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chronic lymphocytic leukaemia

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https://www.readbyqxmd.com/read/28631441/genetic-landscape-and-deregulated-pathways-in-b-cell-lymphoid-malignancies
#1
R Rosenquist, S Beà, M-Q Du, B Nadel, Q Pan-Hammarström
With the introduction of next-generation sequencing, the genetic landscape of the complex group of B-cell lymphoid malignancies has rapidly been unravelled in recent years. This has provided important information about recurrent genetic events and identified key pathways deregulated in each lymphoma subtype. In parallel, there has been intense search and development of novel types of targeted therapy that 'hit' central mechanisms in lymphoma pathobiology, such as BTK, PI3K or BCL2 inhibitors. In this review, we will outline the current view of the genetic landscape of selected entities: follicular lymphoma, diffuse large B-cell lymphoma, mantle cell lymphoma, chronic lymphocytic leukaemia and marginal zone lymphoma...
June 20, 2017: Journal of Internal Medicine
https://www.readbyqxmd.com/read/28628003/clinical-effectiveness-and-cost-effectiveness-results-from-the-randomised-phase-iib-trial-in-previously-untreated-patients-with-chronic-lymphocytic-leukaemia-to-compare-fludarabine-cyclophosphamide-and-rituximab-with-fludarabine-cyclophosphamide-mitoxantrone
#2
Dena R Howard, Talha Munir, Lucy McParland, Andy C Rawstron, Anna Chalmers, Walter M Gregory, John L O'Dwyer, Alison Smith, Roberta Longo, Abraham Varghese, Alexandra Smith, Peter Hillmen
BACKGROUND: The conventional frontline therapy for fit patients with chronic lymphocytic leukaemia (CLL) is fludarabine, cyclophosphamide and rituximab (FCR). Rituximab (Mabthera(®), Roche Products Ltd) targets the CD20 antigen, which is expressed at low levels in CLL. The standard dose of rituximab in CLL (375 mg/m(2) in cycle 1 and 500 mg/m(2) in cycles 2-6) was selected based on toxicity data only. Small doses of rituximab (as low as 20 mg) have biological activity in CLL, with an immediate reduction in circulating CLL cells and down-regulation of CD20...
May 2017: Health Technology Assessment: HTA
https://www.readbyqxmd.com/read/28611188/new-quantitative-features-for-the-morphological-differentiation-of-abnormal-lymphoid-cell-images-from-peripheral-blood
#3
Laura Puigví, Anna Merino, Santiago Alférez, Andrea Acevedo, José Rodellar
AIMS: This work aims to propose a set of quantitative features through digital image analysis for significant morphological qualitative features of different cells for an objective discrimination among reactive, abnormal and blast lymphoid cells. METHODS: Abnormal lymphoid cells circulating in peripheral blood in chronic lymphocytic leukaemia, B-prolymphocytic leukaemia, hairy cell leukaemia, splenic marginal zone lymphoma, mantle cell lymphoma, follicular lymphoma, T-prolymphocytic leukaemia, T large granular lymphocytic leukaemia and Sézary syndrome, normal, reactive and blast lymphoid cells were included...
June 13, 2017: Journal of Clinical Pathology
https://www.readbyqxmd.com/read/28598442/distinct-homotypic-b-cell-receptor-interactions-shape-the-outcome-of-chronic-lymphocytic-leukaemia
#4
Claudia Minici, Maria Gounari, Rudolf Übelhart, Lydia Scarfò, Marcus Dühren-von Minden, Dunja Schneider, Alpaslan Tasdogan, Alabbas Alkhatib, Andreas Agathangelidis, Stavroula Ntoufa, Nicholas Chiorazzi, Hassan Jumaa, Kostas Stamatopoulos, Paolo Ghia, Massimo Degano
Cell-autonomous B-cell receptor (BcR)-mediated signalling is a hallmark feature of the neoplastic B lymphocytes in chronic lymphocytic leukaemia (CLL). Here we elucidate the structural basis of autonomous activation of CLL B cells, showing that BcR immunoglobulins initiate intracellular signalling through homotypic interactions between epitopes that are specific for each subgroup of patients with homogeneous clinicobiological profiles. The molecular details of the BcR-BcR interactions apparently dictate the clinical course of disease, with stronger affinities and longer half-lives in indolent cases, and weaker, short-lived contacts mediating the aggressive ones...
June 9, 2017: Nature Communications
https://www.readbyqxmd.com/read/28589551/centre-characteristics-and-procedure-related-factors-have-an-impact-on-outcomes-of-allogeneic-transplantation-for-patients-with-cll-a-retrospective-analysis-from-the-european-society-for-blood-and-marrow-transplantation-ebmt
#5
Johannes Schetelig, Liesbeth C de Wreede, Niels S Andersen, Carol Moreno, Michel van Gelder, Antonin Vitek, Michal Karas, Mauricette Michallet, Maciej Machaczka, Martin Gramatzki, Dietrich Beelen, Jürgen Finke, Julio Delgado, Liisa Volin, Jakob Passweg, Peter Dreger, Nicolaas Schaap, Eva Wagner, Anja Henseler, Anja van Biezen, Martin Bornhäuser, Simona Iacobelli, Hein Putter, Stefan O Schönland, Nicolaus Kröger
The best approach for allogeneic haematopoietic stem cell transplantations (alloHCT) in patients with chronic lymphocytic leukaemia (CLL) is unknown. We therefore analysed the impact of procedure- and centre-related factors on 5-year event-free survival (EFS) in a large retrospective study. Data of 684 CLL patients who received a first alloHCT between 2000 and 2011 were analysed by multivariable Cox proportional hazards models with a frailty component to investigate unexplained centre heterogeneity. Five-year EFS of the whole cohort was 37% (95% confidence interval [CI], 34-42%)...
June 7, 2017: British Journal of Haematology
https://www.readbyqxmd.com/read/28586310/effective-control-of-acute-myeloid-leukaemia-and-acute-lymphoblastic-leukaemia-progression-by-telomerase-specific-adoptive-t-cell-therapy
#6
Sara Sandri, Francesco De Sanctis, Alessia Lamolinara, Federico Boschi, Ornella Poffe, Rosalinda Trovato, Alessandra Fiore, Sara Sartori, Andrea Sbarbati, Attilio Bondanza, Simone Cesaro, Mauro Krampera, Maria T Scupoli, Michael I Nishimura, Manuela Iezzi, Silvia Sartoris, Vincenzo Bronte, Stefano Ugel
Telomerase (TERT) is a ribonucleoprotein enzyme that preserves the molecular organization at the ends of eukaryotic chromosomes. Since TERT deregulation is a common step in leukaemia, treatments targeting telomerase might be useful for the therapy of hematologic malignancies. Despite a large spectrum of potential drugs, their bench-to-bedside translation is quite limited, with only a therapeutic vaccine in the clinic and a telomerase inhibitor at late stage of preclinical validation. We recently demonstrated that the adoptive transfer of T cell transduced with an HLA-A2-restricted T-cell receptor (TCR), which recognize human TERT with high avidity, controls human B-cell chronic lymphocytic leukaemia (B-CLL) progression without severe side-effects in humanized mice...
May 23, 2017: Oncotarget
https://www.readbyqxmd.com/read/28580636/relationship-between-co-morbidities-at-diagnosis-survival-and-ultimate-cause-of-death-in-patients-with-chronic-lymphocytic-leukaemia-cll-a-prospective-cohort-study
#7
Paolo Strati, Sameer A Parikh, Kari G Chaffee, Neil E Kay, Timothy G Call, Sara J Achenbach, James R Cerhan, Susan L Slager, Tait D Shanafelt
The ultimate cause of death for most patients with newly diagnosed chronic lymphocytic leukaemia (CLL) and its relationship to co-morbid health conditions is poorly defined. We conducted a prospective cohort study that systematically followed 1143 patients diagnosed with CLL between June 2002 and November 2014. Comorbid health conditions at the time of CLL diagnosis and their relationship to survival and cause of death were evaluated. Collectively, 1061 (93%) patients had at least one co-morbid health condition at the time of CLL diagnosis (median number 3)...
June 4, 2017: British Journal of Haematology
https://www.readbyqxmd.com/read/28573664/relationship-between-comorbidities-at-diagnosis-survival-and-ultimate-cause-of-death-in-patients-with-chronic-lymphocytic-leukaemia-cll-a-prospective-cohort-study
#8
EDITORIAL
https://www.readbyqxmd.com/read/28567239/bendamustine-and-its-role-in-the-treatment-of-unfit-patients-with-chronic-lymphocytic-leukaemia-a-perspective-review
#9
REVIEW
Othman Al-Sawaf, Paula Cramer, Valentin Goede, Michael Hallek, Natali Pflug
With a median age of 72 years at first diagnosis, chronic lymphocytic leukaemia (CLL) is a disease of the elderly. At this age, many patients cannot bear an intensive chemoimmunotherapy like fludarabine, cyclophosphamide and rituximab (FCR), and therapeutic decisions are commonly complicated by a high burden of accompanying comorbidities. Clinical trials, on the other hand, are mostly designed to include a far healthier and younger trial population, with a median age in most studies well below 70 years, leading to an insufficient reflection of clinical reality...
June 2017: Therapeutic Advances in Hematology
https://www.readbyqxmd.com/read/28561533/emergence-of-bruton-s-tyrosine-kinase-negative-hodgkin-lymphoma-during-ibrutinib-treatment-of-chronic-lymphocytic-leukaemia
#10
Siobhan Glavey, John Quinn, Mary McCloy, Jeremy Sargent, Yvonne McCartney, Mark Catherwood, Teresa Marafioti, Mary Leader, Philip Murphy, Patrick Thornton
Chronic Lymphocytic Leukaemia (CLL) is a chronic B cell lympho-proliferative disorder in which lymphomatous transformations occur in 5-15% of patients. Histologically these cases resemble diffuse large B cell lymphoma, or Richter's transformation, in over 80% of cases. Rare cases of transformation to Hodgkin lymphoma (HL) have been reported in the literature with an estimated prevalence of 0.4%. We report a case of a 67 year-old female with CLL treated with the novel Bruton's tyrosine kinase (Btk) inhibitor, ibrutinib, who subsequently presented with intractable fevers...
May 31, 2017: European Journal of Haematology
https://www.readbyqxmd.com/read/28557248/ponatinib-induced-widespread-ichthyosiform-eruption
#11
F Derlino, S Barruscotti, P Zappasodi, V Brazzelli, C Vassallo
Ponatinib is a new potent third-generation tyrosine kinase inhibitor (TKI), developed for the treatment of chronic myeloid leukemia (CML) and Philadelphia chromosome-positive acute lymphocytic leukaemia (ALL) resistant to first (imatinib) and second generation (dasatinib and nilotinib) TK-inhibitors. Aimed at wild type and mutant BCR-ABL, ponatinib demonstrates significant anti-leukemic activity and holds much promise in treating other malignancies, including gastrointestinal stromal tumors (GIST)(1;2). This article is protected by copyright...
May 30, 2017: Journal of the European Academy of Dermatology and Venereology: JEADV
https://www.readbyqxmd.com/read/28546881/haematological-malignancies-in-systemic-sclerosis-patients-case-reports-and-review-of-the-world-literature
#12
M Colaci, D Giuggioli, C Vacchi, C Ferri
Background. The association of systemic sclerosis (SSc) and haematological cancers was reported in a large number of case reports and cohort studies, describing SSc patients with highly heterogeneous clinical pictures. Objective. We reviewed the literature to better describe SSc patients with haematological malignancies. Methods. SSc cases complicated by haematological malignancies described in the world literature were collected; other 2 cases referred to our centre were reported. Results. One hundred-thirty SSc subjects were collected from 1954 up to date...
2017: Case Reports in Rheumatology
https://www.readbyqxmd.com/read/28541116/imbruvica-%C3%A2-%C3%A2-ibrutinib-patient-support-programme-for-chronic-lymphocytic-leukaemia-and-mantle-cell-lymphoma
#13
Vidhya Murthy, Susan Weaving, Shankara Paneesha
Single-agent ibrutinib is an effective therapy for three types of non-Hodgkin lymphoma: chronic lymphocytic leukaemia (CLL) and small lymphocytic lymphoma, both in relapsed and refractory cases and as a frontline treatment; relapsed and refractory mantle cell lymphoma; and Waldenstrom's macroglobulinaemia in patients who have been treated previously with a different medication. This novel agent has changed the landscape for the aforementioned three subtypes of lymphoma therapies as an oral alternative to traditional chemoimmunotherapy...
May 25, 2017: British Journal of Nursing: BJN
https://www.readbyqxmd.com/read/28497220/ct-p10-truxima%C3%A2-a-rituximab-biosimilar
#14
Emma D Deeks
CT-P10 (Truxima™) is the first biosimilar of the reference monoclonal anti-CD20 antibody rituximab. It is approved for use in all indications for which reference rituximab is approved, including follicular lymphoma (FL), diffuse large B-cell non-Hodgkin's lymphoma, chronic lymphocytic leukaemia, rheumatoid arthritis (RA), granulomatosis with polyangiitis and microscopic polyangiitis. CT-P10 has similar physicochemical and pharmacodynamic properties to those of reference rituximab, and the pharmacokinetic biosimilarity of the agents has been shown in patients with RA or FL...
May 11, 2017: BioDrugs: Clinical Immunotherapeutics, Biopharmaceuticals and Gene Therapy
https://www.readbyqxmd.com/read/28489572/ck2-and-pi3k-are-direct-molecular-targets-of-quercetin-in-chronic-lymphocytic-leukaemia
#15
Maria Russo, Alfonsina Milito, Carmela Spagnuolo, Virginia Carbone, Anders Rosén, Paola Minasi, Fabio Lauria, Gian Luigi Russo
Despite the encouraging results of the innovative therapeutic treatments, complete remission is uncommon in patients affected by chronic lymphocytic leukaemia, which remains an essentially incurable disease. Recently, clinical trials based on BH3-mimetic drugs showed positive outcomes in subjects with poor prognostic features. However, resistance to treatments occurs in a significant number of patients. We previously reported that the multi-kinase inhibitor quercetin, a natural flavonol, restores sensitivity to ABT-737, a BH3-mimetic compound, in both leukemic cell lines and B-cells isolated from patients...
April 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/28454583/lymphoma-intervention-live-patient-reported-outcome-feedback-and-a-web-based-self-management-intervention-for-patients-with-lymphoma-study-protocol-for-a-randomised-controlled-trial
#16
Lindy P J Arts, Lonneke V van de Poll-Franse, Sanne W van den Berg, Judith B Prins, Olga Husson, Floortje Mols, Angelique V M Brands-Nijenhuis, Lidwine Tick, Simone Oerlemans
BACKGROUND: Patients with lymphoma are at risk of experiencing adverse physical and psychosocial problems from their cancer and its treatment. Regular screening of these symptoms by the use of patient-reported outcomes (PROs) could increase timely recognition and adequate symptom management. Moreover, self-management interventions intend to enhance knowledge and skills and empower patients to better manage their disease and related problems. The objective of the Lymphoma InterVEntion (LIVE) trial is to examine whether feedback to patients on their PROs and access to a web-based, self-management intervention named Living with lymphoma will increase self-management skills and satisfaction with information, and reduce psychological distress...
April 28, 2017: Trials
https://www.readbyqxmd.com/read/28449207/targeting-anti-apoptotic-bcl2-family-proteins-in-haematological-malignancies-from-pathogenesis-to-treatment
#17
REVIEW
Meike Vogler, Harriet S Walter, Martin J S Dyer
The B-cell lymphoma 2 (BCL2) family of proteins comprise key regulators of apoptosis and are implicated in the pathogenesis of many malignancies, including lymphomas and leukaemias. Targeting of BCL2 proteins can be directly toxic to tumour cells or render them more sensitive to chemotherapy. Inhibition of the anti-apoptotic functions of BCL2 proteins using structure-based design to produce specific inhibitors of protein-protein interactions has been achieved for BCL2, MCL1 and BCL-XL (also termed BCL2L1), providing an armamentarium of new targeted therapies called BH3-mimetics...
April 27, 2017: British Journal of Haematology
https://www.readbyqxmd.com/read/28446487/haemophagocytic-lymphohistiocytosis-as-a-consequence-of-untreated-b-cell-chronic-lymphocytic-leukaemia
#18
Chris Bailey, Claire Dearden, Kirit Ardeshna
Haemophagocytic lymphohistiocytosis (HLH) is a rare, life-threatening syndrome characterised by defective cytotoxic function and hypercytokinaemia leading to macrophage expansion and haemophagocytosis. Patients often present with unexplained fevers, hepatosplenomegaly and pancytopenia, with elevation in serum ferritin and triglyceride. Acquired forms are triggered by infection, malignancy or rheumatological disorders. HLH in the setting of chronic lymphocytic leukaemia is rarely reported, however, and is usually associated with infection or as a consequence of chemotherapy...
April 26, 2017: BMJ Case Reports
https://www.readbyqxmd.com/read/28444740/chronic-lymphocytic-leukaemia-genomics-and-the-precision-medicine-era
#19
REVIEW
Hussein Ghamlouch, Florence Nguyen-Khac, Olivier A Bernard
Massive genomic analyses have underscored the diversity of chronic lymphocytic leukaemia (CLL) between patients. Genetic heterogeneity of tumour clones within a patient may fuel tumour evolution. Several recurrently deregulated intra-cellular pathways are candidates for targeted therapies that are very promising and are dramatically changing clinical patients' perspectives. In this review we present an overview of the genetic and epigenetic features of CLL and their clinical and biological implications.
April 25, 2017: British Journal of Haematology
https://www.readbyqxmd.com/read/28439883/an-update-for-richter-syndrome-new-directions-and-developments
#20
REVIEW
Toby A Eyre, Anna Schuh
High-grade transformation of chronic lymphocytic leukaemia [Richter syndrome (RS)] is rare and represents a unique and uncommon clinical challenge. Clonally related diffuse large B cell type RS is a chemotherapy-resistant and devastating disease. Patients are typically elderly, immunosuppressed and present with a rapidly deteriorating performance status. Historical outcomes suggest a median overall survival of approximately 8 months. RS remains is an area of high unmet clinical need. The molecular profile and treatment needs of patients are likely to change over time with the advent of novel B cell receptor inhibitors, monoclonal antibodies and BH3 mimetics...
April 25, 2017: British Journal of Haematology
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