suggests that TET2 mutations can be early events in hematologic cancers and...... recent investigations have shown TET2 mutations in diffuse large B-cell lymphoma. However, the detection rates and the types of TET2 mutations vary, and the relation to global methylation patterns has not been investigated. Here, we show TET2 mutations in 12 of 100 diffuse large B-cell lymphomas with 7...

  2. Anomalous expression of Thy1 (CD90) in B-cell lymphoma cells and proliferation inhibition by anti-Thy1 antibody treatment

    Energy Technology Data Exchange (ETDEWEB)

    Ishiura, Yoshihito [Department of Biochemistry, Kochi University Medical School, Kohasu, Okocho, Nankoku, Kochi 783-8505 (Japan); CREST, Japan Science and Technology Agency, Kawaguchi, Saitama 332-0012 (Japan); Kotani, Norihiro, E-mail: kotani@kochi-u.ac.jp [CREST, Japan Science and Technology Agency, Kawaguchi, Saitama 332-0012 (Japan); Kochi System Glycobiology Center, Kochi University Medical School, Kohasu, Okocho, Nankoku, Kochi 783-8505 (Japan); Yamashita, Ryusuke [Department of Biochemistry, Kochi University Medical School, Kohasu, Okocho, Nankoku, Kochi 783-8505 (Japan); CREST, Japan Science and Technology Agency, Kawaguchi, Saitama 332-0012 (Japan); Yamamoto, Harumi [Laboratory of Membrane Biochemistry and Biophysics, Graduate School of Biostudies, Kyoto University, Yoshida Shimo-Adachi, Sakyo, Kyoto 606-8501 (Japan); Kozutsumi, Yasunori [CREST, Japan Science and Technology Agency, Kawaguchi, Saitama 332-0012 (Japan); Laboratory of Membrane Biochemistry and Biophysics, Graduate School of Biostudies, Kyoto University, Yoshida Shimo-Adachi, Sakyo, Kyoto 606-8501 (Japan); Honke, Koichi [Department of Biochemistry, Kochi University Medical School, Kohasu, Okocho, Nankoku, Kochi 783-8505 (Japan); CREST, Japan Science and Technology Agency, Kawaguchi, Saitama 332-0012 (Japan); Kochi System Glycobiology Center, Kochi University Medical School, Kohasu, Okocho, Nankoku, Kochi 783-8505 (Japan)

    2010-05-28

    The anti-CD20 monoclonal antibody (Ab) rituximab is accepted to be an effective therapeutic Ab for malignant B-cell lymphoma; however, discovery of other cell surface antigens is required for the option of antibody medicine. Considering that many tumor-associated antigens are glycans, we have searched glycoconjugates for the candidate antigens that therapeutic Abs target. To this end, we first focused on the difference in the glycogenes expression in terms of Epstein-Barr virus (EBV) infection of a Burkitt's lymphoma cell line, Akata. Using DNA array, flow cytometry and Western blotting, we found that Thy1 was highly expressed in EBV-positive Akata cells. Subsequently, Thy1 was found to be expressed in other B-cell lymphoma cell lines: BJAB, MutuI, and MutuIII, irrespective of EBV infection. Treatment of these cells with an anti-Thy1 monoclonal antibody inhibited proliferation more strongly than the therapeutic Ab rituximab. The B-cell lymphoma cell lines were classified based on the extent of the proliferation inhibition, which was not correlated with the expression level of Thy1. It is suggested that stable residence of receptor tyrosine kinases in lipid rafts sustains cell growth in B-cell lymphoma cells.

  3. Prolonged myelosuppression with clofarabine in the treatment of patients with relapsed or refractory, aggressive non-Hodgkin lymphoma

    OpenAIRE

    Blum, Kristie A.; Hamadani, Mehdi; Phillips, Gary S.; Lozanski, Gerard; JOHNSON, AMY J.; Lucas, David M.; Smith, Lisa L.; Baiocchi, Robert; Lin, Thomas S; Porcu, Pierluigi; Devine, Steven M; Byrd, John C.

    2009-01-01

    We evaluated the safety and efficacy of the purine nucleoside analogue, clofarabine, in patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) and mantle cell lymphoma (MCL). Six patients with DLBCL (n = 5) or MCL (n = 1) and a median age of 68 years were treated with 40 mg/m2 clofarabine IV over 2 h for 5 days, repeated every 28 days, for 1–2 cycles. The overall response rate was 50% (complete response = 1, complete response unconfirmed = 1, partial response = 1). Median ...

  4. The role of the Chaperonin containing t-complex polypeptide 1, subunit 8 (CCT8) in B-cell non-Hodgkin's lymphoma.

    Science.gov (United States)

    Yin, Haibing; Miao, Xiaobing; Wu, Yaxun; Wei, Yingze; Zong, Guijuan; Yang, Shuyun; Chen, Xudong; Zheng, Guihua; Zhu, Xinghua; Guo, Yan; Li, Chunsun; Chen, Yali; Wang, Yuchan; He, Song

    2016-06-01

    The chaperonin containing t-complex polypeptide 1 (CCT) is known to mediate folding of proteins. CCT, subunit 8 (CCT8), is the θ subunit of CCT complex chaperonin. CCT8 has been reported to be dysregulated in several tumor tissues. In this study, we investigated the role of CCT8 in B-cell non-Hodgkin's lymphoma (NHL). Clinically, the expression levels of CCT8 in reactive lymphoid hyperplasia (RLH) and B-cell NHL specimens were investigated using immunohistochemical analysis. We found that CCT8 was highly expressed in proliferating germinal center cells compared with the quiescent cells of the follicular mantle zone. Furthermore, CCT8 was highly expressed in progressive lymphomas than in indolent lymphomas. Kaplan-Meier curve showed that high expression of CCT8 was significantly associated with shorter overall survival in patients with diffuse large B-cell lymphoma. Moreover, we demonstrated that CCT8 could promote the proliferation of B-cell NHL cells. In addition, we found that CCT8 could accelerate the G1/S transition in B-cell NHL. Finally, we demonstrated that overexpression of CCT8 could reverse cell adhesion-mediated drug resistance (CAM-DR) phenotype. Our study may shed new insights into the important role of CCT8 in cancer development. PMID:27101149

  5. Effect of response quality and line of treatment with rituximab on overall and disease-free survival of patients with B-cell lymphoma:

    OpenAIRE

    Horvat, Mateja; Novakovic, Barbara Jezersek

    2010-01-01

    Background The introduction of rituximab into the treatment of patients with non-Hodgkin’s lymphomas has improved the overall response rate, as well as the response duration and the overall survival of patients with B-cell lymphomas. But only a few studies have addressed the question whether the better response (complete response) and the early introduction of rituximab into the treatment translate into the better survival. The aim of this retrospective study was to assess the potential relat...

  6. Sulfhydryl-based tumor antigen-carrier protein conjugates stimulate superior antitumor immunity against B cell lymphomas.

    Science.gov (United States)

    Betting, David J; Kafi, Kamran; Abdollahi-Fard, Alireza; Hurvitz, Sara A; Timmerman, John M

    2008-09-15

    Therapeutic vaccination of B cell lymphoma patients with tumor-specific Ig (idiotype, or Id) chemically coupled to the immunogenic foreign carrier protein keyhole limpet hemocyanin (KLH) using glutaraldehyde has shown promising results in early clinical trials, and phase III trials are underway. However, glutaraldehyde Id-KLH vaccines fail to elicit anti-Id immune and clinical responses in many patients, possibly because glutaraldehyde reacts with lysine, cysteine, tyrosine, and histidine residues, damaging critical immunogenic epitopes. A sulfhydryl-based tumor Ag-carrier protein conjugation system using maleimide chemistry was used to enhance the efficacy of Id-KLH vaccines. Maleimide Id-KLH conjugates eradicated A20 lymphoma from most tumor-bearing mice, whereas glutaraldehyde Id-KLH had little efficacy. Maleimide Id-KLH elicited tumor-specific IgG Abs and T cells, with CD8(+) T cells being the major effectors of antilymphoma immunity. Maleimide Id-KLH vaccines also demonstrated superior efficacy in 38C13 and BCL-1 lymphoma models, where Abs were shown to be critical for protection. Importantly, standard glutaraldehyde Id-KLH conjugation procedures could result in "overconjugation" of the tumor Ag, leading to decreased efficacy, whereas the heterobifunctional maleimide-based conjugation yielded potent vaccine product regardless of conjugation duration. Under lysosomal processing conditions, the Id-carrier protein linkage was cleavable only after maleimide conjugation. Maleimide KLH conjugation was easily performed with human Igs analogous to those used in Id-KLH clinical trials. These data support the evaluation of sulfhydryl-based Id-KLH vaccines in lymphoma clinical trials and possibly the use of tumor Ag-carrier protein vaccines for other cancers. PMID:18768870

  7. Role of FDG-PET scan in the management of pediatric mature B cell non-Hodgkin’s lymphoma. CCHE experience

    OpenAIRE

    Hany Abdel Rahman; Mohamed Sedky; Asmaa Hamoda; Tarek Raafat; Ayda Youssef; Walid Omar; Omneya Hassanein; Emad Moussa

    2016-01-01

    Aim of work: To evaluate the sensitivity (Se), specificity (Sp), and predictive values (PV) of PET scan during management of pediatric mature B cell non-Hodgkin’s lymphoma (NHL) in comparison with conventional computed tomography (CT) scan. Patients and methods: A retrospective study enrolled on pediatric NHL patients at Children Cancer Hospital Egypt (CCHE) during the period from July 2007 to the end of June 2013. Results: For 115 pediatric patients diagnosed with mature B cell NHL, 15...

  8. Identification of uniquely expressed transcription factors in highly purified B-cell lymphoma samples

    DEFF Research Database (Denmark)

    Andréasson, Ulrika; Edén, Patrik; Peterson, Carsten; Högerkorp, Carl-Magnus; Jerkeman, Mats; Andersen, Niels Smedegaard; Berglund, Mattias; Sundström, Christer; Rosenquist, Richard; Borrebaeck, Carl A K; Ek, Sara

    2010-01-01

    survival, and response to treatment of lymphomas. However, most GEP studies have typically been performed on whole tissue samples, containing varying degrees of tumor cell content, which results in uncertainties in data analysis. In this study, global GEP analyses were performed on highly purified, flow-cytometry...

  9. Development and characterization of APRIL antagonistic monoclonal antibodies for treatment of B-cell lymphomas

    NARCIS (Netherlands)

    M. Guadagnoli; F. Kimberley; U. Phan; K. Cameron; P. Vink; H. Rodermond; E. Eldering; A. Kater; H. van Eenennaam; J.P. Medema

    2011-01-01

    APRIL (A proliferation-inducing ligand) is a TNF family member that binds two TNF receptor family members, TACI and BCMA. It shares these receptors with the closely related TNF family member, B-cell activating factor (BAFF). Contrary to BAFF, APRIL binds heparan sulfate proteoglycans (HSPGs), which

  10. FOXP1 suppresses immune response signatures and MHC class II expression in activated B-cell-like diffuse large B-cell lymphomas

    DEFF Research Database (Denmark)

    Brown, P J; Wong, K K; Felce, S L;

    2016-01-01

    )-treated DLBCL patients (n=150), reduced HLA-DRA (<90% frequency) expression correlated with inferior overall survival (P=0.0003) and progression-free survival (P=0.0012) and with non-GCB subtype stratified by the Hans, Choi or Visco-Young algorithms (all P<0.01). In non-GCB DLBCL cases with <90% HLA-DRA, there......, including human leukocyte antigen DR alpha chain (HLA-DRA), were inversely correlated with FOXP1 transcript expression (P<0.05). FOXP1 knockdown in ABC-DLBCL cells led to increased cel