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https://www.readbyqxmd.com/read/28810819/low-cll-1-expression-is-a-novel-adverse-predictor-in-123-patients-with-de-novo-cd34-acute-myeloid-leukemia
#1
Jin Wang, Yanyu Wang, Wen-Lian Chen, Jie Hao, Zhanyun Liu, Xiangqin Weng, Yan Sheng, Jing Wu, Yongmei Zhu, Bing Chen, Shu-Min Xiong, Yu Chen, Qiusheng Chen, Hui-Ping Sun, Junmin Li
Recent reports state that C-type lectin-like molecule-1 (CLL-1) in acute myeloid leukemia (AML) is expressed primarily on myeloid cells, but there is still no investigation about its prognostic significance on leukemic blast compartment. Hence, this study aimed to evaluate the prognostic value of CLL-1 in 123 patients with de novo CD34+ non-M3 AML. Multiparameter flow cytometry was used to assess the expression of CLL-1 on immature compartment in AML and control groups. We found that CLL-1 expression level on blast compartment was closely linked to clinical characteristics, treatment response and survival outcome of patients...
August 16, 2017: Stem Cells and Development
https://www.readbyqxmd.com/read/28803824/the-clinical-spectrum-of-hepatic-manifestations-in-chronic-lymphocytic-leukemia
#2
REVIEW
Natalia Kreiniz, Ofrat Beyar Katz, Aaron Polliack, Tamar Tadmor
Chronic lymphocytic leukemia (CLL) is the most common leukemia in the Western world, characterized by the presence of long-lived circulating leukemic cells in the peripheral blood that may infiltrate all organs, particularly those of the reticulo-endothelial system. Liver enlargement and elevation of liver enzymes related to specific involvement by the underlying disease are well-recognized features in these patients. In CLL, the differential diagnosis of liver disorders is broad and includes liver infiltration by leukemic cells, immunologic manifestations associated with CLL, primary and secondary hepatic malignancies, drug-induced hepatotoxicity, infections, and Richter transformation...
July 23, 2017: Clinical Lymphoma, Myeloma & Leukemia
https://www.readbyqxmd.com/read/28802891/time-to-second-line-treatment-and-subsequent-relative-survival-in-older-patients-with-relapsed-chronic-lymphocytic-leukemia-small-lymphocytic-lymphoma
#3
Eric M Ammann, Tait D Shanafelt, Melissa C Larson, Kara B Wright, Bradley D McDowell, Brian K Link, Elizabeth A Chrischilles
BACKGROUND: Novel targeted therapies offer excellent short-term outcomes in patients with chronic lymphocytic leukemia and small lymphocytic lymphoma (CLL/SLL). However, there is disagreement over how widely these therapies should be used in place of standard chemo-immunotherapy (CIT). We investigated whether stratification on the length of the interval between first-line (T1) and second-line (T2) treatments could identify a subgroup of older patients with relapsed CLL/SLL with an expectation of normal overall survival, and for whom CIT could be an acceptable treatment choice...
July 19, 2017: Clinical Lymphoma, Myeloma & Leukemia
https://www.readbyqxmd.com/read/28797620/extended-follow-up-of-patients-treated-with-bendamustine-for-lymphoid-malignancies
#4
Mara Penne, Maryam Sarraf Yazdy, Kruti Sheth Nair, Bruce D Cheson
INTRODUCTION: Bendamustine, typically in combination with rituximab, is an effective treatment for chronic lymphocytic leukemia (CLL) and B-cell non-Hodgkin lymphoma. Despite its acceptable short-term toxicity profile, long-term toxicities are less well established. This study investigated the long-term adverse effects of bendamustine and responses to subsequent treatments. PATIENTS AND METHODS: Charts of 194 patients were retrospectively reviewed; 54% had received prior treatment (76% attained complete response [CR] or partial response [PR])...
June 30, 2017: Clinical Lymphoma, Myeloma & Leukemia
https://www.readbyqxmd.com/read/28796569/cost-effectiveness-of-kinase-inhibitors-for-hematologic-malignancies-a-systematic-and-critical-review
#5
Monia Marchetti
Several genetic disruptions lead to constitutive activation of those kinases leukemic cells depend on for survival and proliferation. Kinase inhibitors (KI) are major therapeutic innovations for chronic myeloid leukemia (CML), chronic lymphoid leukemia (CLL) and myelofibrosis (MF) providing a relevant improvement of quality-adjusted survival in patients with high-risk or refractory disease. CML patients are being treated with first-generation KI imatinib since many years, achieving expected survivals longer than 10 years...
August 10, 2017: Expert Review of Pharmacoeconomics & Outcomes Research
https://www.readbyqxmd.com/read/28791248/an-unusual-presentation-of-chronic-lymphocytic-leukemia
#6
Dinesh Atwal, Mihir Raval, Belal Firwana, Jeanette Ramos, Appalanaidu Sasapu
Chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) is a B-cell lymphocytic neoplasm with indolent clinical course. If identified early, observation is opted. Many variables lead to the initiation of treatment. Authors describe a 62-year-old male presenting with shortness of breath and found to have white cell count of 1360 × 10(9)/L and subsequently was diagnosed with CLL/SLL. The patient received leukapheresis along with tumor lysis treatment and systemic chemotherapy with fludarabine, cyclophosphamide, and rituximab regimen...
July 2017: Avicenna Journal of Medicine
https://www.readbyqxmd.com/read/28791187/ibrutinib-treatment-of-mantle-cell-lymphoma-relapsing-at-central-nervous-system-a-case-report-and-literature-review
#7
Donato Mannina, Barbara Loteta
Mantle cell lymphoma (MCL) accounts for about 5% of all lymphomas. Its clinical and histological features are heterogeneous. After a frequently good initial response, the disease generally and repeatedly relapses and finally the outcome is poor. Particularly severe is the prognosis of the rare occurrence of CNSi (Central Nervous System involvement). Ibrutinib, an oral inhibitor of Bruton tyrosine kinase (BTK), has shown strong activity in relapsing patients with Chronic Lymphocytic Leukemia (CLL) and MCL. Few reports are available about treatment with ibrutinib of patients presenting CNSi by lymphoproliferative diseases (LPD)...
2017: Case Reports in Hematology
https://www.readbyqxmd.com/read/28783166/anti-leukemic-activity-of-microrna-26a-in-a-chronic-lymphocytic-leukemia-mouse-model
#8
L D'Abundo, E Callegari, A Bresin, A Chillemi, B K Elamin, P Guerriero, X Huang, E Saccenti, E M A A Hussein, F Casciano, P Secchiero, G Zauli, G A Calin, G Russo, L J Lee, C M Croce, G Marcucci, S Sabbioni, F Malavasi, M Negrini
Dysregulation of microRNAs (miRNAs) plays an important role in the pathogenesis of chronic lymphocytic leukemia (CLL). The Eμ-TCL1 transgenic mouse develops a form of leukemia that is similar to the aggressive type of human B-CLL, and this valuable model has been widely used for testing novel therapeutic approaches. Here, we adopted this model to investigate the potential effects of miR-26a, miR-130an and antimiR-155 in CLL therapy. Improved delivery of miRNA molecules into CLL cells was obtained by developing a novel system based on lipid nanoparticles conjugated with an anti-CD38 monoclonal antibody...
August 7, 2017: Oncogene
https://www.readbyqxmd.com/read/28782884/chronic-lymphocytic-leukemia-2017-update-on-diagnosis-risk-stratification-and-treatment
#9
REVIEW
Michael Hallek
DISEASE OVERVIEW: Chronic lymphocytic leukemia (CLL) is the commonest leukemia in western countries. The disease typically occurs in elderly patients and has a highly variable clinical course. Leukemic transformation is initiated by specific genomic alterations that impair apoptosis of clonal B cells. DIAGNOSIS: The diagnosis is established by blood counts, blood smears, and immunophenotyping of circulating B lymphocytes, which identify a clonal B-cell population carrying the CD5 antigen and B-cell markers...
September 2017: American Journal of Hematology
https://www.readbyqxmd.com/read/28776453/new-drug-discovery-approaches-targeting-recurrent-mutations-in-chronic-lymphocytic-leukemia
#10
Rupal Tripathi, Eriong Lee-Verges, Morihiro Higashi, Neus Gimenez, Laia Rosich, Monica Lopez-Guerra, Dolors Colomer
Next generation sequencing has provided a comprehensive understanding of the mutational landscape in chronic lymphocytic leukemia (CLL), and new drivers have been identified. Some of these drivers could be pharmacologically targeted to choose the most effective personalized therapy in each CLL patient. Areas covered: In this article, the authors uncover the potential role of new targeted therapies against the most recurrent mutations in CLL as well as the recently approved therapies. The authors also provide their expert opinion and give their perspectives for the future...
August 4, 2017: Expert Opinion on Drug Discovery
https://www.readbyqxmd.com/read/28766542/-efficacy-of-a-bendamustine-and-rituximab-combination-in-first-line-therapy-for-chronic-lymphocytic-leukemia-results-of-the-ben-001-study
#11
E A Stadnik, V V Strugov, T O Andreeva, Yu V Virts, A M Rumyantsev, Yu V Mirolyubova, P A Butylin, A Yu Zaritsky
AIM: To evaluate the efficacy and safety of the BR regimen containing bendamustine in patients with chronic lymphocytic leukemia (CLL) who have not previously received specific therapy. SUBJECTS AND METHODS: The results of the Russian prospective observational multicenter study BEN-001 (2012-2015) covering 196 CLL patients from 34 centers of the Russian Federation were analyzed. The diagnosis was confirmed by the results of peripheral blood lymphocyte immunophenotyping...
2017: Terapevticheskiĭ Arkhiv
https://www.readbyqxmd.com/read/28766389/pharmacokinetics-efficacy-and-safety-of-the-rituximab-biosimilar-ct-p10
#12
Bertrand Coiffier
Rituximab, an anti-CD20 monoclonal antibody, is a key therapeutic in the treatment of B cell lymphomas and rheumatoid arthritis (RA). Global rates of non-Hodgkin's lymphoma (NHL), chronic lymphocytic leukemia (CLL) and RA are increasing, with a concomitant rise in individual and overall treatment costs. As such, biosimilar development may help facilitate greater access to treatment. The rituximab biosimilar CT-P10 (Truxima®) has recently received approval in Europe and South Korea for all indications held by reference rituximab (RTX)...
August 2, 2017: Expert Review of Clinical Pharmacology
https://www.readbyqxmd.com/read/28762636/blockage-of-wnt-%C3%AE-catenin-signaling-by-nanoparticles-reduces-survival-and-proliferation-of-cll-cells-in-vitro-preliminary-study
#13
Ida Franiak-Pietryga, Henryk Maciejewski, Barbara Ziemba, Dietmar Appelhans, Brigitte Voit, Tadeusz Robak, Magdalena Jander, Jacek Treliński, Maria Bryszewska, Maciej Borowiec
The Wnt/β-catenin signaling pathway is shown to play a significant role in the control of the survival, proliferation, and differentiation of hematopoietic cells. Studies have confirmed that aberrant activation of canonical Wnt signaling occurs in various forms of leukemia, and is crucial for chronic lymphocytic leukemia (CLL) pathogenesis. The aim of the study is to evaluate the influence of maltotriose (M3) modified fourth generation poly(propylene imine) dendrimers (PPI-G4) on Wnt/β-catenin pathway gene expression in CLL (MEC-1) cells and to compare these findings with those obtained with fludarabine (FA)...
August 1, 2017: Macromolecular Bioscience
https://www.readbyqxmd.com/read/28762081/ibrutinib-versus-previous-standard-of-care-an-adjusted-comparison-in-patients-with-relapsed-refractory-chronic-lymphocytic-leukaemia
#14
Lotta Hansson, Anna Asklid, Joris Diels, Sandra Eketorp-Sylvan, Johanna Repits, Frans Søltoft, Ulrich Jäger, Anders Österborg
This study explored the relative efficacy of ibrutinib versus previous standard-of-care treatments in relapsed/refractory patients with chronic lymphocytic leukaemia (CLL), using multivariate regression modelling to adjust for baseline prognostic factors. Individual patient data were collected from an observational Stockholm cohort of consecutive patients (n = 144) diagnosed with CLL between 2002 and 2013 who had received at least second-line treatment. Data were compared with results of the RESONATE clinical trial...
July 31, 2017: Annals of Hematology
https://www.readbyqxmd.com/read/28755313/targeting-b-cell-signaling-in-chronic-lymphocytic-leukemia
#15
REVIEW
Jon E Arnason, Jennifer R Brown
In recent years, a revolution in the management of chronic lymphocytic leukemia (CLL) has centered on the targeting of the B cell receptor (BCR) signaling pathway. Our improved understanding of the biology of cell signaling in CLL and the development of oral kinase inhibitors directed at the BCR pathway has led to the approval of two new agents and has the potential to radically change the treatment of CLL in both the relapsed/refractory and upfront settings. In this review, we will describe the underlying biology of the BCR signaling pathway...
September 2017: Current Oncology Reports
https://www.readbyqxmd.com/read/28751718/two-mouse-models-reveal-an-actionable-parp1-dependence-in-aggressive-chronic-lymphocytic-leukemia
#16
Gero Knittel, Tim Rehkämper, Darya Korovkina, Paul Liedgens, Christian Fritz, Alessandro Torgovnick, Yussor Al-Baldawi, Mona Al-Maarri, Yupeng Cun, Oleg Fedorchenko, Arina Riabinska, Filippo Beleggia, Phuong-Hien Nguyen, F Thomas Wunderlich, Monika Ortmann, Manuel Montesinos-Rongen, Eugen Tausch, Stephan Stilgenbauer, Lukas P Frenzel, Marco Herling, Carmen Herling, Jasmin Bahlo, Michael Hallek, Martin Peifer, Reinhard Buettner, Thorsten Persigehl, H Christian Reinhardt
Chronic lymphocytic leukemia (CLL) remains an incurable disease. Two recurrent cytogenetic aberrations, namely del(17p), affecting TP53, and del(11q), affecting ATM, are associated with resistance against genotoxic chemotherapy (del17p) and poor outcome (del11q and del17p). Both del(17p) and del(11q) are also associated with inferior outcome to the novel targeted agents, such as the BTK inhibitor ibrutinib. Thus, even in the era of targeted therapies, CLL with alterations in the ATM/p53 pathway remains a clinical challenge...
July 28, 2017: Nature Communications
https://www.readbyqxmd.com/read/28750119/minimal-residual-disease-in-chronic-lymphocytic-leukemia-in-the-era-of-novel-agents-a-review
#17
Meghan Thompson, Danielle Brander, Chadi Nabhan, Anthony Mato
Importance: The landscape of chronic lymphocytic leukemia (CLL) treatment has changed considerably since the first reported assessment of minimal residual disease (MRD) by flow cytometry in 1992. Chemoimmunotherapy (CIT) combinations have become the standard of care for most patients, and novel targeted agents are rapidly being incorporated into the front-line and relapsed settings. Minimal residual disease status has been shown to be a predictor of both progression-free survival (PFS) and overall survival (OS) at the time of response assessment following CIT, but less is known about the relationship between MRD and outcomes after novel oral therapeutics...
July 27, 2017: JAMA Oncology
https://www.readbyqxmd.com/read/28747208/ga101-obinutuzumab-monoclonal-antibody-as-consolidation-therapy-in-cll-galactic-trial-study-protocol-for-a-phase-ii-iii-randomised-controlled-trial
#18
Jamie B Oughton, Laura Collett, Dena R Howard, Anna Hockaday, Talha Munir, Kathryn McMahon, Lucy McParland, Claire Dimbleby, David Phillips, Andy C Rawstron, Peter Hillmen
BACKGROUND: Chronic lymphocytic leukaemia (CLL) is the most common adult leukaemia. Achieving minimal residual disease (MRD) negativity in CLL is an independent predictor of survival even with a variety of different treatment approaches and regardless of the line of therapy. METHODS/DESIGN: GA101 (obinutuzumab) monocLonal Antibody as Consolidation Therapy In CLL (GALACTIC) is a seamless phase II/III, multi-centre, randomised, controlled, open, parallel-group trial for patients with CLL who have recently responded to chemotherapy...
July 26, 2017: Trials
https://www.readbyqxmd.com/read/28744752/radiotherapy-for-ductal-carcinoma-in-situ-and-risk-of-second-non-breast-cancers
#19
Diana R Withrow, Lindsay M Morton, Rochelle E Curtis, Sara J Schonfeld, Amy Berrington de González
PURPOSE: Radiotherapy for ductal carcinoma (DCIS) is increasing, but the risks and benefits of the treatment remain uncertain. We aimed to investigate the relationship between radiotherapy for DCIS and risk of second non-breast cancers in a large US cohort. METHODS: We conducted a retrospective cohort study of 52,556 women in 12 U.S. population-based cancer registries diagnosed with first primary DCIS during 1992-2008 at age 25-79 years. We estimated relative risks (RRs), attributable risks (AR), and excess absolute risks (EAR) of second non-breast cancers associated with radiotherapy using Poisson regression adjusted for age at year of diagnosis, grade, hormonal therapy (yes/no or unknown), and time since diagnosis...
July 25, 2017: Breast Cancer Research and Treatment
https://www.readbyqxmd.com/read/28737232/chlorinated-adenosine-analogue-induces-ampk-and-autophagy-in-chronic-lymphocytic-leukaemia-cells-during-therapy
#20
Christine M Stellrecht, Lisa S Chen, Mary L Ayres, Jennifer B Dennison, Shujun Shentu, Yuling Chen, Michael J Keating, William G Wierda, Varsha Gandhi
8-chloro-adenosine (8-Cl-Ado) is currently in phase-I clinical trials for acute myeloid leukaemia and chronic lymphocytic leukaemia (CLL). Previously, we demonstrated that treatment with 8-Cl-Ado leads to diminished ATP levels. We hypothesized that AMP-activated protein kinase (AMPK) signalling would be initiated in these cells, leading to induction of autophagy. AMPK activation and induction of autophagy were demonstrated during preclinical incubations in CLL cells with the analogues. Importantly, we extended similar observations in CLL lymphocytes during an 8-Cl-Ado phase-I trial...
July 24, 2017: British Journal of Haematology
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