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17p deletion

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https://www.readbyqxmd.com/read/28100265/allogeneic-stem-cell-transplantation-in-adult-patients-with-acute-myeloid-leukaemia-and-17p-abnormalities-in-first-complete-remission-a-study-from-the-acute-leukemia-working-party-alwp-of-the-european-society-for-blood-and-marrow-transplantation-ebmt
#1
Xavier Poiré, Myriam Labopin, Johan Maertens, Ibrahim Yakoub-Agha, Didier Blaise, Norbert Ifrah, Gérard Socié, Tobias Gedde-Dhal, Nicolaas Schaap, Jan J Cornelissen, Stéphane Vigouroux, Jaime Sanz, Lucienne Michaux, Jordi Esteve, Mohamad Mohty, Arnon Nagler
BACKGROUND: Acute myeloid leukaemia (AML) with 17p abnormalities (abn(17p)) carries a very poor prognosis due to high refractoriness to conventional chemotherapy, and allogeneic stem cell transplantation (allo-SCT) appears as the only potential curative option. METHODS: To address outcomes after allo-SCT in patients with abn(17p), we retrospectively analysed de novo or secondary AML undergoing SCT between 2000 and 2013 from the EBMT registry. RESULTS: One hundred thirty-nine patients with confirmed abn(17p) have been selected...
January 18, 2017: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/28089441/prognostic-implications-of-monosomies-in-patients-with-multiple-myeloma
#2
Sang-Yong Shin, Hyeon-Seok Eom, Ji Yeon Sohn, Hyewon Lee, Boram Park, Jungnam Joo, Ja-Hyun Jang, Mi-Na Lee, Jung Kwon Kim, Sun-Young Kong
BACKGROUND: Cytogenetic analysis aides in risk stratification for patients with multiple myeloma (MM). Although several cytogenetic aberrations have been reported to be prognostic, less is known about the association between the presence of monosomies and prognosis. The present study evaluated the prevalence and prognostic implications of monosomies in patients with MM. MATERIALS AND METHODS: Karyotypes were determined using conventional cytogenetics and fluorescence in situ hybridization (FISH)...
December 26, 2016: Clinical Lymphoma, Myeloma & Leukemia
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/27982425/ublituximab-tg-1101-a-novel-glycoengineered-anti-cd20-antibody-in-combination-with-ibrutinib-is-safe-and-highly-active-in-patients-with-relapsed-and-or-refractory-chronic-lymphocytic-leukaemia-results-of-a-phase-2-trial
#6
Jeff P Sharman, Charles M Farber, Daruka Mahadevan, Marshall T Schreeder, Heather D Brooks, Kathryn S Kolibaba, Suzanne Fanning, Leonard Klein, Daniel R Greenwald, Peter Sportelli, Hari P Miskin, Michael S Weiss, John M Burke
Ibrutinib is effective in patients with chronic lymphocytic leukaemia (CLL); however, treatment resistance remains a problem. Ublituximab is a novel, glycoengineered anti-CD20 monoclonal antibody with single-agent activity in relapsed CLL. We report the results of a phase 2 study evaluating combination therapy with ibrutinib and ublituximab in patients with relapsed or refractory CLL. Patients received ibrutinib 420 mg once daily. Ublituximab was administered on days 1, 8 and 15 of cycle 1 followed by day 1 of cycles 2-6...
December 16, 2016: British Journal of Haematology
https://www.readbyqxmd.com/read/27913472/novel-agents-in-chronic-lymphocytic-leukemia
#7
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
#8
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
#9
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/27858991/management-of-central-nervous-system-involvement-in-chronic-lymphocytic-leukaemia-a-retrospective-cohort-of-30-patients
#10
Anne Wanquet, Rudy Birsen, Charlotte Bonnet, Marouane Boubaya, Sylvain Choquet, Jehan Dupuis, Stephane Lepretre, Daniel Re, Jonathan Fahri, Anne-Sophie Michallet, Loïc Ysebaert, Richard Lemal, Thierry Lamy, Richard Delarue, Xavier Troussard, Florence Cymbalista, Vincent Levy, Pierre-Yves Dietrich, Veronique Leblond, Therese Aurran-Schleinitz
Central nervous system involvement (CNSi) is a rare and poorly reported complication of chronic lymphocytic leukaemia (CLL). Establishing cause and effect between the CLL and the neurological symptoms remains challenging. We have analysed a retrospective cohort of 30 CLL patients with CNSi, documented by lymphocytic infiltration either by flow cytometry of the cerebrospinal fluid (CSF; n = 29) or CNS biopsy (n = 1). Neurological symptoms were heterogeneous. At the time of CNSi, less than half of the patients had a progressive CLL and 20 had never been treated for CLL...
January 2017: British Journal of Haematology
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/27803007/management-of-chronic-lymphocytic-leukemia-cll-in-the-elderly-a-position-paper-from-an-international-society-of-geriatric-oncology-siog-task-force
#12
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
#13
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/27756834/ibrutinib-for-relapsed-refractory-chronic-lymphocytic-leukemia-a-uk-and-ireland-analysis-of-outcomes-in-315-patients
#14
(no author information available yet)
In 2014, ibrutinib was made available for relapsed/refractory chronic lymphocytic leukemia patients. The UK Chronic Lymphocytic Leukaemia Forum collected data from UK/Ireland patients with a minimum of 1 year follow-up with pre-planned primary endpoints; the number of patients still on therapy at 1 year "discontinuation-free survival" and 1 year overall survival. With a median of 16 months follow up, data on 315 patients demonstrated a 1 year discontinuation-free survival of 73.7% and a 1 year overall survival of 83...
December 2016: Haematologica
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/27719720/-ighv-mutational-statue-in-patients-with-splenic-marginal-zone-lymphoma
#17
W J Yang, Z Yu, R Lyu, Z J Li, H Li, W J Xiong, S H Yi, W Liu, L G Qiu
Objective: To investigate the IGHV mutational status and its differences from Caucasian in splenic marginal zone lymphoma (SMZL). Methods: A retrospective study on 40 SMZL cases were performed to detect the V-D-J sequence of IGHV by plasmid cloning sequencing, comparing the data with the most homologous germ line V sequence in database, identifying the stereotype of patients through cluster analysis and alignment. The clinical and laboratory characteristics were compared between the patients with IGHV mutation and without mutations...
September 14, 2016: Zhonghua Xue Ye Xue za Zhi, Zhonghua Xueyexue Zazhi
https://www.readbyqxmd.com/read/27698805/genetic-landscape-of-a-case-of-extraovarian-peritoneal-serous-papillary-carcinoma
#18
Zhongping Cheng, Weihong Yang, Jing Guo, Ning Luo, Li Chen, Yan Xie, Xiaoyan Qu, Liping Hu, Hong Dai, Xiaoming Zuo
The present report aimed to study genetic alterations underlying extraovarian peritoneal serous papillary carcinoma (EPSPC), which have not previously been systematically investigated. A case of EPSPC was identified, and its genetic alterations were assessed by combining comparative genomic hybridization and whole-exome sequencing technologies to investigate the genomic landscape, including copy number variations and mutations in EPSPC. It was found that a large number of germline mutations were present, which may have predisposed the patient to the occurrence of this disease...
October 2016: Oncology Letters
https://www.readbyqxmd.com/read/27697588/metachronous-anaplastic-sarcoma-of-the-kidney-and-thyroid-follicular-carcinoma-as-manifestations-of-dicer1-abnormalities
#19
Misa Yoshida, Satoshi Hamanoue, Masafumi Seki, Mio Tanaka, Kenichi Yoshida, Hiroaki Goto, Seishi Ogawa, Junko Takita, Yukichi Tanaka
Anaplastic sarcoma of the kidney (ASK) is a tumor found in the pediatric age group and shows many histopathological similarities to pleuropulmonary blastoma (PPB). We present a 12-year-old girl diagnosed with ASK and, three years later, with thyroid follicular carcinoma (TFC) with DICER1 abnormalities. Germline insertion/deletion (p.G1809_S1814delinsA) and independent somatic mutations (p.E1705K in ASK, p.E1813D in TFC) were identified. All of these abnormalities are in the catalytic domain of RNase IIIb. Single-nucleotide polymorphism genotyping microarray revealed independent copy number alterations (trisomy 8, monosomy 10, loss of 17p and partial gain of 17q in ASK; trisomy 5 and partial loss of Xq in TFC)...
September 30, 2016: Human Pathology
https://www.readbyqxmd.com/read/27686109/pharmacokinetic-and-pharmacodynamic-evaluation-of-ibrutinib-for-the-treatment-of-chronic-lymphocytic-leukemia-rationale-for-lower-doses
#20
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
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