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chronic lymphocytic leukaemia

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https://www.readbyqxmd.com/read/28330607/association-between-anti-thymocyte-globulin-exposure-and-survival-outcomes-in-adult-unrelated-haemopoietic-cell-transplantation-a-multicentre-retrospective-pharmacodynamic-cohort-analysis
#1
Rick Admiraal, Stefan Nierkens, Moniek A de Witte, Eefke J Petersen, Ger-Jan Fleurke, Luka Verrest, Svetlana V Belitser, Robbert G M Bredius, Reinier A P Raymakers, Catherijne A J Knibbe, Monique C Minnema, Charlotte van Kesteren, Jurgen Kuball, Jaap J Boelens
BACKGROUND: Anti-thymocyte globulin (ATG) is used to prevent graft-versus-host disease (GvHD) after allogeneic haemopoietic cell transplantation (HCT). However, ATG can also cause delayed immune reconstitution of T cells, negatively affecting survival. We studied the relation between exposure to ATG and clinical outcomes in adult patients with acute leukaemia and myelodysplastic syndrome. METHODS: We did a retrospective, pharmacokinetic-pharmacodynamic analysis of data from patients with acute lymphoid leukaemia, acute myeloid leukaemia, or myelodysplastic syndrome receiving their first T-cell repleted allogeneic peripheral blood stem cell HCT with ATG (thymoglobulin) as part of non-myeloablative conditioning from March 1, 2004, to June 1, 2015...
March 16, 2017: Lancet Haematology
https://www.readbyqxmd.com/read/28303898/circulating-tumour-dna-reflects-treatment-response-and-clonal-evolution-in-chronic-lymphocytic-leukaemia
#2
Paul Yeh, Tane Hunter, Devbarna Sinha, Sarah Ftouni, Elise Wallach, Damian Jiang, Yih-Chih Chan, Stephen Q Wong, Maria Joao Silva, Ravikiran Vedururu, Kenneth Doig, Enid Lam, Gisela Mir Arnau, Timothy Semple, Meaghan Wall, Andjelija Zivanovic, Rishu Agarwal, Pasquale Petrone, Kate Jones, David Westerman, Piers Blombery, John F Seymour, Anthony T Papenfuss, Mark A Dawson, Constantine S Tam, Sarah-Jane Dawson
Several novel therapeutics are poised to change the natural history of chronic lymphocytic leukaemia (CLL) and the increasing use of these therapies has highlighted limitations of traditional disease monitoring methods. Here we demonstrate that circulating tumour DNA (ctDNA) is readily detectable in patients with CLL. Importantly, ctDNA does not simply mirror the genomic information contained within circulating malignant lymphocytes but instead parallels changes across different disease compartments following treatment with novel therapies...
March 17, 2017: Nature Communications
https://www.readbyqxmd.com/read/28295181/long-term-follow-up-of-patients-receiving-allogeneic-stem-cell-transplant-for-chronic-lymphocytic-leukaemia-mixed-t-cell-chimerism-is-associated-with-high-relapse-risk-and-inferior-survival
#3
Philip A Thompson, Francesco Stingo, Michael J Keating, William G Wierda, Susan M O'Brien, Zeev Estrov, Celina Ledesma, Katayoun Rezvani, Muzaffar Qazilbash, Nina Shah, Simrit Parmar, Uday Popat, Paolo Anderlini, Nieto Yago, Stefan O Ciurea, Partow Kebriaei, Richard Champlin, Elizabeth J Shpall, Chitra M Hosing
There is limited information regarding the immunological predictors of post-allogeneic stem cell transplant (alloSCT) outcome in chronic lymphocytic leukaemia (CLL), such as mixed T-cell chimerism. We analysed 143 consecutive patients with relapsed/refractory CLL, transplanted between 2000 and 2012, to determine the prognostic relevance of mixed chimerism post-alloSCT and the ability of post-transplant immunomodulation to treat relapse. Mixed T-cell chimerism occurred in 50% of patients at 3 months and 43% at 6 months post-alloSCT; upon 3- and 6-month landmark analysis, this was associated with inferior progression-free survival (PFS) [Hazard ratio (HR) 1·93, P = 0·003 and HR 2·58, P < 0·001] and survival (HR 1·66, P = 0·05 and HR 2·17, P < 0·001), independent of baseline patient characteristics, and a lower rate of grade II-IV acute graft-versus-host disease (GHVD) (16% vs...
March 14, 2017: British Journal of Haematology
https://www.readbyqxmd.com/read/28295171/successful-use-of-bruton-s-kinase-inhibitor-ibrutinib-to-control-paraneoplastic-pemphigus-in-a-patient-with-paraneoplastic-autoimmune-multiorgan-syndrome-and-chronic-lymphocytic-leukaemia
#4
Andrew Lee, Suneet Sandhu, Louise Imlay-Gillespie, Stephen Mulligan, Stephen Shumack
We present the case of a 51-year-old man who developed paraneoplastic pemphigus (PNP) in the context of chronic lymphocytic leukemia (CLL). His CLL was successfully controlled with ibrutinib. Concurrently, there was significant improvement of his PNP, suggesting that ibrutinib may be a very useful addition to the treatment options in this potentially life-threatening autoimmune disorder.
March 13, 2017: Australasian Journal of Dermatology
https://www.readbyqxmd.com/read/28267258/normal-human-immune-cells-are-sensitive-to-telomerase-inhibition-by-brassica-derived-3-3-diindolylmethane-partly-mediated-via-er%C3%AE-%C3%AE-ap1-signalling
#5
Corinna Herz, Hoai Thi Thu Tran, Steffen Landerer, Johanna Gaus, Nina Schlotz, Lia Lehr, Wolfgang R Schäfer, Oliver Treeck, Grace Akinyi Odongo, Ivan Skatchov, Evelyn Lamy
SCOPE: Indole-3-carbinol (I3C) and 3,3'-diindolylmethane (DIM) from Brassica plants are regarded as promising anticancer phytochemicals. The enzyme telomerase is a very attractive target for cancer therapeutics; in normal cells such as lymphocytes, it plays a decisive role for cell maintenance. The effect of I3C and DIM on telomerase in normal human immune cells (PBMC) was studied compared to leukaemia cells (HL-60). Signalling of telomerase regulation via estrogen receptor (ER) was addressed...
March 7, 2017: Molecular Nutrition & Food Research
https://www.readbyqxmd.com/read/28257754/treatment-for-relapsed-or-refractory-chronic-lymphocytic-leukaemia-an-ongoing-challenge
#6
Paolo Strati
No abstract text is available yet for this article.
March 2017: Lancet Haematology
https://www.readbyqxmd.com/read/28257752/efficacy-and-safety-of-idelalisib-in-combination-with-ofatumumab-for-previously-treated-chronic-lymphocytic-leukaemia-an-open-label-randomised-phase-3-trial
#7
Jeffrey A Jones, Tadeusz Robak, Jennifer R Brown, Farrukh T Awan, Xavier Badoux, Steven Coutre, Javier Loscertales, Kerry Taylor, Elisabeth Vandenberghe, Malgorzata Wach, Nina Wagner-Johnston, Loic Ysebaert, Lyndah Dreiling, Ronald Dubowy, Guan Xing, Ian W Flinn, Carolyn Owen
BACKGROUND: Idelalisib, a selective inhibitor of PI3Kδ, is approved for the treatment of patients with relapsed chronic lymphocytic leukaemia (CLL) in combination with rituximab. We aimed to assess the efficacy and safety of idelalisib in combination with a second-generation anti-CD20 antibody, ofatumumab, in a similar patient population. METHODS: In this global, open-label, randomised, controlled phase 3 trial, we enrolled patients with relapsed CLL progressing less than 24 months from last therapy...
March 2017: Lancet Haematology
https://www.readbyqxmd.com/read/28236754/lymphohaematopoietic-malignancies-in-scottish-military-veterans-retrospective-cohort-study-of-57-000-veterans-and-173-000-non-veterans
#8
Beverly P Bergman, Daniel F Mackay, Jill P Pell
BACKGROUND: Lymphohaematopoietic malignancies are common in the general population. There have been concerns that military service may be associated with increased risk as a result of occupational exposures. To date, few studies have demonstrated an increased risk, although a disability pension is payable to veterans who were present at nuclear tests and who develop leukaemia (other than chronic lymphocytic leukaemia). The aim of the study was to utilise data from the Scottish Veterans Health Study to examine the risk of lymphohaematopoietic malignancy following military service in a large national cohort of veterans...
February 22, 2017: Cancer Epidemiology
https://www.readbyqxmd.com/read/28220479/a-phase-1-2-trial-of-ublituximab-a-novel-anti-cd20-monoclonal-antibody-in-patients-with-b-cell-non-hodgkin-lymphoma-or-chronic-lymphocytic-leukaemia-previously-exposed-to-rituximab
#9
Ahmed Sawas, Charles M Farber, Marshall T Schreeder, Mazen Y Khalil, Daruka Mahadevan, Changchun Deng, Jennifer E Amengual, Petros G Nikolinakos, Jill M Kolesar, John G Kuhn, Peter Sportelli, Hari P Miskin, Owen A O'Connor
This phase 1/2 study evaluated the safety, pharmacokinetic behavior and anti-tumour activity of ublituximab, a unique type I, chimeric, glycoengineered anti-CD20 monoclonal antibody, in rituximab-relapsed or -refractory patients with B-cell non-Hodgkin lymphoma (B-NHL) or chronic lymphocytic leukaemia (CLL). Induction therapy (doses of 450-1200 mg) consisted of 4 weekly infusions in cycle 1 for NHL and 3 weekly infusions in cycles 1 and 2 for CLL. Patients received ublituximab maintenance monthly during cycles 3-5, then once every 3 months for up to 2 years...
February 21, 2017: British Journal of Haematology
https://www.readbyqxmd.com/read/28209992/from-basic-apoptosis-discoveries-to-advanced-selective-bcl-2-family-inhibitors
#10
REVIEW
Avi Ashkenazi, Wayne J Fairbrother, Joel D Leverson, Andrew J Souers
Members of the B cell lymphoma 2 (BCL-2) gene family have a central role in regulating programmed cell death by controlling pro-apoptotic and anti-apoptotic intracellular signals. In cancer, apoptosis evasion through dysregulation of specific BCL-2 family genes is a recurring event; accordingly, selective inhibition of specific anti-apoptotic BCL-2 family proteins represents an exciting therapeutic opportunity. A combination of nuclear magnetic resonance (NMR)-based screening and structure-based drug design has yielded the first bona fide BCL-2 homology 3 (BH3) mimetics, including the BCL-2 and BCL-XL dual antagonist navitoclax, which is the first BCL-2 family inhibitor to show efficacy in patients with cancer...
February 17, 2017: Nature Reviews. Drug Discovery
https://www.readbyqxmd.com/read/28208230/emerging-role-of-gsk-3%C3%AE-in-the-pathobiology-of-classical-hodgkin-lymphoma
#11
Claudio Agostinelli, Silvia Carloni, Francesco Limarzi, Simona Righi, Maria Antonella Laginestra, Gerardo Musuraca, Michelangelo Fiorentino, Roberta Napolitano, Antonio Cuneo, Daniele Vergara, Pier Luigi Zinzani, Sabattini Elena, Stefano A Pileri, Serena De Matteis
AIMS: GSK-3β is a serine/threonine kinase involved in glycogen metabolism, cell cycle progression, differentiation, embryogenesis, migration, metabolism, survival and cellular senescence. Its main biological function is to inhibit β-catenin by sequestration and promotion of its proteasomal degradation in the Wnt canonical pathway, however GSK-3β interacts with multiple signaling pathways and aberrant expression of the enzyme was reported in many solid neoplasms. This study aimed to investigate the biological relevance of GSK-3β in classical Hodgkin Lymphomas (cHL)...
February 16, 2017: Histopathology
https://www.readbyqxmd.com/read/28199309/phosphatidylinositol-3-kinase-%C3%AE-blockade-increases-genomic-instability-in-b-cells
#12
Mara Compagno, Qi Wang, Chiara Pighi, Taek-Chin Cheong, Fei-Long Meng, Teresa Poggio, Leng-Siew Yeap, Elif Karaca, Rafael B Blasco, Fernanda Langellotto, Chiara Ambrogio, Claudia Voena, Adrian Wiestner, Siddha N Kasar, Jennifer R Brown, Jing Sun, Catherine J Wu, Monica Gostissa, Frederick W Alt, Roberto Chiarle
Activation-induced cytidine deaminase (AID) is a B-cell-specific enzyme that targets immunoglobulin genes to initiate class switch recombination and somatic hypermutation. In addition, through off-target activity, AID has a much broader effect on genomic instability by initiating oncogenic chromosomal translocations and mutations involved in the development and progression of lymphoma. AID expression is tightly regulated in B cells and its overexpression leads to enhanced genomic instability and lymphoma formation...
February 15, 2017: Nature
https://www.readbyqxmd.com/read/28179635/chronic-lymphocytic-leukaemia
#13
Thomas J Kipps, Freda K Stevenson, Catherine J Wu, Carlo M Croce, Graham Packham, William G Wierda, Susan O'Brien, John Gribben, Kanti Rai
No abstract text is available yet for this article.
February 9, 2017: Nature Reviews. Disease Primers
https://www.readbyqxmd.com/read/28166664/-tp53-mutation-analysis-in-chronic-lymphocytic-leukaemia
#14
Viktória Fésüs, Dóra Marosvári, Béla Kajtár, Péter Attila Király, Judit Demeter, Tímea Gurbity Pálfi, Miklós Egyed, Márk Plander, Péter Farkas, Zoltán Mátrai, András Matolcsy, Csaba Bödör
INTRODUCTION: In recent years much progress has been made in the therapy of chronic lymphocytic leukaemia, as the new innovative medicine proved to be effective in managing patients carrying TP53 abnormalities. To identify all these patients, it is essential to screen for both forms of TP53 defects, including both 17p deletions and TP53 mutations. AIM: The aim of this study was to determine the frequency of TP53 mutations and their association with 17p deletions in a large Hungarian cohort of 196 patients suffering from chronic lymphocytic leukaemia...
February 2017: Orvosi Hetilap
https://www.readbyqxmd.com/read/28165464/genome-wide-association-analysis-implicates-dysregulation-of-immunity-genes-in-chronic-lymphocytic-leukaemia
#15
Philip J Law, Sonja I Berndt, Helen E Speedy, Nicola J Camp, Georgina P Sava, Christine F Skibola, Amy Holroyd, Vijai Joseph, Nicola J Sunter, Alexandra Nieters, Silvia Bea, Alain Monnereau, David Martin-Garcia, Lynn R Goldin, Guillem Clot, Lauren R Teras, Inés Quintela, Brenda M Birmann, Sandrine Jayne, Wendy Cozen, Aneela Majid, Karin E Smedby, Qing Lan, Claire Dearden, Angela R Brooks-Wilson, Andrew G Hall, Mark P Purdue, Tryfonia Mainou-Fowler, Claire M Vajdic, Graham H Jackson, Pierluigi Cocco, Helen Marr, Yawei Zhang, Tongzhang Zheng, Graham G Giles, Charles Lawrence, Timothy G Call, Mark Liebow, Mads Melbye, Bengt Glimelius, Larry Mansouri, Martha Glenn, Karen Curtin, W Ryan Diver, Brian K Link, Lucia Conde, Paige M Bracci, Elizabeth A Holly, Rebecca D Jackson, Lesley F Tinker, Yolanda Benavente, Paolo Boffetta, Paul Brennan, Marc Maynadie, James McKay, Demetrius Albanes, Stephanie Weinstein, Zhaoming Wang, Neil E Caporaso, Lindsay M Morton, Richard K Severson, Elio Riboli, Paolo Vineis, Roel C H Vermeulen, Melissa C Southey, Roger L Milne, Jacqueline Clavel, Sabine Topka, John J Spinelli, Peter Kraft, Maria Grazia Ennas, Geoffrey Summerfield, Giovanni M Ferri, Robert J Harris, Lucia Miligi, Andrew R Pettitt, Kari E North, David J Allsup, Joseph F Fraumeni, James R Bailey, Kenneth Offit, Guy Pratt, Henrik Hjalgrim, Chris Pepper, Stephen J Chanock, Chris Fegan, Richard Rosenquist, Silvia de Sanjose, Angel Carracedo, Martin J S Dyer, Daniel Catovsky, Elias Campo, James R Cerhan, James M Allan, Nathanial Rothman, Richard Houlston, Susan Slager
Several chronic lymphocytic leukaemia (CLL) susceptibility loci have been reported; however, much of the heritable risk remains unidentified. Here we perform a meta-analysis of six genome-wide association studies, imputed using a merged reference panel of 1,000 Genomes and UK10K data, totalling 6,200 cases and 17,598 controls after replication. We identify nine risk loci at 1p36.11 (rs34676223, P=5.04 × 10(-13)), 1q42.13 (rs41271473, P=1.06 × 10(-10)), 4q24 (rs71597109, P=1.37 × 10(-10)), 4q35.1 (rs57214277, P=3...
February 6, 2017: Nature Communications
https://www.readbyqxmd.com/read/28154156/lung-consolidation-responding-to-chemotherapy
#16
Prasanth Balasubramaniam, Ram V Nampoothiri, Nalini Gupta, Pankaj Malhotra
Consolidations in the pulmonary parenchyma are mostly infective, although they can rarely be due to autoimmune and neoplastic processes. Consolidations, especially in the setting of underlying immunosuppressive haematological malignancy, are usually presumed infective by the treating physician. Pulmonary involvement in chronic lymphocytic leukaemia presenting as consolidations and type 1 respiratory failure, responding to systemic chemotherapy, is a rare and uncommon presentation.
February 2, 2017: BMJ Case Reports
https://www.readbyqxmd.com/read/28139406/another-treatment-option-for-relapsed-or-refractory-chronic-lymphocytic-leukaemia
#17
Francesca R Mauro
No abstract text is available yet for this article.
January 27, 2017: Lancet Oncology
https://www.readbyqxmd.com/read/28139405/idelalisib-or-placebo-in-combination-with-bendamustine-and-rituximab-in-patients-with-relapsed-or-refractory-chronic-lymphocytic-leukaemia-interim-results-from-a-phase-3-randomised-double-blind-placebo-controlled-trial
#18
Andrew D Zelenetz, Jacqueline C Barrientos, Jennifer R Brown, Bertrand Coiffier, Julio Delgado, Miklós Egyed, Paolo Ghia, Árpád Illés, Wojciech Jurczak, Paula Marlton, Marco Montillo, Franck Morschhauser, Alexander S Pristupa, Tadeusz Robak, Jeff P Sharman, David Simpson, Lukáš Smolej, Eugen Tausch, Adeboye H Adewoye, Lyndah K Dreiling, Yeonhee Kim, Stephan Stilgenbauer, Peter Hillmen
BACKGROUND: Bendamustine plus rituximab is a standard of care for the management of patients with relapsed or refractory chronic lymphocytic leukaemia. New therapies are needed to improve clinically relevant outcomes in these patients. We assessed the efficacy and safety of adding idelalisib, a first-in-class targeted phosphoinositide-3-kinase δ inhibitor, to bendamustine plus rituximab in this population. METHODS: For this international, multicentre, double-blind, placebo-controlled trial, adult patients (≥18 years) with relapsed or refractory chronic lymphocytic leukaemia requiring treatment who had measurable lymphadenopathy by CT or MRI and disease progression within 36 months since their last previous therapy were enrolled...
January 27, 2017: Lancet Oncology
https://www.readbyqxmd.com/read/28130034/nice-guidance-on-ibrutinib-for-previously-treated-chronic-lymphocytic-leukaemia-and-untreated-chronic-lymphocytic-leukaemia-in-the-presence-of-17p-deletion-or-tp53-mutation
#19
Boglarka Mikudina, Melinda Goodall, Amanda I Adler
No abstract text is available yet for this article.
January 24, 2017: Lancet Oncology
https://www.readbyqxmd.com/read/28112199/genome-wide-association-analysis-of-chronic-lymphocytic-leukaemia-hodgkin-lymphoma-and-multiple-myeloma-identifies-pleiotropic-risk-loci
#20
Philip J Law, Amit Sud, Jonathan S Mitchell, Marc Henrion, Giulia Orlando, Oleg Lenive, Peter Broderick, Helen E Speedy, David C Johnson, Martin Kaiser, Niels Weinhold, Rosie Cooke, Nicola J Sunter, Graham H Jackson, Geoffrey Summerfield, Robert J Harris, Andrew R Pettitt, David J Allsup, Jonathan Carmichael, James R Bailey, Guy Pratt, Thahira Rahman, Chris Pepper, Chris Fegan, Elke Pogge von Strandmann, Andreas Engert, Asta Försti, Bowang Chen, Miguel Inacio da Silva Filho, Hauke Thomsen, Per Hoffmann, Markus M Noethen, Lewin Eisele, Karl-Heinz Jöckel, James M Allan, Anthony J Swerdlow, Hartmut Goldschmidt, Daniel Catovsky, Gareth J Morgan, Kari Hemminki, Richard S Houlston
B-cell malignancies (BCM) originate from the same cell of origin, but at different maturation stages and have distinct clinical phenotypes. Although genetic risk variants for individual BCMs have been identified, an agnostic, genome-wide search for shared genetic susceptibility has not been performed. We explored genome-wide association studies of chronic lymphocytic leukaemia (CLL, N = 1,842), Hodgkin lymphoma (HL, N = 1,465) and multiple myeloma (MM, N = 3,790). We identified a novel pleiotropic risk locus at 3q22...
January 23, 2017: Scientific Reports
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