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https://www.readbyqxmd.com/read/28632812/systemic-interferon-alfa-injections-for-the-treatment-of-a-giant-orf
#1
Sumeyre Seda Ertekin, Mehmet Salih Gurel, Aslı Vefa Turgut Erdemir, Cem Leblebici
Orf is a zoonotic infection caused by a parapoxvirus and is endemic in sheep and goats. It may be transmitted to humans by direct contact with infected animals. We report a case of a giant orf in a patient with chronic lymphocytic leukemia (CLL), which proliferated dramatically after surgical excision and resolved after systemic interferon alfa-2a injections.
May 2017: Cutis; Cutaneous Medicine for the Practitioner
https://www.readbyqxmd.com/read/28628003/clinical-effectiveness-and-cost-effectiveness-results-from-the-randomised-phase-iib-trial-in-previously-untreated-patients-with-chronic-lymphocytic-leukaemia-to-compare-fludarabine-cyclophosphamide-and-rituximab-with-fludarabine-cyclophosphamide-mitoxantrone
#2
Dena R Howard, Talha Munir, Lucy McParland, Andy C Rawstron, Anna Chalmers, Walter M Gregory, John L O'Dwyer, Alison Smith, Roberta Longo, Abraham Varghese, Alexandra Smith, Peter Hillmen
BACKGROUND: The conventional frontline therapy for fit patients with chronic lymphocytic leukaemia (CLL) is fludarabine, cyclophosphamide and rituximab (FCR). Rituximab (Mabthera(®), Roche Products Ltd) targets the CD20 antigen, which is expressed at low levels in CLL. The standard dose of rituximab in CLL (375 mg/m(2) in cycle 1 and 500 mg/m(2) in cycles 2-6) was selected based on toxicity data only. Small doses of rituximab (as low as 20 mg) have biological activity in CLL, with an immediate reduction in circulating CLL cells and down-regulation of CD20...
May 2017: Health Technology Assessment: HTA
https://www.readbyqxmd.com/read/28627951/the-safety-of-bruton-s-tyrosine-kinase-inhibitors-for-the-treatment-of-chronic-lymphocytic-leukemia
#3
Phu N Tran, Susan O'Brien
The approval of ibrutinib has revolutionized the therapeutic landscape of chronic lymphocytic leukemia (CLL). Currently ibrutinib is indicated for patients that are both treatment naïve as well as those with relapsed CLL. Ibrutinib is generally well-tolerated with durable responses that improve over time in most patients. Important toxicities include atrial fibrillation and bleeding. Areas Cover: This review covers the pharmacokinetics, pharmacodynamics, safety and efficacy of ibrutinib in the treatment of CLL...
June 19, 2017: Expert Opinion on Drug Safety
https://www.readbyqxmd.com/read/28619982/jak1-2-and-bcl2-inhibitors-synergize-to-counteract-bone-marrow-stromal-cell-induced-protection-of-aml
#4
Riikka Karjalainen, Tea Pemovska, Mihaela Popa, Minxia Liu, Komal K Javarappa, Muntasir M Majumder, Bhagwan Yadav, David Tamborero, Jing Tang, Dmitrii Bychkov, Mika Kontro, Alun Parsons, Minna Suvela, Mireia Mayoral Safont, Kimmo Porkka, Tero Aittokallio, Olli Kallioniemi, Emmet McCormack, Bjørn T Gjertsen, Krister Wennerberg, Jonathan Knowles, Caroline A Heckman
The bone marrow (BM) provides a protective microenvironment to support the survival of leukemic cells and influence their response to therapeutic agents. In acute myeloid leukemia (AML), the high rate of relapse may in part be due to the inability of current treatment to effectively overcome the protective influence of the BM niche. To better understand the impact of the BM microenvironment on drug responses in AML, we conducted a comprehensive evaluation of 304 inhibitors, including approved and investigational agents, comparing ex vivo responses of primary AML cells in BM stroma-derived and standard culture conditions...
June 15, 2017: Blood
https://www.readbyqxmd.com/read/28614781/cell-lines-generated-from-a-chronic-lymphocytic-leukemia-mouse-model-exhibit-constitutive-btk-and-akt-signaling
#5
Simar Pal Singh, Saravanan Y Pillai, Marjolein J W de Bruijn, Ralph Stadhouders, Odilia B J Corneth, Henk Jan van den Ham, Alice Muggen, Wilfred van IJcken, Erik Slinger, Annemieke Kuil, Marcel Spaargaren, Arnon P Kater, Anton W Langerak, Rudi W Hendriks
Chronic lymphocytic leukemia (CLL) is characterized by the accumulation of mature CD5+ B cells in blood. Spontaneous apoptosis of CLL cells in vitro has hampered in-depth investigation of CLL pathogenesis. Here we describe the generation of three monoclonal mouse cell lines, EMC2, EMC4 and EMC6, from the IgH.TEμ CLL mouse model based on sporadic expression of SV40 large T antigen. The cell lines exhibit a stable CD5+CD43+IgM+CD19+ CLL phenotype in culture and can be adoptively transferred into Rag1-/- mice...
May 26, 2017: Oncotarget
https://www.readbyqxmd.com/read/28605616/managing-patients-with-tp53-deficient-chronic-lymphocytic-leukemia
#6
Jennifer Edelmann, John G Gribben
Patients with chronic lymphocytic leukemia (CLL) having a chromosomal loss on the short arm of chromosome 17 including the TP53 gene locus (17p deletion) and/or having mutations in TP53 have a short overall survival and, until recently, limited treatment options. The recent introduction of two novel substance classes, B-cell receptor inhibitors and BH3 mimetics, into CLL treatment has provided enormous clinical progress in this previously difficult-to-treat patient subgroup characterized by high risk for treatment failure with standard chemoimmunotherapy and rapid disease progression...
June 2017: Journal of Oncology Practice
https://www.readbyqxmd.com/read/28603911/cd11c-expression-in-chronic-lymphocytic-leukemia-revisited-related-with-complications-and-survival
#7
E G Umit, M Baysal, Y Durmus, A M Demir
INTRODUCTION: Chronic lymphocytic leukemia (CLL) is a disorder of mature but dysfunctional monoclonal B cells. Microenvironment, antigenic stimulation and genetical mutations are demonstrated in etiopathogenesis. We aimed to evaluate the expression of CD11c in patients with CLL and its possible clinical significance. METHODS: Data of 259 patients with CLL between 2010 and 2016 in Trakya University Faculty of Medicine, including age at diagnosis, sex, whole blood count, stage, percentage of CLL cells in bone marrow, line of treatments, development of Richter's transformation and secondary tumors, autoimmune complications, IgG level, prognostic cytogenetic analysis, and length of survival were recorded from files...
June 12, 2017: International Journal of Laboratory Hematology
https://www.readbyqxmd.com/read/28598442/distinct-homotypic-b-cell-receptor-interactions-shape-the-outcome-of-chronic-lymphocytic-leukaemia
#8
Claudia Minici, Maria Gounari, Rudolf Übelhart, Lydia Scarfò, Marcus Dühren-von Minden, Dunja Schneider, Alpaslan Tasdogan, Alabbas Alkhatib, Andreas Agathangelidis, Stavroula Ntoufa, Nicholas Chiorazzi, Hassan Jumaa, Kostas Stamatopoulos, Paolo Ghia, Massimo Degano
Cell-autonomous B-cell receptor (BcR)-mediated signalling is a hallmark feature of the neoplastic B lymphocytes in chronic lymphocytic leukaemia (CLL). Here we elucidate the structural basis of autonomous activation of CLL B cells, showing that BcR immunoglobulins initiate intracellular signalling through homotypic interactions between epitopes that are specific for each subgroup of patients with homogeneous clinicobiological profiles. The molecular details of the BcR-BcR interactions apparently dictate the clinical course of disease, with stronger affinities and longer half-lives in indolent cases, and weaker, short-lived contacts mediating the aggressive ones...
June 9, 2017: Nature Communications
https://www.readbyqxmd.com/read/28592762/chronic-lymphocytic-leukemia-pathophysiology-and-current-therapy
#9
Jun Takizawa
Chronic lymphocytic leukemia (CLL) is the most frequent adult leukemia in western countries, but it is rare in Japan. Several mutations have been identified in patients with CLL using next-generation sequencing, but disease-specific mutations were not found. Some mutations, such as those in TP53, NOTCH1, SF3B, and BIRC3 are useful for risk stratification and prognosis prediction in patients with CLL. Strategies for treating CLL are rapidly evolving, with targeted agents such as the B-cell receptor signaling pathway inhibitors (ibrutinib, idelalisib), novel anti-CD20 monoclonal antibody (obinutuzumab), and Bcl-2 inhibitor (venetoclax) being approved by the US Food and Drug Administration...
2017: [Rinshō Ketsueki] the Japanese Journal of Clinical Hematology
https://www.readbyqxmd.com/read/28588833/obinutuzumab-induced-serum-sickness-following-salvage-therapy-for-chronic-lymphocytic-leukemia
#10
Julie Saba, Aaron C Logan
The incidence of serum sickness following treatment of CLL with obinutuzumab has not been fully characterized, but is likely rare. Consideration should be given to this diagnosis in appropriate circumstances so that effective corticosteroid therapy can be initiated to alleviate inflammatory symptoms and organ dysfunction in a timely manner.
June 2017: Clinical Case Reports
https://www.readbyqxmd.com/read/28586310/effective-control-of-acute-myeloid-leukaemia-and-acute-lymphoblastic-leukaemia-progression-by-telomerase-specific-adoptive-t-cell-therapy
#11
Sara Sandri, Francesco De Sanctis, Alessia Lamolinara, Federico Boschi, Ornella Poffe, Rosalinda Trovato, Alessandra Fiore, Sara Sartori, Andrea Sbarbati, Attilio Bondanza, Simone Cesaro, Mauro Krampera, Maria T Scupoli, Michael I Nishimura, Manuela Iezzi, Silvia Sartoris, Vincenzo Bronte, Stefano Ugel
Telomerase (TERT) is a ribonucleoprotein enzyme that preserves the molecular organization at the ends of eukaryotic chromosomes. Since TERT deregulation is a common step in leukaemia, treatments targeting telomerase might be useful for the therapy of hematologic malignancies. Despite a large spectrum of potential drugs, their bench-to-bedside translation is quite limited, with only a therapeutic vaccine in the clinic and a telomerase inhibitor at late stage of preclinical validation. We recently demonstrated that the adoptive transfer of T cell transduced with an HLA-A2-restricted T-cell receptor (TCR), which recognize human TERT with high avidity, controls human B-cell chronic lymphocytic leukaemia (B-CLL) progression without severe side-effects in humanized mice...
May 23, 2017: Oncotarget
https://www.readbyqxmd.com/read/28580841/safety-and-efficacy-of-ofatumumab-in-chronic-lymphocytic-leukemia-a-systematic-review-and-meta-analysis
#12
Yougen Wu, Yang Wang, Yuting Gu, Ju Xia, Xiaoyang Kong, Qingqing Qian, Yang Hong
OBJECTIVES: Increasing numbers of clinical studies have been carried out to investigate the therapeutic effect of Ofatumumab for patients with chronic lymphocytic leukemia (CLL) but no studies have yet reported a pooled estimate of the treatment effect. We performed a meta-analysis of evidence from 13 clinical trials to assess effectiveness and safety of Ofatumumab-based therapy in patients with CLL. METHODS: Relevant publications from PubMed, Web of Science, Embase, and ClinicalTrials...
June 3, 2017: Hematology (Amsterdam, Netherlands)
https://www.readbyqxmd.com/read/28573505/comparative-efficacy-of-ibrutinib-versus-obinutuzumab%C3%A2-%C3%A2-chlorambucil-in-first-line-treatment-of-chronic-lymphocytic-leukemia-a-matching-adjusted-indirect-comparison
#13
Suzy Van Sanden, Simona Baculea, Joris Diels, Sarah Cote
INTRODUCTION: Ibrutinib (ibr) monotherapy and the combination of obinutuzumab plus chlorambucil (obi) are approved for previously untreated chronic lymphocytic leukemia (CLL). No trials directly comparing their efficacy are available. Therefore a matching-adjusted indirect comparison (MAIC) was performed to provide insight into their relative efficacy in terms of progression-free survival (PFS) and overall survival (OS). MAIC attempts to adjust for between-trial differences in factors known or suspected to influence treatment effects, to minimize bias...
June 1, 2017: Advances in Therapy
https://www.readbyqxmd.com/read/28572861/genome-wide-dna-methylation-profiling-integrated-with-gene-expression-profiling-identifies-pax9-as-a-novel-prognostic-marker-in-chronic-lymphocytic-leukemia
#14
Lata Rani, Nitin Mathur, Ritu Gupta, Ajay Gogia, Gurvinder Kaur, Jaspreet Kaur Dhanjal, Durai Sundar, Lalit Kumar, Atul Sharma
BACKGROUND: In chronic lymphocytic leukemia (CLL), epigenomic and genomic studies have expanded the existing knowledge about the disease biology and led to the identification of potential biomarkers relevant for implementation of personalized medicine. In this study, an attempt has been made to examine and integrate the global DNA methylation changes with gene expression profile and their impact on clinical outcome in early stage CLL patients. RESULTS: The integration of DNA methylation profile (n = 14) with the gene expression profile (n = 21) revealed 142 genes as hypermethylated-downregulated and; 62 genes as hypomethylated-upregulated in early stage CLL patients compared to CD19+ B-cells from healthy individuals...
2017: Clinical Epigenetics
https://www.readbyqxmd.com/read/28567239/bendamustine-and-its-role-in-the-treatment-of-unfit-patients-with-chronic-lymphocytic-leukaemia-a-perspective-review
#15
REVIEW
Othman Al-Sawaf, Paula Cramer, Valentin Goede, Michael Hallek, Natali Pflug
With a median age of 72 years at first diagnosis, chronic lymphocytic leukaemia (CLL) is a disease of the elderly. At this age, many patients cannot bear an intensive chemoimmunotherapy like fludarabine, cyclophosphamide and rituximab (FCR), and therapeutic decisions are commonly complicated by a high burden of accompanying comorbidities. Clinical trials, on the other hand, are mostly designed to include a far healthier and younger trial population, with a median age in most studies well below 70 years, leading to an insufficient reflection of clinical reality...
June 2017: Therapeutic Advances in Hematology
https://www.readbyqxmd.com/read/28565930/current-perspectives-on-the-role-of-chemotherapy-in-chronic-lymphocytic-leukemia
#16
Clemens-Martin Wendtner, Michael Gregor
Chemotherapy has long been integral to the treatment of chronic lymphocytic leukemia (CLL). Fludarabine/cyclophosphamide, chlorambucil and bendamustine are commonly used as a backbone, depending on the patient's age and general health. The advent of the anti-CD20 monoclonal antibodies, such as rituximab and obinutuzumab, altered the face of treatment, and chemoimmunotherapy still forms the current standard first-line approach. However, the landscape is changing following the emergence of novel targeted agents, such as ibrutinib, idelalisib and venetoclax, which offer the chance for improved efficacy over standard therapy alone, with no substantial increase in toxicity...
June 1, 2017: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/28562380/pharmacokinetics-of-venetoclax-in-patients-with-17p-deletion-chronic-lymphocytic-leukemia
#17
Ahmed Hamed Salem, Martin Dunbar, Suresh K Agarwal
Venetoclax is a first-in-class orally available, B-cell lymphoma (BCL)-2 inhibitor indicated for the treatment of patients with relapsed/refractory chronic lymphocytic leukemia (CLL) harboring the 17p deletion. We used a novel approach for evaluating venetoclax pharmacokinetics using only sparse sampling in 155 patients enrolled in a phase 2, multicenter, open-label study in CLL patients with the 17p deletion. Patients received venetoclax doses within 30 min after the completion of breakfast or the first meal of the day, with no specific recommendations for the fat content in the meal...
May 30, 2017: Anti-cancer Drugs
https://www.readbyqxmd.com/read/28561533/emergence-of-bruton-s-tyrosine-kinase-negative-hodgkin-lymphoma-during-ibrutinib-treatment-of-chronic-lymphocytic-leukaemia
#18
Siobhan Glavey, John Quinn, Mary McCloy, Jeremy Sargent, Yvonne McCartney, Mark Catherwood, Teresa Marafioti, Mary Leader, Philip Murphy, Patrick Thornton
Chronic Lymphocytic Leukaemia (CLL) is a chronic B cell lympho-proliferative disorder in which lymphomatous transformations occur in 5-15% of patients. Histologically these cases resemble diffuse large B cell lymphoma, or Richter's transformation, in over 80% of cases. Rare cases of transformation to Hodgkin lymphoma (HL) have been reported in the literature with an estimated prevalence of 0.4%. We report a case of a 67 year-old female with CLL treated with the novel Bruton's tyrosine kinase (Btk) inhibitor, ibrutinib, who subsequently presented with intractable fevers...
May 31, 2017: European Journal of Haematology
https://www.readbyqxmd.com/read/28559746/estimating-outcomes-and-cost-effectiveness-using-a-single-arm-clinical-trial-ofatumumab-for-double-refractory-chronic-lymphocytic-leukemia
#19
Anthony J Hatswell, Gwilym J Thompson, Penny A Maroudas, Oleg Sofrygin, Thomas E Delea
BACKGROUND: Ofatumumab (Arzerra(®), Novartis) is a treatment for chronic lymphocytic leukemia refractory to fludarabine and alemtuzumab [double refractory (DR-CLL)]. Ofatumumab was licensed on the basis of an uncontrolled Phase II study, Hx-CD20-406, in which patients receiving ofatumumab survived for a median of 13.9 months. However, the lack of an internal control arm presents an obstacle for the estimation of comparative effectiveness. METHODS: The objective of the study was to present a method to estimate the cost effectiveness of ofatumumab in the treatment of DR-CLL...
2017: Cost Effectiveness and Resource Allocation: C/E
https://www.readbyqxmd.com/read/28559149/chronic-lymphocytic-leukemia-patients-with-deletion-11q-have-a-short-time-to-requirement-of-first-line-therapy-but-long-overall-survival-results-of-a-population-based-cohort-in-british-columbia-canada
#20
Jennifer Goy, Tanya L Gillan, Helene Bruyere, Steven J T Huang, Monica Hrynchak, Aly Karsan, Khaled Ramadan, Joseph Connors, Cynthia L Toze, Alina S Gerrie
BACKGROUND: Chronic lymphocytic leukemia (CLL) patients with 11q22.3 deletion (11q-) have an aggressive clinical course, and thus selection of first-line therapy in this group is important. This study aimed to improve our understanding of real-world practice patterns and outcomes of CLL patients with 11q- in a population-based setting. PATIENTS AND METHODS: The British Columbia CLL Database was used to identify patients with 11q-. Overall survival (OS) and treatment-free survival (TFS) were assessed after adjustment for prognostic factors...
May 8, 2017: Clinical Lymphoma, Myeloma & Leukemia
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