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chronic lymphocytic leukaemia

Jan A Burger, Susan O'Brien
During the past 5 years, a number of highly active novel agents, including kinase inhibitors targeting BTK or PI3Kδ, an antagonist of the antiapoptotic protein BCL-2, and new anti-CD20 monoclonal antibodies, have been added to the therapeutic armamentarium for patients with chronic lymphocytic leukaemia (CLL). In these exciting times, care is needed to optimally integrate these novel agents into the traditional treatment algorithm without overlooking or compromising the benefits of established treatments, especially chemoimmunotherapy...
May 18, 2018: Nature Reviews. Clinical Oncology
Kyle Crassini, Yandong Shen, William S Stevenson, Richard Christopherson, Chris Ward, Stephen P Mulligan, O Giles Best
The survival and proliferation of chronic lymphocytic leukaemia (CLL) cells is driven by multiple signalling pathways, including those mediated by the B cell, Toll-like and chemokine receptors. Many of these pathways converge on the same signalling molecules, including those involved in the Raf-1/MEK/Erk1/2-MAPK pathway. We investigated the effects of the MEK1/2 (also termed MAP2K1/2) inhibitor, binimetinib, against CLL cells cultured under conditions that mimic aspects of the tumour microenvironment. Binimetinib blocked CLL cell survival induced by stroma-conditioned media and phorbol myristylate (PMA)...
May 16, 2018: British Journal of Haematology
Nikolaos Ioannou, Alan G Ramsay
No abstract text is available yet for this article.
May 16, 2018: British Journal of Haematology
D B Chen, H Zhang, Y H Zhang, Y Wang, Q J Song, S M Yang, H Cui, Y Zhao, X Z Fang, D H Shen
Objective: To study the clinicopathologic features, diagnosis and differential diagnosis of tumors of haematopoietic and lymphoid tissue in the female productive tract. Methods: Eleven cases of myeloid sarcoma and leukemia, 9 of non Hodgkin lymphoma (NHL) , 13 of cervical lymphoma-like lesions were selected from Peking University People's Hospital from January 2006 to August 2017. According to WHO classification of tumors of haematopoietic and lymphoid tissues (2008) and updated classification(2016), the cases were studied by microscopy, immunohistochemistry and in situ hybridization...
April 25, 2018: Zhonghua Fu Chan Ke za Zhi
Afaf Alharthi, Daniel Beck, Dena R Howard, Peter Hillmen, Melanie Oates, Andrew Pettitt, Simon D Wagner
OBJECTIVES: In vitro culture studies have shown that miR-363 is enriched in extracellular vesicles from chronic lymphocytic leukaemia cells. We wondered whether miR-363 was detectable in plasma, which is an essential precondition for further studies to assess its usefulness as a biomarker. Using samples from two clinical trials: one enrolling patients with advanced disease and the other asymptomatic patients with early stage disease, we determined plasma miR-363 levels and secondly investigated the distribution of this miRNA between plasma and particle bound fractions in patients and normal subjects...
May 8, 2018: BMC Research Notes
Benjamin W Teh, Constantine S Tam, Sasanka Handunnetti, Leon J Worth, Monica A Slavin
Chronic lymphocytic leukaemia (CLL) is the most common leukaemia with infections a leading cause of morbidity and mortality. Recently there has been a paradigm shift from the use of chemo-immunotherapies to agents targeting specific B-lymphocyte pathways. These agents include ibrutinib, idelalisib and venetoclax. In this review, the risks and timing of infections associated with these agents are described, taking into account disease and treatment status. Treatment with ibrutinib as monotherapy or in combination with chemo-immunotherapies is not associated with additional risk for infection...
April 23, 2018: Blood Reviews
Nyanza K L M Timmers, Josanne S de Maar, Rob C M van Kruijsdijk, Saskia K Klein
Central nervous system (CNS) localisation of chronic lymphocytic leukaemia (CLL) can induce various neurological symptoms. Unfamiliarity with this manifestation causes diagnostic delay. We present two cases of leptomeningeal CLL. These cases and our literature review emphasise that CNS localisation of CLL should be considered in patients with any neurological symptom, irrespectively of the stage and systemic activity of CLL.
April 29, 2018: Annals of Hematology
Joel McCay, Joseph Scott
No abstract text is available yet for this article.
April 27, 2018: BMJ Case Reports
Weiyin Zhou, Lynn Goldin, Mingyi Wang, Mary L McMaster, Kristine Jones, Laurie Burdett, Stephen J Chanock, Meredith Yeager, Michael Dean, Neil E Caporaso
Recurrent large-scale somatic copy number alterations (SCNAs), and somatic point mutations can be analysed to stratify patients with chronic lymphocytic leukaemia (CLL) into distinct prognostic groups. To investigate the relationship between SCNAs and somatic mutations, we performed whole-exome sequencing and single nucleotide polymorphism microarray analyses on 98 CLL patients from 40 families with a high burden of CLL. Overall, 69 somatic mutations in 29 CLL driver genes were detected among 45 subjects (46%), with the most frequently mutated genes being TP53 (8·2%), NOTCH1 (8·2%) and ATM (5·1%)...
April 24, 2018: British Journal of Haematology
Emilia Białopiotrowicz, Patryk Górniak, Monika Noyszewska-Kania, Bartosz Puła, Hanna Makuch-Łasica, Grażyna Nowak, Aleksandra Bluszcz, Maciej Szydłowski, Ewa Jabłonska, Karolina Piechna, Tomasz Sewastianik, Anna Polak, Ewa Lech-Marańda, Bożena K Budziszewska, Maja Wasylecka-Juszczyńska, Katarzyna Borg, Krzysztof Warzocha, Wojciech Czardybon, Michał Gałęzowski, Renata Windak, Krzysztof Brzózka, Przemysław Juszczyński
Lymph node microenvironment provides chronic lymphocytic leukaemia (CLL) cells with signals promoting their survival and granting resistance to chemotherapeutics. CLL cells overexpress PIM kinases, which regulate apoptosis, cell cycle and migration. We demonstrate that BCR crosslinking, CD40 stimulation, and coculture with stromal cells increases PIMs expression in CLL cells, indicating microenvironment-dependent PIMs regulation. PIM1 and PIM2 expression at diagnosis was higher in patients with advanced disease (Binet C vs...
April 17, 2018: Journal of Cellular and Molecular Medicine
P Cocco, R Agius
Background: The fraction of ill-health overall attributable to occupational conditions has not been extensively evaluated, thus contributing to the perception of a lesser relevance of education and research in occupational health in respect to other fields of medical research and practice. Aims: To assess the relevance of work-related conditions on the aetiology of human ill-health in different health domains. Methods: We extracted the risk estimates associated with heritability and with occupational risk factors for chronic lymphocytic leukaemia (CLL), major depressive disorder (MDD) and long QT syndrome (LQTS) from 13 published international reports...
April 12, 2018: Occupational Medicine
Gabriel Cea, Andrés Gallardo V, María Elena Cabrera C
Myasthenia gravis (MG) is a rare autoimmune disease of the neuromuscular junction. It is characterized by variable weakness and excessive fatigability of skeletal muscles. In the last few years, numerous reports have been published showing the association between autoimmune diseases, such as systemic erythematous lupus or rheumatoid arthritis, with lymphoid neoplasias. The association between MG and lymphoid neoplasia seems to be less frequent. To analyze this association we reviewed the MG patients in the Department of Neurology, Hospital Salvador of Santiago, Chile...
December 2017: Revista Médica de Chile
Gian Matteo Rigolin, Elena Saccenti, Emanuele Guardalben, Maurizio Cavallari, Luca Formigaro, Barbara Zagatti, Andrea Visentin, Francesca R Mauro, Enrico Lista, Cristian Bassi, Laura Lupini, Francesca Maria Quaglia, Antonio Urso, Maria Antonella Bardi, Laura Bonaldi, Eleonora Volta, Elisa Tammiso, Caterina Ilari, Luciana Cafforio, Aurora Melandri, Francesco Cavazzini, Massimo Negrini, Gianpietro Semenzato, Livio Trentin, Robin Foà, Antonio Cuneo
Complex karyotype (CK) is a negative prognostic factor in chronic lymphocytic leukaemia (CLL). However, CK is a heterogeneous cytogenetic category. Unbalanced rearrangements were present in 73·3% of 90 CLL patients with CK (i.e. ≥3 chromosome aberrations in the same clone), and were associated with a shorter overall survival (P = 0·025) and a shorter time to first treatment (P = 0·043) by multivariate analysis. Patients with unbalanced rearrangements presented a distinct mRNA expression profile. In conclusion, CLL patients with unbalanced rearrangements might represent a subset of very high-risk CLL patients with distinct clinical and biological characteristics...
April 2, 2018: British Journal of Haematology
Robert Stirrups
No abstract text is available yet for this article.
May 2018: Lancet Oncology
Giovanni D'Arena, Candida Vitale, Giovanni Rossi, Marta Coscia, Paola Omedè, Fiorella D'Auria, Teodora Statuto, Luciana Valvano, Stefania Ciolli, Milena Gilestro, Stefano Molica, Silvia Bellesi, Topini Giuseppe, Panichi Valentina, Francesco Autore, Idanna Innocenti, Pellegrino Musto, Silvia Deaglio, Luca Laurenti, Luigi Del Vecchio
CD200, a transmembrane type Ia glycoprotein belonging to the immunoglobulin superfamily, has been shown to have a differential expression in B-cell neoplasms. Here, we retrospectively assessed the diagnostic relevance of CD200 on 427 patients with B-cell chronic neoplasms in leukemic phase (median age, 69 y; range, 35-97 y). The final diagnosis based on the investigator's assessment was chronic lymphocytic leukaemia (CLL) in 75% of cases and non-CLL in 25% of cases. Sensitivity and specificity for the diagnosis of CLL (vs non-CLL) were calculated for the following markers: CD200, CD5, CD22, CD23, CD79b, FMC7, and SmIg...
March 30, 2018: Hematological Oncology
Ewa Wąsik-Szczepanek, Agnieszka Szymczyk, Małgorzata Kowal, Adam Nogalski, Marek Hus
INTRODUCTION: Despite significant recent advances in the treatment of chronic lymphocytic leukaemia (CLL), most cases of the disease are still incurable. Treatment with monoclonal antibodies, such as ofatumumab, is one of the new therapeutic options. OBJECTIVE: Retrospective analysis of the efficacy of ofatumumab in patients with chronic lymphocytic leukaemia (CLL) treated in the Haematooncology and Bone Marrow Transplantation Department of the Medical University of Lublin, Poland, during 2011-2013...
March 14, 2018: Annals of Agricultural and Environmental Medicine: AAEM
Srdana Grgurevic, Patricia Montilla-Perez, Alice Bradbury, Julia Gilhodes, Sophie Queille, Sandrine Pelofy, Aurélien Bancaud, Thomas Filleron, Loïc Ysebaert, Christian Récher, Guy Laurent, Jean-Jacques Fournié, Christophe Cazaux, Anne Quillet-Mary, Jean-Sébastien Hoffmann
Alteration in the DNA Replication, Repair or Recombination processes is a highly relevant mechanism of genomic instability. Despite genomic aberrations manifested in haematological malignancies, such a defect as a source of biomarkers has been underexplored. Here, we investigated prognostic value of expression of 82 genes involved in DNA Replication-Repair-Recombination in a series of 99 patients with chronic lymphocytic leukaemia without detected 17p deletion or TP53 mutation. We unveiled that expression of the POLN gene, encoding the specialized DNA polymerase ν (Polν) correlates with time to relapse after the first-line therapy with fludarabine...
March 22, 2018: Haematologica
Jennifer R Brown, Mehdi Hamadani, John Hayslip, Ann Janssens, Nina Wagner-Johnston, Oliver Ottmann, Jon Arnason, Hervé Tilly, Michael Millenson, Fritz Offner, Nashat Y Gabrail, Siddhartha Ganguly, Sikander Ailawadh, Siddha Kasar, Arnon P Kater, Jeanette K Doorduijn, Lei Gao, Joanne J Lager, Bin Wu, Coumaran Egile, Marie José Kersten
BACKGROUND: Patients with relapsed or refractory lymphoma or chronic lymphocytic leukaemia have a poor prognosis. Therapies targeting more than one isoform of PI3K, as well as mTOR, might increase antitumour activity. We aimed to investigate the efficacy and safety of voxtalisib (also known as XL765 or SAR245409), a pan-PI3K/mTOR inhibitor, in patients with relapsed or refractory lymphoma, or chronic lymphocytic leukaemia/small lymphocytic lymphoma. METHODS: We did a non-randomised, open-label, phase 2 trial at 30 oncology clinics in the USA, Belgium, Germany, France, the Netherlands, and Australia...
March 14, 2018: Lancet Haematology
Liannv Qiu, Yonglie Zhou, Qinhua Yu, Sujie Zheng, Zhenni Wang, Qiang Huang
Chronic lymphocytic leukaemia (CLL) is characterized by an abnormal expansion of mature B cells with variable progression. Follicular T helper (Tfh) cells help B cells differentiate into plasma cells or long-lived memory B cells in germinal centres (GCs). However, the role of Tfh cells in CLL is poorly understand, and whether it plays a critical role in disease progression in vivo is lacking. In this study, we investigate the dynamic change of circulating Tfh cells in peripheral blood from patients with CLL during the treatment periods to evaluate their utility to predict disease progression...
May 2018: Immunology Letters
Sandra D Algaze, Wungki Park, Thomas J Harrington, Raja Mudad
We describe a rare case of severe autoimmune haemolytic anaemia (AIHA) in the setting of underlying chronic lymphocytic leukaemia receiving intravenous immunoglobulin, history of warm IgG autoantibody and treatment with nivolumab for advanced non-small cell lung cancer. In this report, we describe AIHA as a potential serious immune-related adverse event from immune checkpoint inhibitors, discuss other potential contributing factors and review previously described cases of AIHA in patients receiving programmed death 1 (PD-1) inhibitors...
March 9, 2018: BMJ Case Reports
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