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Review Cll

Riccardo Moia, Fary Diop, Chiara Favini, Ahad Ahmed Kodipad, Gianluca Gaidano
Chronic lymphocytic leukemia (CLL) is a highly heterogeneous disease. Deregulation of apoptosis is a major pathogenetic feature, and represents a therapeutic target. TP53 disrupted patients are categorized as high risk patients and are treated with novel target therapies. Among these new drugs, venetoclax, an orally bioavailable BCL2 inhibitor, has shown high efficacy also in relapsed/refractory CLL with TP53 disruption. Venetoclax has also been tested in combination with other drugs without compromising venetoclax dose and with a good safety profile...
March 21, 2018: Expert Review of Hematology
Marc Sorigue, Elisa Orna, Juan-Manuel Sancho
Lenalidomide has been associated with an increased risk of venous thromboembolism (VTE) in multiple myeloma. It is unclear whether patients with non-Hodgkin lymphoma (NHL) and chronic lymphocytic leukemia (CLL) are also at such risk. We conducted a systematic review of the incidence of VTE in prospective trials of lenalidomide-treated patients with NHL or CLL. Sixty-eight unique reports were assessed for inclusion. For grade ≥3 VTE, 98 events were reported in 3043 patients (60 studies) (crude incidence: 3...
March 21, 2018: Leukemia & Lymphoma
Tilly Varughese, Ying Taur, Nina Cohen, M Lia Palomba, Susan K Seo, Tobias M Hohl, Gil Redelman-Sidi
Background: Ibrutinib is a Bruton's tyrosine kinase inhibitor that is used for the treatment of lymphoid malignancies, including chronic lymphocytic leukemia (CLL), Waldenström's macroglobulinemia and mantle cell lymphoma (MCL). Several case series have described opportunistic infections among ibrutinib recipients, but the full extent of these infections is unknown. We sought to determine the spectrum of serious infections associated with ibrutinib treatment. Methods: We reviewed the electronic medical records of patients with lymphoid malignancies at Memorial Sloan Kettering Cancer Center who received ibrutinib during a five-year period from January 1, 2012 to December 31, 2016...
March 2, 2018: Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
Eric Sanchez, Edward J Tanenbaum, Saurabh Patil, Mingjie Li, Camilia M Soof, Aleksandra Vidisheva, Gabriel N Waterman, Tara Hekmati, George Tang, Cathy S Wang, Haiming Chen, James Berenson
B-cell maturation antigen (BCMA) is a cell membrane bound tumor necrosis factor receptor family member that is expressed exclusively on late stage normal and malignant B-cells and plasma cells. Addition of two of its ligands, B-cell activating factor and a proliferation inducting ligand, to normal B-cells cause B-cell proliferation and antibody production. Serum BCMA is elevated among patients with multiple myeloma (MM) and chronic lymphocytic leukemia (CLL), and is a prognostic and monitoring tool for these patients...
March 7, 2018: Expert Review of Molecular Diagnostics
Craig S Boddy, Shuo Ma
PURPOSE OF REVIEW: Chronic lymphocytic leukemia (CLL) has multiple current frontline therapy options, including chemoimmunotherapy (CIT) and most recently, ibrutinib. Here, we review the most recent updates in the frontline treatment of CLL, including updates in CIT, updates in targeted therapies, and ongoing clinical trials. RECENT FINDINGS: Ibrutinib was FDA-approved for the upfront treatment of CLL in 2016 after being studied in older patients and those with 17p deletions or TP53 mutations...
February 26, 2018: Current Hematologic Malignancy Reports
Alma O'Reilly, James Murphy, Sarah Rawe, Mary Garvey
Chronic lymphocytic leukemia (CLL) remains the most prevalent form of leukemia in the Western world, with no cure to date. Ongoing and essential research into this heterogeneous disease has led to a number of new treatment options becoming available to CLL patients in the past decade. The present review presents the recent developments in the field of CLL treatment, with the main focus on elderly patients and CLL patients with coexisting comorbidities. The review discusses the current treatment regimens that provide the most promising outcomes for patients in this subgroup, with a number of important clinical trials summarized...
February 8, 2018: Clinical Lymphoma, Myeloma & Leukemia
Prajwal Boddu, Alessandra Ferrajoli
PURPOSE OF REVIEW: Chronic lymphocytic leukemia is heterogeneous disease characterized by a variable clinical course that is greatly influenced by various patient and disease characteristics. Over the last two decades, advent of new diagnostic methodologies has led to the identification of several factors of prognostic and predictive relevance. Furthermore, recent advances in next-generation sequencing techniques has identified recurrent novel mutations in NOTCH1, SF3B1, BIRC3, and ATM genes whose role as prognostic and predictive markers is currently being investigated...
February 23, 2018: Current Hematologic Malignancy Reports
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
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
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
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
Larry Mansouri, Justyna Anna Wierzbinska, Christoph Plass, Richard Rosenquist
Deregulated transcriptional control caused by aberrant DNA methylation and/or histone modifications is a hallmark of cancer cells. In chronic lymphocytic leukemia (CLL), the most common adult leukemia, the epigenetic 'landscape' has added a new layer of complexity to our understanding of this clinically and biologically heterogeneous disease. Early studies identified aberrant DNA methylation, often based on single gene promoter analysis with both biological and clinical impact. Subsequent genome-wide profiling studies revealed differential DNA methylation between CLLs and controls and in prognostics subgroups of the disease...
February 7, 2018: Seminars in Cancer Biology
Ailsa K Holroyd, Alison M Michie
Mechanistic target for rapamycin (mTOR) is a serine/threonine protein kinase that forms two distinct complexes mTORC1 and mTORC2, integrating mitogen and nutrient signals to regulate cell survival and proliferation; processes which are commonly deregulated in human cancers. mTORC1 and mTORC2 have divergent molecular associations and cellular functions: mTORC1 regulates in mRNA translation and protein synthesis, while mTORC2 is involved in the regulation of cellular survival and metabolism. Through AKT phosphorylation/activation, mTORC2 has also been reported to regulate cell migration...
February 3, 2018: Immunology Letters
Yichao Wan, Ningning Dai, Zilong Tang, Hao Fang
The anti-apoptotic members of B-cell lymphoma-2 (Bcl-2) proteins family, such as Bcl-2 and myeloid cell leukemia-1 (Mcl-1), are the key regulators of the intrinsic pathway of apoptosis and overexpressed in many tumor cells, which have been confirmed as potential drug targets for cancers. A number of Bcl-2 proteins inhibitors have been developed and conducted clinical trials, but no Mcl-1 inhibitors are presented in the clinics. In addition, Mcl-1 is an important reason for the resistance to radio- and chemotherapies, including inhibitors that target other Bcl-2 family members...
January 30, 2018: European Journal of Medicinal Chemistry
Claire Kim, Frances C Wright, Nicole J Look Hong, Gary Groot, Lucy Helyer, Pamela Meiers, May Lynn Quan, Robin Urquhart, Rebecca Warburton, Anna R Gagliardi
OBJECTIVE: Active surveillance (AS) represents a fundamental shift in managing select cancer patients that initiates treatment only upon disease progression to avoid overtreatment. Given uncertain outcomes, patient engagement could support decision-making about AS. Little is known about how to optimize patient engagement for AS decision-making. This scoping review aimed to characterize research on patient and provider communication about AS, and associated determinants and outcomes. METHODS: MEDLINE, EMBASE, CINAHL, and The Cochrane Library were searched from 2006 to October 2016...
2018: PloS One
Amer Abdulrahman Almaiman
Lymphoid (or lymphocytic/lymphoblastic) leukemia, one of two major types of leukemias (lymphoid and myeloid), is divided into two subtypes, acute lymphoid leukemia (ALL) and chronic lymphocytic leukemia (CLL), depending on the maturation stage and speed of multiplication of the bone marrow lymphocytes. Early diagnosis and treatment can make the difference between life and death. Advancements in the field of proteomics may allow the development of early biomarkers and more effective agents to combat both these types of cancer, and to better understand the underlying mechanisms of the disease...
February 2018: Journal of the College of Physicians and Surgeons—Pakistan: JCPSP
José María Bastida, María Teresa Cano-Mozo, Felix Lopez-Cadenas, Victor Eduardo Vallejo, Soraya Merchán, Cecilia Santos-Montón, David González-Calle, Javier Carrillo, Ana Africa Martín, Jose Angel Torres-Hernández, Marcos González, Francisco Martín-Herrero, Pedro Pabón, Jose Ramon González-Porras
BACKGROUND: Acquired hemophilia A (AHA) is a rare bleeding disease caused by autoantibodies against factor VIII. Spontaneous bleeding symptoms usually affect the skin and muscle, while pericardial effusion is an extremely rare manifestation. In the elderly, anticoagulant treatment is frequent and bleeding symptoms are usually associated with this. CLINICAL FINDINGS: We report a hemorrhagic pericardial effusion as the AHA debut in a patient with untreated chronic lymphocytic leukemia and anticoagulated with apixaban for atrial fibrillation and chronic arterial ischemia...
November 2017: Medicine (Baltimore)
Benjamin L Lampson, Jennifer R Brown
Ibrutinib is the first BTK inhibitor to show efficacy in chronic lymphocytic leukemia (CLL) and is also the first BTK inhibitor to which patients have developed resistance. Mutations in BTK and PLCG2 are found in ≈80% of CLL patients with acquired resistance to ibrutinib, but it remains unclear if these mutations are merely associated with disease relapse or directly cause it. Areas covered: Unique properties of both CLL and ibrutinib that complicate attempts to definitively conclude whether BTK/PLCG2 mutations are passengers or drivers of ibrutinib-resistant disease are reviewed...
February 12, 2018: Expert Review of Hematology
Edmund Wee, Michelle S Goh, Vanessa Estall, Albert Tiong, Angela Webb, Catherine Mitchell, William Murray, Phillip Tran, Christopher J McCormack, Michael Henderson, Emma L Hiscutt
BACKGROUND/OBJECTIVES: To describe the characteristics, subsequent management and outcomes of patients referred for further management following Mohs micrographic surgery (MMS) for basal cell carcinoma (BCC) and squamous cell carcinoma (SCC). METHODS: Retrospective analysis of patients referred to a quaternary cancer centre from 2000 to 2015. RESULTS: In total, 83 lesions in 82 patients were referred for further management; 52 (62%) were SCC and 80 (96%) were located in the head and neck...
January 18, 2018: Australasian Journal of Dermatology
Evan Himchak, Etan Marks, Yang Shi, Yanhua Wang
A collision tumor is defined as two histologically distinct tumor types identified at the same anatomic site. Hematolymphoid proliferative disorders (HLPDs), which coincide with non-hematological neoplasms, can mimic an immune response and can easily be overlooked as an immune reaction to a solid organ neoplasm, especially when low grade. In order to avoid a delay in the diagnosis of a HLPD during the workup for a non-hematological neoplasm, we identified a cohort of 100 cases with a HLPD diagnosis during the initial workup and treatment of a non-hematological neoplasm, or vice versa...
January 1, 2018: International Journal of Surgical Pathology
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