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Primary mediastinal large B cell lymphoma

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https://www.readbyqxmd.com/read/29771253/axicabtagene-ciloleucel-for-the-treatment-of-relapsed-refractory-b-cell-non-hodgkin-s-lymphomas
#1
P Sharma, G T King, S S Shinde, E Purev, A Jimeno
B-cell non-Hodgkin's lymphomas are the most common hematological malignancies, which despite improvements in chemo-immunotherapy, carry a uniformly poor prognosis in the relapsed/refractory setting. CD19 is an antigen expressed on the surface of most malignancies arising from the B cells, and adoptive transfer of anti-CD19 chimeric antigen receptor (CAR)-expressing T cells has been shown to be effective in treating these B-cell malignancies. Axicabtagene ciloleucel (axi-cel, KTE-C19) is an autologous anti-CD19 CAR T-cell therapy which has shown high overall response rates and a manageable safety profile in patients with relapsed or refractory B-cell malignancies who lack effective and curative treatment options...
March 2018: Drugs of Today
https://www.readbyqxmd.com/read/29741502/advances-in-the-management-of-primary-mediastinal-large-b-cell-lymphoma
#2
Ranjana H Advani
No abstract text is available yet for this article.
January 2018: Clinical Advances in Hematology & Oncology: H&O
https://www.readbyqxmd.com/read/29741220/nhl-in-adolescents-and-young-adults-a-unique-population
#3
REVIEW
Jessica Hochberg, Allyson Flower, Laurence Brugieres, Mitchell S Cairo
Non-Hodgkin lymphoma (NHL) is a heterogeneous group of lymphoid malignancies with high incidence in adolescents and young adults (AYAs). The most common diseases include diffuse large B-cell lymphoma, anaplastic large cell lymphoma, Burkitt lymphoma, lymphoblastic lymphoma, and primary mediastinal large B-cell lymphoma. In comparison to younger children and adults, AYAs (15-39 years) with NHL present a specific set of challenges including variations in tumor biology, inconsistent treatment, pharmacodynamics, and psychosocial barriers...
May 9, 2018: Pediatric Blood & Cancer
https://www.readbyqxmd.com/read/29665940/-advances-in-the-molecular-diagnosis-and-therapy-of-relapsed-refractory-diffuse-large-b-cell-lymphoma-review
#4
Yi Wang, Bing Xia, Yi-Zhuo Zhang
Diffuse large B-cell lymphoma (DLBCL) is biologically aggressive and most common pathological type of non-Hodgkin's lymphoma (NHL), and about one-third of these patients are refractory or relapsed ultimately. Based on the molecular heterogeneity, DLBCL can be divided into 3 main molecular subtypes: germinal center B-cell like (GCB), activated B-cell like (ABC) and primary mediastinal B-cell lymphoma (PMBL). Arising from B cells at distinct stages of differentiation, these subtypes are also diverse in mechanisms of oncogenic activation...
April 2018: Zhongguo Shi Yan Xue Ye Xue za Zhi
https://www.readbyqxmd.com/read/29660176/the-role-of-radiotherapy-as-salvage-and-or-consolidation-treatment-in-relapsed-refractory-and-high-risk-diffuse-large-b-cell-lymphoma
#5
Eric Grignano, Jérémy Laurent, Bénédicte Deau, Barbara Burroni, Didier Bouscary, Youlia M Kirova
OBJECTIVE: Many salvage therapies have been proposed for relapsed/refractory (R/R) diffuse large B-cell lymphomas or for consolidation in the case of suboptimal response. Radiotherapy (RT) is one modality of salvage therapy, but its place is currently not well defined. METHOD: This paper reports a retrospective review of patients receiving unplanned radiotherapy for R/R diffuse large B-cell lymphoma (DLBCL) or primary mediastinal B-cell lymphoma (PMBCL), or as consolidation therapy after second line chemotherapy, treated in our hospital...
April 16, 2018: European Journal of Haematology
https://www.readbyqxmd.com/read/29655961/chimeric-antigen-receptor-t-cell-therapy-for-non-hodgkin-lymphoma
#6
REVIEW
Armin Ghobadi
Non-Hodgkin lymphoma (NHL) is the most common hematologic malignancy. More than 20,000 people in United States, more than 37,000 people in Europe and more than 199,000 people worldwide die of NHL every year. Recent advances in immunotherapeutic approaches for cancer have resulted in development of new classes of very effective immunotherapeutic approaches including chimeric antigen receptor T (CAR-T) cell therapy that are designed to bypass cancer immune evasion. Here, we review recent advances in CAR-T cell therapy for NHL...
April 11, 2018: Current Research in Translational Medicine
https://www.readbyqxmd.com/read/29564225/mechanisms-of-immune-evasion-and-immune-modulation-by-lymphoma-cells
#7
REVIEW
Thomas Menter, Alexandar Tzankov
Purpose: Targeting cancer cells by modulating the immune system has become an important new therapeutic option in many different malignancies. Inhibition of CTLA4/B7 and PD1/PDL1 signaling is now also being investigated and already successfully applied to various hematologic malignancies. Methods: A literature review of PubMed and results of our own studies were compiled in order to give a comprehensive overview on this topic. Results: We elucidate the pathophysiological role of immunosuppressive networks in lymphomas, ranging from changes in the cellular microenvironment composition to distinct signaling pathways such as PD1/PDL1 or CTLA4/B7/CD28...
2018: Frontiers in Oncology
https://www.readbyqxmd.com/read/29467182/somatic-il4r-mutations-in-primary-mediastinal-large-b-cell-lymphoma-lead-to-constitutive-jak-stat-signaling-activation
#8
Elena Viganò, Jay Gunawardana, Anja Mottok, Tessa Van Tol, Katina Mak, Fong Chun Chan, Lauren Chong, Elizabeth Chavez, Bruce Woolcock, Katsuyoshi Takata, David Twa, Hennady P Shulha, Adèle Telenius, Olga Kutovaya, Stacy S Hung, Shannon Healy, Susana Ben-Neriah, Karen Leroy, Philippe Gaulard, Arjan Diepstra, Robert Kridel, Kerry J Savage, Lisa Rimsza, Randy Gascoyne, Christian Steidl
Primary mediastinal large B-cell lymphoma (PMBCL) is a distinct subtype of diffuse large B-cell lymphoma thought to arise from thymic medullary B cells. Gene mutations underlying the molecular pathogenesis of the disease are incompletely characterized. Here, we describe novel somatic IL4R mutations in 15 of 62 primary cases of PMBCL (24.2%) and in all PMBCL-derived cell lines tested. The majority of mutations (11/21; 52%) were hotspot single nucleotide variants in exon 8, leading to an I242N amino acid change in the transmembrane domain...
May 3, 2018: Blood
https://www.readbyqxmd.com/read/29377256/expression-pattern-of-pd-l1-and-pd-l2-in-classical-hodgkin-lymphoma-primary-mediastinal-large-b-cell-lymphoma-and-gray-zone-lymphoma
#9
Yosuke Tanaka, Akiko Miyagi Maeshima, Junko Nomoto, Shinichi Makita, Suguru Fukuhara, Wataru Munakata, Dai Maruyama, Kensei Tobinai, Yukio Kobayashi
OBJECTIVES: We aimed at investigating the relationship between classical Hodgkin lymphoma (cHL), primary mediastinal large B-cell lymphoma (PMBL), and gray zone lymphoma (GZL) with intermediate characteristics between cHL and PMBL, from the perspective of the aberration in programed cell death 1 and the programed death ligands (PDLs) network. METHODS: We explored the expression levels of PDLs and chromosomal anomalies in 67 cases: 34 cases with cHL, 20 with PMBL, and 13 with GZL, using immunohistochemical analyses and Fluorescence In Situ Hybridization (FISH)...
May 2018: European Journal of Haematology
https://www.readbyqxmd.com/read/29296913/clinicopathologic-consensus-study-of-gray-zone-lymphoma-with-features-intermediate-between-dlbcl-and-classical-hl
#10
Monika Pilichowska, Stefania Pittaluga, Judith A Ferry, Jessica Hemminger, Hong Chang, Jennifer A Kanakry, Laurie H Sehn, Tatyana Feldman, Jeremy S Abramson, Athena Kritharis, Francisco J Hernandez-Ilizaliturri, Izidore S Lossos, Oliver W Press, Timothy S Fenske, Jonathan W Friedberg, Julie M Vose, Kristie A Blum, Deepa Jagadeesh, Bruce Woda, Gaurav K Gupta, Randy D Gascoyne, Elaine S Jaffe, Andrew M Evens
Gray zone lymphoma (GZL) is described as sharing features with classical Hodgkin lymphoma (cHL) and diffuse large B-cell lymphoma (DLBCL). However, there remains complexity in establishing diagnosis, delineating prognosis, and determining optimum therapy. Sixty-eight cases diagnosed as GZL across 15 North American academic centers were evaluated by central pathology review to achieve consensus. Of these, only 26 (38%) were confirmed as GZL. Morphology was critical to GZL consensus diagnosis (eg, tumor cell richness); immunohistochemistry showed universal B-cell derivation, frequent CD30 expression, and rare Epstein-Barr virus (EBV) positivity (CD20+ , 83%; PAX5+ , 100%; BCL6+ , 20%; MUM1+ , 100%; CD30+ , 92%; EBV+ , 4%)...
December 12, 2017: Blood Advances
https://www.readbyqxmd.com/read/29226797/axicabtagene-ciloleucel-car-t-cell-therapy-in-refractory-large-b-cell-lymphoma
#11
MULTICENTER STUDY
Sattva S Neelapu, Frederick L Locke, Nancy L Bartlett, Lazaros J Lekakis, David B Miklos, Caron A Jacobson, Ira Braunschweig, Olalekan O Oluwole, Tanya Siddiqi, Yi Lin, John M Timmerman, Patrick J Stiff, Jonathan W Friedberg, Ian W Flinn, Andre Goy, Brian T Hill, Mitchell R Smith, Abhinav Deol, Umar Farooq, Peter McSweeney, Javier Munoz, Irit Avivi, Januario E Castro, Jason R Westin, Julio C Chavez, Armin Ghobadi, Krishna V Komanduri, Ronald Levy, Eric D Jacobsen, Thomas E Witzig, Patrick Reagan, Adrian Bot, John Rossi, Lynn Navale, Yizhou Jiang, Jeff Aycock, Meg Elias, David Chang, Jeff Wiezorek, William Y Go
BACKGROUND: In a phase 1 trial, axicabtagene ciloleucel (axi-cel), an autologous anti-CD19 chimeric antigen receptor (CAR) T-cell therapy, showed efficacy in patients with refractory large B-cell lymphoma after the failure of conventional therapy. METHODS: In this multicenter, phase 2 trial, we enrolled 111 patients with diffuse large B-cell lymphoma, primary mediastinal B-cell lymphoma, or transformed follicular lymphoma who had refractory disease despite undergoing recommended prior therapy...
December 28, 2017: New England Journal of Medicine
https://www.readbyqxmd.com/read/29222270/primary-mediastinal-b-cell-lymphoma-biology-and-evolving-therapeutic-strategies
#12
REVIEW
Kieron Dunleavy
Primary mediastinal B-cell lymphoma (PMBCL) is recognized as a distinct clinicopathologic entity that predominantly affects adolescents and young adults and is more common in female subjects. Although PMBCL is considered to be a subtype of diffuse large B-cell lymphoma, its clinical, morphologic, and biological characteristics overlap significantly with those of nodular sclerosing Hodgkin lymphoma (NSHL). Over the past few years, the shared biology of these 2 entities has been highlighted in several studies, and mediastinal gray zone lymphoma, with features intermediate between PMBCL and NSHL, has been recognized as a unique molecular entity...
December 8, 2017: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/29195613/interim-fdg-pet-imaging-in-lymphoma
#13
REVIEW
Andrea Gallamini, Colette Zwarthoed
In the present article, the authors reviewed the rationale of FDG-PET/CT performed at an interim time point during therapy (iPET), focusing on the transition from standard, anatomical assessment of tumor shrinkage with CT to document a chemotherapy response, to the use of functional imaging with PET to assess chemosensitivity of the individual tumor. The prognostic or predictive role of iPET in different lymphoma subsets has been reviewed, with particular emphasis on early and advanced-stage Hodgkin lymphoma, diffuse large B-cell lymphoma, peripheral T-cell lymphoma, extranodal natural killer/T-cell lymphoma, and primary mediastinal B-cell lymphoma...
January 2018: Seminars in Nuclear Medicine
https://www.readbyqxmd.com/read/29189264/dendritic-cell-markers-and-pd-l1-are-expressed-in-mediastinal-gray-zone-lymphoma
#14
Kevin Pelland, Stephanie Mathews, Anitha Kamath, Paul Cohen, S David Hudnall, Claudiu V Cotta, Mina L Xu
AIMS: Mediastinal gray zone lymphoma (MGZL) is a rare entity with morphologic, immunophenotypic, and genetic features intermediate between classic Hodgkin lymphoma (CHL) and primary mediastinal large B-cell lymphoma (PMBL). It is challenging to differentiate from CHL and PMBL. A specific dendritic cell gene expression profile can distinguish CHL and MGZL from PMBL. We hypothesized that the dendritic markers fascin and CD123 may be helpful in distinguishing MGZL from CHL and PMBL. We also investigated programmed death-ligand 1 (PD-L1) expression in MGZL, which may have therapeutic significance in this difficulty to treat tumor...
November 20, 2017: Applied Immunohistochemistry & Molecular Morphology: AIMM
https://www.readbyqxmd.com/read/29126866/advances-in-diagnosis-and-management-of-diffuse-large-b-cell-lymphoma
#15
REVIEW
Fernando Cabanillas, Bijal Shah
The management of diffuse large B-cell lymphoma (DLBCL) has been gradually evolving since the discovery of its 2 major forms, the germinal center B-like (GCB) and activated B-cell (ABC) types. Although the reference standard for the identification of these cell types is considered gene expression profiling (GEP), currently the only method commercially available is immunohistochemistry (IHC). The application of various IHC-based algorithms and their correlation with GEP and clinical outcome are discussed. Because of the adverse prognostic implications of the non-GCB type and its potential effects on treatment selection, the recently revised World Health Organization classification has included these biologic cell types...
December 2017: Clinical Lymphoma, Myeloma & Leukemia
https://www.readbyqxmd.com/read/29122656/programmed-death-1-ligands-pd-l1-and-pd-l2-show-distinctive-and-restricted-patterns-of-expression-in-lymphoma-subtypes
#16
Poonam K Panjwani, Vivek Charu, Monique DeLisser, Hernan Molina-Kirsch, Yasodha Natkunam, Shuchun Zhao
The success of immunotherapy using immune checkpoint blockade in solid tumors and in relapsed/refractory classical Hodgkin lymphoma and chronic lymphocytic leukemia holds promise for targeted therapy in hematologic malignancies. Because efficacy of immunomodulatory therapy is correlated with numbers of cells that express programmed death (PD-1) ligands, we evaluated the expression of PD-L1 and PD-L2 proteins using immunohistochemistry in more than 702 diagnostic lymphoma biopsies. In classical Hodgkin lymphoma, PD-L1 and PD-L2 were expressed in 82% and 41% of cases, respectively, and PD-L1 but not PD-L2 expression correlated with Epstein-Barr virus in tumor cells...
January 2018: Human Pathology
https://www.readbyqxmd.com/read/29118007/pd-1-expression-and-clinical-pd-1-blockade-in-b-cell-lymphomas
#17
REVIEW
Zijun Y Xu-Monette, Jianfeng Zhou, Ken H Young
Programmed cell death protein 1 (PD-1) blockade targeting the PD-1 immune checkpoint has demonstrated unprecedented clinical efficacy in the treatment of advanced cancers including hematologic malignancies. This article reviews the landscape of PD-1/programmed death-ligand 1 (PD-L1) expression and current PD-1 blockade immunotherapy trials in B-cell lymphomas. Most notably, in relapsed/refractory classical Hodgkin lymphoma, which frequently has increased PD-1+ tumor-infiltrating T cells, 9p24.1 genetic alteration, and high PD-L1 expression, anti-PD-1 monotherapy has demonstrated remarkable objective response rates (ORRs) of 65% to 87% and durable disease control in phase 1/2 clinical trials...
January 4, 2018: Blood
https://www.readbyqxmd.com/read/29082519/outcomes-of-adults-and-children-with-primary-mediastinal-b-cell-lymphoma-treated-with-dose-adjusted-epoch-r
#18
Lisa Giulino-Roth, Tara O'Donohue, Zhengming Chen, Nancy L Bartlett, Ann LaCasce, William Martin-Doyle, Matthew J Barth, Kimberly Davies, Kristie A Blum, Beth Christian, Carla Casulo, Sonali M Smith, James Godfrey, Amanda Termuhlen, Matthew J Oberley, Sarah Alexander, Sheila Weitzman, Burton Appel, Benjamin Mizukawa, Jakub Svoboda, Zeinab Afify, Melinda Pauly, Hema Dave, Rebecca Gardner, Deborah M Stephens, William A Zeitler, Christopher Forlenza, Jennifer Levine, Michael E Williams, Jody L Sima, Catherine M Bollard, John P Leonard
Treatment with dose-adjusted EPOCH (etoposide, doxorubicin, cyclophosphamide, vincristine, prednisone) chemotherapy and rituximab (DA-EPOCH-R) has become the standard of care for primary mediastinal B-cell lymphoma (PMBCL) at many institutions despite limited data in the multi-centre setting. We report a large, multi-centre retrospective analysis of children and adults with PMBCL treated with DA-EPOCH-R to characterize outcomes and evaluate prognostic factors. We assessed 156 patients with PMBCL treated with DA-EPOCH-R across 24 academic centres, including 38 children and 118 adults...
December 2017: British Journal of Haematology
https://www.readbyqxmd.com/read/29058502/axicabtagene-ciloleucel-a-first-in-class-car-t-cell-therapy-for-aggressive-nhl
#19
Zachary J Roberts, Marc Better, Adrian Bot, Margo R Roberts, Antoni Ribas
The development of clinically functional chimeric antigen receptor (CAR) T cell therapy is the culmination of multiple advances over the last three decades. Axicabtagene ciloleucel (formerly KTE-C19) is an anti-CD19 CAR T cell therapy in development for patients with refractory diffuse large B cell lymphoma (DLBCL), including transformed follicular lymphoma (TFL) and primary mediastinal B cell lymphoma (PMBCL). Axicabtagene ciloleucel is manufactured from patients' own peripheral blood mononuclear cells (PBMC) during which T cells are engineered to express a CAR that redirects them to recognize CD19-expressing cells...
October 23, 2017: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/29054399/determination-of-molecular-subtypes-of-diffuse-large-b-cell-lymphoma-using-a-reverse-transcriptase-multiplex-ligation-dependent-probe-amplification-classifier-a-calym-study
#20
Victor Bobée, Philippe Ruminy, Vinciane Marchand, Pierre-Julien Viailly, Ahmad Abdel Sater, Liana Veresezan, Fanny Drieux, Caroline Bérard, Elodie Bohers, Sylvain Mareschal, Sydney Dubois, Jean-Philippe Jais, Karen Leroy, Martin Figeac, Jean-Michel Picquenot, Thierry Jo Molina, Gilles Salles, Corinne Haioun, Hervé Tilly, Fabrice Jardin
Diffuse large B-cell lymphoma (DLBCL) is the most common non-Hodgkin lymphoma. It includes three major subtypes termed germinal center B-cell-like, activated B-cell-like, and primary mediastinal B-cell lymphoma. With the emergence of novel targeted therapies, accurate methods capable of interrogating this cell-of-origin classification should soon become essential in the clinics. To address this issue, we developed a novel gene expression profiling DLBCL classifier based on reverse transcriptase multiplex ligation-dependent probe amplification...
November 2017: Journal of Molecular Diagnostics: JMD
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