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https://www.readbyqxmd.com/read/28342031/ibrutinib-in-cll-a-focus-on-adverse-events-resistance-and-novel-approaches-beyond-ibrutinib
#1
REVIEW
Varinder Kaur, Arjun Swami
Bruton's tyrosine kinase (BTK), a mediator in B cell receptor signaling has been successfully exploited as a therapeutic target in treatment of chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL). Ibrutinib is a BTK inhibitor that has shown excellent efficacy in treatment-naïve, heavily pre-treated, and high-risk CLL/SLL. With remarkable efficacy, good oral bioavailability, and modest adverse events profile, ibrutinib use is likely to continue to increase. As data with ibrutinib use in CLL matures, concerns regarding adverse events and drug resistance have emerged...
March 24, 2017: Annals of Hematology
https://www.readbyqxmd.com/read/28331288/development-of-venetoclax-for-therapy-of-lymphoid-malignancies
#2
REVIEW
Huayuan Zhu, Alexandru Almasan
B-cell lymphoma-2 (BCL-2) family dysfunction and impairment of apoptosis are common in most B-cell lymphoid malignancies. Venetoclax (Venclexta™, formerly ABT-199, GDC-0199) is a highly selective BCL-2 inhibitor, which mimics its BCL-2 homology 3-domain to induce apoptosis. It was approved for treatment of previously treated chronic lymphocytic leukemia (CLL) patients with 17p deletion early in 2016. It has also been in clinical trials for other B-cell lymphoid malignancies. Unlike the other recently approved targeted agents idelalisib and ibrutinib, so far there has been no relapse reported in some patients...
2017: Drug Design, Development and Therapy
https://www.readbyqxmd.com/read/28295729/targeting-of-b-cell-receptor-signalling-in-b-cell-malignancies
#3
M Jerkeman, M Hallek, M Dreyling, C Thieblemont, E Kimby, L Staudt
Pharmacological agents that inhibit enzymes of the B-cell receptor (BCR) pathway are of increasing importance in the treatment of B-cell malignancies. These include inhibitors of Bruton tyrosine kinase (BTK), phosphatidylinositol 3-kinase (PI3K), splenic tyrosine kinase and protein kinase Cβ. Two agents are already approved in the USA and Europe: ibrutinib, a BTK inhibitor, for the treatment of chronic lymphatic leukaemia (CLL), mantle cell lymphoma (MCL) and Waldenström's macroglobulinemia; and idelalisib, a PI3Kδ inhibitor, for the treatment of CLL and follicular lymphoma...
March 14, 2017: Journal of Internal Medicine
https://www.readbyqxmd.com/read/28284744/thoracic-complications-in-chronic-lymphocytic%C3%A2-leukemia
#4
Sameer Khanijo, Pragati Tandon, Cristina P Sison, Seth Koenig
BACKGROUND: Chronic lymphocytic leukemia (CLL) is the most common lymphoproliferative disorder worldwide. Although thoracic complications are frequent in CLL, only limited data exist regarding the etiologies of these complications. MATERIALS AND METHODS: A retrospective chart review was performed on all patients admitted to a tertiary care, CLL referral center, with CLL and a respiratory complaint from 2001 through 2013, to categorize pulmonary complaints and diagnoses...
February 17, 2017: Clinical Lymphoma, Myeloma & Leukemia
https://www.readbyqxmd.com/read/28282218/immunotoxins-in-cancer-therapy-review-and-update
#5
Bahman Akbari, Safar Farajnia, Shiva Ahdi Khosroshahi, Fatemeh Safari, Mohammadreza Yousefi, Hassan Dariushnejad, Leila Rahbarnia
Immunotoxins are a novel class of cancer therapeutics that contains a cytotoxic agent fused to a targeting moiety. Various toxic agents from different sources are used in immunotoxin development, including bacterial, plant and human origin cytotoxic elements. Although bacterial and plant-derived toxins are highly toxic and commonly used in immunotoxins, their immunogenicity for human restricted their application in cancer therapy. Here, we discuss the advantages and limitations of bacterial toxins such as Pseudomonas and Diphtheria toxins, plant toxins such as ricin and gelonin, and some endogenous protein of human origin such as RNases and Granzymes...
March 1, 2017: International Reviews of Immunology
https://www.readbyqxmd.com/read/28275912/mechanisms-of-resistance-to-targeted-therapies-in-chronic-lymphocytic-leukemia
#6
Francesca Arruga, Silvia Deaglio
Even if treatment options for Chronic Lymphocytic Leukemia (CLL) patients have changed dramatically in the past few years, with the approval of targeted therapeutic agents, the disease remains incurable. Beside intrinsic genetic features characterizing the leukemic cell, signals coming from the microenvironment have a key role in promoting cell survival and in protecting CLL cells from the action of drugs. Consequently, the identification of previously unrecognized genetic lesions is important in risk-stratification of CLL patients and is progressively becoming a critical tool for choosing the best therapeutic strategy...
March 9, 2017: Handbook of Experimental Pharmacology
https://www.readbyqxmd.com/read/28270732/examining-the-medical-resource-utilization-and-costs-of-relapsed-and-refractory-chronic-lymphocytic-leukemia-in-ontario
#7
S Hassan, S J Seung, M C Cheung, G Fraser, B Kuriakose, C Trambitas, N Mittmann
PURPOSE: The purpose of the present study was to collect medical resource utilization data and costs in Ontario for the management of patients with relapsed or refractory chronic lymphocytic lymphoma (cll) who have undergone at least 1 treatment course and have been stratified by Rai staging. METHODS: This retrospective longitudinal cohort study, conducted by chart review, analyzed anonymized patient records from two cancer centres in Ontario. Comprehensive records of 86 patients meeting the inclusion criteria were used to obtain resource utilization, which, multiplied by unit costs, were used to determine overall and mean costs...
February 2017: Current Oncology
https://www.readbyqxmd.com/read/28257957/the-cancer-immunity-cycle-as-rational-design-for-synthetic-cancer-drugs-novel-dc-vaccines-and-car-t-cells
#8
REVIEW
Mohanraj Ramachandran, Anna Dimberg, Magnus Essand
Cell therapy is an advanced form of cancer immunotherapy that has had remarkable clinical progress in the past decade in the search for cure of cancer. Most success has been achieved for chimeric antigen receptor (CAR) T-cells where CAR T-cells targeting CD19 show very high complete response rates for patients with refractory acute B-cell acute lymphoblastic leukemia (ALL) and are close to approval for this indication. CD19 CAR T-cells are also effective against B-cell chronic lymphoblastic leukemia (CLL) and B-cell lymphomas...
February 28, 2017: Seminars in Cancer Biology
https://www.readbyqxmd.com/read/28257752/efficacy-and-safety-of-idelalisib-in-combination-with-ofatumumab-for-previously-treated-chronic-lymphocytic-leukaemia-an-open-label-randomised-phase-3-trial
#9
Jeffrey A Jones, Tadeusz Robak, Jennifer R Brown, Farrukh T Awan, Xavier Badoux, Steven Coutre, Javier Loscertales, Kerry Taylor, Elisabeth Vandenberghe, Malgorzata Wach, Nina Wagner-Johnston, Loic Ysebaert, Lyndah Dreiling, Ronald Dubowy, Guan Xing, Ian W Flinn, Carolyn Owen
BACKGROUND: Idelalisib, a selective inhibitor of PI3Kδ, is approved for the treatment of patients with relapsed chronic lymphocytic leukaemia (CLL) in combination with rituximab. We aimed to assess the efficacy and safety of idelalisib in combination with a second-generation anti-CD20 antibody, ofatumumab, in a similar patient population. METHODS: In this global, open-label, randomised, controlled phase 3 trial, we enrolled patients with relapsed CLL progressing less than 24 months from last therapy...
March 2017: Lancet Haematology
https://www.readbyqxmd.com/read/28246553/the-role-of-combined-fludarabine-cyclophosphamide-and-rituximab-chemoimmunotherapy-in-chronic-lymphocytic-leukemia-current-evidence-and-controversies
#10
REVIEW
Alan P Skarbnik, Stefan Faderl
Chemoimmunotherapy (CIT) has become a cornerstone in the treatment of patients with chronic lymphocytic leukemia (CLL). The combination of fludarabine, cyclophosphamide and rituximab (FCR) has emerged as the standard of care for therapy of previously untreated patients with CLL who are younger than 65 years and have no significant comorbidities. In this article, we review the role of FCR in the current treatment paradigm for CLL.
March 2017: Therapeutic Advances in Hematology
https://www.readbyqxmd.com/read/28245413/-research-progress-in-transgenic-animal-models-of-chronic-lymphocytic-leukemia-review
#11
Fang-Tian Wu, Wei Xu, Jian-Yong Li
Transgenic mouse models of chronic lymphocytic leukemia (CLL) are crucially required for the elucidation of the underlying pathogenic mechanisms and for finding new therapies. So far, several mouse models have been established, mimicking either genetic aberrations or dysregulated gene expression in CLL. Among all the models, TCL1 transgenic model is the most commonly used one. Additionally, there are also other models, such as 13q14-deletion model. In this review, the major genetically engineered mouse models of CLL in current use are summarized, the main problems include TCL-1 transgenic mice, miR15a/16-1 gene knockdown mice and miR29 transgeneic mice, BAFF and APRIL transgeneic mice, BCL-2:Traf2DN double transgeneic mice, IRF4(-/-)Vh11 transgeneic mice and so on...
February 2017: Zhongguo Shi Yan Xue Ye Xue za Zhi
https://www.readbyqxmd.com/read/28245410/-research-progress-of-novel-small-molecule-drugs-in-the-treatment-of-chronic-lymphocytic-leukemia-review
#12
Jing-Qiao Qiao, Miao He, Shu-Ting Zhang, Hai Bai
Chronic lymphocytic leukemia (CLL), the most frequent adult leukemia in Western population, is characterized by accumulation of mature-looking CD5(+)/19(+)/23(+) B cells in peripheral blood, bone marrow, and lymphatic organs. Over the last 20 years, there has been a dramatic change in therapy for CLL, the complete response rate increased from the initial <5% to the current 40%-50%, this remarkable improvement has been attributable to combination of chemoimmunotherapy agents that have contributed to the backbone of therapy for patients with CLL...
February 2017: Zhongguo Shi Yan Xue Ye Xue za Zhi
https://www.readbyqxmd.com/read/28236475/update-of-the-grupo-espa%C3%A3-ol-de-leucemia-linfoc%C3%A3-tica-cr%C3%A3-nica-clinical-guidelines-of-the-management-of-chronic-lymphocytic-leukemia
#13
José A García-Marco, Julio Delgado, José A Hernández-Rivas, Ángel Ramírez Payer, Javier Loscertales Pueyo, Isidro Jarque, Pau Abrisqueta, Pilar Giraldo, Rafael Martínez, Lucrecia Yáñez, Mª José Terol, Marcos González, Francesc Bosch
BACKGROUND AND OBJECTIVE: The broad therapeutic arsenal and the biological heterogeneity of patients with chronic lymphocytic leukemia (CLL) makes it difficult to standardize treatment for CLL patients with specific clinical settings in routine clinical practice. These considerations prompted us to elaborate the present consensus document, which constitutes an update of the previous version published in 2013, mainly focusing on novel treatment strategies that have been developed over last 5 years, namely B-cell receptor inhibitors (ibrutinib and idelalisib), anti-CD20 monoclonal antibodies (ofatumumab and obinutuzumab), and Bcl-2 inhibitors (venetoclax)...
February 21, 2017: Medicina Clínica
https://www.readbyqxmd.com/read/28197963/a-concise-review-of-autoimmune-cytopenias-in-chronic-lymphocytic-leukemia
#14
REVIEW
Mazie Tsang, Sameer A Parikh
Chronic lymphocytic leukemia (CLL) is frequently associated with autoimmune complications such as autoimmune hemolytic anemia, immune thrombocytopenia, pure red cell aplasia, and autoimmune granulocytopenia. It is critical to diagnose cytopenias from these secondary complications of CLL accurately, since prognosis and therapy are substantially different from patients who have cytopenias due to extensive bone marrow infiltration by CLL. The pathogenesis of autoimmune cytopenias in CLL is complex; and it involves antigen presentation by CLL cells to polyclonal B cells resulting in production of autoantibody, and alteration of the T cell milieu tilting the balance in favor of an autoimmune response...
February 14, 2017: Current Hematologic Malignancy Reports
https://www.readbyqxmd.com/read/28195098/biclonal-chronic-lymphocytic-leukemia-a-study-of-two-cases-and-review-of-literature
#15
REVIEW
Kiran Ashok Ghodke, Nikhil V Patkar, P G Subramanian, Sumeet Gujral, Pratibha Aamre Kadam, Prashant R Tembhare
Chronic lymphocytic leukemia (CLL) is a common, immunophenotypically well-defined mature B-cell neoplasm. Demonstration of more than 5000/μL CD5+ B-cell population with co-expression of CD23, weak expression of CD20, and one type of immunoglobin light chain (either kappa or lambda) is necessary for the diagnosis of CLL. However, CLL with two populations of B-cells expressing both kappa as well as lambda (biclonal) light chains are extremely rare and has not been reported from India. We report two cases of biclonal CLL presented with leukocytosis, typical morphological features, and distinct immunophenotype of CLL...
January 2017: Indian Journal of Pathology & Microbiology
https://www.readbyqxmd.com/read/28191372/richter-transformation-of-chronic-lymphocytic-leukemia-a-review-of-fluorodeoxyglucose-positron-emission-tomography-computed-tomography-and-molecular-diagnostics
#16
REVIEW
Faiq Shaikh, Amna Janjua, Frederick Van Gestel, Adeel Ahmad
Chronic lymphocytic leukemia (CLL) is a low-grade B-cell proliferative disease with a generally indolent course. In a few cases, it undergoes transformation and becomes a more aggressive malignancy, such as diffuse large B-cell lymphoma (DLBCL). This process, which is called Richter transformation (RT), is often detected too late and is associated with a poor prognosis. There are multiple molecular diagnostic approaches to detect RT in preexisting CLL. Metabolic imaging using 18-fluorine fluorodeoxyglucose positron emission tomography-computed tomography (18F-FDG PET/CT) can be a very useful tool for early detection of RT and which can hence allow for timely intervention, thereby improving the patient's chances of survival...
January 9, 2017: Curēus
https://www.readbyqxmd.com/read/28182141/obinutuzumab-in-chronic-lymphocytic-leukemia-design-development-and-place-in-therapy
#17
REVIEW
Othman Al-Sawaf, Kirsten Fischer, Anja Engelke, Natali Pflug, Michael Hallek, Valentin Goede
For decades, treatment of chronic lymphocytic leukemia (CLL) has been based on chemotherapy. This changed when the first CD20 antibody rituximab was introduced. Since 2008, the combination of chemotherapy and CD20 antibodies has become the standard of care for most patients, and a significant fraction of patients had very long-lasting remissions after chemoimmunotherapy. Despite the improvement of response rates and overall survival (OS) by the use of chemoimmunotherapy, most CLL patients will relapse eventually...
2017: Drug Design, Development and Therapy
https://www.readbyqxmd.com/read/28160756/receptor-tyrosine-kinase-like-orphan-receptor-1-ror-1-an-emerging-target-for-diagnosis-and-therapy-of-chronic-lymphocytic-leukemia
#18
REVIEW
Leili Aghebati-Maleki, Mahdi Shabani, Behzad Baradaran, Morteza Motallebnezhad, Jafar Majidi, Mehdi Yousefi
Chronic lymphocytic leukemia (CLL) is characterized by reposition of malignant B cells in the blood, bone marrow, spleen and lymph nodes. It remains the most common leukemia in the Western world. Within the recent years, major breakthroughs have been made to prolong the survival and improve the health of patients. Despite these advances, CLL is still recognized as a disease without definitive cure. New treatment approaches, based on unique targets and novel drugs, are highly desired for CLL therapy. The Identification and subsequent targeting of molecules that are overexpressed uniquely in malignant cells not normal ones play critical roles in the success of anticancer therapeutic strategies...
April 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28144729/development-of-acute-myeloid-leukemia-in-patients-with-untreated-chronic-lymphocytic-leukemia
#19
Shoko Ito, Shin-Ichiro Fujiwara, Kiyomi Mashima, Kento Umino, Daisuke Minakata, Hirofumi Nakano, Ryoko Yamasaki, Yasufumi Kawasaki, Miyuki Sugimoto, Masahiro Ashizawa, Chihiro Yamamoto, Kaoru Hatano, Kiyoshi Okazuka, Kazuya Sato, Iekuni Oh, Ken Ohmine, Takahiro Suzuki, Kazuo Muroi, Yoshinobu Kanda
The development of acute myeloid leukemia (AML) in patients with untreated chronic lymphocytic leukemia (CLL) is rare. We experienced a 65-year-old man who developed AML with aberrant CD7 expression and monoallelic CEBPA mutation during watchful waiting for CLL. He failed to achieve complete response (CR) by standard induction therapy for AML. We retrospectively reviewed 27 patients who developed AML with untreated CLL published between 1973 and 2016. The median age at diagnosis of AML was 68 years, and the median duration between the diagnoses of AML and CLL was 4...
February 1, 2017: Annals of Hematology
https://www.readbyqxmd.com/read/28105602/ibrutinib-a-review-in-chronic-lymphocytic-leukaemia
#20
Emma D Deeks
Ibrutinib (Imbruvica(®)) is an oral irreversible inhibitor of Bruton's tyrosine kinase, a B-cell receptor (BCR) signalling kinase expressed by various haematopoietic cells, B-cell lymphomas and leukaemias. The drug is indicated for the treatment of certain haematological malignancies, including chronic lymphocytic leukaemia (CLL)/small lymphocytic lymphoma (SLL), which are the focus of this review. In phase III CLL/SLL trials, ibrutinib monotherapy was more effective than chlorambucil in the first-line treatment of elderly patients (RESONATE-2) and more effective than ofatumumab in previously-treated adults (RESONATE)...
February 2017: Drugs
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