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https://www.readbyqxmd.com/read/28343201/-ibrutinib-new-tool-in-hematologist-hand-new-challenges-for-internist
#1
Maciej Majcherek, Marzena Dworacka, Grzegorz Dworacki
Chronic lymphocytic leukemia is the most common cancer of the lymphatic tissue in adults. The peak incidence falls on the 65-70 year old. Therefore, the majority of patients with chronic lymphocytic leukemia (CLL) has at least one coexisting disease. Successful oncological and supportive treatment, that is common in recent years, significantly prolongs the survival. This paper presents ibrutinib - a new drug used to treat CLL. The aim of this paper is, to show an example of this drug, meaning and benefits of modern methods of pharmacotherapy in the treatment of oncology...
2017: Wiadomości Lekarskie: Organ Polskiego Towarzystwa Lekarskiego
https://www.readbyqxmd.com/read/28336937/results-of-the-randomized-phase-iib-arctic-trial-of-low-dose-rituximab-in-previously-untreated-cll
#2
D R Howard, T Munir, L McParland, A C Rawstron, D Milligan, A Schuh, A Hockaday, D J Allsup, S Marshall, A S Duncombe, J L O'Dwyer, A F Smith, R Longo, A Varghese, P Hillmen
ARCTIC was a multi-center, randomized-controlled, open, phase IIB non-inferiority trial in previously untreated Chronic Lymphocytic Leukemia (CLL). Conventional frontline therapy in fit patients is fludarabine, cyclophosphamide and rituximab (FCR). The trial hypothesized that including mitoxantrone with low-dose rituximab (FCM-miniR) would be non-inferior to FCR. 200 patients were recruited to assess the primary endpoint of complete remission (CR) rates according to IWCLL criteria. Secondary endpoints were progression-free survival (PFS), overall survival (OS), overall response rate, minimal residual disease (MRD) negativity, safety and cost-effectiveness...
March 24, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28331288/development-of-venetoclax-for-therapy-of-lymphoid-malignancies
#3
REVIEW
Huayuan Zhu, Alexandru Almasan
B-cell lymphoma-2 (BCL-2) family dysfunction and impairment of apoptosis are common in most B-cell lymphoid malignancies. Venetoclax (Venclexta™, formerly ABT-199, GDC-0199) is a highly selective BCL-2 inhibitor, which mimics its BCL-2 homology 3-domain to induce apoptosis. It was approved for treatment of previously treated chronic lymphocytic leukemia (CLL) patients with 17p deletion early in 2016. It has also been in clinical trials for other B-cell lymphoid malignancies. Unlike the other recently approved targeted agents idelalisib and ibrutinib, so far there has been no relapse reported in some patients...
2017: Drug Design, Development and Therapy
https://www.readbyqxmd.com/read/28328317/antiproliferative-and-apoptotic-effects-of-novel-anti-ror1-single-chain-antibodies-in-hematological-malignancies
#4
Leili Aghebati-Maleki, Vahid Younesi, Behzad Baradaran, Jalal Abdolalizadeh, Morteza Motallebnezhad, Hamid Nickho, Dariush Shanehbandi, Jafar Majidi, Mehdi Yousefi
Receptor tyrosine kinase-like orphan receptor (ROR) proteins are a conserved family of tyrosine kinase receptors that function in developmental processes including cell survival, differentiation, cell migration, cell communication, cell polarity, proliferation, metabolism, and angiogenesis. ROR1 has recently been shown to be expressed in various types of cancer cells but not normal cells. Pharmacokinetics and pharmacodynamics of single-chain Fragment variable (scFv) antibodies provide potential therapeutic advantages over whole antibody molecules...
April 2017: SLAS Discov
https://www.readbyqxmd.com/read/28324286/prolymphocytic-leukemia-new-insights-in-diagnosis-and-in-treatment
#5
REVIEW
Aude Collignon, Anne Wanquet, Elsa Maitre, Edouard Cornet, Xavier Troussard, Thérèse Aurran-Schleinitz
PURPOSE OF REVIEW: We aimed to produce a comprehensive update on clinical and biological data regarding two rare lymphoid neoplasms, B and T prolymphocytic leukemias, and assess therapeutic management in the light of new molecular insights and the advent of targeted therapies. RECENT FINDINGS: B cell prolymphocytic leukemia (B-PLL) diagnosis remains challenging in the absence of clear immunophenotypic or cytogenetic signature and overlap with mantle cell lymphoma...
April 2017: Current Oncology Reports
https://www.readbyqxmd.com/read/28303898/circulating-tumour-dna-reflects-treatment-response-and-clonal-evolution-in-chronic-lymphocytic-leukaemia
#6
Paul Yeh, Tane Hunter, Devbarna Sinha, Sarah Ftouni, Elise Wallach, Damian Jiang, Yih-Chih Chan, Stephen Q Wong, Maria Joao Silva, Ravikiran Vedururu, Kenneth Doig, Enid Lam, Gisela Mir Arnau, Timothy Semple, Meaghan Wall, Andjelija Zivanovic, Rishu Agarwal, Pasquale Petrone, Kate Jones, David Westerman, Piers Blombery, John F Seymour, Anthony T Papenfuss, Mark A Dawson, Constantine S Tam, Sarah-Jane Dawson
Several novel therapeutics are poised to change the natural history of chronic lymphocytic leukaemia (CLL) and the increasing use of these therapies has highlighted limitations of traditional disease monitoring methods. Here we demonstrate that circulating tumour DNA (ctDNA) is readily detectable in patients with CLL. Importantly, ctDNA does not simply mirror the genomic information contained within circulating malignant lymphocytes but instead parallels changes across different disease compartments following treatment with novel therapies...
March 17, 2017: Nature Communications
https://www.readbyqxmd.com/read/28302090/characterizing-and-prognosticating-chronic-lymphocytic-leukemia-in-the-elderly-prospective-evaluation-on-455-patients-treated-in-the-united-states
#7
Chadi Nabhan, Anthony Mato, Christopher R Flowers, David L Grinblatt, Nicole Lamanna, Mark A Weiss, Matthew S Davids, Arlene S Swern, Shriya Bhushan, Kristen Sullivan, E Dawn Flick, Pavel Kiselev, Jeff P Sharman
BACKGROUND: Median age at diagnosis of patients with chronic lymphocytic leukemia (CLL) is > 70 years. However, the majority of clinical trials do not reflect the demographics of CLL patients treated in the community. We examined treatment patterns, outcomes, and disease-related mortality in patients ≥ 75 years with CLL (E-CLL) in a real-world setting. METHODS: The Connect® CLL registry is a multicenter, prospective observational cohort study, which enrolled 1494 adult patients between 2010-2014, at 199 US sites...
March 16, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28299881/the-regulation-of-tumor-suppressive-microrna-mir-126-in%C3%A2-chronic-lymphocytic-leukemia
#8
Daphne Guinn, Amy Lehman, Catherine Fabian, Lianbo Yu, Kami Maddocks, Leslie A Andritsos, Jeffrey A Jones, Joseph M Flynn, Samantha M Jaglowski, Jennifer A Woyach, John C Byrd, Amy J Johnson
The introduction of miR profiling of chronic lymphocytic leukemia (CLL) patients with different cytogenetic profiles and responses to therapy has allowed incorporation of important miR-mRNA interactions into the understanding of disease biology. In this study, we performed miR expression analysis using NanoString nCounter to discover differentially regulated miRs after therapy with the Bruton tyrosine kinase inhibitor ibrutinib. Of the differentially regulated miRs in the discovery set, miR-29c and miR-126 were confirmed using real-time PCR to be upregulated in CLL patient cells with ibrutinib therapy...
March 15, 2017: Cancer Medicine
https://www.readbyqxmd.com/read/28297623/clinical-implications-of-novel-genomic-discoveries-in-chronic-lymphocytic-leukemia
#9
Gregory Lazarian, Romain Guièze, Catherine J Wu
Chronic lymphocytic leukemia (CLL) is a common B-cell malignancy with a remarkably heterogeneous course, ranging from indolent disease with no need for immediate therapy to rapidly progressive disease associated with therapeutic resistance. The recent US Food and Drug Administration approvals of novel targeted therapies such as inhibitors of B-cell receptor signaling and B-cell lymphoma 2 have opened up new opportunities in the clinical management of patients with CLL and heralded a new era in the clinical treatment of this disease...
March 20, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28295729/targeting-of-b-cell-receptor-signalling-in-b-cell-malignancies
#10
M Jerkeman, M Hallek, M Dreyling, C Thieblemont, E Kimby, L Staudt
Pharmacological agents that inhibit enzymes of the B-cell receptor (BCR) pathway are of increasing importance in the treatment of B-cell malignancies. These include inhibitors of Bruton tyrosine kinase (BTK), phosphatidylinositol 3-kinase (PI3K), splenic tyrosine kinase and protein kinase Cβ. Two agents are already approved in the USA and Europe: ibrutinib, a BTK inhibitor, for the treatment of chronic lymphatic leukaemia (CLL), mantle cell lymphoma (MCL) and Waldenström's macroglobulinemia; and idelalisib, a PI3Kδ inhibitor, for the treatment of CLL and follicular lymphoma...
March 14, 2017: Journal of Internal Medicine
https://www.readbyqxmd.com/read/28295527/factors-predicting-survival-in-chronic-lymphocytic-leukemia-patients-developing-richter-syndrome-transformation-into-hodgkin-lymphoma
#11
Francesca Romana Mauro, Piero Galieni, Alessandra Tedeschi, Luca Laurenti, Giovanni Del Poeta, Gianluigi Reda, Marina Motta, Alessandro Gozzetti, Roberta Murru, Maria Denise Caputo, Melissa Campanelli, Anna Maria Frustaci, Idanna Innocenti, Sara Raponi, Anna Guarini, Fortunato Morabito, Robin Foà, Massimo Gentile
We hereby report the clinical and biologic features of 33 of 4680 (0.7%) patients with chronic lymphocytic leukemia (CLL), managed at 10 Italian centers, who developed Hodgkin lymphoma (HL), a rare variant of Richter syndrome. The median age at CLL and at HL diagnosis were 61 years (range 41-80) and 70 years (range 46-82), respectively, with a median interval from CLL to the diagnosis of HL of 90 months (range 0-258). In 3 cases, CLL and HL were diagnosed simultaneously. Hl was characterized by advanced stage in 79% of cases, International Prognostic Score (IPS) ≥4 in 50%, extranodal involvement in 39%, B symptoms in 70%...
March 10, 2017: American Journal of Hematology
https://www.readbyqxmd.com/read/28295171/successful-use-of-bruton-s-kinase-inhibitor-ibrutinib-to-control-paraneoplastic-pemphigus-in-a-patient-with-paraneoplastic-autoimmune-multiorgan-syndrome-and-chronic-lymphocytic-leukaemia
#12
Andrew Lee, Suneet Sandhu, Louise Imlay-Gillespie, Stephen Mulligan, Stephen Shumack
We present the case of a 51-year-old man who developed paraneoplastic pemphigus (PNP) in the context of chronic lymphocytic leukemia (CLL). His CLL was successfully controlled with ibrutinib. Concurrently, there was significant improvement of his PNP, suggesting that ibrutinib may be a very useful addition to the treatment options in this potentially life-threatening autoimmune disorder.
March 13, 2017: Australasian Journal of Dermatology
https://www.readbyqxmd.com/read/28292720/clinical-relevance-of-hypogammaglobulinemia-clinical-and-biologic-variables-on-the-infection-risk-and-outcome-of-patients-with-stage-a-chronic-lymphocytic-leukemia
#13
Francesca R Mauro, Fortunato Morabito, Iolanda D Vincelli, Luigi Petrucci, Melissa Campanelli, Adriano Salaroli, Giuseppina Uccello, Annamaria Petrungaro, Francesca Ronco, Sara Raponi, Mauro Nanni, Antonino Neri, Manlio Ferrarini, Anna R Guarini, Robin Foà, Massimo Gentile
The prognostic effect of hypogammaglobulinemia (HGG), clinical and biologic characteristics on the infection risk and outcome has been retrospectively analyzed in 899 patients with stage A chronic lymphocytic leukemia (CLL). Low levels of IgG were recorded in 19.9% of patients at presentation, low levels of IgM and/or IgA in 10.4% and an additional 20% of patients developed HGG during the course of the disease. Before the start of any treatment, 160 (12.9%) patients experienced at least one grade ≥3 infection requiring a systemic anti-infective treatment and/or hospitalization...
February 27, 2017: Leukemia Research
https://www.readbyqxmd.com/read/28284744/thoracic-complications-in-chronic-lymphocytic%C3%A2-leukemia
#14
Sameer Khanijo, Pragati Tandon, Cristina P Sison, Seth Koenig
BACKGROUND: Chronic lymphocytic leukemia (CLL) is the most common lymphoproliferative disorder worldwide. Although thoracic complications are frequent in CLL, only limited data exist regarding the etiologies of these complications. MATERIALS AND METHODS: A retrospective chart review was performed on all patients admitted to a tertiary care, CLL referral center, with CLL and a respiratory complaint from 2001 through 2013, to categorize pulmonary complaints and diagnoses...
February 17, 2017: Clinical Lymphoma, Myeloma & Leukemia
https://www.readbyqxmd.com/read/28278728/soluble-cd52-is-an-indicator-of-disease-activity-in-chronic-lymphocytic-leukemia
#15
Fie J Vojdeman, Sarah E M Herman, Nikolai Kirkby, Adrian Wiestner, Mars B van T' Veer, Geir E Tjønnfjord, Maija A Itälä-Remes, Eva Kimby, Mohammed Z Farooqui, Aaron Polliack, Ka Lung Wu, Jeanette K Doorduijn, Wendimagegn G Alemayehu, Shulamiet Wittebol, Tomas Kozak, Jan Walewski, Martine C J Abrahamse-Testroote, Marinus H J van Oers, Christian H Geisler, Carsten U Niemann
CD52 is a glycoprotein expressed on normal as well as leukemic immune cells and shed as soluble CD52 (sCD52). We studied sCD52 levels in three CLL cohorts: the 'early', the 'high-risk', and the 'ibrutinib-treated'. The 'high-risk' patients had significantly higher sCD52 levels than the 'early' patients. For the 'early' patients, high sCD52 levels were associated with a significantly shorter time to first treatment. Regarding prognostic factors, no clear correlations with stage, IGHV, or beta-2-microglobulin were found; in a cox multivariate analysis of the 'early' patients, sCD52 and IGHV both had independent prognostic value...
February 7, 2017: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/28278705/the-inhibitory-receptor-toll-interleukin-1r-8-tir8-il-1r8-sigirr-is-downregulated-in-chronic-lymphocytic-leukemia
#16
Maria Giovanna Vilia, Eleonora Fonte, Tania Veliz Rodriguez, Marta Tocchetti, Pamela Ranghetti, Lydia Scarfò, Nikos Papakonstantinou, Stavroula Ntoufa, Kostas Stamatopoulos, Paolo Ghia, Marta Muzio
Toll interleukin-1 receptor 8 (also known as TIR8, SIGIRR, or IL1R8) is a transmembrane receptor that inhibits inflammation. Accordingly, genetic inactivation of this protein exacerbates chronic inflammation and inflammation-associated tumors in mice. In particular, lack of TIR8 triggers leukemia progression in a mouse model of chronic lymphocytic leukemia (CLL), supporting its role as a novel tumor restrainer. The aim of this study was to measure the amount of TIR8 mRNA and protein in CLL cells, and to analyze its regulation of expression...
February 28, 2017: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/28278697/predicting-time-to-first-treatment-in-early-stage-cll-scores-values-and-comparative-prognostic-models
#17
Estella Matutes, Aaron Polliack
No abstract text is available yet for this article.
July 2017: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/28275912/mechanisms-of-resistance-to-targeted-therapies-in-chronic-lymphocytic-leukemia
#18
Francesca Arruga, Silvia Deaglio
Even if treatment options for Chronic Lymphocytic Leukemia (CLL) patients have changed dramatically in the past few years, with the approval of targeted therapeutic agents, the disease remains incurable. Beside intrinsic genetic features characterizing the leukemic cell, signals coming from the microenvironment have a key role in promoting cell survival and in protecting CLL cells from the action of drugs. Consequently, the identification of previously unrecognized genetic lesions is important in risk-stratification of CLL patients and is progressively becoming a critical tool for choosing the best therapeutic strategy...
March 9, 2017: Handbook of Experimental Pharmacology
https://www.readbyqxmd.com/read/28275031/nccn-guidelines-insights-chronic-lymphocytic-leukemia-small-lymphocytic-leukemia-version-1-2017
#19
William G Wierda, Andrew D Zelenetz, Leo I Gordon, Jeremy S Abramson, Ranjana H Advani, C Babis Andreadis, Nancy Bartlett, John C Byrd, Paolo Caimi, Luis E Fayad, Richard I Fisher, Martha J Glenn, Thomas M Habermann, Nancy Lee Harris, Francisco Hernandez-Ilizaliturri, Richard T Hoppe, Steven M Horwitz, Mark S Kaminski, Christopher R Kelsey, Youn H Kim, Susan Krivacic, Ann S LaCasce, Michael G Martin, Auayporn Nademanee, Pierluigi Porcu, Oliver Press, Rachel Rabinovitch, Nishitha Reddy, Erin Reid, Kenneth Roberts, Ayman A Saad, Erin D Snyder, Lubomir Sokol, Lode J Swinnen, Julie M Vose, Joachim Yahalom, Mary A Dwyer, Hema Sundar
Chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL) are different manifestations of the same disease and managed in much the same way. The advent of novel CD20 monoclonal antibodies led to the development of effective chemoimmunotherapy regimens. More recently, small molecule inhibitors targeting kinases involved in a number of critical signaling pathways and a small molecule inhibitor of the BCL-2 family of proteins have demonstrated activity for the treatment of patients with CLL/SLL. These NCCN Guidelines Insights highlight important updates to the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for CLL/SLL for the treatment of patients with newly diagnosed or relapsed/refractory CLL/SLL...
March 2017: Journal of the National Comprehensive Cancer Network: JNCCN
https://www.readbyqxmd.com/read/28271952/relapsed-chronic-lymphocytic-leukemia-retreated-with-rituximab-interim-results-of-the-perle-study
#20
Driss Chaoui, Sylvain Choquet, Laurence Sanhes, Béatrice Mahé, Maya Hacini, Olivier Fitoussi, Yazid Arkam, Hubert Orfeuvre, Marie-Sarah Dilhuydy, Marly Barry, Eric Jourdan, Brigitte Dreyfus, Adrian Tempescul, Stéphane Leprêtre, Aurélie Bardet, Pierre Leconte, Marc Maynadié, Alain Delmer
This prospective non-interventional study assessed the management of relapsed/refractory CLL after one or two treatments with rituximab, and retreatment with a rituximab-based regimen. An interim analysis was performed at the end of the induction period in 192 evaluable patients. Median age was 72 years [35-89], first relapse (55%), and second relapse (45%). Rituximab administered during first (68%), second (92%), or both treatment lines (20%). R-bendamustine administered in 56% of patients, R-purine analogs (21%), and R-alkylating agents (19%)...
June 2017: Leukemia & Lymphoma
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