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"Chronic lymphocytic leukemia"

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https://www.readbyqxmd.com/read/29473834/ibrutinib-induced-neutrophilic-dermatosis
#1
Layal El Halabi, Khadija Cherif-Rebai, Jean-Marie Michot, David Ghez
We report the case of a 64-year-old woman treated with ibrutinib for a chronic lymphocytic leukemia with 17p deletion, who developed several erythematous, painful, and papulo-nodular skin lesions in the limbs, neck, and face. The skin biopsy was consistent with the diagnosis of neutrophilic dermatosis. Rechallenge with ibrutinib at full dose was followed by the recurrence of the same skin lesions, strongly suggesting a direct relationship.
March 2018: American Journal of Dermatopathology
https://www.readbyqxmd.com/read/29473123/prognostic-factors-in-the-era-of-targeted-therapies-in-cll
#2
REVIEW
Prajwal Boddu, Alessandra Ferrajoli
PURPOSE OF REVIEW: Chronic lymphocytic leukemia is heterogeneous disease characterized by a variable clinical course that is greatly influenced by various patient and disease characteristics. Over the last two decades, advent of new diagnostic methodologies has led to the identification of several factors of prognostic and predictive relevance. Furthermore, recent advances in next-generation sequencing techniques has identified recurrent novel mutations in NOTCH1, SF3B1, BIRC3, and ATM genes whose role as prognostic and predictive markers is currently being investigated...
February 23, 2018: Current Hematologic Malignancy Reports
https://www.readbyqxmd.com/read/29470582/prognostic-factors-for-complete-response-to-ibrutinib-in-patients-with-chronic-lymphocytic-leukemia-a-pooled-analysis-of-2-clinical-trials
#3
Susan M O'Brien, Samantha Jaglowski, John C Byrd, Rajat Bannerji, Kristie A Blum, Christopher P Fox, Richard R Furman, Peter Hillmen, Thomas J Kipps, Marco Montillo, Jeff Sharman, Sam Suzuki, Danelle F James, Alvina D Chu, Steven E Coutre
Importance: Ibrutinib, a first-in-class Bruton tyrosine kinase inhibitor taken once daily, is approved in the United States for patients with chronic lymphocytic leukemia/small lymphocytic lymphoma and allows for treatment without chemotherapy. Extended treatment with ibrutinib has demonstrated increased complete response (CR) rates over time. Objective: To analyze baseline factors that predict CR in patients with chronic lymphocytic leukemia/small lymphocytic lymphoma treated with ibrutinib...
February 22, 2018: JAMA Oncology
https://www.readbyqxmd.com/read/29467486/eric-recommendations-for-tp53-mutation-analysis-in-chronic-lymphocytic-leukemia-update-on-methodological-approaches-and-results-interpretation
#4
REVIEW
J Malcikova, E Tausch, D Rossi, L A Sutton, T Soussi, T Zenz, A P Kater, C U Niemann, D Gonzalez, F Davi, M Gonzalez Diaz, C Moreno, G Gaidano, K Stamatopoulos, R Rosenquist, S Stilgenbauer, P Ghia, S Pospisilova
In chronic lymphocytic leukemia (CLL), TP53 gene defects, due to deletion of the 17p13 locus and/or mutation(s) within the TP53 gene, are associated with resistance to chemoimmunotherapy and a particularly dismal clinical outcome. On these grounds, analysis of TP53 aberrations has been incorporated into routine clinical diagnostics to improve patient stratification and optimize therapeutic decisions. The predictive implications of TP53 aberrations have increasing significance in the era of novel targeted therapies, i...
February 2, 2018: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/29467184/low-catalase-expression-confers-redox-hypersensitivity-and-identifies-an-indolent-clinical-behavior-in-cll
#5
Chiara Cavallini, Roberto Chignola, Ilaria Dando, Omar Perbellini, Elda Mimiola, Ornella Lovato, Carlo Laudanna, Giovanni Pizzolo, Massimo Donadelli, Maria Teresa Scupoli
B-cell receptor (BCR) signaling is a key determinant of variable clinical behavior and a target for therapeutic interventions in chronic lymphocytic leukemia (CLL). Endogenously produced H2 O2 is thought to fine-tune the BCR signaling by reversibly inhibiting phosphatases. However, little is known about how CLL cells sense and respond to such redox cues and what impact they have on CLL. We characterized the response of BCR signaling proteins to exogenous H2 O2 in cells from CLL patients using phospho-specific flow cytometry...
February 21, 2018: Blood
https://www.readbyqxmd.com/read/29465308/cll2-bxx-phase-ii-trials-sequential-targeted-treatment-for-eradication-of-minimal-residual-disease-in-chronic-lymphocytic-leukemia
#6
Paula Cramer, Julia von Tresckow, Jasmin Bahlo, Anja Engelke, Petra Langerbeins, Anna-Maria Fink, Kirsten Fischer, Clemens-Martin Wendtner, Karl-Anton Kreuzer, Stephan Stilgenbauer, Sebastian Böttcher, Barbara Eichhorst, Michael Hallek
AIM: Four Phase II trials (Clinical Trials numbers: NCT02345863, NCT02401503, NCT02445131 and NCT02689141) evaluate a different combination of targeted agents in an all-comer population of approximately 60 patients with chronic lymphocytic leukemia irrespective of prior treatment, physical fitness and genetic risk factors. Patients with a higher tumor load start with a debulking treatment with bendamustine. The subsequent induction and maintenance treatment with an anti-CD20 antibody (obinutuzumab or ofatumumab) and a targeted oral agent (ibrutinib, idelalisib or venetoclax) are continued until achievement of a complete response and minimal residual disease negativity...
February 21, 2018: Future Oncology
https://www.readbyqxmd.com/read/29465275/feasibility-and-safety-of-therapy-with-ibrutinib-after-antiviral-control-of-hepatitis-b-virus-hbv-reactivation-in-chronic-lymphocytic-leukemia-patients
#7
Stefano Molica, Luciano Levato, Rosanna Mirabelli, Alessanda Tedeschi, Mirella Lentini
No abstract text is available yet for this article.
February 21, 2018: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/29465264/ibrutinib-inhibits-free-fatty-acid-metabolism-in-chronic-lymphocytic-leukemia
#8
Uri Rozovski, David M Harris, Ping Li, Zhiming Liu, Preetesh Jain, Alessandra Ferrajoli, Jan Burger, Phillip Thompson, Nitin Jain, William Wierda, Michael J Keating, Zeev Estrov
Unlike normal B-cells, and similar to fat cells, chronic lymphocytic leukemia (CLL) cells aberrantly express lipoprotein lipase (LPL), which contributes to free fatty acids (FFAs) metabolism. Here we show that, in CLL cells, the B-cell receptor (BCR) inhibitor ibrutinib reduced LPL mRNA and protein levels and inhibited FFA metabolism in vitro. Likewise, in CLL cells from ibrutinib-treated patients, FFA metabolism was reduced and eventually stopped. Because ibrutinib disrupts CLL cells' ability to use FFAs for energy production, and because various BCR-dependent cellular functions rely on a continuous supply of chemical energy, ibrutinib interrupts several pathways imperative for cellular function in CLL cells...
February 21, 2018: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/29464716/richter-transformation-driven-by-epstein-barr-virus-reactivation-during-therapy-related-immunosuppression-in-chronic-lymphocytic-leukemia
#9
Maria J García-Barchino, Maria E Sarasquete, Carlos Panizo, Julie Morscio, Antonio Martinez, Miguel Alcoceba, Vicente Fresquet, Blanca Gonzalez-Farre, Bruno Paiva, Ken H Young, Eloy F Robles, Sergio Roa, Jon Celay, Marta Larrayoz, Davide Rossi, Gianluca Gaidano, Santiago Montes-Moreno, Miguel A Piris, Ana Balanzategui, Cristina Jimenez, Idoia Rodriguez, Maria J Calasanz, Maria J Larrayoz, Victor Segura, Ricardo Garcia-Muñoz, Maria P Rabasa, Shuhua Yi, Jianyong Li, Mingzhi Zhang, Zijun Y Xu-Monette, Noemi Puig-Moron, Alberto Orfao, Sebastian Böttcher, Jesus M Hernandez-Rivas, Jesus San Miguel, Felipe Prosper, Thomas Tousseyn, Xavier Sagaert, Marcos Gonzalez, Jose A Martinez-Climent
The increased risk of Richter transformation (RT) in patients with chronic lymphocytic leukemia (CLL) due to Epstein-Barr virus (EBV) reactivation during immunosuppressive therapy with fludarabine or other targeted agents remains controversial. Among 31 RT cases classified as diffuse large B-cell lymphoma (DLBCL), seven (23%) showed EBV expression. In comparison to EBV-negative tumors, EBV+ DLBCLs derived predominantly from IGVH-hypermutated CLL and exhibited CLL-unrelated IGVH sequences more frequently. Intriguingly, despite having different cellular origins, clonally related and unrelated EBV+ DLBCLs shared a previous history of immunosuppressive chemo-immunotherapy, a non-germinal center DLBCL phenotype, EBV latency programs type II/III, and a very short survival...
February 21, 2018: Journal of Pathology
https://www.readbyqxmd.com/read/29463802/clonal-dynamics-towards-the-development-of-venetoclax-resistance-in-chronic-lymphocytic-leukemia
#10
Carmen D Herling, Nima Abedpour, Jonathan Weiss, Anna Schmitt, Ron Daniel Jachimowicz, Olaf Merkel, Maria Cartolano, Sebastian Oberbeck, Petra Mayer, Valeska Berg, Daniel Thomalla, Nadine Kutsch, Marius Stiefelhagen, Paula Cramer, Clemens-Martin Wendtner, Thorsten Persigehl, Andreas Saleh, Janine Altmüller, Peter Nürnberg, Christian Pallasch, Viktor Achter, Ulrich Lang, Barbara Eichhorst, Roberta Castiglione, Stephan C Schäfer, Reinhard Büttner, Karl-Anton Kreuzer, Hans Christian Reinhardt, Michael Hallek, Lukas P Frenzel, Martin Peifer
Deciphering the evolution of cancer cells under therapeutic pressure is a crucial step to understand the mechanisms that lead to treatment resistance. To this end, we analyzed whole-exome sequencing data of eight chronic lymphocytic leukemia (CLL) patients that developed resistance upon BCL2-inhibition by venetoclax. Here, we report recurrent mutations in BTG1 (2 patients) and homozygous deletions affecting CDKN2A/B (3 patients) that developed during treatment, as well as a mutation in BRAF and a high-level focal amplification of CD274 (PD-L1) that might pinpoint molecular aberrations offering structures for further therapeutic interventions...
February 20, 2018: Nature Communications
https://www.readbyqxmd.com/read/29460654/cumulative-experience-and-long-term-follow-up-of-pentostatin-based-chemoimmunotherapy-trials-for-patients-with-chronic-lymphocytic-leukemia
#11
Neil E Kay, Betsy R LaPlant, Adam M Pettinger, Timothy G Call, Jose F Leis, Wei Ding, Sameer A Parikh, Michael J Conte, Deborah A Bowen, Tait D Shanafelt
BACKGROUND: 7 regimens of pentostatin based chemoimmunotherapy (CIT) for progressive previously untreated CLL primarily with long term follow-up to update both efficacy and toxicity. RESEARCH DESIGN AND METHODS: Prognostic markers including assessment of IGVH and FISH status were done on all. Response rates and 95% binomial confidence intervals were calculated for each regimen and in the combined cohort. Overall survival and treatment-free survival were evaluated using Kaplan-Meier methods...
February 20, 2018: Expert Review of Hematology
https://www.readbyqxmd.com/read/29457831/low-t3-syndrome-as-a-predictor-of-poor-prognosis-in-chronic-lymphocytic-leukemia
#12
Rui Gao, Rui-Ze Chen, Yi Xia, Jin-Hua Liang, Li Wang, Hua-Yuan Zhu, Jia-Zhu Wu, Lei Fan, Jian-Yong Li, Tao Yang, Wei Xu
Low triiodothyronine (T3) state is associated with poor prognosis in critical acute and prolonged illness. However, the information on thyroid dysfunction and cancer is limited. The aim of our study was to evaluate the prognostic value of low T3 syndrome in chronic lymphocytic leukemia (CLL). Two hundred and fifty-eight patients with detailed thyroid hormone profile at CLL diagnosis were enrolled. Low T3 syndrome was defined by low free T3 (FT3) level accompanied by normal-to-low free tetraiodothyronine (FT4) and thyroid-stimulating hormone (TSH) levels...
February 19, 2018: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/29455840/cardiac-surgery-outcomes-in-patients-with-chronic-lymphocytic-leukemia
#13
Yuanjia Zhu, Andrew J Toth, Ashley M Lowry, Eugene H Blackstone, Brian T Hill, Stephanie L Mick
BACKGROUND: Surgical outcomes of patients with chronic lymphocytic leukemia (CLL) undergoing cardiac surgery are limited. Our objectives were to investigate hospital morbidity and mortality after open cardiac surgery in CLL versus non-CLL patients. METHODS: From May 1995 to May 2015, 157 patients with CLL and 55,917 without and older than 47 years underwent elective cardiac surgery at Cleveland Clinic. By Rai criteria, 79 CLL patients (56%) were low risk (class 0), 13 (9...
February 15, 2018: Annals of Thoracic Surgery
https://www.readbyqxmd.com/read/29455639/role-of-bruton-s-tyrosine-kinase-in-b-cells-and-malignancies
#14
REVIEW
Simar Pal Singh, Floris Dammeijer, Rudi W Hendriks
Bruton's tyrosine kinase (BTK) is a non-receptor kinase that plays a crucial role in oncogenic signaling that is critical for proliferation and survival of leukemic cells in many B cell malignancies. BTK was initially shown to be defective in the primary immunodeficiency X-linked agammaglobulinemia (XLA) and is essential both for B cell development and function of mature B cells. Shortly after its discovery, BTK was placed in the signal transduction pathway downstream of the B cell antigen receptor (BCR). More recently, small-molecule inhibitors of this kinase have shown excellent anti-tumor activity, first in animal models and subsequently in clinical studies...
February 19, 2018: Molecular Cancer
https://www.readbyqxmd.com/read/29453968/lipoprotein-lipase-biosynthesis-regulatory-factors-and-its-role-in-atherosclerosis-and-other-diseases
#15
REVIEW
Ping-Ping He, Ting Jiang, Xin-Ping OuYang, Ya-Qin Liang, Jie-Qiong Zou, Yan Wang, Qian-Qian Shen, Li Liao, Xi-Long Zheng
Lipoprotein lipase (LPL) is a rate-limiting enzyme that catalyzes hydrolysis of the triglyceride (TG) core of circulating TG-rich lipoproteins including chylomicrons (CM), low-density lipoproteins (LDL) and very low-density lipoproteins (VLDL). A variety of parenchymal cells can synthesize and secrete LPL. Recent studies have demonstrated that complicated processes are involved in LPL biosynthesis, secretion and transport. The enzyme activity of LPL is regulated by many factors, such as apolipoproteins, angiopoietins, hormones and miRNAs...
February 14, 2018: Clinica Chimica Acta; International Journal of Clinical Chemistry
https://www.readbyqxmd.com/read/29453626/drug-approval-based-on-randomized-phase-3-trials-for-relapsed-malignancy-analysis-of-oncologic-drugs-granted-accelerated-approval-publications-and-clinical-trial-databases
#16
Sumimasa Nagai, Keiya Ozawa
Background As relapsed disease is frequently the first target of newly developed therapies, it is vital to address the difficulty in demonstrating the efficacy of new drugs for relapsed malignancy in randomized phase 3 trials. Methods We analyzed the approved indications, target populations, and development status of post-marketing confirmatory trials of all oncology-related drugs that were granted accelerated approval for both hematological and solid malignancies. Furthermore, we searched for randomized phase 3 trials for adult patients with relapsed lymphoid malignancy, other than chronic lymphocytic leukemia (CLL) and multiple myeloma (MM)...
February 17, 2018: Investigational New Drugs
https://www.readbyqxmd.com/read/29453281/the-pi3k%C3%AE-selective-inhibitor-idelalisib-minimally-interferes-with-immune-effector-function-mediated-by-rituximab-or-obinutuzumab-and-significantly-augments-b-cell-depletion-in-vivo
#17
Adam Palazzo, Sylvia Herter, Laura Grosmaire, Randy Jones, Christian R Frey, Florian Limani, Marina Bacac, Pablo Umana, Robert J Oldham, Michael J E Marshall, Kerry L Cox, Anna H Turaj, Mark S Cragg, Christian Klein, Matthew J Carter, Stacey Tannheimer
Idelalisib is a highly selective oral inhibitor of PI3Kδ indicated for the treatment of patients with relapsed chronic lymphocytic leukemia in combination with rituximab. Despite additive clinical effects, previous studies have paradoxically demonstrated that targeted therapies potentially negatively affect anti-CD20 mAb effector mechanisms. To address these potential effects, we investigated the impact of PI3Kδ inhibition by idelalisib on the effector mechanisms of rituximab and obinutuzumab. At clinically relevant concentrations, idelalisib minimally influenced rituximab- and obinutuzumab-mediated Ab-dependent cellular cytotoxicity and phagocytosis on human lymphoma cell lines, while maintaining the superiority of obinutuzumab-mediated Ab-dependent cellular cytotoxicity...
February 16, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29452669/optimal-management-of-the-young-patient-cll-patient
#18
REVIEW
John N Allan, Richard R Furman
The emergence of targeted therapy for patients with chronic lymphocytic leukemia (CLL) has permanently altered the therapeutic landscape. In both upfront and relapsed settings, safe and effective oral kinase inhibitors are available which rival the responses and durability seen with standard chemo immunotherapy regimens. In 2016, ibrutinib was granted Federal Drug Administration approval for first-line therapy in patients with CLL. While its role as initial therapy for older, unfit or deleted 17p CLL patients is less controversial, its role as first-line treatment for younger fit patients is less clear, begging the question, what is the optimal treatment for these patients, novel agents or standard CIT strategies? In this review, we aim to provide guidance for what we believe is the optimal management of young fit patients with CLL...
March 2018: Best Practice & Research. Clinical Haematology
https://www.readbyqxmd.com/read/29450641/chronic-lymphocytic-leukemia-cells-acquire-regulatory-b-cell-properties-in-response-to-tlr9-and-cd40-activation
#19
Shimrit Ringelstein-Harlev, Irit Avivi, Mona Fanadka, Netanel A Horowitz, Tami Katz
Circulating chronic lymphocytic leukemia (CLL) cells share phenotypic features with certain subsets of regulatory B-cells (Bregs). The latter cells have been reported to negatively regulate immune cell responses, mostly by provision of IL-10. The purpose of the current study was to identify and delineate Breg properties of CLL cells. B-cells and T-cells were obtained from the peripheral blood of untreated CLL patients diagnosed according to the 2008 Guidelines of the International Workshop on Chronic Lymphocytic Leukemia...
February 15, 2018: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/29450576/immunopet-imaging-of-cd38-in-murine-lymphoma-models-using-89-zr-labeled-daratumumab
#20
Lei Kang, Dawei Jiang, Christopher G England, Todd E Barnhart, Bo Yu, Zachary T Rosenkrans, Rongfu Wang, Jonathan W Engle, Xiaojie Xu, Peng Huang, Weibo Cai
PURPOSE: CD38 is considered a potential biomarker for multiple myeloma (MM) and has shown a strong link with chronic lymphocytic leukemia due to high and uniform expression on plasma cells. In vivo evaluation of CD38 expression may provide useful information about lesion detection and prognosis of treatment in MM. In this study, immunoPET imaging with89 Zr-labeled daratumumab was used for differentiation of CD38 expression in murine lymphoma models to provide a potential non-invasive method for monitoring CD38 in the clinic...
February 15, 2018: European Journal of Nuclear Medicine and Molecular Imaging
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