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Richters transformation

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https://www.readbyqxmd.com/read/29316456/disease-characteristics-and-clinical-outcomes-in-patients-aged-less-than-40-with-chronic-lymphocytic-leukemia
#1
Bartlomiej M Getta, Sean Devlin, Jae H Park, Martin S Tallman, Ellin Berman
Outcomes in very young CLL patients (age ≤40) are not well characterized. We compared 71 consecutive patients aged ≤40 with 142 "older" matched patients >40 from our institution and used SEER database as an independent comparison group. Patients in the two age groups were diagnosed at similar Rai stage. At diagnosis, very young patients had a similar rate of adverse cytogenetics, IGHV mutation and ZAP70 expression and had lower beta-2-microglobulin and a lower incidence of second malignancies. There was no difference between the groups with respect to incidence of autoimmune manifestations, family history of lymphoma, time to initiation of CLL therapy, response to therapy, or Richter's transformation...
January 3, 2018: Leukemia Research
https://www.readbyqxmd.com/read/29296799/near-tetraploidy-is-associated-with-richter-transformation-in-chronic-lymphocytic-leukemia-patients-receiving-ibrutinib
#2
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
#3
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/29246803/venetoclax-for-chronic-lymphocytic-leukaemia-progressing-after-ibrutinib-an-interim-analysis-of-a-multicentre-open-label-phase-2-trial
#4
Jeffrey A Jones, Anthony R Mato, William G Wierda, Matthew S Davids, Michael Choi, Bruce D Cheson, Richard R Furman, Nicole Lamanna, Paul M Barr, Lang Zhou, Brenda Chyla, Ahmed Hamed Salem, Maria Verdugo, Rod A Humerickhouse, Jalaja Potluri, Steven Coutre, Jennifer Woyach, John C Byrd
BACKGROUND: Therapy targeting Bruton's tyrosine kinase (BTK) with ibrutinib has transformed the treatment of chronic lymphocytic leukaemia. However, patients who are refractory to or relapse after ibrutinib therapy have poor outcomes. Venetoclax is a selective, orally bioavailable inhibitor of BCL-2 active in previously treated patients with relapsed or refractory chronic lymphocytic leukaemia. In this study, we assessed the activity and safety of venetoclax in patients with chronic lymphocytic leukaemia who are refractory to or relapse during or after ibrutinib therapy...
December 12, 2017: Lancet Oncology
https://www.readbyqxmd.com/read/29235166/the-south-african-universal-preschool-year-a-case-study-of-policy-development-and-implementation
#5
L Richter, M-L Samuels
BACKGROUND: South Africa is the first sub-Saharan African country to legislate, fund and implement free preschool education. Human rights and restitution were at the forefront of the political struggle for democracy in South Africa. Levelling the playing fields by improving the school readiness of children disadvantaged by the racist policies of Apartheid is essential to the transformation of South African society. METHODS: A review of published and unpublished documents on Grade R was undertaken, and access and enrolment data come from the National Department of Basic Education's Education Management Information System (EMIS)...
January 2018: Child: Care, Health and Development
https://www.readbyqxmd.com/read/29211475/optimization-of-orally-bioavailable-enhancer-of-zeste-homolog-2-ezh2-inhibitors-using-ligand-and-property-based-design-strategies-identification-of-development-candidate-r-5-8-dichloro-7-methoxy-oxetan-3-yl-methyl-2-4-methoxy-6-methyl-2-oxo-1-2-dihydropyridin
#6
Pei-Pei Kung, Patrick Bingham, Alexei Brooun, Michael Collins, Ya-Li Deng, Dac Dinh, Connie Fan, Ketan S Gajiwala, Rita Grantner, Hovhannes J Gukasyan, Wenyue Hu, Buwen Huang, Robert Kania, Susan E Kephart, Cody Krivacic, Robert A Kumpf, Penney Khamphavong, Manfred Kraus, Wei Liu, Karen A Maegley, Lisa Nguyen, Shijian Ren, Dan Richter, Robert A Rollins, Neal Sach, Shikhar Sharma, John Sherrill, Jillian Spangler, Albert E Stewart, Scott Sutton, Sean Uryu, Dominique Verhelle, Hui Wang, Shuiwang Wang, Martin Wythes, Shuibo Xin, Shinji Yamazaki, Huichun Zhu, JinJiang Zhu, Luke Zehnder, Martin Edwards
A new series of lactam-derived EZH2 inhibitors was designed via ligand-based and physicochemical-property-based strategies to address metabolic stability and thermodynamic solubility issues associated with previous lead compound 1. The new inhibitors incorporated an sp3 hybridized carbon atom at the 7-position of the lactam moiety present in lead compound 1 as a replacement for a dimethylisoxazole group. This transformation enabled optimization of the physicochemical properties and potency compared to compound 1...
December 27, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29190672/first-in-human-phase-i-study-of-isth0036-an-antisense-oligonucleotide-selectively-targeting-transforming-growth-factor-beta-2-tgf-%C3%AE-2-in-subjects-with-open-angle-glaucoma-undergoing-glaucoma-filtration-surgery
#7
Norbert Pfeiffer, Bogomil Voykov, Giulia Renieri, Katharina Bell, Paul Richter, Melanie Weigel, Hagen Thieme, Barbara Wilhelm, Katrin Lorenz, Martin Feindor, Katja Wosikowski, Michel Janicot, Daniela Päckert, Regina Römmich, Carola Mala, Petra Fettes, Eugen Leo
PURPOSE: To evaluate the safety and tolerability of intravitreal ISTH0036, an antisense oligonucleotide selectively targeting transforming growth factor beta 2 (TGF-β2), in patients with primary open angle glaucoma (POAG) undergoing trabeculectomy (TE; glaucoma filtration surgery). METHODS: In this prospective phase I trial glaucoma patients scheduled for TE with mitomycin C (MMC) received a single intravitreal injection of ISTH0036 at the end of surgery in escalating total doses of 6...
2017: PloS One
https://www.readbyqxmd.com/read/29159711/treatment-of-richter-s-syndrome
#8
REVIEW
Adalgisa Condoluci, Davide Rossi
Based on the available literature, mostly derived from retrospective or non-randomized phase I or II studies, it is difficult to define an optimized treatment approach for patients developing Richter's syndrome (RS). Early recognition of chronic lymphocytic leukemia (CLL) patients presenting clinical features suspected for a transformation is useful to avoid exposing them to multiple lines of therapy that, being targeted to CLL progression, have poor efficacy against RS. Because of the low specificity (~ 50-60%) of clinical signs of RS (such as rapid and discordant bulky localized lymphadenopathies, elevated LDH levels, emergent physical deterioration, and/or fever in the absence of infection), a 18FDG PET/CT and a biopsy are recommended to confirm RS...
November 21, 2017: Current Treatment Options in Oncology
https://www.readbyqxmd.com/read/29146406/central-nervous-involvement-by-chronic-lymphocytic-leukaemia
#9
Dariusz Szczepanek, Ewa Wąsik-Szczepanek, Agnieszka Szymczyk, Małgorzata Wach, Maria Cioch, Monika Podhorecka, Ewelina Grywalska, Marek Hus
Inclusion of the central nervous system (CNS) in the course of chronic lymphocytic leukaemia (CLL) is rare. At the moment no risk factors or proven treatment methods are known. The disease is described both in its early phase and during its acceleration period, thus it has been suggested that there might be independent mechanisms influencing the development of this condition. As there are no unified diagnostic procedure algorithms each patient needs to be assessed individually. CLL can manifest mostly in elderly people, for whom a possibility of development of neurological disorders with their aetiology different from leukaemia, should also be taken into consideration...
November 1, 2017: Neurologia i Neurochirurgia Polska
https://www.readbyqxmd.com/read/29118007/pd-1-expression-and-clinical-pd-1-blockade-in-b-cell-lymphomas
#10
Zijun Y Xu-Monette, Jianfeng Zhou, Ken H Young
PD-1 blockade targeting the PD-1 immune checkpoint has demonstrated unprecedented clinical efficacy in the treatment of advanced cancers including hematologic malignancies. This article reviews the landscape of PD-1/PD-L1 expression and current PD-1 blockade immunotherapy trials in B-cell lymphomas. Most notably, in relapsed/refractory classical Hodgkin lymphoma, which frequently has increased PD-1+ tumor-infiltrating T cells, 9p24 genetic alteration and high PD-L1 expression, anti-PD-1 monotherapy has demonstrated remarkable objective response rates (ORR) of 65-87% and durable disease control in phase I/II clinical trials...
November 8, 2017: Blood
https://www.readbyqxmd.com/read/29063177/approach-to-richter-transformation-of-chronic-lymphocytic-leukemia-in-the-era-of-novel-therapies
#11
REVIEW
Maliha Khan, Rabbia Siddiqi, Philip A Thompson
Chronic lymphocytic leukemia (CLL) has a highly variable clinical course. About 2-10% of CLL patients develop aggressive histological transformation, most commonly to diffuse large B cell lymphoma (DLBCL), historically called Richter transformation (RT). Clinical features suggestive of RT include elevated LDH and non-specific symptoms such as fever, weight loss, and lymphadenopathy. 18-fluorodeoxyglucose (18-FDG) uptake is increased on PET scan (standardized uptake value max most commonly ≥ 10). PET/CT study can identify optimal site for excisional biopsy, which is the gold standard for RT diagnosis, as well as aid in disease staging and prognostication...
October 23, 2017: Annals of Hematology
https://www.readbyqxmd.com/read/29051895/chronic-lymphocytic-leukemia-a-rare-cause-of-pathological-fracture-of-the-femur
#12
Parita Soni, Nidhi Aggarwal, Anand Rai, Vivek Kumar, Kamholz Stephan, Yoon Taek, Kupfer Yizhak
The incidence rate of chronic lymphocytic leukemia (CLL) in the United States is approximately 0.005%; men are at slightly higher risk than women. Bony involvement or pathological fracture rarely occurs in CLL, and it may be the initial presentation. An 85-year-old woman presented with acute respiratory failure secondary to pneumonia. Symptomatology included dyspnea. She was found to have pathological fracture of the femur caused by CLL. The diagnosis of CLL had been made 6 years previously, but the patient had refused therapy...
October 2017: Journal of Investigative Medicine High Impact Case Reports
https://www.readbyqxmd.com/read/29031279/rotationally-inelastic-collisions-of-excited-nak-and-nacs-molecules-with-noble-gas-and-alkali-atom-perturbers
#13
J Jones, K Richter, T J Price, A J Ross, P Crozet, C Faust, R F Malenda, S Carlus, A P Hickman, J Huennekens
We report measurements of rate coefficients at T ≈ 600 K for rotationally inelastic collisions of NaK molecules in the 2(A)(1)Σ(+) electronic state with helium, argon, and potassium atom perturbers. Several initial rotational levels J between 14 and 44 were investigated. Collisions involving molecules in low-lying vibrational levels (v = 0, 1, and 2) of the 2(A)(1)Σ(+) state were studied using Fourier-transform spectroscopy. Collisions involving molecules in a higher vibrational level, v = 16, were studied using pump/probe, optical-optical double resonance spectroscopy...
October 14, 2017: Journal of Chemical Physics
https://www.readbyqxmd.com/read/29028194/temporal-scalability-of-dynamic-volume-data-using-mesh-compensated-wavelet-lifting
#14
Wolfgang Schnurrer, Niklas Pallast, Thomas Richter, Andre Kaup
Due to their high resolution, dynamic medical 2D+t and 3D+t volumes from computed tomography (CT) and magnetic resonance tomography (MR) reach a size which makes them very unhandy for teleradiologic applications. A lossless scalable representation offers the advantage of a down-scaled version which can be used for orientation or previewing, while the remaining information for reconstructing the full resolution is transmitted on demand. The wavelet transform offers the desired scalability. A very high quality of the lowpass sub-band is crucial in order to use it as a down-scaled representation...
October 12, 2017: IEEE Transactions on Image Processing: a Publication of the IEEE Signal Processing Society
https://www.readbyqxmd.com/read/29024083/stimulated-transitions-of-directed-nonequilibrium-self-assemblies
#15
Alexander A Steinschulte, Andrea Scotti, Khosrow Rahimi, Oleksii Nevskyi, Alex Oppermann, Sabine Schneider, Steffen Bochenek, Marie F Schulte, Karen Geisel, Felicitas Jansen, Andre Jung, Sabrina Mallmann, Roland Winter, Walter Richtering, Dominik Wöll, Ralf Schweins, Nicholas J Warren, Felix A Plamper
Near-equilibrium stimulus-responsive polymers have been used extensively to introduce morphological variations in dependence of adaptable conditions. Far-less-well studied are triggered transformations at constant conditions. These require the involvement of metastable states, which are either able to approach the equilibrium state after deviation from metastability or can be frozen on returning from nonequilibrium to equilibrium. Such functional nonequilibrium macromolecular systems hold great promise for on-demand transformations, which result in substantial changes in their material properties, as seen for triggered gelations...
October 10, 2017: Advanced Materials
https://www.readbyqxmd.com/read/28994094/novel-prognostic-molecular-factors-a-quantum-leap-in-the-field-of-chronic-lymphocytic-leukemia
#16
Ewelina Zakrzewska, Marta Pirog, Joanna Purkot, Krzysztof Giannopoulos
Cytogenetic lesions do not completely explain clinical heterogeneity of chronic lymphocytic leukemia (CLL). The 2016 revision of the World Health Organization classification 2008 introduced that molecular lesions of TP53, NOTCH1, SF3B1 and BIRC3 have potential clinical relevance and could be integrated into an updated risk profile. The negative clinical implications of TP53 disruptions are well constituted and patients with these mutations should be considered for novel, small molecule signal transduction inhibitors therapies...
October 10, 2017: Folia Histochemica et Cytobiologica
https://www.readbyqxmd.com/read/28975027/second-lung-malignancy-and-richter-syndrome-in-chronic-lymphocytic-leukemia-case-report-and-literature-review
#17
Ghassen Soussi, Selsabil Daboussi, Samira Mhamdi, Zied Moatemri, Hela Ghedira, Chiraz Aichaouia, Mohsen Khadhraoui, Faouzi El Mezni, Rezaik Cheikh
BACKGROUND: Chronic lymphocytic leukemia (CLL) is the most frequent lymphoproliferative disease. Transformation into Richter disease and occurrence of second malignancies involving the lungs are rare complications. The hallmarks of any thoracic involvement are still unknown. CASE PRESENTATION: We report a case of a 56-year-old male patient, with history of tobacco smoking, who presented with recurrent hemoptysis, fatigue and weight loss. Physical examination was normal except a slightly enlarged supraclavicular lymph node...
2017: Multidisciplinary Respiratory Medicine
https://www.readbyqxmd.com/read/28970470/nfat2-is-a-critical-regulator-of-the-anergic-phenotype-in-chronic-lymphocytic-leukaemia
#18
Melanie Märklin, Jonas S Heitmann, Alexander R Fuchs, Felicia M Truckenmüller, Michael Gutknecht, Stefanie Bugl, Sebastian J Saur, Juliane Lazarus, Ursula Kohlhofer, Leticia Quintanilla-Martinez, Hans-Georg Rammensee, Helmut R Salih, Hans-Georg Kopp, Michael Haap, Andreas Kirschniak, Lothar Kanz, Anjana Rao, Stefan Wirths, Martin R Müller
Chronic lymphocytic leukaemia (CLL) is a clonal disorder of mature B cells. Most patients are characterised by an indolent disease course and an anergic phenotype of their leukaemia cells, which refers to a state of unresponsiveness to B cell receptor stimulation. Up to 10% of CLL patients transform from an indolent subtype to an aggressive form of B cell lymphoma over time (Richter´s syndrome) and show a significantly worse treatment outcome. Here we show that B cell-specific ablation of Nfat2 leads to the loss of the anergic phenotype culminating in a significantly compromised life expectancy and transformation to aggressive disease...
October 2, 2017: Nature Communications
https://www.readbyqxmd.com/read/28949401/kronisk-myeloisk-leukemi-f%C3%A3-rebild-f%C3%A3-r-m%C3%A3-lstyrd-terapi-revolutionerande-%C3%A3-verlevnadsvinster-med-definitiv-bot-i-sikte-och-kraftigt-f%C3%A3-rb%C3%A3-ttrad-h%C3%A3-lsoekonomi
#19
Johan Richter, Leif Stenke
Chronic myeloid leukemia - a model disease for targeted therapy Chronic myeloid leukemia (CML) pioneered as the first human malignancy linked to a specific cytogenetic aberration (the Philadelphia chromosome), which led the way to specific targeted therapies with imatinib (Glivec) and later tyrosine kinase inhibitors (TKI). Continuous TKI administration, blocking the oncogenic fusion protein Bcr-Abl, has revolutionized the outcome of CML, transforming an almost uniformly deadly disease into a chronic disorder with a near to normal life expectancy for many patients...
September 21, 2017: Läkartidningen
https://www.readbyqxmd.com/read/28937430/cutaneous-richter-syndrome-mimicking-primary-cutaneous-cd4-positive-small-medium-t-cell-lymphoma-case-report-and-review-of-the-literature
#20
Miguel Rito, José Cabeçadas, Joaninha Costa Rosa, Mariana Cravo, Alistair Robson
Richter syndrome represents the transformation of chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma into an aggressive large B-cell lymphoma. Skin involvement is exceptionally rare, with <20 cases reported and its presence as the first presentation of CLL/small lymphocytic lymphoma, as an isolated skin lesion has never been described. Primary cutaneous CD4-positive small/medium T-cell lymphoma (CD4 PCSM-TCL) characteristically presents with a dense dermal infiltrate consisting primarily of small-/medium-sized pleomorphic T-cells and less than 30% large pleomorphic cells...
September 12, 2017: American Journal of Dermatopathology
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