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https://www.readbyqxmd.com/read/27913474/prognostication-of-chronic-lymphocytic-leukemia-in-the-era-of-new-agents
#1
Barbara Eichhorst, Michael Hallek
The prognosis of chronic lymphocytic leukemia (CLL) is very heterogeneous. Therefore, a plethora of prognostic factors has been identified to allow a better prediction of the individual prognosis of a given patient. The clinical staging systems by Rai and Binet have been the backbone of clinical management for several decades. The advent of genetic and biochemical markers, as well as next-generation sequencing has provided several markers that can predict the prognosis of patients with CLL. Using this knowledge, several scores have been created to improve predicting overall survival and/or treatment-free survival...
December 2, 2016: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/27913473/first-line-therapy-for-young-patients-with-cll
#2
Nitin Jain, Susan O'Brien
A 61-year-old man with a history of chronic lymphocytic leukemia (CLL) presents with complaints of worsening fatigue and night sweats. He was diagnosed with CLL 3 years ago on routine blood count testing. He has no major medical comorbidities. On examination, he has several 2- to 3-cm lymph nodes in the cervical and axillary area. Spleen is palpable 5 cm below the costal margin. Blood counts show lymphocytosis with thrombocytopenia and anemia. Prognostic markers include deletion 13q by fluorescence in situ hybridization analysis and mutated IGHV You are asked by the hematology fellow you are supervising about the best treatment of this patient...
December 2, 2016: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/27913472/novel-agents-in-chronic-lymphocytic-leukemia
#3
Nicole Lamanna, Susan O'Brien
The advent of novel small-molecule inhibitors has transformed the treatment approaches for patients with chronic lymphocytic leukemia (CLL). These therapies are becoming increasingly used in patients with relapsed disease, patients with 17p deletion, and, as of recently, also in the frontline setting for previously untreated patients with CLL. Moreover, many of these are oral therapies that are significantly less myelosuppressive than chemoimmunotherapy. However, these agents have their own set of unique toxicities with which providers must gain familiarity...
December 2, 2016: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/27913471/sequencing-of-chronic-lymphocytic-leukemia-therapies
#4
Jacqueline C Barrientos
It is an unprecedented time for the treatment of patients with chronic lymphocytic leukemia (CLL) with the recent approval of several targeted agents for use in frontline, relapsed, refractory, and high-risk disease. Traditionally, frontline management of CLL has been a combination of chemotherapy (fludarabine, cyclophosphamide, bendamustine, or chlorambucil) with an anti-CD20 monoclonal antibody (rituximab, ofatumumab, obinutuzumab). The current landscape is rapidly evolving with the advent of therapies that demonstrate selective inhibition of important pathways necessary for CLL proliferation and survival...
December 2, 2016: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/27909342/ristocetin-induced-platelet-aggregation-for-monitoring-of-bleeding-tendency-in-cll-treated-with-ibrutinib
#5
L Kazianka, C Drucker, C Skrabs, W Thomas, T Melchardt, S Struve, M Bergmann, P B Staber, E Porpaczy, C Einberger, M Heinz, A Hauswirth, M Raderer, I Pabinger, R Thalhammer, A Egle, C-M Wendtner, G Follows, G Hoermann, P Quehenberger, B Jilma, U Jaeger
Bleeding because of impaired platelet function is a major side effect of the Bruton's tyrosine kinase (BTK) inhibitor ibrutinib. We quantitatively assessed ristocetin-induced platelet aggregation (RIPA) in 64 patients with chronic lymphocytic leukemia (CLL) under ibrutinib at 287 time points. Eighty-seven bleeding episodes in 39 patients were registered (85 Common Toxicity Criteria (CTC) grade 1 or 2, 2 CTC grade 3) during a median observation period of 10.9 months. At times of bleeding, RIPA values were significantly lower (14 vs 28 U; P<0...
December 2, 2016: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/27905140/herpes-simplex-infection-simulating-richter-transformation-a-series-of-four-cases-and-review-of-the-literature
#6
Alireza Salem, Sanam Loghavi, Joseph D Khoury, Rose Lou Marie C Agbay, Jeffrey L Jorgensen, Jeffrey L Medeiros
AIMS: Richter transformation (RT) occurs in 5-10% of patients with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) and is associated with a poor outcome. Histologic manifestations of RT are variable and include an increase in the proportion of large cells including prolymphocytes, immunoblasts and other pleomorphic cells along with an increased proliferation rate and often necrosis. Rarely, superimposed Herpes simplex virus (HSV) infection involving lymph nodes in patients with CLL/SLL may mimic RT clinically and histologically...
December 1, 2016: Histopathology
https://www.readbyqxmd.com/read/27904138/cirmtuzumab-inhibits-wnt5a-induced-rac1-activation-in-chronic-lymphocytic-leukemia-treated-with-ibrutinib
#7
J Yu, L Chen, B Cui, C Wu, M Y Choi, Y Chen, L Zhang, L Z Rassenti, G F Widhopf, T J Kipps
Signaling via the B cell receptor (BCR) plays an important role in the pathogenesis and progression of chronic lymphocytic leukemia (CLL). This is underscored by the clinical effectiveness of ibrutinib, an inhibitor of Bruton's tyrosine kinase (BTK) that can block BCR-signaling. However, ibrutinib cannot induce complete responses (CR) or durable remissions without continued therapy, suggesting alternative pathways also contribute to CLL growth/survival that are independent of BCR-signaling. ROR1 is a receptor for Wnt5a, which can promote activation of Rac1 to enhance CLL-cell proliferation and survival...
December 1, 2016: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/27899962/new-emerging-therapies-in-the-management-of-chronic-lymphocytic-leukemia
#8
Xiao-Lin Li, Ci-Xian Zhang
Chronic lymphocytic leukemia (CLL) is considered incurable despite advances in management strategies. New drugs targeting cell pathways are currently being developed for the efficient management of CLL. Various strategies involving different targets have been developed, or are currently in the developing stage. A search was conducted in the electronic database PubMed, for pre-clinical as well as clinically controlled trials reporting various strategies against CLL currently under investigation. Novel strategies included use of antibodies, small cell inhibitors, such as spleen tyrosine kinase, LYN, cyclin-dependent kinase, and histone deacetylase inhibitors...
November 2016: Oncology Letters
https://www.readbyqxmd.com/read/27891482/treatment-emergent-agranulocytosis-with-skin-and-gingival-lesions-in-a-chronic-lymphocytic-leukemia-patient-a-case-report
#9
Ramesh Amirisetty, Varun Zade, Meenakshi Boddun, Rolly Gupta, Micky Kumari, Hema Suryawanshi
Chronic Lymphocytic Leukaemia (CLL) is a monoclonal lymphoid malignancy characterized by progressive accumulation of small, mature but functionally incompetent neoplastic lymphocytes in the peripheral blood, bone marrow and lymphoid organs. Patients present a variable course and may not require early intervention unlike other malignancies. Patients with rapidly deteriorating blood counts, and organomegaly need treatment. Alkylating agent live Bendamustine combined with Rituximab, anti-CD 20 monoclonal antibody have shown promising results in such patients...
October 2016: Journal of Clinical and Diagnostic Research: JCDR
https://www.readbyqxmd.com/read/27890931/a-tlr7-agonist-enhances-the-anti-tumor-efficacy-of-obinutuzumab-in-murine-lymphoma-models-via-nk-cells-and-cd4-t-cells
#10
E J Cheadle, G Lipowska-Bhalla, S J Dovedi, E Fagnano, C Klein, J Honeychurch, T M Illidge
Anti-CD20 mAb such as rituximab have proven highly effective at improving outcome in B-cell malignancies. However, many patients ultimately relapse and become refractory to treatment. The glycoengineered anti-CD20 mAb obinutuzumab was developed to induce enhanced antibody dependent cellular cytotoxicity, antibody dependent phagocytosis and direct cell death and was shown to lead to improved outcomes in a randomized study in B-chronic lymphocytic leukemia (B-CLL). We hypothesized that immune stimulation through TLR7 agonism in combination with obinutuzumab would further enhance lymphoma clearance and the generation of long-term anti-tumor immune responses...
November 28, 2016: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/27889784/targeted-therapy-of-cll
#11
Othman Al-Sawaf, Kirsten Fischer, Barbara Eichhorst, Michael Hallek
The landscape of chronic lymphocytic leukemia (CLL) has undergone profound changes in the past years. First, the addition of CD20-targeting antibodies to conventional chemotherapy has improved the therapeutic outcome in the majority of CLL patients. Since the establishment of the critical role of the B cell receptor signaling pathway in the pathogenesis of CLL, several agents have been developed to target this pathway. Ibrutinib and idelalisib, 2 potent kinase inhibitors, have both become available for CLL therapy in the first and second line...
2016: Oncology Research and Treatment
https://www.readbyqxmd.com/read/27888629/inhibition-of-bcr-signaling-using-the-syk-inhibitor-tak-659-prevents-stroma-mediated-signaling-in-chronic-lymphocytic-leukemia-cells
#12
Noelia Purroy, Júlia Carabia, Pau Abrisqueta, Leire Egia, Meritxell Aguiló, Cecilia Carpio, Carles Palacio, Marta Crespo, Francesc Bosch
Proliferation and survival of chronic lymphocytic leukemia (CLL) cells depend on microenvironmental signals coming from lymphoid organs. One of the key players involved in the crosstalk between CLL cells and the microenvironment is the B-cell receptor (BCR). Syk protein, a tyrosine kinase essential for BCR signaling, is therefore a rational candidate for targeted therapy in CLL. Against this background, we tested the efficacy of the highly specific Syk inhibitor TAK-659 in suppressing the favorable signaling derived from the microenvironment...
November 24, 2016: Oncotarget
https://www.readbyqxmd.com/read/27885886/atrial-fibrillation-in-patients-with-chronic-lymphocytic-leukemia-cll
#13
Tait D Shanafelt, Sameer A Parikh, Peter A Noseworthy, Valentin Goede, Kari G Chaffee, Jasmin Bahlo, Timothy G Call, Susan M Schwager, Wei Ding, Barbara Eichhorst, Kirsten Fischer, Jose F Leis, Asher Alban Chanan-Khan, Michael Hallek, Susan L Slager, Neil E Kay
Although preliminary data suggests that ibrutinib may increase risk of atrial fibrillation (AF), the incidence of AF in a general cohort of chronic lymphocytic leukemia (CLL) patients is unknown. We evaluated the prevalence of AF at CLL diagnosis and incidence of AF during follow-up in 2444 patients with newly diagnosed CLL. A prior history of AF was present at CLL diagnosis in 148 (6.1%). Among the 2292 patients without history of AF, 139 (6.1%) developed incident AF during follow-up (incidence approximately 1%/year)...
November 25, 2016: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/27881887/changes-in-sexuality-body-image-and-health-related-quality-of-life-in-patients-treated-for-hematologic-malignancies-a-longitudinal-study
#14
Cecilia Olsson, Ann-Kristin Sandin-Bojö, Kaisa Bjuresäter, Maria Larsson
Longitudinal studies exploring sexuality, body image and health-related quality of life (HRQoL) are lacking in patients treated with chemo- or chemoimmuno-therapy for hematologic malignancies. The aim was to describe and explore changes in sexuality, body image and HRQoL in patients treated for hematologic malignancies, from baseline until 6 months after treatment. Twenty patients above 45 years (median age 62) treated for DLBCL, CLL or AML participated. Data were collected at baseline, 1- and 6-months after treatment by means of three instruments: SAQ-S, BIS and EORTC QLQ-C30...
2016: Sexuality and Disability
https://www.readbyqxmd.com/read/27880061/the-safety-profile-of-monoclonal-antibodies-for-chronic-lymphocytic-leukemia
#15
Anna Korycka-Wołowiec, Dariusz Wołowiec, Tadeusz Robak
Monoclonal antibodies (MoAbs), non-chemotherapeutic agents targeting the antigens present on chronic lymphocytic leukemia (CLL) lymphocytes, are being implemented increasingly more often as treatment options. Areas covered: This article reviews the similarities and differences in the structure, mechanism of action, efficacy and safety profile of commercially-available MoAbs and prevents new agents potentially useful for CLL treatment. Publications in English before June 2016 were surveyed on the MEDLINE database for articles...
November 23, 2016: Expert Opinion on Drug Safety
https://www.readbyqxmd.com/read/27878835/first-line-therapy-for-chronic-lymphocytic-leukemia-in-patients-older-than-79%C3%A2-years-is-feasible-and-achieves-good-results-a-filo-retrospective-study
#16
Godelieve Meunier, Loic Ysebaert, Phi Linh Nguyen-Thi, Stéphane Lepretre, Anne Quinquenel, Jehan Dupuis, Richard Lemal, Thérèse Aurran, Cécile Tomowiak, Florence Cymbalista, Marie Sarah Dilhuydy, Annie Brion, Pierre Morel, Bruno Cazin, Véronique Leblond, Guillaume Cartron, Daniel Ré, Marie Christine Béné, Anne Sophie Michallet, Pierre Feugier
The mean age at diagnosis of chronic lymphocytic leukemia (CLL) is 72 years, with 22.8% of patients being older than 80 years. However, the elderly are underrepresented in clinical studies of CLL. We performed a retrospective study of CLL patients aged 80 years or older at the initiation of first-line therapy in hospitals affiliated with the French intergroup on CLL (French Innovative Leukemia Organization) between 2003 and 2013. Here, we describe the clinical and biological characteristics, treatment, and outcomes for 201 patients...
November 22, 2016: Hematological Oncology
https://www.readbyqxmd.com/read/27875673/recent-advances-in-engineered-t-cell-therapies-targeting-b-cell-malignancies
#17
Nathan Singh
Immunotherapy using engineered autologous T cells has been attempted for decades, but clinical trials have only recently demonstrated efficacy. The combination of enhanced manufacturing techniques, highly efficient engineering, appropriate target selection and synthetic receptors with potent T cell activating domains has led to the development of highly-active cellular therapy products. B-cell malignancies have served as the paradigmatic diseases to initially evaluate and subsequently hone engineered T cells targeting cancer...
October 2016: Discovery Medicine
https://www.readbyqxmd.com/read/27870563/economic-burden-of-chronic-lymphocytic-leukemia-in-the-era-of-oral-targeted-therapies-in-the-united-states
#18
Qiushi Chen, Nitin Jain, Turgay Ayer, William G Wierda, Christopher R Flowers, Susan M O'Brien, Michael J Keating, Hagop M Kantarjian, Jagpreet Chhatwal
Purpose Oral targeted therapies represent a significant advance for the treatment of patients with chronic lymphocytic leukemia (CLL); however, their high cost has raised concerns about affordability and the economic impact on society. Our objective was to project the future prevalence and cost burden of CLL in the era of oral targeted therapies in the United States. Methods We developed a simulation model that evaluated the evolving management of CLL from 2011 to 2025: chemoimmunotherapy (CIT) as the standard of care before 2014, oral targeted therapies for patients with del(17p) and relapsed CLL from 2014, and for first-line treatment from 2016 onward...
November 21, 2016: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/27862308/alemtuzumab-consolidation-in-chronic-lymphocytic-leukaemia-a-phase-i-ii-multicentre-trial
#19
Othman Al-Sawaf, Kirsten Fischer, Carmen D Herling, Matthias Ritgen, Sebastian Böttcher, Jasmin Bahlo, Thomas Elter, Stephan Stilgenbauer, Barbara F Eichhorst, Raymonde Busch, Ute Elberskirch, Wolfgang Abenhardt, Michael Kneba, Michael Hallek, Clemens-Martin Wendtner
OBJECTIVE: Despite high rates of long-lasting remissions in patients with chronic lymphocytic leukaemia (CLL) treated with chemoimmunotherapy, none of the current therapeutic approaches is curative with the exception of allogeneic transplantation. One strategy to extend progression-free survival and long-term survival might be the establishment of consolidation therapies. METHODS: In this trial, patients with complete or partial second remission after fludarabine-based treatment received consolidation therapy with alemtuzumab...
November 9, 2016: European Journal of Haematology
https://www.readbyqxmd.com/read/27861736/real-world-clinical-experience-in-the-connect-%C3%A2-chronic-lymphocytic-leukaemia-registry-a-prospective-cohort-study-of-1494-patients-across-199-us-centres
#20
Anthony Mato, Chadi Nabhan, Neil E Kay, Mark A Weiss, Nicole Lamanna, Thomas J Kipps, David L Grinblatt, Ian W Flinn, Mark F Kozloff, Christopher R Flowers, Charles M Farber, Pavel Kiselev, Arlene S Swern, Kristen Sullivan, E Dawn Flick, Jeff P Sharman
The clinical course of chronic lymphocytic leukaemia (CLL) is heterogeneous, and treatment options vary considerably. The Connect(®) CLL registry is a multicentre, prospective observational cohort study that provides a real-world perspective on the management of, and outcomes for, patients with CLL. Between 2010 and 2014, 1494 patients with CLL and that initiated therapy, were enrolled from 199 centres throughout the USA (179 community-, 17 academic-, and 3 government-based centres). Patients were grouped by line of therapy at enrolment (LOT)...
December 2016: British Journal of Haematology
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