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17p deletion

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https://www.readbyqxmd.com/read/29603773/treatment-patterns-and-clinical-outcomes-in-high-risk-newly-diagnosed-multiple-myeloma-patients-carrying-the-17p-deletion-an-observational-multi-center-retrospective-study
#1
Yael C Cohen, Avi Saranga, Moshe E Gatt, Noa Lavi, Chezi Ganzel, Hila Magen, Irit Avivi, Tamar Tadmor, Celia Suriu, Osnat Jarchowsky Dolberg, Amitai Papushado, Svetlana Trestman, Ron Ram
Del17p is a genomic imbalance occurring in ∼7-10% of myeloma at diagnosis (NDMM) and comprises a poor prognostic factor. The goal of this study is to analyze real world data and outcomes among NDMM patients carrying 17p deletion. We report an observational, retrospective, multicenter study. Sixty consecutive patients diagnosed with multiple myeloma in the 8 participating centers diagnosed between 1/2008-1/2016 proven to carry 17p deletion by means of FISH were identified. Most received a bortezomib-based induction, over half underwent autologous hematopoietic cell transplantation (HCT); 30% of the patients gained early access to new novel agents via clinical trials, access programs or private insurance...
March 31, 2018: American Journal of Hematology
https://www.readbyqxmd.com/read/29582169/medulloblastoma-wnt-activated-shh-activated-clinical-impact-of-molecular-analysis-and-histogenetic-evaluation
#2
REVIEW
Eduardo Cambruzzi
PURPOSE: Medulloblastoma (MDB) is a small cell poorly differentiated embryonal tumor of the cerebellum, which more frequently compromises children. Overall prognosis is favorable, but dependent of stage, histopathological pattern and molecular group. Approximately 30% of the affected patients will die from the disease. WHO 2016 Classification of Tumors of the Central Nervous System (CNS) has been classified MDB into four principal groups: WNT-activated MDB, SHH-activated MDB, group 3 MDB, and group 4 MDB...
March 26, 2018: Child's Nervous System: ChNS: Official Journal of the International Society for Pediatric Neurosurgery
https://www.readbyqxmd.com/read/29567785/dna-polymerase-%C3%AE-gene-expression-influences-fludarabine-resistance-in-chronic-lymphocytic-leukemia-independently-from-p53-status
#3
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/29563506/a-multiple-myeloma-specific-capture-sequencing-platform-discovers-novel-translocations-and-frequent-risk-associated-point-mutations-in-igll5
#4
Brian S White, Irena Lanc, Julie O'Neal, Harshath Gupta, Robert S Fulton, Heather Schmidt, Catrina Fronick, Edward A Belter, Mark Fiala, Justin King, Greg J Ahmann, Mary DeRome, Elaine R Mardis, Ravi Vij, John F DiPersio, Joan Levy, Daniel Auclair, Michael H Tomasson
Multiple myeloma (MM) is a disease of copy number variants (CNVs), chromosomal translocations, and single-nucleotide variants (SNVs). To enable integrative studies across these diverse mutation types, we developed a capture-based sequencing platform to detect their occurrence in 465 genes altered in MM and used it to sequence 95 primary tumor-normal pairs to a mean depth of 104×. We detected cases of hyperdiploidy (23%), deletions of 1p (8%), 6q (21%), 8p (17%), 14q (16%), 16q (22%), and 17p (4%), and amplification of 1q (19%)...
March 21, 2018: Blood Cancer Journal
https://www.readbyqxmd.com/read/29562156/venetoclax-rituximab-in-relapsed-or-refractory-chronic-lymphocytic-leukemia
#5
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/29523661/idelalisib-and-rituximab-in-17p-deletion-positive-splenic-marginal-zone-lymphoma
#6
Aby Z Philip
Splenic marginal zone lymphoma (SMZL) is a rare indolent B-cell malignancy involving the spleen and bone marrow. Various cytogenetic abnormalities with prognostic value have been identified in SMZL. Complexity of karyotype, 14q aberrations, and TP53 deletions have been found to be poor prognostic indicators. We report an unusual case of SMZL with a complex karyotype including 17p deletion, primarily refractory to 2 chemoimmunotherapy regimens, that responded well to treatment with phosphatidylinositol-3-kinase delta (PI3Kδ) inhibitors idelalisib and rituximab...
March 2018: Journal of the National Comprehensive Cancer Network: JNCCN
https://www.readbyqxmd.com/read/29480432/frontline-therapy-of-cll-evolving-treatment-paradigm
#7
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/29477371/venetoclax-a-new-wave-in-haemato-oncology
#8
REVIEW
Jana Mihalyova, Tomas Jelinek, Katerina Growkova, Matous Hrdinka, Michal Simicek, Roman Hajek
Inhibitors of anti-apoptotic proteins of the BCL2 family can successfully restart the deregulated process of apoptosis in malignant cells. While non-selective agents have been limited by their affinity to different BCL2 members, and thus inducing excessive toxicity, the highly selective BCL2 inhibitor, venetoclax (ABT-199, Venclexta™), has an acceptable safety profile. To date, it has been approved in monotherapy for the treatment of relapsed or refractory chronic lymphocytic leukaemia (CLL) with 17p deletion...
February 22, 2018: Experimental Hematology
https://www.readbyqxmd.com/read/29473834/ibrutinib-induced-neutrophilic-dermatosis
#9
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
#10
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/29445583/deep-sustained-response-to-daratumumab-monotherapy-associated-with-t-cell-expansion-in-triple-refractory-myeloma
#11
Saad Z Usmani, Imran Khan, Christopher Chiu, David Foureau, Lawrence J Druhan, Katherine Rigby, Tineke Casneuf, A Kate Sasser
Background: Daratumumab, a human CD38 monoclonal antibody that has direct on-tumor and immunomodulatory mechanisms of action, demonstrated clinical benefit as monotherapy or in combination with established regimens in patients with multiple myeloma with one or more prior lines of therapy. Case presentation: A male patient, who was 70 years of age at the time of diagnosis of multiple myeloma in 2011, relapsed after five lines of therapy, including autologous stem cell transplantation...
2018: Experimental Hematology & Oncology
https://www.readbyqxmd.com/read/29383113/proteasome-and-heat-shock-protein-70-hsp70-inhibitors-as-therapeutic-alternative-in-multiple-myeloma
#12
Angela Isabel Pereira Eugênio, Veruska Lia Fook-Alves, Mariana Bleker de Oliveira, Rodrigo Carlini Fernando, Daniela B Zanatta, Bryan Eric Strauss, Maria Regina Regis Silva, Marimélia Aparecida Porcionatto, Gisele Wally Braga Colleoni
HSP70 connects multiple signaling pathways that work synergistically to protect tumor cells from death by proteotoxic stress and represents a possible target to establish a new approach for multiple myeloma treatment. Therefore, bioluminescent cell lines RPMI8226-LUC-PURO and U266-LUC-PURO were treated with HSP70 (VER155008) and/or proteasome (bortezomib) inhibitors and immunodeficient mice were used for subcutaneous xenograft models to evaluate tumor growth reduction and tumor growth inhibition after treatment...
December 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/29338825/efficacy-of-rituximab-for-patients-with-chronic-lymphocytic-leukemia
#13
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
https://www.readbyqxmd.com/read/29333561/pharmacokinetics-of-the-b-cell-lymphoma-2-bcl-2-inhibitor-venetoclax-in-female-subjects-with-systemic-lupus-erythematosus
#14
Mukul Minocha, Jiewei Zeng, Jeroen K Medema, Ahmed A Othman
BACKGROUND AND OBJECTIVE: Venetoclax is an oral selective Bcl-2 inhibitor approved for the treatment of patients with chronic lymphocytic leukemia with 17p deletion. Mechanistic and preclinical evidence warranted evaluation of venetoclax for the treatment of systemic lupus erythematosus (SLE). This work characterized the pharmacokinetics of venetoclax in female subjects with SLE. METHODS: Single (10-500 mg) and multiple (30-600 mg) escalating doses of venetoclax or matching placebo were evaluated using randomized, double-blind, placebo-controlled designs (6 active and 2 placebo per dose with 73 unique SLE patients enrolled, 25 of whom enrolled twice)...
January 15, 2018: Clinical Pharmacokinetics
https://www.readbyqxmd.com/read/29305552/venetoclax-for-patients-with-chronic-lymphocytic-leukemia-who-progressed-during-or-after-idelalisib-therapy
#15
Steven Coutre, Michael Choi, Richard R Furman, Herbert Eradat, Leonard Heffner, Jeffrey A Jones, Brenda Chyla, Lang Zhou, Suresh Agarwal, Tina Waskiewicz, Maria Verdugo, Rod A Humerickhouse, Jalaja Potluri, William G Wierda, Matthew S Davids
B-cell receptor pathway inhibitors (BCRi) have transformed treatment for chronic lymphocytic leukemia (CLL); however, efficacy of therapies for patients whose disease is refractory to/relapses after (R/R) BCRi is unknown. Venetoclax is a selective, orally bioavailable BCL-2 inhibitor with activity in patients with CLL, including those who are heavily pretreated or have 17p deletion. This phase 2 study prospectively evaluated venetoclax in patients with R/R CLL after ibrutinib or idelalisib; here we report on patients who received idelalisib as the last BCRi prior to enrollment...
January 5, 2018: Blood
https://www.readbyqxmd.com/read/29296799/near-tetraploidy-is-associated-with-richter-transformation-in-chronic-lymphocytic-leukemia-patients-receiving-ibrutinib
#16
Cecelia R Miller, Amy S Ruppert, Nyla A Heerema, Kami J Maddocks, Jadwiga Labanowska, Heather Breidenbach, Gerard Lozanski, Weiqiang Zhao, Amber L Gordon, Jeffrey A Jones, Joseph M Flynn, Samantha M Jaglowski, Leslie A Andritsos, Kristie A Blum, Farrukh T Awan, Kerry A Rogers, Michael R Grever, Amy J Johnson, Lynne V Abruzzo, Erin K Hertlein, James S Blachly, Jennifer A Woyach, John C Byrd
Ibrutinib is a highly effective targeted therapy for chronic lymphocytic leukemia (CLL). However, ibrutinib must be discontinued in a subset of patients due to progressive CLL or transformation to aggressive lymphoma (Richter transformation). Transformation occurs early in the course of therapy and has an extremely poor prognosis. Thus, identification of prognostic markers associated with transformation is of utmost importance. Near-tetraploidy (4 copies of most chromosomes within a cell) has been reported in various lymphomas, but its incidence and significance in CLL has not been described...
August 22, 2017: Blood Advances
https://www.readbyqxmd.com/read/29296715/clonal-evolution-underlying-leukemia-progression-and-richter-transformation-in-patients-with-ibrutinib-relapsed-cll
#17
Sabah Kadri, Jimmy Lee, Carrie Fitzpatrick, Natalie Galanina, Madina Sukhanova, Girish Venkataraman, Shruti Sharma, Brad Long, Kristin Petras, Megan Theissen, Mei Ming, Yuri Kobzev, Wenjun Kang, Ailin Guo, Weige Wang, Nifang Niu, Howard Weiner, Michael Thirman, Wendy Stock, Sonali M Smith, Chadi Nabhan, Jeremy P Segal, Pin Lu, Y Lynn Wang
Ibrutinib has generated remarkable responses in patients with chronic lymphocytic leukemia (CLL), including those with an unfavorable cytogenetic profile. However, patients develop resistance, with poor outcomes and no established treatment options. Mutations in BTK and PLCG2 have emerged as main mechanisms of drug resistance, but not all patients carry these mutations. Further understanding of mechanisms of resistance is urgently needed and will support rational development of new therapeutic strategies. To that end, we characterized the genomic profiles of serial samples from 9 patients with ibrutinib-relapsed disease, including 6 who had Richter transformation...
May 9, 2017: Blood Advances
https://www.readbyqxmd.com/read/29239031/molecular-alterations-of-neuroendocrine-tumours-of-the-lung
#18
REVIEW
Giulio Rossi, Luca Bertero, Caterina Marchiò, Mauro Papotti
Neuroendocrine tumours of the lung comprise low [typical carcinoid (TC)], intermediate [atypical carcinoid (AC)] and high-grade [small-cell lung cancer (SCLC) and large-cell neuroendocrine carcinoma (LCNEC)] malignancies, while a pre-invasive lesion [diffuse idiopathic pulmonary neuroendocrine cell hyperplasia (DIPNECH)] may generate a subset of peripheral carcinoid tumours. These neoplasms are differentiated conventionally based on mitotic rate, presence of necrosis and cytological details, according to the 2015 World Health Organisation (WHO) classification...
January 2018: Histopathology
https://www.readbyqxmd.com/read/29222670/venetoclax-for-treating-chronic-lymphocytic-leukaemia-an-evidence-review-group-perspective-of-a-nice-single-technology-appraisal
#19
REVIEW
Hema Mistry, Chidozie Nduka, Martin Connock, Jill Colquitt, Theodoros Mantopoulos, Emma Loveman, Renata Walewska, James Mason
Venetoclax is licensed to treat relapsed or refractory (R/R) chronic lymphocytic leukaemia (CLL). As part of the Single Technology Appraisal (STA) ID944, the National Institute for Health and Care Excellence (NICE) invited AbbVie, the manufacturer, to submit evidence on the use of venetoclax, within its licensed indication. The Evidence Review Group (ERG), Warwick Evidence, was asked to provide an independent and critical review of the submitted evidence. Evidence came from three single-arm trials in CLL patients with or without 17p deletion [del(17p])/TP53 chromosomal abnormalities...
April 2018: PharmacoEconomics
https://www.readbyqxmd.com/read/29222278/safety-profiles-of-novel-agent-therapies-in-cll
#20
REVIEW
Inhye E Ahn, Matthew S Davids
A 70-year-old man with relapsed/refractory chronic lymphocytic leukemia has multiple comorbidities including atrial fibrillation (on warfarin for anticoagulation), irritable bowel syndrome, and chronic renal insufficiency. Two years ago, he received bendamustine and rituximab as first-line therapy for chronic lymphocytic leukemia and achieved partial response, but now has relapsed. Fluorescence in situ hybridization cytogenetics reveals deletion 17p. Which novel agent would you recommend for this patient?
December 8, 2017: Hematology—the Education Program of the American Society of Hematology
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