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17p chronic lymphocytic leukemia

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https://www.readbyqxmd.com/read/29905151/chronic-lymphocytic-leukemia-with-t-14-18-and-trisomy-12-a-case-report
#1
Maïlys Le Guyader, Marie Coude, Kamel Laribi, Anne Besançon, Habib Ghnaya, Nathalie Denizon, Sabine Defasque, Fabienne Pineau-Vincent, Mohamed Kaabar, Pierre Lemaire
Chronic lymphocytic leukemia (CLL) is a B-cell neoplasm defined by the presence of at least 5×109 G/L monoclonal B lymphocytes in the peripheral blood. It is the most common type of leukemia in adult patients from Western countries. CLL is characterized by a gradual accumulation of small, longliving, immunologically dysfunctional, morphologically mature-appearing B-lymphocytes in blood, bone marrow and lymphoid tissues. It has also been reported that CLL cells have a proliferation rate higher than previously recognized, particularly in the lymphoid tissues...
June 15, 2018: Annales de Biologie Clinique
https://www.readbyqxmd.com/read/29895707/comprehensive-safety-analysis-of-venetoclax-monotherapy-for-patients-with-relapsed-refractory-chronic-lymphocytic-leukemia
#2
Matthew S Davids, Michael Hallek, William Wierda, Andrew W Roberts, Stephan Stilgenbauer, Jeffrey A Jones, John F Gerecitano, Su Young Kim, Jalaja Potluri, Todd Busman, Andrea Best, Maria E Verdugo, Elisa Cerri, Monali Desai, Peter Hillmen, John F Seymour
PURPOSE: The oral BCL-2 inhibitor venetoclax is an effective therapy for patients with relapsed/refractory (R/R) chronic lymphocytic leukemia (CLL), including disease with high-risk genomic features such as chromosome 17p deletion (del[17p]) or progressive disease following B-cell receptor pathway inhibitors. EXPERIMENTAL DESIGN: We conducted a comprehensive analysis of the safety of 400mg daily venetoclax monotherapy in 350 patients with CLL using an integrated dataset from three phase-I/II studies...
June 12, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29880613/real-world-outcomes-and-management-strategies-for-venetoclax-treated-chronic-lymphocytic-leukemia-patients-in-the-united-states
#3
Anthony R Mato, Meghan Thompson, John N Allan, Danielle M Brander, John M Pagel, Chaitra S Ujjani, Brian T Hill, Nicole Lamanna, Frederick Lansigan, Ryan Jacobs, Mazyar Shadman, Alan P Skarbnik, Jeffrey J Pu, Paul M Barr, Alison R Sehgal, Bruce D Cheson, Clive S Zent, Hande H Tuncer, Stephen J Schuster, Peter V Pickens, Nirav N Shah, Andre Goy, Allison M Winter, Christine Garcia, Kaitlin Kennard, Krista Isaac, Colleen Dorsey, Lisa M Gashonia, Arun K Singavi, Lindsey E Roeker, Andrew Zelenetz, Annalynn Williams, Christina Howlett, Hanna Weissbrot, Naveed Ali, Sirin Khajavian, Andrea Sitlinger, Eve Tranchito, Joanna Rhodes, Joshua Felsenfeld, Neil Bailey, Bhavisha Patel, Timothy F Burns, Melissa Yacur, Mansi Malhotra, Jakub Svoboda, Richard R Furman, Chadi Nabhan
Venetoclax is a BCL2 inhibitor approved for 17p-deleted relapsed/refractory chronic lymphocytic leukemia with activity following kinase inhibitors. We conducted a multicenter retrospective cohort analysis of patients with CLL treated with venetoclax to describe outcomes, toxicities, and treatment selection following venetoclax discontinuation. A total of 141 chronic lymphocytic leukemia patients were included (98% relapsed/refractory). Median age at venetoclax initiation was 67 years (range 37-91), median prior therapies was 3 (0-11), 81% unmutated IGHV, 45% del(17p), and 26...
June 7, 2018: Haematologica
https://www.readbyqxmd.com/read/29877241/-chronic-lymphocytic-leukemia-update-on-pathophysiology-and-management
#4
Junji Suzumiya
Chronic lymphocytic leukemia (CLL) is the most common hematological malignancy in the Western countries. Although a multi-step model has been proposed for the pathogenesis of CLL as well as other malignancies, the precise mechanism underlying the development of CLL remains complicated and unclear. In addition, several studies have investigated adverse prognostic factors, including gene abnormalities and the evolution of clones with the disease progression. FCR (fludarabine, cyclophosphamide, and rituximab) has been the standard first-line therapy for "fit" younger patients without TP53 abnormality/17p deletion...
2018: [Rinshō Ketsueki] the Japanese Journal of Clinical Hematology
https://www.readbyqxmd.com/read/29787358/targeting-b-cell-lymphoma-2-a-lethal-shortcut-in-del-17p-chronic-lymphocytic-leukemia
#5
Anthony Letai
No abstract text is available yet for this article.
May 22, 2018: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/29759975/restoring-the-switch-for-cancer-cell-death-targeting-the-apoptosis-signaling-pathway
#6
REVIEW
Clement Chung
PURPOSE: The relevance of apoptosis to cancer development and pharmacologic agents that target this pathway in selected malignancies are described. SUMMARY: Apoptosis is a tightly regulated biological process mediated by both proapoptotic (i.e., prodeath) and antiapoptotic (i.e., prosurvival) proteins. While apoptosis represents a well-established effector mechanism induced by conventional chemotherapy in many malignancies, the development of apoptosis-based targeted therapy is relatively new...
May 14, 2018: American Journal of Health-system Pharmacy: AJHP
https://www.readbyqxmd.com/read/29747654/bcl-2-as-therapeutic-target-for-hematological-malignancies
#7
REVIEW
Guilherme Fleury Perini, Glaciano Nogueira Ribeiro, Jorge Vaz Pinto Neto, Laura Tojeiro Campos, Nelson Hamerschlak
Disruption of the physiologic balance between cell proliferation and cell death is an important step of cancer development. Increased resistance to apoptosis is a key oncogenic mechanism in several hematological malignancies and, in many cases, especially in lymphoid neoplasias, has been attributed to the upregulation of BCL-2. The BCL-2 protein is the founding member of the BCL-2 family of apoptosis regulators and was the first apoptosis modulator to be associated with cancer. The recognition of the important role played by BCL-2 for cancer development and resistance to treatment made it a relevant target for therapy for many diseases, including solid tumors and hematological neoplasias...
May 11, 2018: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/29742083/update-on-signal-inhibitors-in-chronic-lymphocytic-leukemia
#8
Prajwal Boddu, Nitin Jain
The last decade has seen major progress in our understanding of the pathobiology of chronic lymphocytic leukemia (CLL) and the identification of potential new therapeutic targets. As a result, researchers have developed novel targeted therapies, several of which are already approved and many of which are in advanced stages of clinical development. These new agents are much less toxic than chemoimmunotherapy and may be preferred for their superior efficacy in patients with certain high-risk features, such as del(17p)...
April 2018: Clinical Advances in Hematology & Oncology: H&O
https://www.readbyqxmd.com/read/29732004/s55746-is-a-novel-orally-active-bcl-2-selective-and-potent-inhibitor-that-impairs-hematological-tumor-growth
#9
Patrick Casara, James Davidson, Audrey Claperon, Gaëtane Le Toumelin-Braizat, Meike Vogler, Alain Bruno, Maïa Chanrion, Gaëlle Lysiak-Auvity, Thierry Le Diguarher, Jérôme-Benoît Starck, Ijen Chen, Neil Whitehead, Christopher Graham, Natalia Matassova, Pawel Dokurno, Christopher Pedder, Youzhen Wang, Shumei Qiu, Anne-Marie Girard, Emilie Schneider, Fabienne Gravé, Aurélie Studeny, Ghislaine Guasconi, Francesca Rocchetti, Sophie Maïga, Jean-Michel Henlin, Frédéric Colland, Laurence Kraus-Berthier, Steven Le Gouill, Martin J S Dyer, Roderick Hubbard, Mike Wood, Martine Amiot, Gerald M Cohen, John A Hickman, Erick Morris, James Murray, Olivier Geneste
Escape from apoptosis is one of the major hallmarks of cancer cells. The B-cell Lymphoma 2 (BCL-2) gene family encodes pro-apoptotic and anti-apoptotic proteins that are key regulators of the apoptotic process. Overexpression of the pro-survival member BCL-2 is a well-established mechanism contributing to oncogenesis and chemoresistance in several cancers, including lymphoma and leukemia. Thus, BCL-2 has become an attractive target for therapeutic strategy in cancer, as demonstrated by the recent approval of ABT-199 (Venclexta™) in relapsed or refractory Chronic Lymphocytic Leukemia with 17p deletion...
April 13, 2018: Oncotarget
https://www.readbyqxmd.com/read/29715056/venetoclax-for-patients-with-chronic-lymphocytic-leukemia-with-17p-deletion-results-from-the-full-population-of-a-phase-ii-pivotal-trial
#10
Stephan Stilgenbauer, Barbara Eichhorst, Johannes Schetelig, Peter Hillmen, John F Seymour, Steven Coutre, Wojciech Jurczak, Stephen P Mulligan, Anna Schuh, Sarit Assouline, Clemens-Martin Wendtner, Andrew W Roberts, Matthew S Davids, Johannes Bloehdorn, Talha Munir, Sebastian Böttcher, Lang Zhou, Ahmed Hamed Salem, Monali Desai, Brenda Chyla, Jennifer Arzt, Su Young Kim, Maria Verdugo, Gary Gordon, Michael Hallek, William G Wierda
Purpose Venetoclax is an orally bioavailable B-cell lymphoma 2 inhibitor. US Food and Drug Administration and European Medicines Agency approval for patients with 17p deleted relapsed/refractory chronic lymphocytic leukemia [del(17p) CLL] was based on results from 107 patients. An additional 51 patients were enrolled in a safety expansion cohort. Extended analysis of all enrolled patients, including the effect of minimal residual disease (MRD) negativity on outcome, is now reported. Patients and Methods Overall, 158 patients with relapsed/refractory or previously untreated (n = 5) del(17p) CLL received venetoclax 400 mg per day after an initial dose ramp up...
May 1, 2018: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/29674504/efficacy-of-bendamustine-and-rituximab-as-first-salvage-treatment-in-chronic-lymphocytic-leukemia-and-indirect-comparison-with-ibrutinib-a-gimema-eric-and-uk-cll-forum-study
#11
Antonio Cuneo, George Follows, Gian Matteo Rigolin, Alfonso Piciocchi, Alessandra Tedeschi, Livio Trentin, Angeles Medina Perez, Marta Coscia, Luca Laurenti, Gerardo Musuraca, Lucia Farina, Alfredo Rivas Delgado, Ester Maria Orlandi, Piero Galieni, Francesca Romana Mauro, Carlo Visco, Angela Amendola, Atto Billio, Roberto Marasca, Annalisa Chiarenza, Vittorio Meneghini, Fiorella Ilariucci, Monia Marchetti, Stefano Molica, Francesca Re, Gianluca Gaidano, Marcos Gonzalez, Francesco Forconi, Stefania Ciolli, Agostino Cortelezzi, Marco Montillo, Lukas Smolej, Anna Schuh, Toby A Eyre, Ben Kennedy, Kris M Bowles, Marco Vignetti, Javier de la Serna, Carol Moreno, Robin Foà, Paolo Ghia
We performed an observational study on the efficacy of bendamustine and rituximab as first salvage regimen in chronic lymphocytic leukemia. In an intention-to-treat analysis including 237 patients, the median progression free survival was 25 months. The presence of del(17p), unmutated IGHV and advanced stage were associated with a shorter progression free survival at multivariate analysis. The median time-to-next treatment was 31.3 months. Front-line treatment with a chemoimmunotherapy regimen was the only predictive factor for a shorter time to next treatment at multivariate analysis...
April 19, 2018: Haematologica
https://www.readbyqxmd.com/read/29567785/dna-polymerase-%C3%AE-gene-expression-influences-fludarabine-resistance-in-chronic-lymphocytic-leukemia-independently-from-p53-status
#12
Srdana Grgurevic, Patricia Montilla-Perez, Alice Bradbury, Julia Gilhodes, Sophie Queille, Sandrine Pelofy, Aurélien Bancaud, Thomas Filleron, Loïc Ysebaert, Christian Récher, Guy Laurent, Jean-Jacques Fournié, Christophe Cazaux, Anne Quillet-Mary, Jean-Sébastien Hoffmann
Alteration in the DNA Replication, Repair or Recombination processes is a highly relevant mechanism of genomic instability. Despite genomic aberrations manifested in haematological malignancies, such a defect as a source of biomarkers has been underexplored. Here, we investigated prognostic value of expression of 82 genes involved in DNA Replication-Repair-Recombination in a series of 99 patients with chronic lymphocytic leukaemia without detected 17p deletion or TP53 mutation. We unveiled that expression of the POLN gene, encoding the specialized DNA polymerase ν (Polν) correlates with time to relapse after the first-line therapy with fludarabine...
March 22, 2018: Haematologica
https://www.readbyqxmd.com/read/29562156/venetoclax-rituximab-in-relapsed-or-refractory-chronic-lymphocytic-leukemia
#13
RANDOMIZED CONTROLLED TRIAL
John F Seymour, Thomas J Kipps, Barbara Eichhorst, Peter Hillmen, James D'Rozario, Sarit Assouline, Carolyn Owen, John Gerecitano, Tadeusz Robak, Javier De la Serna, Ulrich Jaeger, Guillaume Cartron, Marco Montillo, Rod Humerickhouse, Elizabeth A Punnoose, Yan Li, Michelle Boyer, Kathryn Humphrey, Mehrdad Mobasher, Arnon P Kater
BACKGROUND: Venetoclax inhibits BCL2, an antiapoptotic protein that is pathologically overexpressed and that is central to the survival of chronic lymphocytic leukemia cells. We evaluated the efficacy of venetoclax in combination with rituximab in patients with relapsed or refractory chronic lymphocytic leukemia. METHODS: In this randomized, open-label, phase 3 trial, we randomly assigned 389 patients to receive venetoclax for up to 2 years (from day 1 of cycle 1) plus rituximab for the first 6 months (venetoclax-rituximab group) or bendamustine plus rituximab for 6 months (bendamustine-rituximab group)...
March 22, 2018: New England Journal of Medicine
https://www.readbyqxmd.com/read/29484684/clinical-pathological-and-biological-characterization-of-richter-syndrome-developing-after-ibrutinib-treatment-for-relapsed-chronic-lymphocytic-leukemia
#14
Idanna Innocenti, Davide Rossi, Giulio Trapè, Francesco Autore, Luigi Maria Larocca, Vincenzo Gomes, Michaela Cerri, Paolo Falcucci, Simona Sica, Gianluca Gaidano, Luca Laurenti
Richter syndrome, a transformation of chronic lymphocytic leukemia (CLL) into a diffuse large B-cell lymphoma, is a rare complication of patients treated with chemo-immunotherapy. Richter syndrome might be both clonally related or unrelated to the underlying CLL and often showed mutations of the TP53 and NOTCH1 genes. Recently, ibrutinib was approved for patients with relapsed/refractory CLL or for untreated CLL patients with del 17p or TP53 mutation. The clinical picture, pathology, and genetics of Richter transformation after IBR treatment are largely unknown...
February 27, 2018: Hematological Oncology
https://www.readbyqxmd.com/read/29480432/frontline-therapy-of-cll-evolving-treatment-paradigm
#15
REVIEW
Craig S Boddy, Shuo Ma
PURPOSE OF REVIEW: Chronic lymphocytic leukemia (CLL) has multiple current frontline therapy options, including chemoimmunotherapy (CIT) and most recently, ibrutinib. Here, we review the most recent updates in the frontline treatment of CLL, including updates in CIT, updates in targeted therapies, and ongoing clinical trials. RECENT FINDINGS: Ibrutinib was FDA-approved for the upfront treatment of CLL in 2016 after being studied in older patients and those with 17p deletions or TP53 mutations...
April 2018: Current Hematologic Malignancy Reports
https://www.readbyqxmd.com/read/29473834/ibrutinib-induced-neutrophilic-dermatosis
#16
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/29452669/optimal-management-of-the-young-patient-cll-patient
#17
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/29358183/clinical-implications-of-cancer-gene-mutations-in-patients-with-chronic-lymphocytic-leukemia-treated-with-lenalidomide
#18
Koichi Takahashi, Boyu Hu, Feng Wang, Yuanqing Yan, Ekaterina Kim, Candida Vitale, Keyur P Patel, Paolo Strati, Curtis Gumbs, Latasha Little, Samantha Tippen, Xingzhi Song, Jianhua Zhang, Nitin Jain, Philip Thompson, Guillermo Garcia-Manero, Hagop Kantarjian, Zeev Estrov, Kim-Anh Do, Michael Keating, Jan A Burger, William G Wierda, P Andrew Futreal, Alessandra Ferrajoli
Lenalidomide is clinically active in chronic lymphocytic leukemia (CLL), but its effectiveness in the context of the CLL mutational landscape is unknown. We performed targeted capture sequencing of 295 cancer genes in specimens from 102 CLL patients with treatment-naïve disease (TN patients) and 186 CLL patients with relapsed/refractory disease (R/R patients) who received lenalidomide-based therapy at our institution. The most frequently mutated gene was SF3B1 (15%), followed by NOTCH1 (14%) and TP53 (14%), with R/R patients having significantly more TP53 mutations than did TN patients...
April 19, 2018: Blood
https://www.readbyqxmd.com/read/29352719/prognostic-testing-patterns-and-outcomes-of-chronic-lymphocytic-leukemia-patients-stratified-by-fluorescence-in-situ-hybridization-cytogenetics-a-real-world-clinical-experience-in-the-connect-cll-registry
#19
Anthony Mato, Chadi Nabhan, Neil E Kay, Nicole Lamanna, Thomas J Kipps, David L Grinblatt, Christopher R Flowers, Charles M Farber, Matthew S Davids, Pavel Kiselev, Arlene S Swern, Shriya Bhushan, Kristen Sullivan, E Dawn Flick, Jeff P Sharman
INTRODUCTION: Prognostic genetic testing is recommended for patients with chronic lymphocytic leukemia (CLL) to guide clinical management. Specific abnormalities, such as del(17p), del(11q), and unmutated IgHV, can predict the depth and durability of the response to CLL therapy. PATIENTS AND METHODS: In the present analysis of the Connect CLL Registry (ClinicalTrials.gov identifier, NCT01081015), a prospective observational cohort study of patients treated across 199 centers, the patterns of prognostic testing and outcomes of patients with unfavorable-risk genetics were analyzed...
February 2018: Clinical Lymphoma, Myeloma & Leukemia
https://www.readbyqxmd.com/read/29338825/efficacy-of-rituximab-for-patients-with-chronic-lymphocytic-leukemia
#20
Heng Li, Wen Jie Xiong, Hui Min Liu, Shu Hua Yi, Rui Lü, Ting Yu Wang, Zhen Yu, Lu Gui Qiu, Zeng Jun Li
Objective To evaluate the efficacy of rituximab in treating chronic lymphocytic leukemia (CLL). Methods The clinical data of CLL patients receiving fludarabine,cyclophosphamide±rituximab (with or without rituximab) regimen or cyclophosphamide,vincristine,and prednisone±doxorubicin±rituximab regimen in our hospital from March 2000 to February 2015 were analyzed retrospectively. Therapeutic efficacies and survivals of patients treated with different regimens were evaluated and compared. Results The complete response (CR) rate and the overall response rate (ORR) in 72 patients (43...
December 20, 2017: Zhongguo Yi Xue Ke Xue Yuan Xue Bao. Acta Academiae Medicinae Sinicae
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