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chronic lymphocytic leukaemia

Melody Caramins, Nicole Chia, Stephen Mulligan
No abstract text is available yet for this article.
February 2016: Pathology
Jamma Li, Oliver G Best, Stephen P Mulligan, Suran L Fernando
No abstract text is available yet for this article.
February 2016: Pathology
Jamma Li, Oliver G Best, Stephen P Mulligan, Suran L Fernando
No abstract text is available yet for this article.
February 2016: Pathology
(no author information available yet)
In 2014, ibrutinib was made available for relapsed/refractory chronic lymphocytic leukaemia (CLL) patients. The UK CLL Forum collected data from UK/Ireland patients with a minimum of 1 year follow-up with pre-planned primary endpoints; the number of patients still on therapy at 1 year (Discontinuation Free Survival; DFS) and 1 year overall survival (OS). With a median 16 months follow-up, data on 315 patients demonstrated 1 year DFS of 73.7% and 1 year OS of 83.8%. Patients with better pre-treatment performance status (PS 0/1 vs 2+) had superior DFS (77...
October 18, 2016: Haematologica
M Burgess, S Mapp, R Mazzieri, C Cheung, L Chambers, S R Mattarollo, P Mollee, D Gill, N A Saunders
Resistance to therapeutic antibodies in chronic lymphocytic leukaemia (CLL) is common. In this study, we show that therapeutic antibodies against CD62L (CD62L-Ab) or CD20 (obinutuzumab) were able to induce antibody-dependent cell-mediated cytotoxicity (ADCC) and phagocytosis (ADP) in primary cultures of CLL cells. CLL cells derived from patients with active disease requiring treatment displayed resistance to these antibodies, whereas patients with stable disease were sensitive. Using enrichment strategies and transcriptomic analyses, we show that antibody-dependent tumour cell killing was FcγR-dependent and mediated by macrophages...
October 17, 2016: Oncogene
A Prica, F Baldassarre, L K Hicks, K Imrie, T Kouroukis, M Cheung
Rituximab is the first monoclonal antibody to be approved for use by the US Food and Drug Administration in cancer. Its role in the treatment of non-Hodgkin lymphoma, including chronic lymphocytic leukaemia (CLL), has evolved significantly. We aimed to systematically review and update the literature on rituximab in lymphoma and CLL, and provide evidence-based consensus guidelines for its rational use. Validated methodology from the Cancer Care Ontario Program in Evidence-based Care was used. A comprehensive literature search was completed by a methodologist from the Hematology Disease Site Group of Cancer Care Ontario...
October 13, 2016: Clinical Oncology: a Journal of the Royal College of Radiologists
Julio Delgado, Neus Villamor, Armando López-Guillermo, Elías Campo
Next-generation sequencing provides a comprehensive understanding of the genomic, epigenomic and transcriptomic underpinnings of chronic lymphocytic leukaemia. Recent studies have uncovered new drivers, including mutations in non-coding regions, and signalling pathways whose role in cancer was previously unknown or poorly understood. Moreover, massive scale epigenomics and transcriptomics have supplied the foundations for the cellular origin of the disease. Some drivers could be targeted pharmacologically, and the ability to detect mutations present in minority subclones might even allow treatment before clonal selection occurs, thus preventing disease refractoriness...
March 2016: Best Practice & Research. Clinical Haematology
Brian Koffman, Andrew Schorr
The 21st century has seen rapid, positive changes in the management of chronic lymphocytic leukaemia from the patient's perspective. New prognostic and predictive markers have ushered in the start of more precise and individualized therapy. For the first time, combined therapy [fludarabine, cyclophosphamide and rituximab] has been shown to prolong life significantly. Clinical trials have become more adaptive, faster and more patient friendly. Perhaps the greatest change of all is the development of novel oral agents (ibrutinib and idelalisib) and powerful monoclonal antibodies that offer robust and durable disease control...
March 2016: Best Practice & Research. Clinical Haematology
Emili Montserrat, Tycho Bauman, Julio Delgado
Medicine has been 'personalized' (i.e. centred in persons) since its foundation. Recently, however, the term 'personalized medicine' (or, better, 'precision medicine') has been introduced to define 'a form of medicine that uses information about a person's genes, proteins, and environment to prevent, diagnose, and treat disease'. This concept has gained momentum thanks to next-generation-sequencing (NGS) techniques that allow identification of molecular characteristics unique to the patient and to the tumour...
March 2016: Best Practice & Research. Clinical Haematology
Isabel González-Gascón Y Marín, Ana África Martín, María Hernández-Sanchez, Cristina Robledo, María Lourdes Hermosín, Natalia de Las Heras, Laura Lacalle, Josefina Galende, Felipe de Arriba, Ana Eugenia Rodríguez-Vicente, José-Ángel Hernández, Jesús María Hernández-Rivas
: The presence of chromosomal gains other than trisomy 12 in chronic lymphocytic leukaemia (CLL) is unusual. However, some patients may show gains on several chromosomes simultaneously suggesting a hyperdiploid karyotype. OBJECTIVE: The objective of this study was to analyse by FISH the frequency and prognostic impact of hyperdiploidy in CLL. METHOD: A review of 1359 consecutive cases diagnosed with CLL referred for FISH analysis to a unique institution was carried out...
September 26, 2016: European Journal of Haematology
M Ladetto, C Buske, M Hutchings, M Dreyling, G Gaidano, S Le Gouill, S Luminari, C Pott, A Zamò, E Zucca
The European Society for Medical Oncology (ESMO) consensus conference on mature B-cell lymphomas and chronic lymphocytic leukaemia (CLL) was held on 20 June 2015 in Lugano, Switzerland, and included a multidisciplinary panel of 25 leading experts. The aim of the conference was to develop recommendations on critical subjects difficult to consider in detail in the ESMO Clinical Practice Guidelines. The following areas were identified: (i) the elderly patient, (ii) prognostic factors suitable for clinical use and (iii) the 'ultra-high-risk' group...
October 4, 2016: Annals of Oncology: Official Journal of the European Society for Medical Oncology
Rachael J M Bashford-Rogers, Anne L Palser, Clare Hodkinson, Joanna Baxter, George A Follows, George S Vassiliou, Paul Kellam
Chronic lymphocytic leukaemia (CLL) is characterised by the accumulation of clonally-derived mature CD5(high) B-cells, however the cellular origin of CLL is still unknown. Patients with CLL also harbour variable numbers of CD5(low) B-cells, but the clonal relationship of these cells to the bulk disease is unknown and can have important implications for monitoring, treating and understanding the biology of CLL. Here we use B-cell receptors (BCRs) as molecular barcodes to first show that the great majority of CD5(low) B-cells in the blood of CLL patients are clonally related to CD5(high) CLL B-cells by single-cell BCR sequencing...
September 27, 2016: Experimental Hematology
Barry D Hock, Nicholas D McIntosh, Judith L McKenzie, John F Pearson, Jeremy W Simcock, Sean A MacPherson
BACKGROUND AND AIM: Chronic lymphocytic leukemia (CLL) is associated with an increased incidence and aggressiveness of skin cancers, in particular cutaneous squamous cell carcinoma (cSCC), but little is known of cSCC incidence in Australasian CLL patients. In this retrospective study we analysed the incidence of cSCC in patients seen at a tertiary hospital in New Zealand (NZ). METHODS: We retrospectively assessed the clinical history and histology data of CLL patients (n = 371) who were seen at the Haematology Department, Christchurch Hospital, NZ during the period 1996-2015...
September 24, 2016: Internal Medicine Journal
B Eichhorst, T Robak, E Montserrat, P Ghia, P Hillmen, M Hallek, C Buske
No abstract text is available yet for this article.
September 2016: Annals of Oncology: Official Journal of the European Society for Medical Oncology
Lucie Poppova, Pavlina Janovska, Karla Plevova, Lenka Radova, Hana Plesingerova, Marek Borsky, Jana Kotaskova, Barbara Kantorova, Michaela Hlozkova, Jana Figulova, Yvona Brychtova, Michaela Machalova, Milan Urik, Michael Doubek, Alois Kozubik, Sarka Pospisilova, Sarka Pavlova, Vitezslav Bryja
The canonical Wnt pathway, dependent on β-catenin-controlled transcription, is the most explored Wnt pathway, known to drive the malignant transformation of multiple cell types. Several reports have suggested that this pathway also participates in chronic lymphocytic leukaemia (CLL) pathogenesis. To get a better insight into the role of the Wnt/β-catenin pathway in CLL we analysed in detail the expression of the most overexpressed Wnt ligand, encoded by the WNT3 gene, in a well-defined cohort of 137 CLL patients...
September 21, 2016: British Journal of Haematology
Dena R Howard, Talha Munir, Anna Hockaday, Andy C Rawstron, Laura Collett, Jamie B Oughton, David Allsup, Adrian Bloor, David Phillips, Peter Hillmen
BACKGROUND: Chronic lymphocytic leukaemia (CLL) is the most common adult leukaemia. Combination immunochemotherapy such as fludarabine, cyclophosphamide and rituximab is the standard first line therapy in fit patients, but there is limited evidence regarding the optimal treatment of patients after relapse. Ofatumumab as monotherapy has been proven to be effective in the treatment of relapsed, refractory CLL, and as it is not myelotoxic, it is an ideal drug to combine with chemotherapy...
2016: Trials
Susan O'Brien, Jeffrey A Jones, Steven E Coutre, Anthony R Mato, Peter Hillmen, Constantine Tam, Anders Österborg, Tanya Siddiqi, Michael J Thirman, Richard R Furman, Osman Ilhan, Michael J Keating, Timothy G Call, Jennifer R Brown, Michelle Stevens-Brogan, Yunfeng Li, Fong Clow, Danelle F James, Alvina D Chu, Michael Hallek, Stephan Stilgenbauer
BACKGROUND: The TP53 gene, encoding tumour suppressor protein p53, is located on the short arm of chromosome 17 (17p). Patients with 17p deletion (del17p) chronic lymphocytic leukaemia have poor responses and survival after chemoimmunotherapy. We assessed the activity and safety of ibrutinib, an oral covalent inhibitor of Bruton's tyrosine kinase, in relapsed or refractory patients with del17p chronic lymphocytic leukaemia or small lymphocytic lymphoma. METHODS: We did a multicentre, international, open-label, single-arm study at 40 sites in the USA, Canada, Europe, Australia, and New Zealand...
October 2016: Lancet Oncology
Florence Nguyen-Khac, Claire Borie, Evelyne Callet-Bauchu, Virginie Eclache, Stéphanie Struski
Acquired recurrent cytogenetic abnormalities are frequent in chronic lymphocytic leukaemia (CLL). They can be associated with good or poor prognostic factors, and also with gene mutations. Chromosomal abnormalities could be clonal or sub-clonal. Assessing the TP53 status (deletion/mutation) is currently mandatory before treating patients. The search for 11q deletion (ATM gene) is also recommended. Finally, the prognostic value of other chromosomal abnormalities including complex karyotype is still debated.
October 1, 2016: Annales de Biologie Clinique
Peggy Paola Ríos Germán, Belén Loeches Yagües, Alicia Rico Nieto
No abstract text is available yet for this article.
September 9, 2016: Revista Española de Geriatría y Gerontología
Philip A Thompson, Vincent Lévy, Constantine S Tam, Chadi Al Nawakil, François-Xavier Goudot, Anne Quinquenel, Loic Ysebaert, Anne-Sophie Michallet, Marie-Sarah Dilhuydy, Eric Van Den Neste, Jehan Dupuis, Michael J Keating, Christophe Meune, Florence Cymbalista
Atrial fibrillation (AF) occurs in 5-9% of patients treated with ibrutinib for chronic lymphocytic leukaemia (CLL); the clinical consequences and optimal management are unclear. We retrospectively studied 56 CLL patients who received ibrutinib and developed AF. Median time to onset was 3·8 months. AF was persistent in 35/56 (62%) cases despite treatment. Clinical consequences included: three episodes of severe cardiac failure (one fatal) and one stroke; eight non-thrombocytopenic patients (14%) experienced severe bleeding adverse events...
September 9, 2016: British Journal of Haematology
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