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"Chronic lymphocytic leukemia"

Peter Valent, Emir Hadzijusufovic, Thomas Grunt, Heidrun Karlic, Barbara Peter, Harald Herrmann, Gregor Eisenwort, Gregor Hoermann, Axel Schulenburg, Michael Willmann, Rainer Hubmann, Medhat Shehata, Edgar Selzer, Karoline V Gleixner, Thomas Rülicke, Wolfgang R Sperr, Brigitte Marian, Michael Pfeilstöcker, Hubert Pehamberger, Felix Keil, Ulrich Jäger, Christoph Zielinski
In 2008 the Ludwig Boltzmann Cluster Oncology (LBC ONC) was established on the basis of two previous Ludwig Boltzmann Institutes working in the field of hematology and cancer research. The general aim of the LBC ONC is to improve treatment of hematopoietic neoplasms by eradicating cancer-initiating and disease-propagating cells, also known as leukemic stem cells (LSC) in the context of leukemia. In a first phase, the LBC ONC characterized the phenotype and molecular aberration profiles of LSC in various malignancies...
July 13, 2018: Wiener Klinische Wochenschrift
William J Archibald, Philip J Meacham, AnnaLynn M Williams, Andrea M Baran, Adrienne I Victor, Paul M Barr, Deepak M Sahasrahbudhe, Clive S Zent
Melanoma is significantly more common and is associated with a poorer prognosis in patients with an underlying B-cell malignancy. This study reports on the management of patients with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL) and a subsequent diagnosis of melanoma. In the Wilmot Cancer Institute CLL cohort, which includes 470 patients followed for 2849 person-years, 18 patients (3.8%) developed 22 melanomas. Fourteen melanomas were invasive, a significantly higher rate as compared with the age and sex matched general population (standardized incidence ratio [SIR] 6...
July 6, 2018: Leukemia Research
Emanuela Rosati, Stefano Baldoni, Filomena De Falco, Beatrice Del Papa, Erica Dorillo, Chiara Rompietti, Elisa Albi, Franca Falzetti, Mauro Di Ianni, Paolo Sportoletti
Chronic lymphocytic leukemia (CLL) is an incurable B-cell neoplasm characterized by highly variable clinical outcomes. In recent years, genomic and molecular studies revealed a remarkable heterogeneity in CLL, which mirrored the clinical diversity of this disease. These studies profoundly enhanced our understanding of leukemia cell biology and led to the identification of new biomarkers with potential prognostic and therapeutic significance. Accumulating evidence indicates a key role of deregulated NOTCH1 signaling and NOTCH1 mutations in CLL...
2018: Frontiers in Oncology
Peter Dreger, Paolo Ghia, Johannes Schetelig, Michel van Gelder, Eva Kimby, Mauricette Michallet, Carol Moreno, Tadeusz Robak, Stephan Stilgenbauer, Emili Montserrat
High-risk chronic lymphocytic leukemia (CLL) has been defined by clinical and/or genetic resistance ( TP53 abnormalities) to treatment with chemoimmunotherapy (CIT). With the availability of pathway inhibitors (PI), such as kinase inhibitors and BCL2 antagonists, the outlook of CIT-resistant patients has dramatically improved. Here, we propose a revision of the concept of high-risk CLL, driven by TP53 abnormalities and response to treatment with PI. CLL high-risk-I, CIT-resistant is defined by clinically CIT-resistant disease with TP53 aberrations, but fully responsive to PI...
July 11, 2018: Blood
Xixi Xiang, Yu-Ping Wang, Hongbao Cao, Xi Zhang
Objective To investigate whether previously curated chronic lymphocytic leukemia (CLL) risk genes could be leveraged in gene marker selection for the diagnosis and prediction of CLL. Methods A CLL genetic database (CLL_042017) was developed through a comprehensive CLL-gene relation data analysis, in which 753 CLL target genes were curated. Expression values for these genes were used for case-control classification of four CLL datasets, with a sparse representation-based variable selection (SRVS) approach employed for feature (gene) selection...
January 1, 2018: Journal of International Medical Research
Ravi Kumar Jairam, Sadanand Rangnathrao Mallurwar, Suresh P Sulochana, Devaraj V Chandrasekar, Ravi Kanth Bhamidipati, Wolfgang Richter, Nuggehally R Srinivas, Ramesh Mullangi
Bendamustine, an alkylating anticancer agent, is used to treat chronic lymphocytic leukemia by intravenous infusion alone or in combination. The work aimed to develop a method to predict time vs. concentration profile for humans based on preclinical pharmacokinetics using the assumption of superimposability of normalized time course profiles of animals and humans. Standard allometric equations with/without correction factors (CF) were also used in prediction. The Vss was predicted by simple allometry of 0.312W0...
July 11, 2018: Drug Research
Muhammad Omar, Vasantha Gali, Arvin Santos, Mark Huber, Nishant Parmar
Dysproteinemia is excessive production of immunoglobulins from clonal proliferation of plasma or B cells. Cryoglobulins are a special group of immunoglobulins that precipitate below 37 degrees C. Type 1 cryoglobulinemia consists mostly of IgM and IgG that infrequently leads to glomerulonephritis. In these situations, an underlying malignancy is even rare with only 21 cases described so far with only four having chronic lymphocytic leukemia (CLL). We present a case of a 68-year-old male admitted with hypertension and kidney dysfunction who upon work up was found to have CLL...
February 2018: South Dakota Medicine: the Journal of the South Dakota State Medical Association
David Wanner, Michael Steurer
At ASH (American Society of Hematology) 2017 three out of a plethora of trials showed remarkable and promising results. The combinations of venetoclax with rituximab and ibrutinib with venetoclax convinced with striking efficacy together with a manageable safety profile in relapsed/refractory setting as well as in first line therapy of high-risk disease. These two combinations are potential new standard treatment options in chronic lymphocytic leukemia.
2018: Memo
Talal Hilal, Jeffrey A Betcher, Jose F Leis
PURPOSE OF REVIEW: Small molecule tyrosine kinase inhibitors (TKIs) and BCL2 inhibitors are oral targeted therapies that have changed the treatment approach to patients with chronic lymphocytic leukemia (CLL). The aim of this review is to summarize the relevant literature on the economic impact of oral novel therapies for the treatment of CLL and discuss the underlying factors and suggested solutions for high drug prices. RECENT FINDINGS: The cost of therapy for CLL has increased substantially since the introduction of oral therapies...
July 7, 2018: Current Hematologic Malignancy Reports
Jing Chang, Haiyong Peng, Brian C Shaffer, Sivasubramanian Baskar, Ina C Wecken, Matthew G Cyr, Gustavo J Martinez, Jo Soden, Jim Freeth, Adrian Wiestner, Christoph Rader
Although the five-year survival rate of chronic lymphocytic leukemia (CLL) patients has risen to >80%, the only potentially curative treatment is allogeneic hematopoietic stem cell transplantation (alloHSCT). To identify possible new monoclonal antibody (mAb) drugs and targets for CLL, we previously developed a phage display-based human mAb platform to mine the antibody repertoire of patients who responded to alloHSCT. We had selected a group of highly homologous post-alloHSCT mAbs that bound to an unknown CLL cell surface antigen...
July 6, 2018: Cancer Immunology Research
Filipa Mousinho, Tatiana Mendes, Paula Sousa E Santos, Maria João Acosta, José Pereira, Maria Arroz, Cândido Silva, Ana Paula Azevedo, Rita Oliveira, Martinha Chorão, Fernando Lima
Early-stage chronic lymphocytic leukemia (CLL) with neurologic involvement is a rare condition and should require a careful follow-up. Although no standard protocol exists for this condition, intrathecal chemotherapy, combined with systemic chemoimmunotherapy, has been used previously. This case describes the treatment of a patient with CLL and symptomatic compromise of the central nervous system. Our results suggest that a combination of chemotherapy, radiotherapy, and ibrutinib, administered sequentially over a 2-year period, led to a near-complete resolution of the cerebral spinal fluid neoplastic infiltration...
2018: Case Reports in Hematology
Véronique Leblond, Melih Aktan, Christelle M Ferra Coll, Caroline Dartigeas, Jens Kisro, Marco Montillo, João Raposo, Jean-Louis Merot, Susan Robson, Ekaterina Gresko, Francesc Bosch, Stephan Stilgenbauer, Robin Foà
The safety of obinutuzumab, alone or with chemotherapy, was studied in a non-randomized, open-label, non-comparative, Phase 3b study (GREEN) in previously untreated or relapsed/refractory chronic lymphocytic leukemia. Patients received obinutuzumab 1000 mg, alone or with chemotherapy (investigator's choice of fludarabine-cyclophosphamide for fit patients, chlorambucil for unfit patients or bendamustine for any patient), on day 1, 8 and 15 of cycle 1, and day 1 of cycles 2-6 (28-day cycles), with the cycle 1/day 1 dose administered over 2 days...
July 5, 2018: Haematologica
Lynne V Abruzzo, Carmen D Herling, George A Calin, Christopher Oakes, Lynn L Barron, Haley E Banks, Vikram Katju, Michael J Keating, Kevin R Coombes
Although +12 chronic lymphocytic leukemia comprises about 20% of cases, relatively little is known about its pathophysiology. These cases often demonstrate atypical morphologic and immunophenotypic features, high proliferative rates, unmutated immunoglobulin heavy chain variable region genes, and a high frequency of NOTCH1 mutation. Patients with +12 chronic lymphocytic leukemia have an intermediate prognosis, and show higher incidences of thrombocytopenia, Richter's transformation, and other second cancers...
July 5, 2018: Haematologica
Silvia Martinelli, Rossana Maffei, Stefania Fiorcari, Chiara Quadrelli, Patrizia Zucchini, Stefania Benatti, Leonardo Potenza, Mario Luppi, Roberto Marasca
No abstract text is available yet for this article.
July 5, 2018: Haematologica
Parag Mahale, Eric A Engels, Jill Koshiol
Hepatitis B virus (HBV) infection causes hepatocellular carcinoma (HCC). Associations with other cancers are not established. We systematically assessed associations between HBV infection and cancers in the US elderly population. We conducted a case-control study using the Surveillance, Epidemiology, and End Results (SEER)-Medicare database in US adults aged ≥66 years. Cases (N=1,825,316) were people with first cancers diagnosed in SEER registries (1993-2013). Controls (N=200,000) were randomly selected, cancer-free individuals who were frequency-matched to cases on age, sex, race, and calendar year...
July 4, 2018: International Journal of Cancer. Journal International du Cancer
Jennifer R Brown
No abstract text is available yet for this article.
July 2018: Haematologica
Silvia Mele, Stephen Devereux, Andrea G Pepper, Elvira Infante, Anne J Ridley
CD38 is a transmembrane exoenzyme that is associated with poor prognosis in chronic lymphocytic leukemia (CLL). High CD38 levels in CLL cells are linked to increased cell migration, but the molecular basis is unknown. CD38 produces nicotinic acid adenine dinucleotide phosphate and adenosine 5'-diphosphate-ribose, both of which can act to increase intracellular Ca2+ levels. Here we show that CD38 expression increases basal intracellular Ca2+ levels and stimulates CLL cell migration both with and without chemokine stimulation...
July 10, 2018: Blood Advances
Bolun Wang, Hui Lyu, Shanshan Pei, Deye Song, Jiangdong Ni, Bolin Liu
Cladribine (2CdA), a synthetic purine analog interfering with DNA synthesis, is a medication used to treat hairy cell leukemia (HCL) and B-cell chronic lymphocytic leukemia. Entinostat, a selective class I histone deacetylase (HDAC) inhibitor, shows antitumor activity in various human cancers, including hematological malignancies. The therapeutic potential of cladribine and entinostat against multiple myeloma (MM) remains unclear. Here we investigate the combinatorial effects of cladribine and entinostat within the range of their clinical achievable concentrations on MM cells...
July 3, 2018: Cell Cycle
Francesca R Mauro, Maria D Caputo, Serena Rosati, Sara Pepe, Daniela De Benedittis, Maria L De Luca, Robin Foà
In recent years, innovative mechanism-based drugs have enriched the therapeutic armamentarium for patients with chronic lymphocytic leukemia [CLL] and are widely used in the clinical practice. These small molecules targeting the B-cell receptor signaling pathway and the Bcl-2 anti-apoptotic protein offer new chemo-free options to both unfit patients and high-risk patients who show a poor response to chemoimmunotherapy. Nonetheless, treatment with ibrutinib, idelalisib and venetoclax is associated with unique side effects...
July 3, 2018: Expert Review of Hematology
Andrea Kaifie, Christian Schikowsky, Theresa Vasko, Thomas Kraus, Tim Henrik Brümmendorf, Patrick Ziegler
No abstract text is available yet for this article.
July 3, 2018: Leukemia & Lymphoma
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