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Chronic lymphocytic leukemia

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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
#1
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
https://www.readbyqxmd.com/read/28935990/notch1-mutations-are-associated-with-high-cd49d-expression-in-chronic-lymphocytic-leukemia-link-between-the-notch1-and-the-nf-kb-pathways
#2
D Benedetti, E Tissino, F Pozzo, T Bittolo, C Caldana, C Perini, D Martorelli, V Bravin, T D'Agaro, F M Rossi, R Bomben, E Santinelli, F Zaja, G Pozzato, A Chiarenza, F Di Raimondo, G Del Poeta, D Rossi, G Gaidano, M Dal Bo, V Gattei, A Zucchetto
In chronic lymphocytic leukemia (CLL), stabilizing mutations of NOTCH1, affecting up to 10-15% of cases, have been associated to poor prognosis, disease progression and refractoriness to chemotherapy. NOTCH1 mutations are significantly overrepresented in trisomy 12 CLL, a disease subset frequently expressing CD49d, the α4 chain of the VLA-4 integrin, a well-known key regulator of microenviromental interactions and negative prognosticator in CLL. In the present study, by analysing a wide cohort of 1180 CLL, we observed a very strong association between the presence of NOTCH1 mutations and the expression of CD49d (P<0...
September 22, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28935694/cellular-kinetics-of-ctl019-in-relapsed-refractory-b-cell-acute-lymphoblastic-leukemia-and-chronic-lymphocytic-leukemia
#3
Karen Thudium Mueller, Shannon L Maude, David L Porter, Noelle Frey, Patricia Wood, Xia Han, Edward Waldron, Abhijit Chakraborty, Rakesh Awasthi, Bruce L Levine, J Joseph Melenhorst, Stephan A Grupp, Carl H June, Simon F Lacey
Tisagenlecleucel (CTL019) is an investigational immunotherapy that involves reprogramming a patient's own T cells with a transgene encoding a chimeric antigen receptor to identify and eliminate CD19-expressing cells. We previously reported that CTL019 achieved impressive clinical efficacy in patients with relapsed/refractory B-cell acute lymphoblastic leukemia (ALL) and chronic lymphocytic leukemia (CLL), including the expansion and persistence of CTL019 cells, which correlates with response to therapy. Here, we performed formal cellular kinetic analyses of CTL019 in a larger cohort of 103 patients treated with CTL019 in 2 different diseases (ALL and CLL)...
September 21, 2017: Blood
https://www.readbyqxmd.com/read/28931525/ectopic-ilt3-controls-bcr-dependent-activation-of-akt-in-b-cell-chronic-lymphocytic-leukemia
#4
Vanessa Zurli, Giuliana Wimmer, Francesca Cattaneo, Veronica Candi, Emanuele Cencini, Alessandro Gozzetti, Donatella Raspadori, Giuseppe Campoccia, Francesca Sanseviero, Monica Bocchia, Cosima Tatiana Baldari, Anna Kabanova
The high proportion of long-term non-progressors among chronic lymphocytic leukemia (CLL) patients suggests the existence of a regulatory network which restrains the proliferation of tumor B cells. The identification of molecular determinants composing such network is hence fundamental for our understanding of CLL pathogenesis. Based on our previous finding establishing a deficiency in the signaling adaptor p66Shc in CLL cells, we undertook to identify unique phenotypic traits caused by this defect. Here we show that a lack of p66Shc shapes the transcriptional profile of CLL cells and leads to an upregulation of the surface receptor ILT3, the immunoglobulin-like transcript 3 which is normally found on myeloid cells...
September 20, 2017: Blood
https://www.readbyqxmd.com/read/28926801/epidemiology-of-venous-thromboembolism-in-hematological-cancers-the-scandinavian-thrombosis-and-cancer-stac-cohort
#5
Inger Lise Gade, Sigrid Brækkan, Inger Anne Næss, John-Bjarne Hansen, Frits Rosendaal, Suzanne Cannegieter, Kim Overvad, Hilde Jensvoll, Jens Hammerstrøm, Olga Vikhammer Gran, Anne Tjønneland, Søren Risom Kristensen, Marianne Tang Severinsen
INTRODUCTION: Venous thromboembolism (VTE) is an important cause of morbidity and mortality in cancer patients, however the risk of VTE differs according to cancer type. Hematological cancers have varying phenotypes. Incidence rates (IR) of VTE in different hematological cancer types have not been investigated in a cancer-exposed subset of the general population. METHODS: In a population-based cohort, we estimated incidence rates of VTE among patients with six subtypes of hematological cancer and among age and sex matched reference subjects...
September 5, 2017: Thrombosis Research
https://www.readbyqxmd.com/read/28925785/risk-adjusted-therapy-in-chronic-lymphocytic-leukemia-a-phase-ii-cancer-trials-ireland-ctrial-ie-icorg-07-01-study-of-fludarabine-cyclophosphamide-and-rituximab-therapy-evaluating-response-adapted-abbreviated-frontline-therapy-with-fcr-in-non-del-17p-cll
#6
Niamh Appleby, David O'Brien, Fiona M Quinn, Liam Smyth, Johanna Kelly, Imelda Parker, Kathleen Scott, Mary R Cahill, Gerard Crotty, Helen Enright, Brian Hennessy, Andrew Hodgson, Maeve Leahy, Hilary O'Leary, Michael O'Dwyer, Amjad Hayat, Elisabeth A Vandenberghe
Minimal residual disease negative complete response (MRD-negative CR) provides an early marker for time to treatment failure (TTF) in CLL treated with fludarabine, cyclophosphamide, and rituximab (FCR). MRD was assessed after four FCR cycles (FCR4); MRD-negative CR patients discontinued treatment. Fifty-two patients (35M; 17F) were enrolled. Eighteen (18/52; 34.6%) patients reached MRD-negative CR after FCR4 and 29/52 (55.8%) were MRD-negative CR at end of treatment (EOT). Median TTF was 71.1 months (95% CI 61...
September 19, 2017: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/28925330/preoperative-positron-emission-tomography-for-node-positive-head-and-neck-cutaneous-squamous-cell-carcinoma
#7
Nir Hirshoren, Elizabeth Olayos, Alan Herschtal, Aravind S Ravi Kumar, David E Gyorki
Objectives Surgery is the primary treatment modality for node-positive cutaneous squamous cell carcinoma of the head and neck with no distant disease (HNcSCC-M0). The role of preoperative positron emission tomography/computed tomography (PET/CT) scan for these patients is unclear. We compared preoperative PET/CT with final histopathology among patients undergoing lymphadenectomy and/or parotidectomy for HNcSCC-M0. Study Design Case series with chart review. Setting Single Australian center. Subjects and Methods Investigation included disease parameters and preoperative CT and PET/CT findings of 64 patients with node-positive HNcSCC without distant metastatic disease...
September 1, 2017: Otolaryngology—Head and Neck Surgery
https://www.readbyqxmd.com/read/28924243/refined-karyotype-based-prognostic-stratification-of-chronic-lymphocytic-leukemia-with-a-low-and-very-low-risk-genetic-profile
#8
I Del Giudice, G M Rigolin, S Raponi, L Cafforio, C Ilari, W Jiguang, M Bordyuh, A Piciocchi, M Marinelli, M Nanni, S Tavolaro, M Filetti, A Bardi, E Tammiso, E Volta, M Negrini, E Saccenti, F R Mauro, D Rossi, G Gaidano, A Guarini, R Rabadan, A Cuneo, R Foà
Leukemia accepted article preview online, 19 September 2017. doi:10.1038/leu.2017.292.
September 19, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28924241/clinical-impact-of-the-subclonal-architecture-and-mutational-complexity-in-chronic-lymphocytic-leukemia
#9
F Nadeu, G Clot, J Delgado, D Martín-García, T Baumann, I Salaverria, S Beà, M Pinyol, P Jares, A Navarro, H Suárez-Cisneros, M Aymerich, M Rozman, N Villamor, D Colomer, M González, M Alcoceba, M J Terol, B Navarro, E Colado, Á R Payer, X S Puente, C López-Otín, A López-Guillermo, A Enjuanes, E Campo
Genome studies of chronic lymphocytic leukemia (CLL) have revealed the remarkable subclonal heterogeneity of the tumors, but the clinical implications of this phenomenon are not well known. We assessed the mutational status of 28 CLL driver genes by deep-targeted next-generation sequencing and copy number alterations (CNA) in 406 previously untreated patients and 48 sequential samples. We detected small subclonal mutations (0.6-25% of cells) in nearly all genes (26/28), and they were the sole alteration in 22% of the mutated cases...
September 19, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28923920/microrna-dysregulation-to-identify-therapeutic-target-combinations-for-chronic-lymphocytic-leukemia
#10
Laura Z Rassenti, Veronica Balatti, Emanuela M Ghia, Alexey Palamarchuk, Luisa Tomasello, Paolo Fadda, Yuri Pekarsky, George F Widhopf, Thomas J Kipps, Carlo M Croce
Loss of miR-15/16 is the most common genetic lesion in chronic lymphocytic leukemia (CLL), promoting overexpression of BCL2, which factors in leukemia pathogenesis. Indeed, an inhibitor of Bcl2, venetoclcax, is highly active in the treatment of patients with CLL. However, single-agent venetoclcax fails to eradicate minimal residual disease in most patients. Accordingly, we were interested in other genes that may be regulated by miR-15/16, which may target other drivers in CLL. We found that miR-15/16 targets ROR1, which encodes an onco-embryonic surface protein expressed on the CLL cells of over 90% of patients, but not on virtually all normal postpartum tissues...
September 18, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28921505/nfatc1-activation-by-dna-hypomethylation-in-chronic-lymphocytic-leukemia-correlates-with-clinical-staging-and-can-be-inhibited-by-ibrutinib
#11
Christine Wolf, Angela Garding, Katharina Filarsky, Jasmin Bahlo, Sandra Robrecht, Natalia Becker, Manuela Zucknick, Arefeh Rouhi, Anja Weigel, Rainer Claus, Dieter Weichenhan, Barbara Eichhorst, Kirsten Fischer, Michael Hallek, Florian Kuchenbauer, Christoph Plass, Hartmut Döhner, Stephan Stilgenbauer, Peter Lichter, Daniel Mertens
B cell receptor (BCR) signaling is key for survival of chronic lymphocytic leukemia (CLL) cells, and BCR signaling inhibitors are clinically active. However, relapse and resistance to treatment require novel treatment options. In order to detect novel candidate therapeutic targets, we performed a genome-wide DNA methylation screen with custom arrays and identified aberrant promoter DNA methylation in 2192 genes. The transcription factor NFATC1 that is a downstream effector of BCR signaling was among the top hypomethylated genes and was concomitantly transcriptionally upregulated in CLL...
September 18, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/28919818/standard-of-care-and-direct-medical-costs-of-the-treatment-of-chronic-lymphocytic-leukemia-among-the-adult-population-in-ukraine-russia-and-kazakhstan-data-from-the-leukospect-study
#12
Averyan Vasylyev, Valentina Molostvova, Boris A Rebrov, Janina Makarova, Andrey Zaritskey, Vadim Ptushkin, Raigul Ramazanova, Yuriy Popovych, Orest Tsyapka, Evgeny Pashanov
PURPOSE: The LEUKOSPECT study aimed to describe health service utilization and to estimate the direct medical costs (DMCs) of chronic lymphocytic leukemia (CLL) in 2013 in the adult population of three post-Soviet countries - Russia, Ukraine, and Kazakhstan. As oncologic medical care is provided by federal state-owned, specialized medical institutions, the cost estimation in this study primarily informs from a state budget perspective. Patients' contributions to medical costs were not included in the cost evaluation...
2017: Cancer Management and Research
https://www.readbyqxmd.com/read/28918689/chronic-lymphocytic-leukemia-is-becoming-more-complex-how-to-define-complex-karyotype
#13
Natalia Kreinitz, Aaron Polliack, Tamar Tadmor
No abstract text is available yet for this article.
September 18, 2017: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/28915641/reevaluation-of-atr-signaling-in-primary-resting-chronic-lymphocytic-leukemia-cells-evidence-for-pro-survival-or-pro-apoptotic-function
#14
Maxime Beyaert, Eliza Starczewska, Ana Cristina González Pérez, Nicolas Vanlangendonck, Pascale Saussoy, Gaëlle Tilman, Anne De Leener, Marie-Christiane Vekemans, Eric Van Den Neste, Françoise Bontemps
ATM, primarily activated by DNA double-strand breaks, and ATR, activated by single-stranded DNA, are master regulators of the cellular response to DNA damage. In primary chronic lymphocytic leukemia (CLL) cells, ATR signaling is considered to be switched off due to ATR downregulation. Here, we hypothesized that ATR, though expressed at low protein level, could play a role in primary resting CLL cells after genotoxic stress. By investigating the response of CLL cells to UV-C irradiation, a prototypical activator of ATR, we could detect phosphorylation of ATR at Thr-1989, a marker for ATR activation, and also observed that selective ATR inhibitors markedly decreased UV-C-induced phosphorylation of ATR targets, including H2AX and p53...
August 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28905668/the-impact-of-agent-orange-exposure-on-prognosis-and-management-in-patients-with-chronic-lymphocytic-leukemia-a-national-veteran-affairs-tumor-registry-study
#15
Craig Mescher, David Gilbertson, Nicole M Randall, Gobind Tarchand, Julie Tomaska, Lisa Baumann Kreuziger, Vicki A Morrison
Exposure to Agent Orange (AO) has been associated with the development of chronic lymphocytic leukemia (CLL). We performed a retrospective study of 2052 Vietnam veterans identified in the National VA Tumor Registry to assess the impact of AO exposure on CLL prognosis, treatment and survival. Prognostic factors did not differ based on exposure. Veterans exposed to AO were diagnosed younger (63.2 vs. 70.5 years, p < .0001) and had longer overall survival (median not reached vs. 91 months, p < .001)...
September 14, 2017: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/28903739/evolving-dna-methylation-and-gene-expression-markers-of-b-cell-chronic-lymphocytic-leukemia-are-present-in-pre-diagnostic-blood-samples-more-than-10%C3%A2-years-prior-to-diagnosis
#16
Panagiotis Georgiadis, Irene Liampa, Dennie G Hebels, Julian Krauskopf, Aristotelis Chatziioannou, Ioannis Valavanis, Theo M C M de Kok, Jos C S Kleinjans, Ingvar A Bergdahl, Beatrice Melin, Florentin Spaeth, Domenico Palli, R C H Vermeulen, J Vlaanderen, Marc Chadeau-Hyam, Paolo Vineis, Soterios A Kyrtopoulos
BACKGROUND: B-cell chronic lymphocytic leukemia (CLL) is a common type of adult leukemia. It often follows an indolent course and is preceded by monoclonal B-cell lymphocytosis, an asymptomatic condition, however it is not known what causes subjects with this condition to progress to CLL. Hence the discovery of prediagnostic markers has the potential to improve the identification of subjects likely to develop CLL and may also provide insights into the pathogenesis of the disease of potential clinical relevance...
September 13, 2017: BMC Genomics
https://www.readbyqxmd.com/read/28903342/patients-with-chronic-lymphocytic-leukemia-and-complex-karyotype-show-an-adverse-outcome-even-in-absence-of-tp53-atm-fish-deletions
#17
Anna Puiggros, Rosa Collado, Maria José Calasanz, Margarita Ortega, Neus Ruiz-Xivillé, Alfredo Rivas-Delgado, Elisa Luño, Teresa González, Blanca Navarro, MaDolores García-Malo, Alberto Valiente, José Ángel Hernández, María Teresa Ardanaz, María Ángeles Piñan, María Laura Blanco, María Hernández-Sánchez, Ana Batlle-López, Rocío Salgado, Marta Salido, Ana Ferrer, Pau Abrisqueta, Eva Gimeno, Eugènia Abella, Christelle Ferrá, María José Terol, Francisco Ortuño, Dolors Costa, Carol Moreno, Félix Carbonell, Francesc Bosch, Julio Delgado, Blanca Espinet
Genomic complexity identified by chromosome banding analysis (CBA) predicts a worse clinical outcome in CLL patients treated either with standard or new treatments. Herein, we analyzed the clinical impact of complex karyotypes (CK) with or without high-risk FISH deletions (ATM and/or TP53, HR-FISH) in a cohort of 1045 untreated MBL/CLL patients. In all, 99/1045 (9.5%) patients displayed a CK. Despite ATM and TP53 deletions were more common in CK (25% vs 7%; P < 0.001; 40% vs 5%; P < 0.001, respectively), only 44% (40/90) patients with TP53 deletions showed a CK...
August 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28901789/cardiac-side-effects-of-bruton-tyrosine-kinase-btk-inhibitors
#18
Chloe Pek Sang Tang, Julie McMullen, Constantine Tam
The development of bruton tyrosine kinase inhibitors (BTKi) has been a significant advancement in the treatment of chronic lymphocytic leukemia and related B-cell malignancies. As experience in using ibrutinib increased, the first drug to be licensed in its class, atrial fibrillation (AF) emerged as an important side effect. The intersection between BTKi therapy for B-cell malignancies and AF represents a complex area of management with scant evidence for guidance. Consideration needs to be taken regarding the interplay of increased bleeding risk versus thromboembolic complications of AF, drug interactions between ibrutinib and anticoagulants and antiarrhythmic agents, and the potential for other, as yet seldom reported cardiac side effects...
September 13, 2017: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/28900606/lymphocyte-recovery-is-an-independent-predictor-of-relapse-in-allogeneic-hematopoietic-cell-transplantation-recipients-for-acute-leukemia
#19
Moussab Damlaj, Samer Ghazi, Walid Mashaqbeh, Gamal Gmati, Hend Salama, Khadega A Abuelgasim, Mushtaq Rather, Ali Hajeer, Mohsen Al-Zahrani, Abdul-Rahman Jazieh, Ayman Alhejazi, Ahmed Alaskar
AIM: To examine the optimal absolute lymphocyte count (ALC) cut-off utilizing receiver operator characteristics (ROC) in addition to graft characteristics associated with early ALC recovery. METHODS: Patients who received T-cell replete peripheral hematopoietic cell transplantation (HCT) for acute leukemia were identified. ALC cut-off was established using ROC analysis and subsequently the cohort was stratified. Time to endpoint analysis and cox regression modelling was computed to analyze outcomes...
August 24, 2017: World Journal of Transplantation
https://www.readbyqxmd.com/read/28899929/pathogen-specific-b-cell-receptors-drive-chronic-lymphocytic-leukemia-by-light-chain-dependent-cross-reaction-with-autoantigens
#20
Nereida Jiménez de Oya, Marco De Giovanni, Jessica Fioravanti, Rudolf Übelhart, Pietro Di Lucia, Amleto Fiocchi, Stefano Iacovelli, Dimitar G Efremov, Federico Caligaris-Cappio, Hassan Jumaa, Paolo Ghia, Luca G Guidotti, Matteo Iannacone
Several lines of evidence indirectly suggest that antigenic stimulation through the B-cell receptor (BCR) supports chronic lymphocytic leukemia (CLL) development. In addition to self-antigens, a number of microbial antigens have been proposed to contribute to the selection of the immunoglobulins expressed in CLL. How pathogen-specific BCRs drive CLL development remains, however, largely unexplored. Here, we utilized mouse models of CLL pathogenesis to equip B cells with virus-specific BCRs and study the effect of antigen recognition on leukemia growth...
September 12, 2017: EMBO Molecular Medicine
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