keyword
MENU ▼
Read by QxMD icon Read
search

17p chronic lymphocytic leukemia

keyword
https://www.readbyqxmd.com/read/28100580/venetoclax-in-patients-with-previously-treated-chronic-lymphocytic-leukemia
#1
Andrew W Roberts, Stephan Stilgenbauer, John F Seymour, David C S Huang
Venetoclax is the first BCL2 inhibitor to enter routine clinical practice. It is an orally bioavailable small molecule that binds BCL2 very specifically. Acting as a pharmacological mimic of the proteins that initiate apoptosis (a so-called BH3-mimetic), venetoclax rapidly induces apoptosis in chronic lymphocytic leukemia (CLL) cells which express high levels of BCL2 and rely on it to maintain their survival. As a single agent, daily venetoclax treatment induced durable responses in 79% of patients with relapsed or refractory CLL or small lymphocytic lymphoma in a Phase 1 study, including complete remissions in 20% of patients...
January 18, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28091403/chronic-lymphocytic-leukemia-prognostic-index-a-new-integrated-scoring-system-to-predict-the-time-to-first-treatment-in-chinese-patients-with-chronic-lymphocytic-leukemia
#2
Heng Li, Shu-Hua Yi, Wen-Jie Xiong, Hui-Min Liu, Rui Lyu, Ting-Yu Wang, Wei Liu, Shi-Zhen Zhong, Zhen Yu, De-Hui Zou, Yan Xu, Gang An, Zeng-Jun Li, Lu-Gui Qiu
BACKGROUND: The established clinical staging systems (Rai/Binet) of chronic lymphocytic leukemia (CLL) cannot accurately predict the appropriate treatment of patients in the earlier stages. In the past two decades, several prognostic factors have been identified to predict the outcome of patients with CLL, but only a few studies investigated more markers together. To predict the time to first treatment (TTFT) in patients of early stages, we evaluated the prognostic role of conventional markers as well as cytogenetic abnormalities and combined them together in a new prognostic scoring system, the CLL prognostic index (CLL-PI)...
2017: Chinese Medical Journal
https://www.readbyqxmd.com/read/28056525/venetoclax
#3
Amber C King, Tim J Peterson, Troy Z Horvat, Mabel Rodriguez, Laura A Tang
OBJECTIVE: To review the pharmacology, efficacy, and safety of venetoclax for treatment of lymphoid malignancies. DATA SOURCES: A literature search was performed of PubMed and MEDLINE databases (2005 to September 2016), abstracts from the American Society of Hematology and the American Society of Clinical Oncology, and ongoing studies from clinicaltrials.gov. Searches were performed utilizing the following key terms: venetoclax, ABT-199, GDC-199, obatoclax, GX15-070, BCL-2 inhibitor, navitoclax, ABT-263, and Venclexta...
December 1, 2016: Annals of Pharmacotherapy
https://www.readbyqxmd.com/read/27990281/mitochondrial-apoptosis-and-bh3-mimetics
#4
REVIEW
Haiming Dai, X Wei Meng, Scott H Kaufmann
The BCL2-selective BH3 mimetic venetoclax was recently approved for the treatment of relapsed, chromosome 17p-deleted chronic lymphocytic leukemia (CLL) and is undergoing extensive testing, alone and in combination, in lymphomas, acute leukemias, and solid tumors. Here we summarize recent advances in understanding of the biology of BCL2 family members that shed light on the action of BH3 mimetics, review preclinical and clinical studies leading to the regulatory approval of venetoclax, and discuss future investigation of this new class of antineoplastic agent...
2016: F1000Research
https://www.readbyqxmd.com/read/27982454/relationship-between-venetoclax-exposure-rituximab-coadministration-and-progression-free-survival-in-patients-with-relapsed-or-refractory-chronic-lymphocytic-leukemia-demonstration-of-synergy
#5
Kevin J Freise, Aksana K Jones, Rajeev M Menon, Maria E Verdugo, Rod A Humerickhouse, Walid M Awni, Ahmed Hamed Salem
Venetoclax is indicated at a dosage of 400 mg daily (QD) for the treatment of patients with chronic lymphocytic leukemia (CLL) with 17p deletion who have received at least 1 prior therapy. Ongoing trials are evaluating venetoclax in combination with CD20 targeting monoclonal antibodies, such as rituximab. The objective of this research was to characterize the relationship between venetoclax exposures and progression-free survival (PFS) and to evaluate the effect of rituximab coadministration on PFS in patients with relapsed or refractory (R/R) CLL/small lymphocytic lymphoma (SLL)...
December 16, 2016: Hematological Oncology
https://www.readbyqxmd.com/read/27913472/novel-agents-in-chronic-lymphocytic-leukemia
#6
Nicole Lamanna, Susan O'Brien
The advent of novel small-molecule inhibitors has transformed the treatment approaches for patients with chronic lymphocytic leukemia (CLL). These therapies are becoming increasingly used in patients with relapsed disease, patients with 17p deletion, and, as of recently, also in the frontline setting for previously untreated patients with CLL. Moreover, many of these are oral therapies that are significantly less myelosuppressive than chemoimmunotherapy. However, these agents have their own set of unique toxicities with which providers must gain familiarity...
December 2, 2016: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/27913471/sequencing-of-chronic-lymphocytic-leukemia-therapies
#7
Jacqueline C Barrientos
It is an unprecedented time for the treatment of patients with chronic lymphocytic leukemia (CLL) with the recent approval of several targeted agents for use in frontline, relapsed, refractory, and high-risk disease. Traditionally, frontline management of CLL has been a combination of chemotherapy (fludarabine, cyclophosphamide, bendamustine, or chlorambucil) with an anti-CD20 monoclonal antibody (rituximab, ofatumumab, obinutuzumab). The current landscape is rapidly evolving with the advent of therapies that demonstrate selective inhibition of important pathways necessary for CLL proliferation and survival...
December 2, 2016: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/27881039/fludarabine-cyclophosphamide-and-lenalidomide-in-patients-with-relapsed-refractory-chronic-lymphocytic-leukemia-a-multicenter-phase-i-ii-gimema-trial
#8
Francesca R Mauro, Angelo M Carella, Stefano Molica, Francesca Paoloni, Anna M Liberati, Francesco Zaja, Valeria Belsito, Agostino Cortellezzi, Rita Rizzi, Patrizia Tosi, Mauro Spriano, Antonietta Ferretti, Mauro Nanni, Marilisa Marinelli, Maria S De Propris, Sonia M Orlando, Marco Vignetti, Antonio Cuneo, Anna R Guarini, Robin Foà
The activity and safety of a regimen combining lenalidomide with fludarabine and cyclophosphamide (FC) was investigated in patients with relapsed/refractory (R/R) chronic lymphocytic leukemia (CLL). Treatment consisted of six monthly courses of the FC regimen combined with 14 days of lenalidomide given at the starting dose of 2.5 mg during course 1. The maximum tolerated dose of lenalidomide was 5 mg. Forty patients were assessed for response, 66% were IGHV unmutated, 45% showed deletion 11q or 17p. The overall response and complete remission rates were 62...
November 23, 2016: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/27872727/identifying-high-risk-chronic-lymphocytic-leukemia-a-pathogenesis-oriented-appraisal-of-prognostic-and-predictive-factors-in-patients-treated-with-chemotherapy-with-or-without-immunotherapy
#9
REVIEW
Sara Martinelli, Antonio Cuneo, Luca Formigaro, Maurizio Cavallari, Enrico Lista, Francesca Maria Quaglia, Maria Ciccone, Antonella Bardi, Eleonora Volta, Elisa Tammiso, Elena Saccenti, Olga Sofritti, Giulia Daghia, Massimo Negrini, Melissa Dabusti, Paolo Tomasi, Sabrina Moretti, Francesco Cavazzini, Gian Matteo Rigolin
Chronic lymphocytic leukemia (CLL) displays an extremely variable clinical behaviour. Accurate prognostication and prediction of response to treatment are important in an era of effective first-line regimens and novel molecules for high risk patients. Because a plethora of prognostic biomarkers were identified, but few of them were validated by multivariable analysis in comprehensive prospective studies, we applied in this survey stringent criteria to select papers from the literature in order to identify the most reproducible prognostic/predictive markers...
2016: Mediterranean Journal of Hematology and Infectious Diseases
https://www.readbyqxmd.com/read/27870563/economic-burden-of-chronic-lymphocytic-leukemia-in-the-era-of-oral-targeted-therapies-in-the-united-states
#10
Qiushi Chen, Nitin Jain, Turgay Ayer, William G Wierda, Christopher R Flowers, Susan M O'Brien, Michael J Keating, Hagop M Kantarjian, Jagpreet Chhatwal
Purpose Oral targeted therapies represent a significant advance for the treatment of patients with chronic lymphocytic leukemia (CLL); however, their high cost has raised concerns about affordability and the economic impact on society. Our objective was to project the future prevalence and cost burden of CLL in the era of oral targeted therapies in the United States. Methods We developed a simulation model that evaluated the evolving management of CLL from 2011 to 2025: chemoimmunotherapy (CIT) as the standard of care before 2014, oral targeted therapies for patients with del(17p) and relapsed CLL from 2014, and for first-line treatment from 2016 onward...
January 10, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/27821812/karyotypic-complexity-rather-than-chromosome-8-abnormalities-aggravates-the-outcome-of-chronic-lymphocytic-leukemia-patients-with-tp53-aberrations
#11
Gonzalo Blanco, Anna Puiggros, Panagiotis Baliakas, Anastasia Athanasiadou, MªDolores García-Malo, Rosa Collado, Aliki Xochelli, María Rodríguez-Rivera, Margarita Ortega, Mª José Calasanz, Elisa Luño, MªTeresa Vargas, Javier Grau, Carolina Martínez-Laperche, Alberto Valiente, José Cervera, Achilles Anagnostopoulos, Eva Gimeno, Eugènia Abella, Evangelia Stalika, Jesús Mª Hernández-Rivas, Francisco José Ortuño, Diego Robles, Ana Ferrer, David Ivars, Marcos González, Francesc Bosch, Pau Abrisqueta, Kostas Stamatopoulos, Blanca Espinet
Patients with chronic lymphocytic leukemia (CLL) harboring TP53 aberrations (TP53abs; chromosome 17p deletion and/or TP53 mutation) exhibit an unfavorable clinical outcome. Chromosome 8 abnormalities, namely losses of 8p (8p-) and gains of 8q (8q+) have been suggested to aggravate the outcome of patients with TP53abs. However, the reported series were small, thus hindering definitive conclusions. To gain insight into this issue, we assessed a series of 101 CLL patients harboring TP53 disruption. The frequency of 8p- and 8q+ was 14...
November 4, 2016: Oncotarget
https://www.readbyqxmd.com/read/27815572/phase-i-ii-study-of-lenalidomide-and-alemtuzumab-in-refractory-chronic-lymphocytic-leukemia-cll-effects-on-t-cells-and-immune-checkpoints
#12
Maria Winqvist, Fariba Mozaffari, Marzia Palma, Sandra Eketorp Sylvan, Lotta Hansson, Håkan Mellstedt, Anders Österborg, Jeanette Lundin
This phase I-II study explored safety, immunomodulatory and clinical effects of lenalidomide (weeks 1-16) and alemtuzumab (weeks 5-16) in 23 patients with refractory chronic lymphocytic leukemia. Most patients had Rai stage III/IV disease and were heavily pretreated (median 4 prior therapies), and 61% had del(17p)/del(11q). Eleven of 19 evaluable patients (58%) responded, with a median response duration of 12 months (1-29+); time to progression was short in non-responders. Lenalidomide had a narrow therapeutic dose range, 2...
November 4, 2016: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/27803007/management-of-chronic-lymphocytic-leukemia-cll-in-the-elderly-a-position-paper-from-an-international-society-of-geriatric-oncology-siog-task-force
#13
R Stauder, B Eichhorst, M E Hamaker, K Kaplanov, V A Morrison, A Österborg, I Poddubnaya, J A Woyach, T Shanafelt, L Smolej, L Ysebaert, V Goede
Chronic lymphocytic leukemia (CLL) mainly affects older people: the median age at diagnosis is > 70 years. Elderly patients with CLL are heterogeneous with regard both to the biology of their disease and aging. Following the diagnosis of CLL in an elderly individual, careful risk assessment is essential when treatment options are evaluated. This includes not only clinical staging and evaluation of disease-specific prognostic biomarkers such as 17p deletion and TP53 mutation, but also of comorbidities, physical capacity, nutritional status, cognitive capacity, ability to perform activities of daily living and social support...
November 1, 2016: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/27797975/long-term-follow-up-of-treatment-with-ibrutinib-and-rituximab-ir-in-patients-with-high-risk-chronic-lymphocytic-leukemia-cll
#14
Preetesh Jain, Michael J Keating, William Wierda, Mariela Sivina, Philip A Thompson, Alessandra Ferrajoli, Zeev Estrov, Hagop Kantarjian, Susan O'Brien, Jan Burger
BACKGROUND: Ibrutinib is an active therapy with acceptable safety profile for patients with CLL, including high-risk patients with del17p or with TP53 mutations. Ibrutinib is broadly indicated for the treatment of patients with chronic lymphocytic leukemia and specifically including those with 17p deletion. The optimal use of ibrutinib in combination with other agents, remains controversial. METHODS: We report the long term outcome [median follow up of 47 months (range 36-51 months)] of 40 patients with high risk CLL, treated on the first ibrutinib combination trial with rituximab (IR)...
October 19, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/27742075/tp53-dysfunction-in-cll-implications-for-prognosis-and-treatment
#15
Gera D Te Raa, Arnon P Kater
Despite the availability of novel targeted agents, TP53 defects remain the most important adverse prognostic factor in chronic lymphocytic leukemia (CLL). Detection of deletion of TP53 locus (17p deletion) by fluorescent in situ hybridization (FISH) has become standard and performed prior to every line of treatment as the incidence dramatically increases as relapses occur. As monoallelic mutations of TP53 equally affect outcome, novel methods are being developed to improve detection of TP53 defects and include next-generation sequencing (NGS) and functional assays...
March 2016: Best Practice & Research. Clinical Haematology
https://www.readbyqxmd.com/read/27742074/biomarkers-in-chronic-lymphocytic-leukemia-clinical-applications-and-prognostic-markers
#16
REVIEW
Carlos I Amaya-Chanaga, Laura Z Rassenti
Chronic lymphocytic leukemia (CLL) is a heterogeneous disease with a variable clinical course. The Rai and Binet staging systems are often used to predict survival. However, they do not take into account other biological characteristics of CLL cells that may influence the disease course and response to treatment. Prognostic factors such as chromosome abnormalities (trisomy 12, 11q deletions and 17p deletions), β2 microglobulin, thymidine kinase, CD38 and ZAP-70 expression, IGHV mutation status, and mutations in genes such as NOTCH1, MYD88, SF3B1, and ATM are also predictors of prognosis...
March 2016: Best Practice & Research. Clinical Haematology
https://www.readbyqxmd.com/read/27686109/pharmacokinetic-and-pharmacodynamic-evaluation-of-ibrutinib-for-the-treatment-of-chronic-lymphocytic-leukemia-rationale-for-lower-doses
#17
Prithviraj Bose, Varsha V Gandhi, Michael J Keating
Ibrutinib, a first-in-class covalent inhibitor of Bruton's tyrosine kinase (BTK), is approved in many countries for the treatment of relapsed/refractory chronic lymphocytic leukemia (CLL) and for previously untreated disease with a 17p deletion and, most recently, as a frontline therapy for CLL. In controlled trials in CLL, ibrutinib produced high response rates and improved survival in both the frontline and relapsed settings. While ibrutinib controls CLL with impressive efficacy, it only infrequently induces complete remissions, particularly of relapsed CLL, and does not eradicate minimal residual disease...
October 11, 2016: Expert Opinion on Drug Metabolism & Toxicology
https://www.readbyqxmd.com/read/27683974/cross-resistance-and-synergy-with-bendamustine-in-chronic-lymphocytic-leukemia
#18
Sara E F Kost, Eric D J Bouchard, Élise LaBossière, Xibiao Ye, Michelle L Queau, William S Liang, Versha Banerji, Spencer B Gibson, Sachin Katyal, James B Johnston
Bendamustine (BEN) has structural similarities to an alkylating agent and a nucleoside analog, and effective against tumor cells that are resistant to standard therapy. In this study we compared the activities of BEN against that of the alkylating agent, chlorambucil (CLB), and the nucleoside analogs, fludarabine (FLU) and deoxyadenosine/pentostatin (dADO/PEN), in primary chronic lymphocytic leukemia (CLL) cells in vitro. Cross-resistance was observed between BEN, CLB and FLU, with previously treated patients or those with a deletion 17p being most resistant...
September 20, 2016: Leukemia Research
https://www.readbyqxmd.com/read/27650502/alterations-of-mitochondrial-biogenesis-in-chronic-lymphocytic-leukemia-cells-with-loss-of-p53
#19
Marcia A Ogasawara, Jinyun Liu, Helene Pelicano, Naima Hammoudi, Carlo M Croce, Michael J Keating, Peng Huang
Deletion of chromosome 17p with a loss of p53 is an unfavorable cytogenetic change in chronic lymphocytic leukemia (CLL) with poor clinical outcome. Since p53 affects mitochondrial function and integrity, we examined possible mitochondrial changes in CLL mice with TCL1-Tg/p53(-/-) and TCL1-Tg/p53(+/+) genotypes and in primary leukemia cells from CLL patients with or without 17p-deletion. Although the expression of mitochondrial COX1, ND2, and ND6 decreased in p53(-/-)CLL cells, there was an increase in mitochondrial biogenesis as evidenced by higher mitochondrial mass and mtDNA copy number associated with an elevated expression of TFAM and PGC-1α...
November 2016: Mitochondrion
https://www.readbyqxmd.com/read/27638334/impact-of-venetoclax-exposure-on-clinical-efficacy-and-safety-in-patients-with-relapsed-or-refractory-chronic-lymphocytic-leukemia
#20
Kevin J Freise, Aksana K Jones, Doerthe Eckert, Sven Mensing, Shekman L Wong, Rod A Humerickhouse, Walid M Awni, Ahmed Hamed Salem
BACKGROUND: Venetoclax is a selective, potent, first-in-class B-cell lymphoma-2 inhibitor that restores apoptosis in cancer cells and has demonstrated efficacy in a variety of hematological malignancies. OBJECTIVE: The objective of this research was to characterize the relationship between venetoclax exposures and efficacy and safety in patients with relapsed or refractory (R/R) chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL). METHODS: A total of 272 and 338 patients from four clinical studies were pooled for the exposure-efficacy and exposure-safety analyses, respectively...
September 15, 2016: Clinical Pharmacokinetics
keyword
keyword
43591
1
2
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read
×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"