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Chronic lymphocytic leukemia

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https://www.readbyqxmd.com/read/29352719/prognostic-testing-patterns-and-outcomes-of-chronic-lymphocytic-leukemia-patients-stratified-by-fluorescence-in-situ-hybridization-cytogenetics-a-real-world-clinical-experience-in-the-connect-cll-registry
#1
Anthony Mato, Chadi Nabhan, Neil E Kay, Nicole Lamanna, Thomas J Kipps, David L Grinblatt, Christopher R Flowers, Charles M Farber, Matthew S Davids, Pavel Kiselev, Arlene S Swern, Shriya Bhushan, Kristen Sullivan, E Dawn Flick, Jeff P Sharman
INTRODUCTION: Prognostic genetic testing is recommended for patients with chronic lymphocytic leukemia (CLL) to guide clinical management. Specific abnormalities, such as del(17p), del(11q), and unmutated IgHV, can predict the depth and durability of the response to CLL therapy. PATIENTS AND METHODS: In the present analysis of the Connect CLL Registry (ClinicalTrials.gov identifier, NCT01081015), a prospective observational cohort study of patients treated across 199 centers, the patterns of prognostic testing and outcomes of patients with unfavorable-risk genetics were analyzed...
December 6, 2017: Clinical Lymphoma, Myeloma & Leukemia
https://www.readbyqxmd.com/read/29352038/microenvironment-induced-cd44v6-promotes-early-disease-progression-in-chronic-lymphocytic-leukemia
#2
Julia C Gutjahr, Eva Szenes, Lisa Tschech, Daniela Asslaber, Michaela Schlederer, Simone Roos, Xiaobing Yu, Tamara Girbl, Christina Sternberg, Alexander Egle, Fritz Aberger, Ronen Alon, Lukas Kenner, Richard Greil, Veronique Orian-Rousseau, Tanja N Hartmann
Chronic lymphocytic leukemia (CLL) outgrowth depends on signals from the microenvironment. We have previously found that in vitro reconstitution of this microenvironment induces specific variant isoforms of the adhesion molecule CD44, which confer human CLL with high affinity to hyaluronan (HA). Here, we determined the in vivo contribution of standard CD44 and its variants to leukemic B-cell homing and proliferation in Tcl1 transgenic mice with a B-cell-specific CD44 deficiency. In these mice, leukemia onset was delayed and leukemic infiltration of spleen, liver, and lungs, but not of bone marrow was decreased...
January 19, 2018: Blood
https://www.readbyqxmd.com/read/29346066/expression-of-autophagy-related-genes-in-chronic-lymphocytic-leukemia-is-associated-with-disease-course
#3
Yi-Lin Kong, Ying Huang, Jia-Zhu Wu, Xin Cao, Jin-Hua Liang, Yi Xia, Wei Wu, Lei Cao, Hua-Yuan Zhu, Li Wang, Lei Fan, Jian-Yong Li, Wei Xu
Autophagy leads cells to different fates in various cell types and under diverse contexts. Chronic lymphocytic leukemia (CLL), an incurable hematologic neoplasm, has highly variable course and its heterogeneity prompts interest in exploring autophagic trajectories in CLL. We detected the mRNA levels of two autophagy-related genes, BECN1 and ATG5, assessed the association between expression levels and clinical characteristics, and did survival analysis. One hundred and six patients with CLL and fifty healthy controls were enrolled in the present study...
January 3, 2018: Leukemia Research
https://www.readbyqxmd.com/read/29344090/overexpression-of-the-proneural-transcription-factor-ascl1-in-chronic-lymphocytic-leukemia-with-a-t-12-14-q23-2-q32-3
#4
Theodora Malli, Melanie Rammer, Sabrina Haslinger, Jonathan Burghofer, Sonja Burgstaller, Hans-Christian Boesmueller, Renate Marschon, Wolfgang Kranewitter, Martin Erdel, Sabine Deutschbauer, Gerald Webersinke
Background: Translocations of the IGH locus on 14q32.3 are present in about 8% of patients with chronic lymphocytic leukemia (CLL) and contribute to leukemogenesis by deregulating the expression of the IGH-partner genes. Identification of these genes and investigation of the downstream effects of their deregulation can reveal disease-causing mechanisms. Case presentation: We report on the molecular characterization of a novel t(12;14)(q23.2;q32.3) in CLL. As a consequence of the rearrangement ASCL1 was brought into proximity of the IGHJ-Cμ enhancer and was highly overexpressed in the aberrant B-cells of the patient, as shown by qPCR and immunohistochemistry...
2018: Molecular Cytogenetics
https://www.readbyqxmd.com/read/29343153/cryptococcal-infections-in-two-patients-receiving-ibrutinib-therapy-for-chronic-lymphocytic-leukemia
#5
Matthew Stankowicz, Megan Banaszynski, Russell Crawford
Cryptococcal infections are responsible for significant morbidity and mortality in immunocompromised patients. Reports of these infections in patients on small molecular kinase inhibitors have not been widely reported in clinical trials. We describe one case of cryptococcal meningoencephalitis and one case of cryptococcal pneumonia in two patients who were receiving ibrutinib for chronic lymphocytic leukemia. Despite different sites of cryptococcal infection, both patients had similar presentations of acute illness...
January 1, 2018: Journal of Oncology Pharmacy Practice
https://www.readbyqxmd.com/read/29341268/evans-syndrome-secondary-to-undiagnosed-chronic-lymphocytic-leukemia-in-a-patient-with-unexplained-bleeding
#6
Christopher B Hergott, Olga Pozdnyakova
No abstract text is available yet for this article.
January 17, 2018: American Journal of Hematology
https://www.readbyqxmd.com/read/29341235/concomitant-cutaneous-squamous-cell-carcinoma-and-cll-in-a-patient-the-utility-of-18-f-fdg-pet-ct-in-differentiation-of-nodal-metastasis
#7
Kerem Ozturk, Celalettin Ustun, Sobia Khaja, Faqian Li, Matthew Rischall, Zuzan Cayci
INTRODUCTION: Head and neck cutaneous squamous cell carcinoma (cSCC) often presents with cervical lymph node metastases. Lymphoma is the second most common malignancy in the cervical region, however, it is rarely synchronous with head and neck cSCC. METHODS: We describe the unusual presentation of a patient with small lymphocytic lymphoma/chronic lymphocytic leukemia (SLL/CLL) and metastatic head and neck cSCC on 18-fluorodeoxyglucose positron emission tomography (18 F-FDG PET/CT)...
January 17, 2018: American Journal of Hematology
https://www.readbyqxmd.com/read/29338825/efficacy-of-rituximab-for-patients-with-chronic-lymphocytic-leukemia
#8
Heng Li, Wen Jie Xiong, Hui Min Liu, Shu Hua Yi, Rui Lü, Ting Yu Wang, Zhen Yu, Lu Gui Qiu, Zeng Jun Li
Objective To evaluate the efficacy of rituximab in treating chronic lymphocytic leukemia (CLL). Methods The clinical data of CLL patients receiving fludarabine,cyclophosphamide±rituximab (with or without rituximab) regimen or cyclophosphamide,vincristine,and prednisone±doxorubicin±rituximab regimen in our hospital from March 2000 to February 2015 were analyzed retrospectively. Therapeutic efficacies and survivals of patients treated with different regimens were evaluated and compared. Results The complete response (CR) rate and the overall response rate (ORR) in 72 patients (43...
December 20, 2017: Zhongguo Yi Xue Ke Xue Yuan Xue Bao. Acta Academiae Medicinae Sinicae
https://www.readbyqxmd.com/read/29333561/pharmacokinetics-of-the-b-cell-lymphoma-2-bcl-2-inhibitor-venetoclax-in-female-subjects-with-systemic-lupus-erythematosus
#9
Mukul Minocha, Jiewei Zeng, Jeroen K Medema, Ahmed A Othman
BACKGROUND AND OBJECTIVE: Venetoclax is an oral selective Bcl-2 inhibitor approved for the treatment of patients with chronic lymphocytic leukemia with 17p deletion. Mechanistic and preclinical evidence warranted evaluation of venetoclax for the treatment of systemic lupus erythematosus (SLE). This work characterized the pharmacokinetics of venetoclax in female subjects with SLE. METHODS: Single (10-500 mg) and multiple (30-600 mg) escalating doses of venetoclax or matching placebo were evaluated using randomized, double-blind, placebo-controlled designs (6 active and 2 placebo per dose with 73 unique SLE patients enrolled, 25 of whom enrolled twice)...
January 15, 2018: Clinical Pharmacokinetics
https://www.readbyqxmd.com/read/29333021/efficacy-and-safety-of-ibrutinib-in-indian-patients-with-relapsed-or-refractory-chronic-lymphocytic-leukemia-and-mantle-cell-lymphoma-cases-from-a-named-patient-program
#10
Mohan B Agarwal, Dinesh Bhurani, Chirag Shah, Nitin Sood, Manish Singhal, Anil Kamat, Subash Chezhian, Suryaprakash Mishra, Dinesh Nagrale
Context: This named patient program evaluated the safety and efficacy of ibrutinib, a selective inhibitor of Bruton's tyrosine kinase in Indian patients with relapsed/refractory chronic lymphocytic leukemia (CLL, with/without chromosome 17 deletion [del17p]) and mantle cell lymphoma (MCL). Subjects and Methods: The eight enrolled patients (relapsed/refractory CLL: n = 6 [4/6 patients with del17p] and relapsed/refractory MCL: n = 2) had median age of 55 years (range, 52-60) and had received a median of 3 (CLL patients) and 4 (MCL patients) prior therapies...
October 2017: Indian Journal of Medical and Paediatric Oncology
https://www.readbyqxmd.com/read/29329700/-a-listeria-breast-abscess-in-a-man
#11
E Marsaudon, J Berthy, S Mamoune, A Deniel, S Ksiyer, D Tiuca
INTRODUCTION: Listeriosis is a food-borne illness leading to bacteriemia or central nervous system infection especially in pregnant women or high-risk patients. It is rarely a localized infection. Breast contamination has rarely been reported in lactating women. We report a breast abscess in man. CASE REPORT: A 80 year old man, hypertensive and arrhythmic, was explored for weakness and dehydration. Type 2 diabetes and chronic lymphocytic leukemia were diagnosed...
January 9, 2018: La Revue de Médecine Interne
https://www.readbyqxmd.com/read/29326436/p66shc-deficiency-enhances-cxcr4-and-ccr7-recycling-in-cll-b-cells-by-facilitating-their-dephosphorylation-dependent-release-from-%C3%AE-arrestin-at-early-endosomes
#12
Laura Patrussi, Nagaja Capitani, Francesca Cattaneo, Noemi Manganaro, Alessandra Gamberucci, Federica Frezzato, Veronica Martini, Andrea Visentin, Pier Giuseppe Pelicci, Mario M D'Elios, Livio Trentin, Gianpietro Semenzato, Cosima T Baldari
Neoplastic cell traffic abnormalities are central to the pathogenesis of chronic lymphocytic leukemia (CLL). Enhanced CXC chemokine receptor-4 (CXCR4) and chemokine receptor-7 (CCR7) recycling contributes to the elevated surface levels of these receptors on CLL cells. Here we have addressed the role of p66Shc, a member of the Shc family of protein adaptors the expression of which is defective in CLL cells, in CXCR4/CCR7 recycling. p66Shc reconstitution in CLL cells reduced CXCR4/CCR7 recycling, lowering their surface levels and attenuating B-cell chemotaxis, due to their accumulation in Rab5+ endosomes as serine-phosphoproteins bound to β-arrestin...
January 12, 2018: Oncogene
https://www.readbyqxmd.com/read/29326230/base-resolution-analysis-of-dna-methylation-patterns-downstream-of-dnmt3a-in-mouse-na%C3%A3-ve-b-cells
#13
Christopher G Duncan, Hrisavgi D Kondilis-Mangum, Sara A Grimm, Pierre R Bushel, Kaliopi Chrysovergis, John D Roberts, Frederick L Tyson, B Alex Merrick, Paul A Wade
The DNA methyltransferase, Dnmt3a, is dynamically regulated throughout mammalian B cell development and upon activation by antigenic stimulation. Dnmt3a inactivation in hematopoietic stem cells has been shown to drive B cell-related malignancies, including chronic lymphocytic leukemia (CLL), and associates with specific DNA methylation patterns in transformed cells. However, while it is clear that inactivation of Dnmt3a in hematopoietic stem cells has profound functional impacts, the consequences of Dnmt3a inactivation in cells of the B lineage are unclear...
January 11, 2018: G3: Genes—Genomes—Genetics
https://www.readbyqxmd.com/read/29326123/tnf-receptor-signaling-is-a-driver-of-chronic-lymphocytic-leukemia-that-can-be-therapeutically-targeted-by-the-flavonoid-wogonin
#14
Claudia Dürr, Bola S Hanna, Angela Schulz, Fabienne Lucas, Manuela Zucknick, Axel Benner, Andrew Clear, Sibylle Ohl, Selcen Öztürk, Thorsten Zenz, Stephan Stilgenbauer, Min Li-Weber, Peter H Krammer, John G Gribben, Peter Lichter, Martina Seiffert
Chronic lymphocytic leukemia is a malignancy of mature B cells that strongly depend on microenvironmental factors and their deprivation has been identified as promising treatment approach for this incurable disease. Cytokine array screening of 247 chronic lymphocytic leukemia serum samples revealed elevated levels of TNF receptor-1 which were associated with poor clinical outcome. We detected a microenvironment-induced expression of TNF receptor-1 in chronic lymphocytic leukemia cells in vitro and aberrantly high expression of this receptor in proliferation centers of patients' lymph nodes...
January 11, 2018: Haematologica
https://www.readbyqxmd.com/read/29320898/did-i-miss-it-discovering-hidden-coexisting-hematological-neoplasms-a-single-institutional-review-of-100-collision-tumors
#15
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
https://www.readbyqxmd.com/read/29317997/experience-with-ibrutinib-for-first-line-use-in-patients-with-chronic-lymphocytic-leukemia
#16
REVIEW
Gilad Itchaki, Jennifer R Brown
Ibrutinib is the first in-class, orally administered, Bruton's tyrosine kinase (BTK) inhibitor that abrogates the critical signaling downstream of the B-cell receptor (BCR). This signaling is required for B-cell survival, proliferation and interaction with the microenvironment. Ibrutinib proved active in preclinical models of lymphoproliferative diseases and achieved impressive response rates in heavily pretreated relapsed and refractory (R/R) patients with chronic lymphocytic leukemia (CLL). Ibrutinib prolonged survival compared to standard therapy and mitigated the effect of most poor prognostic factors in CLL, thus becoming the main therapeutic option in high-risk populations...
January 2018: Therapeutic Advances in Hematology
https://www.readbyqxmd.com/read/29317454/casein-kinase-1-is-a-therapeutic-target-in-chronic-lymphocytic-leukemia
#17
Pavlina Janovska, Jan Verner, Jiri Kohoutek, Lenka Bryjova, Michaela Gregorova, Marta Dzimkova, Hana Skabrahova, Tomasz Radaszkiewicz, Petra Ovesna, Olga Vondalova Blanarova, Tereza Nemcova, Zuzana Hoferova, Katerina Vasickova, Lucie Smyckova, Alexander Egle, Sarka Pavlova, Lucie Poppova, Karla Plevova, Sarka Pospisilova, Vitezslav Bryja
Casein kinase (CK) 1δ/ε is a key component of non-canonical Wnt signaling pathways, which were shown previously to drive pathogenesis of chronic lymphocytic leukemia (CLL). In this study we investigated thoroughly the effects of CK1δ/ε inhibition on the primary CLL cells and analyzed the therapeutic potential in vivo using two murine model systems based on the Eµ-TCL1-induced leukemia (syngeneic adoptive transfer model and spontaneous disease development), which resemble closely the human CLL. We can demonstrate that CK1δ/ε inhibitor PF-670462 significantly blocks microenvironmental interactions - chemotaxis, invasion and communication with stromal cells in primary CLL cells in all major subtypes of CLL...
January 9, 2018: Blood
https://www.readbyqxmd.com/read/29316456/disease-characteristics-and-clinical-outcomes-in-patients-aged-less-than-40-with-chronic-lymphocytic-leukemia
#18
Bartlomiej M Getta, Sean Devlin, Jae H Park, Martin S Tallman, Ellin Berman
Outcomes in very young CLL patients (age ≤40) are not well characterized. We compared 71 consecutive patients aged ≤40 with 142 "older" matched patients >40 from our institution and used SEER database as an independent comparison group. Patients in the two age groups were diagnosed at similar Rai stage. At diagnosis, very young patients had a similar rate of adverse cytogenetics, IGHV mutation and ZAP70 expression and had lower beta-2-microglobulin and a lower incidence of second malignancies. There was no difference between the groups with respect to incidence of autoimmune manifestations, family history of lymphoma, time to initiation of CLL therapy, response to therapy, or Richter's transformation...
January 3, 2018: Leukemia Research
https://www.readbyqxmd.com/read/29316199/usefulness-of-the-cllflow-score
#19
Marc Sorigue, Mireia Franch-Sarto, Edurne Sarrate, Jordi Junca
BACKGROUND: The CLLflow score was recently suggested as an improvement over the Moreau score for the diagnosis and classification of B-cell lymphoproliferative disorders (B-LPD). METHODS: We determined the CLLflow score in peripheral blood or bone marrow of a series of cases with an inconclusive immunophenotype, including samples with a Moreau score of 3 (n=52) and CD5-positive with a score of 2 (n=38). As controls, B-LPD with a Moreau score of 0-1 (n=95), CD5-negative score 2 (n=24) and score 4-5 (i...
January 6, 2018: Cytometry. Part B, Clinical Cytometry
https://www.readbyqxmd.com/read/29315094/cd19-chimeric-antigen-receptor-t-cells-from-patients-with-chronic-lymphocytic-leukemia-display-an-elevated-ifn-%C3%AE-production-profile
#20
Isabelle Magalhaes, Ingrid Kalland, James N Kochenderfer, Anders Österborg, Michael Uhlin, Jonas Mattsson
CD19 chimeric antigen receptor (CAR) T cell immunotherapy has demonstrated dramatic results for the treatment of B cell malignancies such as chronic lymphocytic leukemia (CLL). As T cell defects are common in patients with CLL, we compared the T cells from these patients with healthy donors (HDs), and subsequently the CD19 CAR T cells produced from patients and HDs. Despite initial differences when comparing the phenotype of circulating T cells in patients with CLL and HDs, the CD19 CAR T cells manufactured from patients' or HDs' cells showed a similar phenotype (effector memory or terminally differentiated), both were specifically activated by and killed CD19 target cells, and secreted cytokines (ie, IL-2, TNF, and IFN-γ)...
January 8, 2018: Journal of Immunotherapy
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