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https://www.readbyqxmd.com/read/29468645/humoral-immune-failure-defined-by-immunoglobulin-class-and-immunoglobulin-g-subclass-deficiency-is-associated-with-shorter-treatment-free-and-overall-survival-in-chronic-lymphocytic-leukaemia
#1
Kyle R Crassini, Eva Zhang, Shalini Balendran, Jane A Freeman, O Giles Best, Cecily J Forsyth, Naomi J Mackinlay, Ping Han, William S Stevenson, Stephen P Mulligan
Immune dysfunction attributed to hypogammaglobulinaemia is common in chronic lymphocytic leukaemia (CLL) and infection is a major contributor to morbidity and mortality. A higher incidence of multiple immunoglobulin and immunoglobulin G (IgG) subclass deficiency was associated with more advanced disease (P < 0·001 and P < 0·001, respectively) in a cohort of 147 CLL patients. Multiple immunoglobulin and IgG subclass deficiency were significantly associated with shorter treatment-free survival (TFS) (P < 0·001 and P = 0·006, respectively)...
February 21, 2018: British Journal of Haematology
https://www.readbyqxmd.com/read/29467486/eric-recommendations-for-tp53-mutation-analysis-in-chronic-lymphocytic-leukemia-update-on-methodological-approaches-and-results-interpretation
#2
REVIEW
J Malcikova, E Tausch, D Rossi, L A Sutton, T Soussi, T Zenz, A P Kater, C U Niemann, D Gonzalez, F Davi, M Gonzalez Diaz, C Moreno, G Gaidano, K Stamatopoulos, R Rosenquist, S Stilgenbauer, P Ghia, S Pospisilova
In chronic lymphocytic leukemia (CLL), TP53 gene defects, due to deletion of the 17p13 locus and/or mutation(s) within the TP53 gene, are associated with resistance to chemoimmunotherapy and a particularly dismal clinical outcome. On these grounds, analysis of TP53 aberrations has been incorporated into routine clinical diagnostics to improve patient stratification and optimize therapeutic decisions. The predictive implications of TP53 aberrations have increasing significance in the era of novel targeted therapies, i...
February 2, 2018: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/29463802/clonal-dynamics-towards-the-development-of-venetoclax-resistance-in-chronic-lymphocytic-leukemia
#3
Carmen D Herling, Nima Abedpour, Jonathan Weiss, Anna Schmitt, Ron Daniel Jachimowicz, Olaf Merkel, Maria Cartolano, Sebastian Oberbeck, Petra Mayer, Valeska Berg, Daniel Thomalla, Nadine Kutsch, Marius Stiefelhagen, Paula Cramer, Clemens-Martin Wendtner, Thorsten Persigehl, Andreas Saleh, Janine Altmüller, Peter Nürnberg, Christian Pallasch, Viktor Achter, Ulrich Lang, Barbara Eichhorst, Roberta Castiglione, Stephan C Schäfer, Reinhard Büttner, Karl-Anton Kreuzer, Hans Christian Reinhardt, Michael Hallek, Lukas P Frenzel, Martin Peifer
Deciphering the evolution of cancer cells under therapeutic pressure is a crucial step to understand the mechanisms that lead to treatment resistance. To this end, we analyzed whole-exome sequencing data of eight chronic lymphocytic leukemia (CLL) patients that developed resistance upon BCL2-inhibition by venetoclax. Here, we report recurrent mutations in BTG1 (2 patients) and homozygous deletions affecting CDKN2A/B (3 patients) that developed during treatment, as well as a mutation in BRAF and a high-level focal amplification of CD274 (PD-L1) that might pinpoint molecular aberrations offering structures for further therapeutic interventions...
February 20, 2018: Nature Communications
https://www.readbyqxmd.com/read/29460654/cumulative-experience-and-long-term-follow-up-of-pentostatin-based-chemoimmunotherapy-trials-for-patients-with-chronic-lymphocytic-leukemia
#4
Neil E Kay, Betsy R LaPlant, Adam M Pettinger, Timothy G Call, Jose F Leis, Wei Ding, Sameer A Parikh, Michael J Conte, Deborah A Bowen, Tait D Shanafelt
BACKGROUND: 7 regimens of pentostatin based chemoimmunotherapy (CIT) for progressive previously untreated CLL primarily with long term follow-up to update both efficacy and toxicity. RESEARCH DESIGN AND METHODS: Prognostic markers including assessment of IGVH and FISH status were done on all. Response rates and 95% binomial confidence intervals were calculated for each regimen and in the combined cohort. Overall survival and treatment-free survival were evaluated using Kaplan-Meier methods...
February 20, 2018: Expert Review of Hematology
https://www.readbyqxmd.com/read/29459607/forgotten-encrusted-ureteral-stents-removal-multimodal-endourologic-approach
#5
P K Saha, M S Hossain, K C Ghosh, M S Alam, S Nabi, B K Saha, F H Pathan
Ureteral stent placement is a common procedure in urologic practice. Forgotten, encrusted D/J stents represent a difficult problem for urologists. The major complications are infection, impaired renal function, migration, encrustation, stone formation and multiple fragmentation of stent. A consensus on the best therapeutic approach is still lacking. Here we present our experience with endoscopic management of this challenging problem and discuss the multimodal endourologic approaches for treating forgotten, encrusted ureteral stents...
January 2018: Mymensingh Medical Journal: MMJ
https://www.readbyqxmd.com/read/29457831/low-t3-syndrome-as-a-predictor-of-poor-prognosis-in-chronic-lymphocytic-leukemia
#6
Rui Gao, Rui-Ze Chen, Yi Xia, Jin-Hua Liang, Li Wang, Hua-Yuan Zhu, Jia-Zhu Wu, Lei Fan, Jian-Yong Li, Tao Yang, Wei Xu
Low triiodothyronine (T3) state is associated with poor prognosis in critical acute and prolonged illness. However, the information on thyroid dysfunction and cancer is limited. The aim of our study was to evaluate the prognostic value of low T3 syndrome in chronic lymphocytic leukemia (CLL). Two hundred and fifty-eight patients with detailed thyroid hormone profile at CLL diagnosis were enrolled. Low T3 syndrome was defined by low free T3 (FT3) level accompanied by normal-to-low free tetraiodothyronine (FT4) and thyroid-stimulating hormone (TSH) levels...
February 19, 2018: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/29456888/an-observational-study-on-risk-of-secondary-cancers-in-chronic-myeloid-leukemia-patients-in-the-tki-era-in-the-united-states
#7
Vivek Kumar, Mohit Garg, Neha Chaudhary, Abhinav Binod Chandra
Introduction: The treatment with tyrosine kinase inhibitors (TKIs) has drastically improved the outcome of chronic myeloid leukemia (CML) patients. This study was conducted to examine the risk of secondary cancers (SCs) in the CML patients who were diagnosed and treated in the TKI era in the United States. Methods: The surveillance epidemiology and end results (SEER) database was used to identify CML patients who were diagnosed and received treatment during January 2002-December 2014...
2018: PeerJ
https://www.readbyqxmd.com/read/29455840/cardiac-surgery-outcomes-in-patients-with-chronic-lymphocytic-leukemia
#8
Yuanjia Zhu, Andrew J Toth, Ashley M Lowry, Eugene H Blackstone, Brian T Hill, Stephanie L Mick
BACKGROUND: Surgical outcomes of patients with chronic lymphocytic leukemia (CLL) undergoing cardiac surgery are limited. Our objectives were to investigate hospital morbidity and mortality after open cardiac surgery in CLL versus non-CLL patients. METHODS: From May 1995 to May 2015, 157 patients with CLL and 55,917 without and older than 47 years underwent elective cardiac surgery at Cleveland Clinic. By Rai criteria, 79 CLL patients (56%) were low risk (class 0), 13 (9...
February 15, 2018: Annals of Thoracic Surgery
https://www.readbyqxmd.com/read/29455639/role-of-bruton-s-tyrosine-kinase-in-b-cells-and-malignancies
#9
REVIEW
Simar Pal Singh, Floris Dammeijer, Rudi W Hendriks
Bruton's tyrosine kinase (BTK) is a non-receptor kinase that plays a crucial role in oncogenic signaling that is critical for proliferation and survival of leukemic cells in many B cell malignancies. BTK was initially shown to be defective in the primary immunodeficiency X-linked agammaglobulinemia (XLA) and is essential both for B cell development and function of mature B cells. Shortly after its discovery, BTK was placed in the signal transduction pathway downstream of the B cell antigen receptor (BCR). More recently, small-molecule inhibitors of this kinase have shown excellent anti-tumor activity, first in animal models and subsequently in clinical studies...
February 19, 2018: Molecular Cancer
https://www.readbyqxmd.com/read/29452670/what-is-the-optimal-management-of-older-cll-patients
#10
REVIEW
Jennifer A Woyach
CLL is the most common leukemia in older adults with a median age at diagnosis of 71. Therefore, management of patients with this disease must take into account the older age of most patients and consequences of this in terms of functional status and organ function. This review will discuss the management of CLL with regards to observation prior to the initiation of therapy, functional status, and initial treatment. We will discuss criteria for the initiation of therapy, and how initial therapy is different between older and younger patients...
March 2018: Best Practice & Research. Clinical Haematology
https://www.readbyqxmd.com/read/29452669/optimal-management-of-the-young-patient-cll-patient
#11
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/29444977/microenvironmental-regulation-of-the-il-23r-il-23-axis-overrides-chronic-lymphocytic-leukemia-indolence
#12
Giovanna Cutrona, Claudio Tripodo, Serena Matis, Anna Grazia Recchia, Carlotta Massucco, Marina Fabbi, Monica Colombo, Laura Emionite, Sabina Sangaletti, Alessandro Gulino, Daniele Reverberi, Rosanna Massara, Simona Boccardo, Daniela de Totero, Sandra Salvi, Michele Cilli, Mariavaleria Pellicanò, Martina Manzoni, Sonia Fabris, Irma Airoldi, Francesca Valdora, Silvano Ferrini, Massimo Gentile, Ernesto Vigna, Sabrina Bossio, Laura De Stefano, Angela Palummo, Giovanni Iaquinta, Martina Cardillo, Simonetta Zupo, Giannamaria Cerruti, Adalberto Ibatici, Antonino Neri, Franco Fais, Manlio Ferrarini, Fortunato Morabito
Although the progression of chronic lymphocytic leukemia (CLL) requires the cooperation of the microenvironment, the exact cellular and molecular mechanisms involved are still unclear. We investigated the interleukin (IL)-23 receptor (IL-23R)/IL-23 axis and found that circulating cells from early-stage CLL patients with shorter time-to-treatment, but not of those with a more benign course, expressed a defective form of the IL-23R complex lacking the IL-12Rβ1 chain. However, cells from both patient groups expressed the complete IL-23R complex in tissue infiltrates and could be induced to express the IL-12Rβ1 chain when cocultured with activated T cells or CD40L + cells...
February 14, 2018: Science Translational Medicine
https://www.readbyqxmd.com/read/29444501/quercetin-therapy-for-selected-patients-with-pim1-kinase-positive-chronic-lymphocytic-leukemia-small-lymphocytic-lymphoma-a-pilot-study
#13
Beverly W Baron, Michael J Thirman, Mihai C Giurcanu, Joseph M Baron
We reported that PIM1 kinase is expressed in the lymphocytes of patients with chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL). Quercetin, a naturally occurring flavonoid, is a dietary supplement and inhibits many kinases, including PIM1, in vitro. Under an Institutional Review Board-approved protocol, we performed an open-label, single-arm pilot study to evaluate the antitumor activity of quercetin in patients with CLL/SLL. Q-ForceTM chews were administered orally, 500 mg twice daily, for 3 months...
February 14, 2018: Acta Haematologica
https://www.readbyqxmd.com/read/29441498/cost-of-illness-of-japanese-patients-with-chronic-lymphocytic-leukemia-cll-and-budget-impact-of-the-market-introduction-of-ibrutinib
#14
Jörg Mahlich, Shinichiro Okamoto, Akiko Tsubota
BACKGROUND: Ibrutinib was introduced in Japan in 2016 as a new oral treatment option for patients with relapsed/refractory (RR) chronic lymphocytic leukemia (CLL). There is increasing interest from the Japanese government to assess economic aspects of new medical interventions, especially in the area of oncology. OBJECTIVE: We describe the treatment patterns of Japanese patients with CLL, estimate the cost of the disease from a health insurance perspective, and predict the budget impact of the introduction of ibrutinib...
September 2017: PharmacoEconomics Open
https://www.readbyqxmd.com/read/29440231/-ex-vivo-activity-of-cytotoxic-drugs-and-targeted-agents-in-small-intestinal-nets
#15
Kosmas Daskalakis, Olov Norlen, Andreas Karakatsanis, Per Hellman, Rolf Larsson, Peter Nygren, Peter Stalberg
Small intestinal endocrine tumours (SI-NETs) are generally considered resistant to systemic treatment. To date, predictive markers for drug activity are lacking. Tumour samples from 27 patients with SI-NETs were analyzed ex vivo for sensitivity to a panel of cytotoxic drugs and targeted agents using a short-term total cell kill assay. Samples of renal cancer, colorectal cancer (CRC), ovarian cancer, and chronic lymphocytic leukemia (CLL) were included for comparison. For the SI-NET subset, drug sensitivity was analyzed in relation to clinico-pathological variables and pre-treatment biomarkers...
February 12, 2018: Endocrine-related Cancer
https://www.readbyqxmd.com/read/29434893/bone-marrow-stromal-cells-enhance-the-survival-of-chronic-lymphocytic-leukemia-cells-by-regulating-hes-1-gene-expression-and-h3k27me3-demethylation
#16
Zhenshu Xu, Donglian Xiong, Jushun Zhang, Jingyan Zhang, Xiuli Chen, Zhizhe Chen, Rong Zhan
The majority of patients with chronic lymphocytic leukemia (CLL) are not cured by traditional chemotherapy. One possible explanation for this is that the microenvironment protects CLL cells from both spontaneous- and cytotoxic-mediated apoptosis. The present study was designed to investigate the mechanisms accounting for these effects, since this information is crucial to understanding CLL physiopathology and identifying potential treatment targets. The CLL cell line L1210 and primary CLL cells were cultured under different conditions: With serum, cyclophosphamide (CTX), or with monolayers and conditioned medium (CM) from the stromal cell line HESS-5...
February 2018: Oncology Letters
https://www.readbyqxmd.com/read/29428267/disseminated-cerebral-toxoplasmosis-in-a-patient-with-chronic-lymphocytic-leukemia
#17
Jordan Xu, Rod J Nault, Andres Maldonado-Naranjo, Leonardo A Frizon, Kuruvilla John, Katherine Holman, Sean J Nagel
Infections are one of the most common causes of mortality in immunocompromised patients. In patients diagnosed with hematologic malignancies, treatment with stem cell transplants (SCT) or T-cell suppressing chemotherapy increases the risk of central nervous system (CNS) infections, of which toxoplasmosis is the most common. We report the case of a 63 year-old woman with chronic lymphocytic leukemia (CLL) that presented with gait instability and visual changes. Intracranial lesions were noted on initial neuro-imaging...
February 7, 2018: Journal of Clinical Neuroscience: Official Journal of the Neurosurgical Society of Australasia
https://www.readbyqxmd.com/read/29427355/rituximab-cladribine-and-cyclophosphamide-rcc-induction-with-rituximab-maintenance-in-chronic-lymphocytic-leukemia-palg-cll4-ml21283-trial
#18
Tadeusz Robak, Jerzy Blonski, Aleksander Bartłomiej Skotnicki, Magdalena Piotrowska, Tomasz Wróbel, Justyna Rybka, Janusz Kłoczko, Łukasz Bołkun, Bożena Katarzyna Budziszewska, Urszula Walczak, Anatoly Uss, Marta Fidecka, Piotr Smolewski
OBJECTIVES: PALG CLL4 is the first, randomized, phase IIIb study with cladribine, cyclophosphamide and rituximab (RCC) induction and subsequent maintenance with rituximab in previously untreated chronic lymphocytic leukemia (CLL) patients. METHODS: The induction treatment consisted of six RCC cycles regimen. Patients with complete response (CR) or partial response (PR) after an induction phase were randomized into a maintenance arm with rituximab or an observational arm...
February 10, 2018: European Journal of Haematology
https://www.readbyqxmd.com/read/29423051/del17p-does-not-always-significantly-influence-the-survival-of-b-cell-chronic-lymphoproliferative-disorders
#19
Shuhua Yi, Zengjun Li, Dehui Zou, Wenjie Xiong, Heng Li, Rui Cui, Chengwen Li, Yuting Yan, Wei Liu, Rui Lv, Zhen Yu, Weiwei Chen, Yan Xu, Gang An, Huijun Wang, Kun Ru, Tao Cheng, Jianxiang Wang, Lugui Qiu
B-cell chronic lymphoproliferative disorders (B-CLPD) comprise several entities with indolent clinical manifestations but heterogeneous survival. Cytogenetic aberrations are now the standard prognostic predictors in chronic lymphocytic leukemia (CLL) but have been less investigated in other subtypes of B-CLPD. In this study, we detected cytogenetic aberrations by fluorescence in situ hybridization (FISH) in 875 B-CLPD patients, based on a panel probes locating at 13q14, 11q22, 17p13 and CEP12. We identified del17p acted as the independent adverse cytogenetic predictor for overall survival (OS) in CLL...
January 9, 2018: Oncotarget
https://www.readbyqxmd.com/read/29415938/-acquisition-of-igh-ccnd1-translocation-during-the-natural-disease-course-in-a-patient-with-chronic-lymphocytic-leukemia
#20
Kosuke Arai, Fumisato Takagi, Saeko Sonokawa, Sayaka Suzuki, Eisaku Ito, Kengo Takeuchi, Takashi Kumagai
A 69-year-old man visited a doctor because of systemic lymphadenopathy. Peripheral blood examination revealed leukocytosis, anemia, and decreased platelet count (WBC, 103,060/µl; lymph, 92.2%; Hb, 8.9 g/dl; and Plt, 4.1×10 4 /µl). Bone marrow biopsy revealed that approximately 70% of nucleated cells were small, mature lymphoid cells with positive immunostaining for CD5, CD20, and CD23. He was diagnosed with chronic lymphocytic leukemia (CLL). The IgH/CCND1 translocation and ATM locus loss in 20% and 95% peripheral cells, respectively, were detected by fluorescence in situ hybridization...
2018: [Rinshō Ketsueki] the Japanese Journal of Clinical Hematology
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