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chronic lymphocytic leukaemia

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https://www.readbyqxmd.com/read/28105602/ibrutinib-a-review-in-chronic-lymphocytic-leukaemia
#1
Emma D Deeks
Ibrutinib (Imbruvica(®)) is an oral irreversible inhibitor of Bruton's tyrosine kinase, a B-cell receptor (BCR) signalling kinase expressed by various haematopoietic cells, B-cell lymphomas and leukaemias. The drug is indicated for the treatment of certain haematological malignancies, including chronic lymphocytic leukaemia (CLL)/small lymphocytic lymphoma (SLL), which are the focus of this review. In phase III CLL/SLL trials, ibrutinib monotherapy was more effective than chlorambucil in the first-line treatment of elderly patients (RESONATE-2) and more effective than ofatumumab in previously-treated adults (RESONATE)...
January 20, 2017: Drugs
https://www.readbyqxmd.com/read/28102226/chronic-lymphocytic-leukaemia
#2
Thomas J Kipps, Freda K Stevenson, Catherine J Wu, Carlo M Croce, Graham Packham, William G Wierda, Susan O'Brien, John Gribben, Kanti Rai
Chronic lymphocytic leukaemia (CLL) is a malignancy of CD5(+) B cells that is characterized by the accumulation of small, mature-appearing lymphocytes in the blood, marrow and lymphoid tissues. Signalling via surface immunoglobulin, which constitutes the major part of the B cell receptor, and several genetic alterations play a part in CLL pathogenesis, in addition to interactions between CLL cells and other cell types, such as stromal cells, T cells and nurse-like cells in the lymph nodes. The clinical progression of CLL is heterogeneous and ranges from patients who require treatment soon after diagnosis to others who do not require therapy for many years, if at all...
January 19, 2017: Nature Reviews. Disease Primers
https://www.readbyqxmd.com/read/28102205/chronic-lymphocytic-leukaemia
#3
(no author information available yet)
No abstract text is available yet for this article.
January 19, 2017: Nature Reviews. Disease Primers
https://www.readbyqxmd.com/read/28089635/venetoclax-plus-rituximab-in-relapsed-or-refractory-chronic-lymphocytic-leukaemia-a-phase-1b-study
#4
John F Seymour, Shuo Ma, Danielle M Brander, Michael Y Choi, Jacqueline Barrientos, Matthew S Davids, Mary Ann Anderson, Anne W Beaven, Steven T Rosen, Constantine S Tam, Betty Prine, Suresh K Agarwal, Wijith Munasinghe, Ming Zhu, L Leanne Lash, Monali Desai, Elisa Cerri, Maria Verdugo, Su Young Kim, Rod A Humerickhouse, Gary B Gordon, Thomas J Kipps, Andrew W Roberts
BACKGROUND: Selective BCL2 inhibition with venetoclax has substantial activity in patients with relapsed or refractory chronic lymphocytic leukaemia. Combination therapy with rituximab enhanced activity in preclinical models. The aim of this study was to assess the safety, pharmacokinetics, and activity of venetoclax in combination with rituximab. METHODS: Adult patients with relapsed or refractory chronic lymphocytic leukaemia (according to the 2008 Modified International Workshop on CLL guidelines) or small lymphocytic lymphoma were eligible for this phase 1b, dose-escalation trial...
January 12, 2017: Lancet Oncology
https://www.readbyqxmd.com/read/28089631/chronic-lymphocytic-leukaemia-a-step-ahead-in-the-journey-toward-eradication
#5
Lorenzo De Paoli, Gianluca Gaidano
No abstract text is available yet for this article.
January 12, 2017: Lancet Oncology
https://www.readbyqxmd.com/read/28089238/ruxolitinib-for-symptom-control-in-patients-with-chronic-lymphocytic-leukaemia-a-single-group-phase-2-trial
#6
Preetesh Jain, Michael Keating, Sarah Renner, Charles Cleeland, Huang Xuelin, Graciela Nogueras Gonzalez, David Harris, Ping Li, Zhiming Liu, Ivo Veletic, Uri Rozovski, Nitin Jain, Phillip Thompson, Prithviraj Bose, Courtney DiNardo, Alessandra Ferrajoli, Susan O'Brien, Jan Burger, William Wierda, Srdan Verstovsek, Hagop Kantarjian, Zeev Estrov
BACKGROUND: Disease-related symptoms impair the quality of life of patients with chronic lymphocytic leukaemia (CLL) who do not require systemic therapy. Available therapies are not specifically aimed at symptom control. Because stimulation of the B-cell receptor activates JAK2 in CLL cells and the JAK2 inhibitor ruxolitinib improves symptoms in patients with myelofibrosis, we postulated that ruxolitinib would improve disease-related symptoms in patients with CLL. We did a phase 2 trial of ruxolitinib to test this hypothesis...
January 11, 2017: Lancet Haematology
https://www.readbyqxmd.com/read/28072473/pharmacokinetics-of-obinutuzumab-in-chinese-patients-with-b-cell-lymphomas
#7
John Zhai, Yan Qin, Jun Zhu, Yuqin Song, Zhixiang Shen, Xin Du, Candice Jamois, Michael Brewster, Yuankai Shi, Jun Shi
AIM: The Phase Ib GERSHWIN study (NCT01680991) assessed the pharmacokinetic (PK) profile of obinutuzumab following multiple intravenous (i.v.) doses to Chinese patients with B-cell lymphomas, and compared findings with previous obinutuzumab PK studies in mainly Caucasian (non-Chinese) patients. METHODS: GERSHWIN was an open-label, single-arm intervention study. Patients aged >18 years with CD20+ relapsed/refractory chronic lymphocytic leukaemia (CLL), diffuse large B-cell lymphoma (DLBCL) or follicular lymphoma (FL) were enrolled from four centres in China...
January 10, 2017: British Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/28062796/integrated-cellular-and-plasma-proteomics-of-contrasting-b-cell-cancers-reveals-common-unique-and-systemic-signatures
#8
Harvey E Johnston, Matthew J Carter, Kerry L Cox, Melanie Dunscombe, Antigoni Manousopoulou, Paul A Townsend, Spiro D Garbis, Mark S Cragg
Approximately 800,000 leukaemia and lymphoma cases are diagnosed worldwide each year. Burkitt's lymphoma (BL) and chronic lymphocytic leukaemia (CLL), are examples of contrasting B-cell cancers; BL is a highly aggressive lymphoid tumour, frequently affecting children, whilst CLL typically presents as an indolent, slow-progressing leukaemia affecting the elderly. The B-cell-specific over-expression of the myc and tcl1 oncogenes in mice induce spontaneous malignancies modelling BL and CLL, respectively. Quantitative mass spectrometry proteomics and isobaric labelling were employed to examine the biology underpinning contrasting Eμ-myc and Eμ-TCL1 B-cell tumours...
January 4, 2017: Molecular & Cellular Proteomics: MCP
https://www.readbyqxmd.com/read/28060374/heterogeneous-expression-of-the-collagen-receptor-ddr1-in-chronic-lymphocytic-leukaemia-and-correlation-with-progression
#9
G Barisione, M Fabbi, G Cutrona, L De Cecco, S Zupo, B Leitinger, M Gentile, M Manzoni, A Neri, F Morabito, M Ferrarini, S Ferrini
No abstract text is available yet for this article.
January 6, 2017: Blood Cancer Journal
https://www.readbyqxmd.com/read/28032335/eradication-of-minimal-residual-disease-improves-overall-and-progression-free-survival-in-patients-with-chronic-lymphocytic-leukaemia-evidence-from-ncrn-cll207-a-phase-ii-trial-assessing-alemtuzumab-consolidation
#10
Abraham M Varghese, Dena R Howard, Christopher Pocock, Andy C Rawstron, George Follows, Helen McCarthy, Claire Dearden, Christopher Fegan, Donald Milligan, Alexandra F Smith, Walter Gregory, Peter Hillmen
With immunochemotherapy, remission duration and survival in patients with chronic lymphocytic leukaemia is dependent on the level of minimal residual disease (MRD) after treatment. This phase II trial assessed alemtuzumab consolidation post-chemotherapy in patients who responded with persistent low levels of detectable disease. Blood was screened for MRD using multi-parameter flow cytometry, 6-24 months post-chemotherapy. MRD-positive participants received alemtuzumab 30 mg subcutaneously 3 times weekly for 6 weeks...
December 29, 2016: British Journal of Haematology
https://www.readbyqxmd.com/read/28027513/major-infections-secondary-cancers-and-autoimmune-diseases-occur-in-different-clinical-subsets-of-chronic-lymphocytic-leukaemia-patients
#11
Andrea Visentin, Silvia Imbergamo, Carmela Gurrieri, Federica Frezzato, Valentina Trimarco, Veronica Martini, Filippo Severin, Flavia Raggi, Edoardo Scomazzon, Monica Facco, Francesco Piazza, Gianpietro Semenzato, Livio Trentin
BACKGROUND: Major infections (MIs), secondary cancers (SCs) and autoimmune diseases (ADs) are the most common and relevant complications in patients with chronic lymphocytic leukaemia. METHODS: We performed a single-centre retrospective study to investigate the prevalence of the above quoted complications, the association with most important prognostic markers and their impact on survival (n = 795). RESULTS: Almost one out of three patients experienced at least one complication and only 0...
December 24, 2016: European Journal of Cancer
https://www.readbyqxmd.com/read/27993930/absorption-metabolism-and-excretion-of-a-novel-bcl-2-inhibitor-venetoclax-in-humans
#12
Hong Liu, Melissa J Michmerhuizen, Yanbin Lao, Katty Wan, Ahmed Hamed Salem, James Sawicki, Michael Serby, Srirajan Vaidyanathan, Shekman L Wong, Suresh Agarwal, Martin Dunbar, Jens Sydor, Sonia Maria de Morais, Anthony J Lee
Venetoclax (also known as ABT-199) is a B-cell lymphoma-2 (Bcl-2) family protein inhibitor and is currently in clinical development for the treatment of chronic lymphocytic leukaemia (CLL) and other hematological malignancies. The objective of this study was to characterize the absorption, metabolism, and excretion of venetoclax in humans. Following a single oral dose of 200 mg (100 μ - Ci) of [(14)C]venetoclax to four healthy volunteers, recovery of total radioactive dose was 100% (± 5%), with feces being the major route of elimination of the administered dose, whereas urinary excretion was minimal (<0...
December 19, 2016: Drug Metabolism and Disposition: the Biological Fate of Chemicals
https://www.readbyqxmd.com/read/27984636/rationale-for-combinatory-chronic-lymphocytic-leukaemia-treatment-paradigms-in-the-era-of-the-b-cell-receptor-pathway-and-anti-apoptotic-inhibitors-how-do-we-mix-match-and-move-forward
#13
EDITORIAL
https://www.readbyqxmd.com/read/27982425/ublituximab-tg-1101-a-novel-glycoengineered-anti-cd20-antibody-in-combination-with-ibrutinib-is-safe-and-highly-active-in-patients-with-relapsed-and-or-refractory-chronic-lymphocytic-leukaemia-results-of-a-phase-2-trial
#14
Jeff P Sharman, Charles M Farber, Daruka Mahadevan, Marshall T Schreeder, Heather D Brooks, Kathryn S Kolibaba, Suzanne Fanning, Leonard Klein, Daniel R Greenwald, Peter Sportelli, Hari P Miskin, Michael S Weiss, John M Burke
Ibrutinib is effective in patients with chronic lymphocytic leukaemia (CLL); however, treatment resistance remains a problem. Ublituximab is a novel, glycoengineered anti-CD20 monoclonal antibody with single-agent activity in relapsed CLL. We report the results of a phase 2 study evaluating combination therapy with ibrutinib and ublituximab in patients with relapsed or refractory CLL. Patients received ibrutinib 420 mg once daily. Ublituximab was administered on days 1, 8 and 15 of cycle 1 followed by day 1 of cycles 2-6...
December 16, 2016: British Journal of Haematology
https://www.readbyqxmd.com/read/27982015/evolution-of-multiple-cell-clones-over-a-29-year-period-of-a-cll-patient
#15
Zhikun Zhao, Lynn Goldin, Shiping Liu, Liang Wu, Weiyin Zhou, Hong Lou, Qichao Yu, Shirley X Tsang, Miaomiao Jiang, Fuqiang Li, MaryLou McMaster, Yang Li, Xinxin Lin, Zhifeng Wang, Liqin Xu, Gerald Marti, Guibo Li, Kui Wu, Meredith Yeager, Huanming Yang, Xun Xu, Stephen J Chanock, Bo Li, Yong Hou, Neil Caporaso, Michael Dean
Chronic lymphocytic leukaemia (CLL) is a frequent B-cell malignancy, characterized by recurrent somatic chromosome alterations and a low level of point mutations. Here we present single-nucleotide polymorphism microarray analyses of a single CLL patient over 29 years of observation and treatment, and transcriptome and whole-genome sequencing at selected time points. We identify chromosome alterations 13q14-, 6q- and 12q+ in early cell clones, elimination of clonal populations following therapy, and subsequent appearance of a clone containing trisomy 12 and chromosome 10 copy-neutral loss of heterogeneity that marks a major population dominant at death...
December 16, 2016: Nature Communications
https://www.readbyqxmd.com/read/27977057/randomized-phase-2-study-of-otlertuzumab-and-bendamustine-versus-bendamustine-in-patients-with-relapsed-chronic-lymphocytic-leukaemia
#16
Tadeusz Robak, Andrzej Hellmann, Janusz Kloczko, Javier Loscertales, Ewa Lech-Maranda, John M Pagel, Anthony Mato, John C Byrd, Farrukh T Awan, Holger Hebart, Jose A Garcia-Marco, Brian T Hill, Michael Hallek, Amy J Eisenfeld, Scott C Stromatt, Ulrich Jaeger
Otlertuzumab (TRU-016) is a humanized anti-CD37 protein therapeutic that triggers direct caspase-independent apoptosis of malignant B cells and induces antibody-dependent cell-mediated cytotoxicity. Patients with relapsed chronic lymphocytic leukaemia (CLL) received either otlertuzumab (20 mg/kg) weekly by IV infusion for two 28-day cycles then every 14 days for four 28-day cycles and IV bendamustine (70 mg/m(2) ) on Days 1 and 2 of each cycle for up to six 28-day cycles or bendamustine alone. Thirty-two patients were treated with otlertuzumab and bendamustine and 33 with bendamustine alone...
December 15, 2016: British Journal of Haematology
https://www.readbyqxmd.com/read/27973568/yessotoxin-a-marine-toxin-exhibits-anti-allergic-and-anti-tumoural-activities-inhibiting-melanoma-tumour-growth-in-a-preclinical-model
#17
Araceli Tobío, Amparo Alfonso, Iris Madera-Salcedo, Luis M Botana, Ulrich Blank
Yessotoxins (YTXs) are a group of marine toxins produced by the dinoflagellates Protoceratium reticulatum, Lingulodinium polyedrum and Gonyaulax spinifera. They may have medical interest due to their potential role as anti-allergic but also anti-cancer compounds. However, their biological activities remain poorly characterized. Here, we show that the small molecular compound YTX causes a slight but significant reduction of the ability of mast cells to degranulate. Strikingly, further examination revealed that YTX had a marked and selective cytotoxicity for the RBL-2H3 mast cell line inducing apoptosis, while primary bone marrow derived mast cells were highly resistant...
2016: PloS One
https://www.readbyqxmd.com/read/27972537/cost-effectiveness-of-ibrutinib-in-adult-patients-with-relapsed-chronic-lymphocytic-leukaemia-in-the-netherlands
#18
H Welten, T J Ignacio, B G Verheggen
No abstract text is available yet for this article.
November 2016: Value in Health: the Journal of the International Society for Pharmacoeconomics and Outcomes Research
https://www.readbyqxmd.com/read/27972387/ofatumumab-as-a-combination-therapy-versus-other-treatment-regimens-in-patients-with-untreated-relapsed-or-refractory-chronic-lymphocytic-leukaemia-a-systematic-review-of-randomised-controlled-trials
#19
H R Gadi, P Patel, S Shaikh, M K Rai
No abstract text is available yet for this article.
November 2016: Value in Health: the Journal of the International Society for Pharmacoeconomics and Outcomes Research
https://www.readbyqxmd.com/read/27970559/modelling-the-cost-effectiveness-of-treatment-strategies-in-chronic-lymphocytic-leukaemia-follicular-lymphoma-and-multiple-myeloma-a-review-and-critical-appraisal-of-the-published-literature
#20
Tchewonpi H Kankeu, A Manca
No abstract text is available yet for this article.
November 2016: Value in Health: the Journal of the International Society for Pharmacoeconomics and Outcomes Research
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