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Relapsed diffuse large b cell lymphoma

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https://www.readbyqxmd.com/read/29157092/single-agent-and-synergistic-combinatorial-efficacy-of-first-in-class-small-molecule-imipridone-onc201-in-hematological-malignancies
#1
Varun V Prabhu, Mala K Talekar, Amriti R Lulla, C Leah B Kline, Lanlan Zhou, Junior Hall, A Pieter J Van den Heuvel, David T Dicker, Jawad Babar, Stephan A Grupp, Mathew J Garnett, Ultan McDermott, Cyril H Benes, Jeffrey J Pu, David F Claxton, Nadia Khan, Wolfgang Oster, Joshua E Allen, Wafik S El-Deiry
ONC201, founding member of the imipridone class of small molecules, is currently being evaluated in advancer cancer clinical trials. We explored single agent and combinatorial efficacy of ONC201 in preclinical models of hematological malignancies. ONC201 demonstrated (GI50 1-8 µM) dose- and time-dependent efficacy in acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), chronic myelogenous leukemia (CML), chronic lymphocytic leukemia (CLL), diffuse large B-cell lymphoma (DLBCL), mantle cell lymphoma (MCL), Burkitt's lymphoma, anaplastic large cell lymphoma (ALCL), cutaneous T-cell lymphoma (CTCL), Hodgkin's lymphoma (nodular sclerosis) and multiple myeloma (MM) cell lines including cells resistant to standard of care (dexamethasone in MM) and primary samples...
November 20, 2017: Cell Cycle
https://www.readbyqxmd.com/read/29156774/micrornas-as-predictors-for-cns-relapse-of-systemic-diffuse-large-b-cell-lymphoma
#2
Nir Pillar, Osnat Bairey, Neta Goldschmidt, Yakov Fellig, Yevgenia Rosenblat, Itchak Shehtman, Danielle Haguel, Pia Raanani, Noam Shomron, Tali Siegal
Systemic diffuse large B-cell lymphoma (DLBCL) is a potentially curable disease using current regimen of immunochemotherapy. Central nervous system (CNS) relapse is a complication that occurs in approximately 5% of DLBCL patients and is associated with a high fatality rate. Early identification of molecular markers for CNS involvement may serve for the highly needed accurate stratification of patients into risk groups regarding CNS relapse. MicroRNAs (miRNAs) are small non-coding RNA molecules that regulate gene expression at the post-transcriptional level and are known to be involved in DLBCL pathophysiology...
October 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29137041/efficacy-of-rituximab-combined-with-chop-for-treating-patients-with-diffuse-large-b-cell-lymphoma
#3
Xin Hu, Min Zeng, Shun-E Yang, Xiao Liang, Shan-Shan Ding, Li Guo, Shan Li, Shu-Juan Wen
BACKGROUND: This study aimed to evaluate the efficacy and safety of rituximab combined with cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) for treating patients with diffuse large B-cell lymphoma (DLBCL). METHODS: A total of 144 patients with DLBCL were randomly divided into intervention group and control group, 72 patients in each group. The patients in the control group received cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) chemotherapy, while the participants in the intervention group received R-CHOP...
November 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/29131834/plasma-microrna-profiling-exploring-better-biomarkers-for-lymphoma-surveillance
#4
Drirh Khare, Neta Goldschmidt, Aya Bardugo, Devorah Gur-Wahnon, Iddo Z Ben-Dov, Batia Avni
Early detection of relapsed lymphoma improves response and survival. Current tools lack power for detection of early relapse, while being cumbersome and expensive. We searched for sensitive biomarkers that precede clinical relapse, and serve for further studies on therapy response and relapse. We recruited 20 healthy adults, 14 diffuse large B-cell lymphoma (DLBCL) patients and 11 Hodgkin lymphoma (HL) patients at diagnosis. Using small-RNA sequencing we identified in DLBCL patients increased plasma levels of miR-124 and miR-532-5p, and decreased levels of miR-425, miR-141, miR-145, miR-197, miR-345, miR-424, miR-128 and miR-122...
2017: PloS One
https://www.readbyqxmd.com/read/29127587/copanlisib-first-global-approval
#5
Anthony Markham
Bayer are developing copanlisib (Aliqopa™)-a pan-class I phosphoinositide 3-kinase (PI3K) inhibitor-as a treatment for various haematological and solid malignancies. The US FDA has granted copanlisib accelerated approval for the treatment of adults with relapsed follicular lymphoma who have received at least two prior systemic therapies based on the results of a phase II trial. Phase III trials are underway evaluating copanlisib as treatment for relapsed/refractory diffuse large B-cell lymphoma and in combination with rituximab or rituximab-based chemotherapy or standard immunochemotherapy in patients with relapsed indolent B-cell non-Hodgkin's lymphoma...
November 10, 2017: Drugs
https://www.readbyqxmd.com/read/29125192/long-term-outcomes-among-2-year-survivors-of-autologous-hematopoietic-cell-transplantation-for-hodgkin-and-diffuse-large-b-cell-lymphoma
#6
Regina M Myers, Brian T Hill, Bronwen E Shaw, Soyoung Kim, Heather R Millard, Minoo Battiwalla, Navneet S Majhail, David Buchbinder, Hillard M Lazarus, Bipin N Savani, Mary E D Flowers, Anita D'Souza, Matthew J Ehrhardt, Amelia Langston, Jean A Yared, Robert J Hayashi, Andrew Daly, Richard F Olsson, Yoshihiro Inamoto, Adriana K Malone, Zachariah DeFilipp, Steven P Margossian, Anne B Warwick, Samantha Jaglowski, Amer Beitinjaneh, Henry Fung, Kimberly A Kasow, David I Marks, Jana Reynolds, Keith Stockerl-Goldstein, Baldeep Wirk, William A Wood, Mehdi Hamadani, Prakash Satwani
BACKGROUND: Autologous hematopoietic cell transplantation (auto-HCT) is a standard therapy for relapsed classic Hodgkin lymphoma (cHL) and diffuse large B-cell lymphoma (DLBCL); however, long-term outcomes are not well described. METHODS: This study analyzed survival, nonrelapse mortality, late effects, and subsequent malignant neoplasms (SMNs) in 1617 patients who survived progression-free for ≥2 years after auto-HCT for cHL or DLBCL between 1990 and 2008. The median age at auto-HCT was 40 years; the median follow-up was 10...
November 10, 2017: Cancer
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
#7
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. Since 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 over 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...
November 6, 2017: Human Pathology
https://www.readbyqxmd.com/read/29118007/pd-1-expression-and-clinical-pd-1-blockade-in-b-cell-lymphomas
#8
Zijun Y Xu-Monette, Jianfeng Zhou, Ken H Young
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/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 genetic alteration and high PD-L1 expression, anti-PD-1 monotherapy has demonstrated remarkable objective response rates (ORR) of 65-87% and durable disease control in phase I/II clinical trials...
November 8, 2017: Blood
https://www.readbyqxmd.com/read/29115587/anticancer-effect-of-quinacrine-on-diffuse-large-b%C3%A2-cell-lymphoma-via-inhibition-of-msi2%C3%A2-numb-signaling-pathway
#9
Shujun Yang, Lixia Sheng, Kaihong Xu, Yi Wang, Huiling Zhu, Ping Zhang, Qitian Mu, Guifang Ouyang
Diffuse large B‑cell lymphoma (DLBCL) is the most common subtype of non‑Hodgkin's lymphoma. Despite improvements in the clinical outcomes of DLBCL, ~30% of patients will develop relapse/refractory disease. Therefore, novel therapeutic drugs have been investigated to improve disease outcomes. Previous studies have revealed the anticancer effects of quinacrine (QC) on tumor cells in vitro, although its role in human DLBCL is yet to be identified. The present study sought to examine the cytotoxic effect of QC on DLBCL cells...
October 26, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29112015/pd-l1-and-pd-l2-are-differentially-expressed-by-macrophages-or-tumor-cells-in-primary-cutaneous-diffuse-large-b-cell-lymphoma-leg-type
#10
Sarah Menguy, Martina Prochazkova-Carlotti, Marie Beylot-Barry, Fréderic Saltel, Béatrice Vergier, Jean-Philippe Merlio, Anne Pham-Ledard
As checkpoint molecules' inhibition may represent a therapeutic option in relapsing cases, we assessed programmed death ligands' (PD-L1/PD-L2) expression in a series of 29 primary cutaneous diffuse large B-cell lymphoma, leg-type (PCDLBCL-LT) cases. Double immunostaining for either PD-L1 or PD-L2 was associated either with PAX5 staining to evaluate tumor cells or with CD68 or CD163 staining for macrophages. The microenvironment of PCDLBCL-LT was characterized by immunostainings for CD3 (tumor-infiltrating lymphocytes), FOXP3 (regulatory T cells), programmed cell death-1, and CD33 (myeloid-derived suppressor cells)...
November 3, 2017: American Journal of Surgical Pathology
https://www.readbyqxmd.com/read/29097500/a-bio-clinical-prognostic-model-using-myc-and-bcl2-predicts-outcome-in-relapsed-refractory-diffuse-large-b-cell-lymphoma
#11
Mark Bosch, Ariz Akhter, Bingshu E Chen, Adnan Mansoor, David Lebrun, David Good, Michael Crump, Lois Shepherd, David W Scott, Douglas A Stewart
The objective of this study was to create a bio-clinical model, based on clinical and molecular predictors of event-free and overall survival for relapsed/refractory diffuse large B-cell lymphoma patients treated on the Canadian Cancer Trials Group LY12 prospective study. Sufficient histologic material was available for 91 cases to create tissue microarrays and perform immunohistochemistry staining for CD10, BCL6, MUM1/IRF4, FOXP1, LMO2, BCL2, MYC, P53 and pySTAT3 expression. 67 cases had material sufficient for fluorescent in-situ hybridization for MYC and BCL2...
November 2, 2017: Haematologica
https://www.readbyqxmd.com/read/29083044/relapse-in-stage-i-e-diffuse-large-b-cell-lymphoma
#12
Marcel Nijland, Karin Boslooper, Gustaaf van Imhoff, Robbie Kibbelaar, Peter Joosten, Huib Storm, Eric N van Roon, Arjan Diepstra, Hanneke C Kluin-Nelemans, Mels Hoogendoorn
Despite a general favourable outcome in limited stage diffuse large B-cell lymphoma (DLBCL), relapses occur in about 10 to 20% of patients. Prognostic models only partially identify patients at risk for relapse. Moreover, it is not known whether the outcome after such a relapse is similar to the outcome after relapse in advanced stages. From January 2004 through December 2012, all newly diagnosed patients with stage I(E) DLBCL were retrospectively analysed from 2 clinical databases to investigate the relapse pattern and outcome in relation to initial treatment and clinical characteristics...
October 30, 2017: Hematological Oncology
https://www.readbyqxmd.com/read/29079283/consolidative-radiotherapy-after-autologous-stem-cell-transplantation-for-relapsed-or-refractory-diffuse-large-b-cell-lymphoma
#13
Brendan G Coutu, Christopher T Wilke, Jianling Yuan, Qing Cao, Matthew R Vernon, Chung Lee, Veronika Bachanova, Kathryn E Dusenbery
INTRODUCTION: We evaluated the role of consolidative radiotherapy (RT) for patients undergoing high-dose chemotherapy (HDC) and autologous stem cell transplantation (ASCT) for relapsed or refractory diffuse large B-cell lymphoma (DLBCL). MATERIALS AND METHODS: We reviewed the medical records of 72 consecutive patients who had undergone ASCT for relapsed or refractory DLBCL at our institution from 2006 to 2014. Pretransplant conditioning consisted of HDC and total body irradiation...
September 20, 2017: Clinical Lymphoma, Myeloma & Leukemia
https://www.readbyqxmd.com/read/29076131/minimal-residual-disease-in-non-hodgkin-lymphoma-current-applications-and-future-directions
#14
REVIEW
Matthew L Chase, Philippe Armand
Non-Hodgkin Lymphomas (NHLs) are a heterogeneous group of tumours with distinct treatment paradigms, but in all cases the goal of treatment is to maximize quality and duration of remission while minimizing therapy-related toxicity. Identification of persistent disease or relapse is most often the trigger to intensify or re-initiate anti-neoplastic therapy, respectively. In the current era of NHL treatment, this determination is mostly based on imaging and clinical evaluations, tools with imperfect sensitivity and specificity...
October 26, 2017: British Journal of Haematology
https://www.readbyqxmd.com/read/29072976/international-assessment-of-event-free-survival-at-24-months-and-subsequent-survival-in-peripheral-t-cell-lymphoma
#15
Matthew J Maurer, Fredrik Ellin, Line Srour, Mats Jerkeman, N Nora Bennani, Joseph M Connors, Graham W Slack, Karin E Smedby, Stephen M Ansell, Brian K Link, James R Cerhan, Thomas Relander, Kerry J Savage, Andrew L Feldman
Purpose Peripheral T-cell lymphomas (PTCLs) have aggressive clinical behavior. We have previously shown that event-free survival (EFS) at 24 months (EFS24) is a clinically useful end point in diffuse large B-cell lymphoma. Here, we assess EFS24 and subsequent overall survival (OS) in large, multinational PTCL cohorts. Patients and Methods Patients with systemic PTCL newly diagnosed from 2000 to 2012 and treated with curative intent were included from the United States and Sweden (initial cohorts) and from Canada (replication cohort)...
October 26, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/29050112/-clinical-pathologic-characteristics-and-treatment-outcomes-of-19-relapsed-pediatric-b-cell-lymphoma
#16
S Huang, L Jin, J Yang, Y L Duan, M Zhang, C J Zhou, X L Ma, Y H Zhang
Objective: To review the clinical-pathology characteristics of 19 relapsed pediatric mature B cell lymphoma and to find the risk factors for recurrence and the feasible treatment after relapse. Method: Data of 212 pediatric B cell lymphomas cases in Beijing Children's Hospital from January 2006 to June 2015 were collected retrospectively. All the patients were treated according to the B cell lymphoma regimen of Beijing Children's Hospital. During the study period, 19 of 212 cases were relapsed; the clinio-pathological characteristics of relapsed patients before treatment and after relapse were analyzed retrospectively, the treatment outcomes after relapse were summarized and the patients were followed-up...
October 2, 2017: Zhonghua Er Ke za Zhi. Chinese Journal of Pediatrics
https://www.readbyqxmd.com/read/29047108/clinicopathologic-characteristics-and-outcomes-of-transformed-diffuse-large-b-cell-lymphoma-in-hepatitis-c-virus-infected-patients
#17
Jeff Hosry, Roberto N Miranda, Felipe Samaniego, Minas P Economides, Harrys A Torres
Hepatitis C virus (HCV) causes a chronic but curable infection associated with the development of marginal zone lymphoma (MZL) and diffuse large B-cell lymphoma (DLBCL). Preliminary data have shown frequent transformation of indolent lymphoma to DLBCL in HCV-infected patients. To compare their clinicopathologic characteristics and oncologic outcomes, we reviewed the medical records and pathology reports of HCV-infected and uninfected patients with DLBCL that transformed from indolent lymphoma seen at The University of Texas MD Anderson Cancer Center (June 2004 to May 2015)...
October 19, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/29045503/maintenance-therapy-following-induction-chemoimmunotherapy-in-patients-with-diffuse-large-b-cell-lymphoma-current-perspective
#18
N M Reddy, C Thieblemont
Background: Maintenance therapy has proven efficacy in indolent non-Hodgkin lymphoma (NHL), yet its role in diffuse large B-cell lymphoma (DLBCL) is an area of ongoing investigation. While DLBCL is potentially curable, >30% of patients relapse following front-line therapy and have a poor prognosis, especially those with refractory disease. Maintenance therapy holds promise to maintain response post-induction. Patients and methods: Keyword searches were carried out in PubMed and congress abstracts of 'diffuse large B-cell lymphoma' and 'maintenance' and focused on phase II/III studies of maintenance following front-line induction...
November 1, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/29025286/-thalidomide-therapy-in-relapsed-diffuse-large-b-cell-lymphoma-in-elderly-patients-three-cases
#19
Nikolett Wohner, Gergely Varga, Péter Szloboda, Péter Farkas, András Masszi, Laura Horváth, Gergely Szombath, Judit Várkonyi, Szabolcs Benedek, Tamás Masszi
Diffuse large B-cell lymphoma (DLBCL), a high-grade lymphoproliferative disease, is the most common lymphoma in adults, representing 31% of non-Hodgkin lymphomas (NHL). In elderly patients treatment is problematic because of the high toxicity of standard chemotherapy protocols, especially in relapsed cases, where high-dose chemotherapy and haematopoietic stem cell transplantation would be the best choice. More and more data is becoming available on alternative treatment of refractory/relapsed NHL, including studies on the positive effect of thalidomide and second generation IMiDs in DLBCL, which are already part of the standard treatment protocol in myeloma multiplex and myelodysplasia...
October 2017: Orvosi Hetilap
https://www.readbyqxmd.com/read/29021515/clinicopathological-analysis-of-320-cases-of-diffuse-large-b-cell-lymphoma-using-the-hans-classifier
#20
Akifumi Ichiki, Joaquim Carreras, Masashi Miyaoka, Yara Yukie Kikuti, Tadashi Jibiki, Kei Tazume, Shigeki Watanabe, Tamotsu Sasao, Yoshiaki Obayashi, Makoto Onizuka, Ken Ohmachi, Fumiaki Yoshiba, Yukari Shirasugi, Yoshiaki Ogawa, Hiroshi Kawada, Naoya Nakamura, Kiyoshi Ando
The estimation of clinical prognosis for diffuse large B-cell lymphoma (DLBCL) with a quick, cost-efficient method is necessary because of the clinical heterogeneity of this disease, which leads to death, relapsed or refractory disease in approximately 40% of patients. We analyzed 320 cases diagnosed from 2007 to 2013 treated with R-CHOP therapy at Tokai University Hospital and associated institutions. DLBCL was classified according to the cell-of-origin using the Hans algorithm [germinal center B-cell-like (GCB) vs non-GCB subtypes], and into 6 subgroups derived from combinations of CD10, BCL6 and MUM1 markers...
2017: Journal of Clinical and Experimental Hematopathology: JCEH
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