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"Chronic lymphocytic leukemia"

Susan M O'Brien, John C Byrd, Peter Hillmen, Steven Coutre, Jennifer R Brown, Paul M Barr, Jacqueline C Barrientos, Stephen Devereux, Tadeusz Robak, Nishitha M Reddy, Thomas J Kipps, Alessandra Tedeschi, Florence Cymbalista, Paolo Ghia, Stephen Chang, Joi Ninomoto, Danelle F James, Jan A Burger
The efficacy of ibrutinib has been demonstrated in patients with chronic lymphocytic leukemia (CLL), including as first-line therapy. However, outcomes after ibrutinib discontinuation have previously been limited to higher-risk populations with relapsed/refractory (R/R) disease. The objective of this study was to evaluate outcomes of ibrutinib-treated patients based on prior lines of therapy, including after ibrutinib discontinuation. Data were analyzed from two multicenter phase 3 studies of single-agent ibrutinib: RESONATE (PCYC-1112) in patients with R/R CLL and RESONATE-2 (PCYC-1115) in patients with treatment-naive (TN) CLL without del(17p)...
February 14, 2019: American Journal of Hematology
Ajay Gogia, Ritu Gupta, Lalit Kumar, Atul Sharma, Lata Soni
No abstract text is available yet for this article.
January 2019: South Asian Journal of Cancer
Serdal Korkmaz, Selahattin Erdem, Ebru Akay, Erdem Arzu Taşdemir, Hatice Karaman, Muzaffer Keklik
Background/aim: PD-1 (programmed death-1) is an immune checkpoint receptor that modulates T-cell activity in peripheral tissues via interaction with its ligands, PD-L1 (programmed death-ligand 1) and PD-L2 (programmed death-ligand 2). Tumor cells upregulate PD-L1 or PD-L2 to inhibit this T lymphocyte attack. Our goal was to determine the PD-1 and PD-L2 expression rates of various hematologic malignancies, and evaluate whether PD-1 and PD-L2 expressions have an impact on prognosis. Materials and methods: For this purpose, pretreatment bone marrow biopsy specimens of 83 patients [42 multiple myeloma (MM), 21 acute leukemia, and 20 chronic lymphocytic leukemia (CLL)] were stained with monoclonal antibody immunostains of PD-1 and PD-L2...
February 11, 2019: Turkish Journal of Medical Sciences
Noemí Aguilera-Montilla, Elvira Bailón, Rebeca Uceda-Castro, Estefanía Ugarte-Berzal, Andrea Santos, Alejandra Gutiérrez-González, Cristina Pérez-Sánchez, Philippe E Van den Steen, Ghislain Opdenakker, José A García-Marco, Angeles García-Pardo
We previously showed that MMP-9 contributes to CLL pathology by regulating cell survival and migration and that, when present at high levels, MMP-9 induces cell arrest. To further explore the latter function, we studied whether MMP-9 influences the gene-expression profile in CLL. Microarray analyses rendered 131 differentially expressed genes in MEC-1 cells stably transfected with MMP-9 (MMP-9-cells) versus cells transfected with empty vector (Mock-cells). Ten out of twelve selected genes were also differentially expressed in MEC-1 cells expressing the catalytically inactive MMP-9MutE mutant (MMP-9MutE-cells)...
February 13, 2019: Oncogene
Yair Herishanu, Tamar Tadmor, Andrei Braester, Osnat Bairey, Ariel Aviv, Naomi Rahimi-Levene, Riva Fineman, Itai Levi, Mona Yuklea, Rosa Ruchlemer, Lev Shvidel, Aaron Polliack
Chronic lymphocytic leukemia (CLL) is a disease of elderly patients. The fludarabine, cyclophosphamide and rituximab (FCR) regimen is considered the treatment of choice for young fit patients with CLL, however, this combination is toxic for older patients. At the time this study was first planned and initiated, there was no standard chemo-immunotherapy regimen regarded as standard therapy for the less fit elderly patient with CLL. Here we conducted a single arm, phase II trial to examine the efficacy and safety of lower-dose fludarabine and cyclophosphamide combined with a standard dose of rituximab (LD-FCR) in elderly patients with previously untreated CLL...
February 12, 2019: Hematological Oncology
Abdulrahman Albakr, Wajda Alhothali, Peyman Samghabadi, Lauren Maeda, Seema Nagpal, Abdulrazag Ajlan
Chronic lymphocytic leukemia (CLL) is the most common type of leukemia that affects older adults in the Western world. Symptomatic nervous system invasion in undiagnosed CLL is rare, poorly understood, challenging to treat, and associated with decreased survival. The average survival of CLL patients with central nervous system (CNS) involvement is 3.79 years as compared to six years in CLL patients without CNS involvement. Autopsy studies demonstrated a high incidence of undiagnosed CLL with CNS involvement, suggesting that CNS involvement is either underdiagnosed or subclinical...
November 30, 2018: Curēus
Ian W Flinn, Carole B Miller, Kirit M Ardeshna, Scott Tetreault, Sarit E Assouline, Jiri Mayer, Michele Merli, Scott D Lunin, Andrew R Pettitt, Zoltan Nagy, Olivier Tournilhac, Karem-Etienne Abou-Nassar, Michael Crump, Eric D Jacobsen, Sven de Vos, Virginia M Kelly, Weiliang Shi, Lori Steelman, NgocDiep Le, David T Weaver, Stephanie Lustgarten, Nina D Wagner-Johnston, Pier Luigi Zinzani
PURPOSE: Indolent non-Hodgkin lymphoma (iNHL) remains largely incurable and often requires multiple lines of treatment after becoming refractory to standard therapies. Duvelisib was approved by the Food and Drug Administration for relapsed or refractory (RR) chronic lymphocytic leukemia or small lymphocytic lymphoma (SLL) and RR follicular lymphoma (FL) after two or more prior systemic therapies. On the basis of the activity of duvelisib, a first-in-class oral dual inhibitor of phosphoinositide 3-kinase-δ,-γ, in RR iNHL in a phase I study, the safety and efficacy of duvelisib monotherapy was evaluated in iNHL refractory to rituximab and either chemotherapy or radioimmunotherapy...
February 11, 2019: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
Qian Sun, Li Wang, Hua-Yuan Zhu, Yi Miao, Wei Wu, Jin-Hua Liang, Lei Cao, Yi Xia, Jia-Zhu Wu, Yan Wang, Rong Wang, Lei Fan, Wei Xu, Jian-Yong Li
BACKGROUND: Serum antinuclear antibodies (ANAs) are positive in some patients with chronic lymphocytic leukemia (CLL), but the prognostic value of ANAs remains unknown. The aim of this study was to evaluate the role of ANAs as a prognostic factor in CLL. METHODS: This study retrospectively analyzed clinical data from 216 newly diagnosed CLL subjects with ANAs test from 2007 to 2017. Multivariate Cox regression analyses were used to screen the independent prognostic factors related to time to first treatment (TTFT), progression free survival (PFS) and overall survival (OS)...
February 6, 2019: Chinese Medical Journal
Xiao-Wen Ma, Lin-Hua Yang
Chronic lymphocytic leukemia(CLL)is a malignant hematologic disease with heterogeneous clinical course, about two thirds of patients exhibit a long survival, but the remaining third of patients show aggressiveness of disease or poor response to conventional treatment even drug resistance. Studies suggested that tumor microenvironment possesses a critical effect in CLL disease progression in recent years. Monocyte/macrophage, as an important componens of tumor microenvironment, play a promotive role in the growth and drug reistance of tumor cells by direct cell-to-cell contact, secreting cytokines and suppressing antitumor responses...
February 2019: Zhongguo Shi Yan Xue Ye Xue za Zhi
Sophia Stock, Rudolf Übelhart, Maria-Luisa Schubert, Fuli Fan, Bailin He, Jean-Marc Hoffmann, Lei Wang, Sanmei Wang, Wenjie Gong, Brigitte Neuber, Angela Hückelhoven-Krauss, Ulrike Gern, Christiane Christ, Monika Hexel, Anita Schmitt, Patrick Schmidt, Jürgen Krauss, Dirk Jäger, Carsten Müller-Tidow, Peter Dreger, Michael Schmitt, Leopold Sellner
Despite encouraging results with chimeric antigen receptor T (CART) cells, outcome can still be improved by optimization of the CART cell generation process. The proportion of less-differentiated T cells within the transfused product is linked to enhanced in vivo CART cell expansion and long-term persistence. The clinically approved PI3Kδ inhibitor idelalisib is well established in the treatment of B cell malignancies. Besides B cell receptor pathway inhibition, idelalisib can modulate T cell differentiation and function...
February 9, 2019: International Journal of Cancer. Journal International du Cancer
Emily M McWilliams, Christopher R Lucas, Timothy Chen, Bonnie K Harrington, Ronni Wasmuth, Amanda Campbell, Kerry A Rogers, Carolyn M Cheney, Xiaokui Mo, Leslie A Andritsos, Farrukh T Awan, Jennifer Woyach, William E Carson, Jonathan Butchar, Susheela Tridandapani, Erin Hertlein, Carlos E Castro, Natarajan Muthusamy, John C Byrd
The Bruton tyrosine kinase inhibitor (BTKi) ibrutinib has transformed chronic lymphocytic leukemia (CLL) therapy but requires continuous administration. These factors have spurred interest in combination treatments. Unlike with chemotherapy, CD20-directed antibody therapy has not improved the outcome of BTKi treatment. Whereas CD20 antigen density on CLL cells decreases during ibrutinib treatment, the B-cell activating factor (BAFF) and its receptor (BAFF-R) remain elevated. Furthermore, BAFF signaling via noncanonical NF-κB remains elevated with BTKi treatment...
February 12, 2019: Blood Advances
Natascha D Diaco, Bettina Strohdach, Anna L Falkowski, Nicolin Hainc, Philippe Brunner, Jonas Rutishauser, Lorenz Jost, Philip E Tarr
Infections may constitute a serious complication in patients with chronic lymphocytic leukemia (CLL). New treatment agents including obinutuzumab and ibrutinib have improved the progression-free survival in CLL, and data suggest a similar overall infection risk and a limited risk of opportunistic infections when compared to standard chemo-immunotherapy. Nevertheless, cases of opportunistic infections including non-tuberculous mycobacterial (NTM) in CLL patients have recently been published. We present a case of a 74-year old man with extensive prior CLL treatment history, including most recently obinutuzumab...
February 7, 2019: Journal of Clinical Medicine
Kate J Johnstone, Geoffrey M Strutton
BRAF mutation status is a critical predictive and prognostic biomarker in guiding management of unresectable and metastatic melanoma.1 We recently observed a case of BRAF V600E-mutated chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) intermixed with BRAF V600E wild-type melanoma reported to harbor BRAF V600E mutation on molecular testing. Our observation underscores the importance of appropriate tumor selection for molecular studies and knowledge of mutational status of co-existing tumors. This article is protected by copyright...
February 7, 2019: Journal of Cutaneous Pathology
María Paulina Nava-Rodríguez, Martín Daniel Domínguez-Cruz, Lilia Beatriz Aguilar-López, César Borjas-Gutiérrez, María Teresa Magaña-Torres, Juan Ramón González-García
Background: The most frequent cytogenetic abnormality detected in chronic lymphocytic leukemia (CLL) patients is the presence of a deletion within the chromosome band 13q14. Deletions can be heterogeneous in size, generally encompassing the DLEU1 and DLEU2 genes (minimal deleted region), but at times also including the RB1 gene. The latter, larger type of deletions are associated with worse prognosis.Genomic instability is a characteristic of most cancers and it has been observed in CLL patients mainly associated with telomere shortening...
2019: Molecular Cytogenetics
Prithviraj Bose, Lisa S Chen, Varsha Gandhi
No abstract text is available yet for this article.
February 6, 2019: Leukemia & Lymphoma
Audrey Mohr, Marie Cumin, Cristina Bagacean, Pierre Pochard, Christelle Le Dantec, Sophie Hillion, Yves Renaudineau, Christian Berthou, Adrian Tempescul, Hussam Saad, Jacques-Olivier Pers, Anne Bordron, Christophe Jamin
Chronic lymphocytic leukemia (CLL) is associated with abnormal T-cell responses responsible for defective anti-tumor activities. Intriguingly, CLL B cells share phenotypical characteristics with regulatory B (Breg) cells suggesting that they might negatively control the T-cell activation and immune responses. We elaborated an in vitro co-culture system with T cells to evaluate the Breg capacities of CLL B cells following innate Toll-like receptor 9 (TLR9) engagement. We demonstrated that B cells from half of the patients exhibited regulatory capacities, whilst B cells from the remaining patients were unable to develop a Breg function...
2019: Oncoimmunology
Alberto J Arribas, Andrea Rinaldi, Giorgia Chiodin, Ivo Kwee, Afua Adjeiwaa Mensah, Luciano Cascione, Davide Rossi, Meena Kanduri, Richard Rosenquist, Emanuele Zucca, Peter W Johnson, Gianluca Gaidano, Christopher C Oakes, Francesco Bertoni, Francesco Forconi
Classic hairy cell leukemia (HCL) is a tumor of mature clonal B cells with unique genetic, morphologic, and phenotypic features. DNA methylation profiling has provided a new tier of investigation to gain insight into the origin and behavior of B-cell malignancies; however, the methylation profile of HCL has not been specifically investigated. DNA methylation profiling was analyzed with the Infinium HumanMethylation27 array in 41 mature B-cell tumors, including 11 HCL, 7 splenic marginal zone lymphomas (SMZLs), and chronic lymphocytic leukemia with an unmutated (n = 7) or mutated (n = 6) immunoglobulin gene heavy chain variable (IGHV) region or using IGHV3-21 (n = 10)...
February 12, 2019: Blood Advances
Hidekazu Nishikii, Naoki Kurita, Atsushi Shinagawa, Tatsuhiro Sakamoto, Manabu Kusakabe, Yasuhisa Yokoyama, Takayasu Kato, Mamiko Sakata-Yanagimoto, Naoshi Obara, Yuichi Hasegawa, Naoya Nakamura, Shigeru Chiba
A 38-year-old woman with aggressive clinical course of chronic lymphocytic leukemia (CLL) was treated with 8 courses of R-CHOP. Clinical remission was achieved, while B-cell clonality remained. Allogeneic hematopoietic stem cell transplantation was performed with reduced intensity conditioning (fludarabine and 2-Gy total body irradiation). However, autologous hematopoietic recovery occurred within a month after the transplant. Nevertheless, B-cell clonality became undetectable at 14 days after transplant, which has been kept so for over 10 years with clinical remission...
2019: Case Reports in Hematology
Nezeen Z Abualhaj, Zain Dardas, Belal Azab, Dema Ali, Maher A Sughayer, Tariq N Aladily, Mamoun Ahram
The transmembrane receptor NOTCH1 is thought to be associated with the development and progression of T-acute lymphoblastic leukemia (T-ALL)/T-lymphoblastic lymphoma (T-LBL) and chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL). The current study aimed to characterize NOTCH1 expression and elucidate the variants in the functional PEST domain of the receptor in T-ALL/LBL and CLL/SLL. The nuclear expression of NOTCH1 protein was detected in 25% and 5% of cases of T-ALL/LBL and CLL/SLL, respectively, whereas cytoplasmic expression was detected in 33...
January 24, 2019: Annals of Diagnostic Pathology
Yangyang Xu, Xiangxiang Zhou, Ying Li, Ya Zhang, Xin Wang
Chronic lymphocytic leukemia (CLL) constitutes the largest percentage of adult leukemia cases in Western countries. Classically, fludarabine (Flu) is an effective drug used as a first-line therapy for CLL; however, Flu resistance limits its clinical effect. Minichromosome maintenance (MCM) complex components 2-7 exert important functions in maintaining genomic stability. Replication stress occurs upon dysregulation of MCM7, which potentiates malignant phenotypes. In this study, primary CLL cells and CLL-derived cell lines displayed elevated MCM7 expression...
February 4, 2019: Leukemia & Lymphoma
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