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"Chronic lymphocytic leukemia"

K I Korubo, H C Okoye, C C Efobi
Background: Hematological malignancies are a significant cause of morbidity and mortality. They constitute an economic burden for the patients, their relatives, and the society because of the cost associated with their management, which is usually long term. We aimed to determine the total direct cost of managing patients with premalignant hematological disorders (PMHDs) and malignant hematological disorders (MHDs). Materials and Methods: A hospital-based retrospective study was carried out between 1997 and 2015...
November 2018: Nigerian Journal of Clinical Practice
Mart Bittremieux, Rita M La Rovere, Marleen Schuermans, Tomas Luyten, Katsuhiko Mikoshiba, Peter Vangheluwe, Jan B Parys, Geert Bultynck
The anti-apoptotic protein Bcl-2 is upregulated in several cancers, including diffuse large B-cell lymphoma (DLBCL) and chronic lymphocytic leukemia (CLL). In a subset of these cancer cells, Bcl-2 blocks Ca2+ -mediated apoptosis by suppressing the function of inositol 1,4,5-trisphosphate (IP3 ) receptors (IP3 Rs) located at the endoplasmic reticulum (ER). A peptide tool, called Bcl-2/IP3 receptor disruptor-2 (BIRD-2), was developed to disrupt Bcl-2/IP3 R complexes, triggering pro-apoptotic Ca2+ signals and killing Bcl-2-dependent cancer cells...
2018: Cell Death Discovery
Davide Facchinelli, Gessica Marchesini, Gianpaolo Nadali, Livio Pagano
This review summarizes the more recent evidence about epidemiology and risk factors for invasive fungal infections (IFI) in patients affected by Chronic Lymphocytic Leukemia (CLL), indolent Non Hodgkin Lymphoma (iNHL) and Multiple Myeloma (MM). Despite advances in the prognosis and treatment of hematological malignancies in recent years, susceptibility to infection remains a significant challenge to patient care. A large amount of data regarding patients with acute leukemia has been published while little information is available on the incidence of IFI in chronic lymphoproliferative disorders (CLD)...
2018: Mediterranean Journal of Hematology and Infectious Diseases
Alessio Montresor, Lara Toffali, Antonella Rigo, Isacco Ferrarini, Fabrizio Vinante, Carlo Laudanna
Bruton's tyrosine kinase (BTK) regulates the B-cell receptor (BCR) signaling pathway, which, in turn, plays a critical role in B-cell chronic lymphocytic leukemia (B-CLL) pathogenesis. The BTK-specific inhibitor Ibrutinib blocks BCR signaling and is now approved as effective B-CLL therapy. Chemokines, such as the homeostatic chemokine CXCL12, play a central role in B-CLL pathogenesis and progression, by regulating CLL cell interaction with the stromal microenvironment, leading to cells survival and proliferation...
October 12, 2018: Oncotarget
Jian Hua, Shiro Ide, Shin Ohara, Tomoyuki Uchida, Morihiro Inoue, Kazuteru Ohashi, Masao Hagihara
We report a 40-year-old woman who presented with multiple osteolytic bone lesions and hypercalcemia, which are rarely caused by chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL). Although receiving intensive chemotherapy and allogeneic transplantation, the patient had a poor outcome with an overall survival of 2 years. To our knowledge, this presentation is extremely rare for B-chronic lymphocytic leukemia, and new treatment strategies may be needed for long-term control of the disease.
November 9, 2018: Journal of Clinical and Experimental Hematopathology: JCEH
Frank Meiss, Kristin Technau-Hafsi, Johannes S Kern, Annette M May
BACKGROUND: Skin diseases are frequent in patients with chronic lymphocytic leukemia and other hematological neoplasias. Eosinophilic dermatosis of hematologic malignancy (ED) has long been considered a nonspecific cutaneous reaction pattern. Recently neoplastic cells have been shown to be present in ED thus challenging the classification as a nonspecific dermatosis. METHODS: We report 5 patients with ED in association with chronic lymphocytic leukemia (CLL). We further investigated the presence of neoplastic B-cells in the skin infiltrate by immunohistochemistry and immunoglobulin heavy chain rearrangement and compared these to extracutaneous manifestations of CLL...
November 8, 2018: Journal of Cutaneous Pathology
Katrien Van Roosbroeck, Recep Bayraktar, Steliana Calin, Johannes Bloehdorn, Mihnea Paul Dragomir, Keishi Okubo, Maria Teresa Sabrina Bertilaccio, Simonetta Zupo, M James You, Gianluca Gaidano, Davide Rossi, Shih-Shih Chen, Nicholas Chiorazzi, Philip Thompson, Alessandra Ferrajoli, Francesco Bertoni, Stephan Stilgenbauer, Michael J Keating, George A Calin
Richter syndrome represents the transformation of the most frequent type of leukemia, chronic lymphocytic leukemia into an aggressive lymphoma. Patients with Richter syndrome have limited response to therapies and dismal survival. The underlying mechanisms of transformation are insufficiently understood and there is a major lack of knowledge regarding the roles of microRNAs that have already proved to be causative for most cases of chronic lymphocytic leukemia. Here, by using four types of genomic platforms and independent sets of patients from three institutions, we identified microRNAs involved in the transformation of chronic lymphocytic leukemia to Richter syndrome...
November 8, 2018: Haematologica
AnnaLynn M Williams, Andrea M Baran, Carla Casulo, Patrick Reagan, Jonathan W Friedberg, Margaret Helber, Jeremiah Moore, Elizabeth Baloga, Clive S Zent, Paul M Barr
BACKGROUND: As oral targeted agents, such as ibrutinib, become more widely used, understanding the impact of suboptimal dosing on overall survival (OS) and progression-free survival (PFS) outside of clinical trials is imperative. PATIENTS AND METHODS: Data on ibrutinib discontinuation, dose reductions, and treatment interruptions were collected on 170 non-Hodgkin lymphoma and chronic lymphocytic leukemia (CLL; n = 115, 64%) patients treated with ibrutinib at a single institution...
October 13, 2018: Clinical Lymphoma, Myeloma & Leukemia
Jacob D Soumerai, Ai Ni, Guan Xing, Julie Huang, Richard R Furman, Jeffrey Jones, Jeffrey P Sharman, Michael Hallek, Adeboye H Adewoye, Ronald Dubowy, Lyndah Dreiling, Andrew D Zelenetz
The CLL-IPI is a risk-weighted prognostic model for previously untreated patients with chronic lymphocytic leukemia (CLL), but has not been evaluated in patients with relapsed CLL or on novel therapies. We evaluated the CLL-IPI in 897 patients with relapsed/refractory CLL in 3 randomized trials testing idelalisib (PI3Kδ inhibitor). The CLL-IPI identified patients as low (2.2%), intermediate (12.8%), high (48.7%), and very high (36.2%) risk and was prognostic for survival (log-rank p < .0001; C-statistic 0...
November 8, 2018: Leukemia & Lymphoma
Stephanie L Skala, David R Lucas, Rajan Dewar
CONTEXT.—: Histiocytic sarcoma is a rare neoplasm of mature histiocytes with an aggressive clinical course that can arise de novo or from a low-grade B-cell lymphoma. In particular, chronic lymphocytic leukemia/small lymphocytic lymphoma is a very common malignancy in the Western hemisphere, and most cases of chronic lymphocytic leukemia/small lymphocytic lymphoma have an indolent course and behavior. However, 2% to 8% of chronic lymphocytic leukemia/small lymphocytic lymphoma cases transform...
November 2018: Archives of Pathology & Laboratory Medicine
Cecilia M Rodriguez, Claudio Bussi, Daniela S Arroyo, Dario Sastre, Viviana Heller, Carmen Stanganelli, Irma Slavutsky, Pablo Iribarren
No abstract text is available yet for this article.
November 8, 2018: Leukemia & Lymphoma
Joel D Leverson, Dan Cojocari
BCL-2 family proteins regulate the intrinsic pathway of programmed cell death (apoptosis) and play a key role in the development and health of multicellular organisms. The dynamics of these proteins' expression and interactions determine the survival of all cells in an organism, whether the healthy cells of a fully competent immune system or the diseased cells of an individual with cancer. Anti-apoptotic proteins like BCL-2, BCL-XL , and MCL-1 are well-known for maintaining tumor cell survival and are therefore attractive drug targets...
2018: Frontiers in Oncology
Manuel R Espinoza-Gutarra, Sherri L Cervantez, Zohra Nooruddin
CNS involvement by CLL is a rare occurrence, usually happening in the context of a transformation to a more aggressive lymphoma in what is known as Richter's transformation. We report a patient with active CLL who developed confusion and was found to have West Nile encephalitis that initially mimicked CNS involvement by CLL. The patient recovered with supportive treatment and later restarted ibrutinib therapy. This case illustrates the importance of maintaining a broad differential among cancer patients with new onset confusion as well as that of questioning malignant infiltration of CNS when there is concomitant active CNS infection...
2018: Case Reports in Hematology
Yann Rateau, Michael Harbouche, Gandhi Damaj, Xavier Troussard
Environmental factors have an impact on the effectiveness of treatments for chronic lymphocytic leukemia: vulnerability, organization of the supply of care and proximity of the patient to health professionals. The disparity of care was assessed; vulnerability by the European index of deprivation, the provision of care by values of localized potential accessibility to general practitioners, nurses and pharmacists and hospital supply by the density of hematologists and time access to the center. The data, extracted from the public databases for each grouped island for statistical information, were cross-referenced to apply a principal component analysis and group them into 4 clusters...
November 2, 2018: Bulletin du Cancer
Caspar da Cunha-Bang, Carsten Utoft Niemann
Bruton's tyrosine kinase (BTK) is crucial in B-cell development and survival. The role of BTK as a downstream kinase in the B-cell receptor (BCR) signaling pathway is well described. As a key player in the pathogenesis of B-cell malignancies, targeting of dysregulated BCR signaling has been explored by development of inhibitors of downstream mediators. Discovery of the biological function of BTK and the development of covalent inhibitors for clinical use, ibrutinib as the lead agent and acalabrutinib as the second clinically approved BTK inhibitor, have revolutionized the treatment options for B-cell malignancies...
November 3, 2018: Drugs
Jialei Song, Chunmao Yuan, Jue Yang, Tangjingjun Liu, Yao Yao, Xiao Xiao, Babu Gajendran, Dahai Xu, You-Jun Li, Chunlin Wang, Wuling Liu, Min Wen, David Spaner, Jorge Filmus, Eldad Zacksenhaus, Yiguo Zhang, Xiaojiang Hao, Yaacov Ben-David
E26 transformation-specific (ETS) gene family contains a common DNA binding domain, the ETS domain, responsible for sequence-specific DNA recognition on target promoters. The Fli-1 oncogene, a member of ETS gene family, plays a critical role in hematopoiesis and is overexpressed in diverse hematological malignancies. This ETS transcription factor regulates genes controlling several hallmarks of cancer and thus represents an excellent target for cancer therapy. Through screening compounds isolated from the medicinal plant Dysoxylum binectariferum in China, we identified two chemically related flavagline-like compounds including 4'-demethoxy-3',4'-methylenedioxyrocaglaol and rocaglaol that strongly inhibited Fli-1 transactivation ability...
November 2, 2018: FEBS Journal
Yasir Khan, Susan O'Brien
Acalabrutinib received an accelerated US FDA approval for patients with relapsed/refractory mantle cell lymphoma in 2017 and is currently being evaluated in chronic lymphocytic leukemia (CLL). To date, Ibrutinib is the only Bruton tyrosine kinase (BTK) inhibitor that's approved for treatment of CLL. Acalabrutinib is a second generation BTK inhibitor that binds covalently to the Cys481 residue on BTK and has half maximal inhibitory concentration (IC50 ) of 3 nM. In preclinical mouse models, acalabrutinib significantly reduced proliferation of CLL cells...
November 1, 2018: Future Oncology
Eleanor Russell-Goldman, Jason L Hornick, Xiaohua Qian, Vickie Y Jo
BACKGROUND: Ewing sarcoma (ES) is a round cell sarcoma that can be challenging to diagnose on cytologic material given its significant overlap with numerous mesenchymal, epithelial, and lymphoid cytomorphologic mimics. The objective of this study was to assess the utility of a novel marker, NKX2.2, in the diagnosis of ES in cytologic material and its ability to distinguish ES from its mimics. METHODS: NKX2.2 immunohistochemistry was performed on cell blocks from 107 fine-needle aspirations, and nuclear expression was scored semiquantitatively for extent and intensity...
November 2018: Cancer Cytopathology
Samantha Drennan, Giorgia Chiodin, Annalisa D'Avola, Ian Tracy, Peter Wm Johnson, Livio Trentin, Andrew J Steele, Graham Packham, Freda K Stevenson, Francesco Forconi
PURPOSE: In chronic lymphocytic leukemia (CLL), disease progression associates with surface IgM (sIgM) levels and signaling capacity. These are variably down-modulated in vivo and recover in vitro, suggesting a reversible influence of tissue-located antigen. Therapeutic targeting of sIgM function via ibrutinib, an inhibitor of Bruton's tyrosine kinase (BTK), causes inhibition and tumor cell redistribution into the blood, with significant clinical benefit. Circulating CLL cells persist in an inhibited state, offering a tool to investigate the effects of drug on BTK-inhibited sIgM...
October 29, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Rodolfo Patussi Correia, Flávia Amoroso Matos E Silva, Nydia Strachman Bacal, Paulo Vidal Campregher, Nelson Hamerschlak, Gustavo Pessini Amarante-Mendes
Background: Although chronic lymphocytic leukemia is basically a B cell disease, its pathophysiology and evolution are thought to be significantly influenced by T cells, as these are probably the most important interaction partner of neoplastic B cells, participating in their expansion, differentiation and survival. Chronic lymphocytic leukemia B cells may also drive functional and phenotypic changes of non-malignant T cells. There are few data about the association between memory T cells and prognosis, especially related to ZAP-70, a common reliable surrogate of the gold standard chronic lymphocytic leukemia prognostic markers...
October 2018: Hematology, transfusion and cell therapy
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