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https://www.readbyqxmd.com/read/28728469/characterizing-patients-with-multiple-chromosomal-aberrations-detected-by-fish-in-chronic-lymphocytic-leukemia
#1
Isabel González-Gascón Y Marín, María Hernández-Sanchez, Ana Eugenia Rodríguez-Vicente, Anna Puiggros, Rosa Collado, Elisa Luño, Teresa González, Neus Ruiz-Xivillé, Margarita Ortega, Eva Gimeno, Carolina Muñoz, Maria Stefania Infante, Julio Delgado, María Teresa Vargas, Marcos González, Francesc Bosch, Blanca Espinet, Jesús María Hernández-Rivas, José Ángel Hernández
We analyzed the features of chronic lymphocytic leukemia (CLL) with multiple abnormalities (MA) detected by FISH. A local database including 2095 CLL cases was used and 323 with MA (15.4%) were selected. MA was defined by the presence of two or more alterations (deletions of 13q14 (13q-), 11q22 (11q-), 17p13 (17p-) or trisomy 12 (+12)). The combination of 13q- with 11q- and 13q- with 17p-, accounted for 58.2% of the series, in contrast to 11q- with 17p- (3.7%). Patients carrying MA since diagnosis presented a short time to first therapy(TTFT) (27 months) and overall survival (OS) (76 months)...
July 21, 2017: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/28726646/the-prognostic-significance-of-combaind-expression-of-zap-70-and-cd38-in-chronic-lymphocytic-leukemia
#2
T Kirtava, T Vatsadze, E Azrmaiparashili, D Ghirdaladze
Our aim was to assess the inter links of the markers CD38 and ZAP-70 based on our materials, the attitude according to the disease stage, and to document which of them had leading meaning for prognosis and treatmend of the disease. In our study we have used flow cytometry for detection CD38 and ZAP-70+ markers expression. (58 patients to assessments their prognostic value in сhronic lymphocytic leukemia (CLL), Correlation to Rai stages and relationships between this markers and outcome of therapy). We divided all patients in two groups based on level of ZAP-70+ cell and CD38+cells,(I group-patients) ZAP-70+ cells <20% CD38+<30% and ZAP-70+ cells >20% and CD38>30%,(II group) becaus our in investigation shows, that ZAP -70+ is very importance independent prognoctic marker as why in ZAP-70+ cases when its number was <20%, patients had favorable prognosis - the big part of them (13(40...
June 2017: Georgian Medical News
https://www.readbyqxmd.com/read/28724540/targeting-bcl-2-in-b-cell-lymphomas
#3
Matthew S Davids
The B-cell leukemia/lymphoma-2 (BCL-2) family of proteins governs the intrinsic pathway of mitochondrial apoptosis. Dysregulation of BCL-2 has long been known to be a crucial part of the pathophysiology of B-cell lymphomas, yet several early attempts to target this pathway therapeutically were unsuccessful due to toxicity, lack of efficacy, or both. Recently, a highly potent and selective oral BCL-2 antagonist, venetoclax, was approved in chronic lymphocytic leukemia (CLL), where it has proven to be highly active, even in patients with high risk del(17p) disease...
July 19, 2017: Blood
https://www.readbyqxmd.com/read/28720054/impact-of-novel-agents-on-patient-relevant-outcomes-in-patients-with-previously-untreated-cll-who-are-not-eligible-for-fludarabine-based-therapy
#4
Moushmi Singh, Stuart Mealing, Simona Baculea, Sarah Cote, Jo Whelan
BACKGROUND: Chronic lymphocytic leukemia (CLL) is an orphan disease that primarily affects the elderly. The majority of symptomatic patients eligible for frontline treatment are unfit for fludarabine based chemoimmunotherapy. Historical treatment includes chlorambucil (Chl), bendamustine/rituximab (BR), and chlorambucil/rituximab/ChlR combination. Clinical guidelines now recommend the use of novel agents, such as ibrutinib (Ibr), in both frontline and relapse settings and other novel agents, such as idelalisib (with rituximab), in relapse settings...
July 19, 2017: Journal of Medical Economics
https://www.readbyqxmd.com/read/28718694/updating-survival-estimates-in-patients-with-chronic-lymphocytic-leukemia-or-small-lymphocytic-lymphoma-cll-sll-based-on-treatment-free-interval-length
#5
Eric M Ammann, Tait D Shanafelt, Kara B Wright, Bradley D McDowell, Brian K Link, Elizabeth A Chrischilles
We hypothesized that the length of treatment-free survival following (a) initial diagnosis and (b) first-line treatment would be associated with improved subsequent five-year relative survival (RS5) in patients with chronic lymphocytic leukemia or small lymphocytic lymphoma (CLL/SLL). 19,879 patients incident CLL/SLL cases (median age = 76 years) were identified from SEER-Medicare. RS5 improved from 0.73 (95% CI: 0.72, 0.74) at diagnosis to 0.81 (95% CI: 0.80, 0.82) at year 1 and 0.89 (95% CI: 0.83, 0.96) at year 10 among those who had not received treatment...
July 18, 2017: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/28715249/durable-molecular-remissions-in-chronic-lymphocytic-leukemia-treated-with-cd19-specific-chimeric-antigen-receptor-modified-t-cells-after-failure-of-ibrutinib
#6
Cameron J Turtle, Kevin A Hay, Laïla-Aïcha Hanafi, Daniel Li, Sindhu Cherian, Xueyan Chen, Brent Wood, Arletta Lozanski, John C Byrd, Shelly Heimfeld, Stanley R Riddell, David G Maloney
Purpose We evaluated the safety and feasibility of anti-CD19 chimeric antigen receptor-modified T (CAR-T) cell therapy in patients with chronic lymphocytic leukemia (CLL) who had previously received ibrutinib. Methods Twenty-four patients with CLL received lymphodepleting chemotherapy and anti-CD19 CAR-T cells at one of three dose levels (2 × 10(5), 2 × 10(6), or 2 × 10(7) CAR-T cells/kg). Nineteen patients experienced disease progression while receiving ibrutinib, three were ibrutinib intolerant, and two did not experience progression while receiving ibrutinib...
July 17, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28714866/ibrutinib-treatment-improves-t-cell-number-and-function-in-cll-patients
#7
Meixiao Long, Kyle Beckwith, Priscilla Do, Bethany L Mundy, Amber Gordon, Amy M Lehman, Kami J Maddocks, Carolyn Cheney, Jeffrey A Jones, Joseph M Flynn, Leslie A Andritsos, Farrukh Awan, Joseph A Fraietta, Carl H June, Marcela V Maus, Jennifer A Woyach, Michael A Caligiuri, Amy J Johnson, Natarajan Muthusamy, John C Byrd
BACKGROUND: Ibrutinib has been shown to have immunomodulatory effects by inhibiting Bruton's tyrosine kinase (BTK) and IL-2-inducible T cell kinase (ITK). The relative importance of inhibiting these 2 kinases has not been examined despite its relevance to immune-based therapies. METHODS: Peripheral blood mononuclear cells from chronic lymphocytic leukemia (CLL) patients on clinical trials of ibrutinib (BTK/ITK inhibitor; n = 19) or acalabrutinib (selective BTK inhibitor; n = 13) were collected serially...
July 17, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28710251/role-for-zap-70-signaling-in-the-differential-effector-functions-of-rituximab-and-obinutuzumab-ga101-in-chronic-lymphocytic-leukemia-b-cells
#8
Sladjana Skopelja-Gardner, Jonathan D Jones, B JoNell Hamilton, Alexey V Danilov, William F C Rigby
Rituximab (RTX) has been the hallmark anti-CD20 mAb for the treatment of B cell neoplasms, including B cell chronic lymphocytic leukemia (B-CLL). Recently, a novel humanized anti-CD20 mAb obinutuzumab (GA101) has been implemented as first-line CLL therapy. Treatment of CLL patients with RTX is associated with CD20 loss via an FcγR-mediated process, trogocytosis. RTX-induced trogocytosis has been characterized as both the means of resistance to therapy, via loss of cell surface target proteins (antigenic modulation), as well as a process that alters B cell phenotype and function...
July 14, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28708231/ibrutinib-treatment-of-a-patient-with-relapsing-chronic-lymphocytic-leukemia-and-sustained-remission-of-richter-syndrome
#9
Elisa Albi, Stefano Baldoni, Patrizia Aureli, Erica Dorillo, Beatrice Del Papa, Stefano Ascani, Mauro Di Ianni, Franca Falzetti, Paolo Sportoletti
PURPOSE: Richter syndrome (RS) is a rare event in chronic lymphocytic leukemia (CLL) that is influenced by biological factors and prior CLL treatments. Ibrutinib is a Bruton tyrosine kinase inhibitor that has shown remarkable efficacy in CLL; however, little is known about its relationship to RS. We report a case of ibrutinib efficacy against CLL in a patient with prolonged remission of RS. METHODS: The patient was diagnosed with CLL in 2003. Biological findings at onset included absent ZAP70 expression, mutated IGVH, and NOTCH1 mutation...
July 5, 2017: Tumori
https://www.readbyqxmd.com/read/28696801/analysis-of-the-risk-of-infection-in-patients-with-chronic-lymphocytic-leukemia-in-the-era-of-novel-therapies
#10
AnnaLynn M Williams, Andrea M Baran, Philip J Meacham, Megan M Feldman, Hugo E Valencia, Catherine Newsom-Stewart, Nealansh Gupta, Michelle C Janelsins, Paul M Barr, Clive S Zent
We studied the risk of infections in patients with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL). Major infections were defined as requiring hospital admission or intravenous antimicrobial treatment. Incidence rate (IR) ratios (IRR) were used to compare infection rates. Of 263 CLL patients followed for 936.9 person-years, 60% required treatment for progressive CLL (66 received ibrutinib). Infections occurred in 71.9% patients (IR 92.4/100 person-years) with 31.9% having major infections (IR 20...
July 11, 2017: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/28685928/management-of-patients-with-previously-untreated-chronic-lymphocytic-leukaemia-with-obinutuzumab-and-chlorambucil
#11
REVIEW
Constantine Tam, Bryone Kuss, Stephen Opat, Joy Boulos, Paula Marlton
Patients with chronic lymphocytic leukaemia (CLL) are generally older, with many considered 'unfit' for fludarabine-cyclophosphamide-rituximab therapy. In these patients, the combination of obinutuzumab-chlorambucil may be an appropriate therapeutic choice. Obinutuzumab-chlorambucil has been demonstrated to improve overall survival rates compared to chlorambucil alone and to improve progression-free survival and overall response rates compared to rituximab-chlorambucil. This combination can lead to certain toxicities that need to be addressed through appropriate patient selection, pre-medication and management...
July 2017: Internal Medicine Journal
https://www.readbyqxmd.com/read/28685851/risk-of-cutaneous-t-cell-lymphoma-in-patients-with-chronic-lymphocytic-leukemia-and-other-subtypes-of-non-hodgkin-lymphoma
#12
Timothy W Chang, Amy L Weaver, Tait D Shanafelt, Thomas M Habermann, Cooper C Wriston, James R Cerhan, Timothy G Call, Jerry D Brewer
BACKGROUND: Second hematologic cancers in patients with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL) are well documented and include Hodgkin lymphoma, therapy-related acute myeloid leukemia/myelodysplastic syndromes, and transformation to diffuse large B-cell lymphoma. Although cutaneous T-cell lymphoma (CTCL) has been reported in patients with CLL, the incidence and comparison to expected rates are unknown. We evaluated the incidence of CTCL among patients with CLL or other non-Hodgkin lymphoma (NHL) subtypes using data from the Surveillance, Epidemiology, and End Results (SEER) Program...
July 7, 2017: International Journal of Dermatology
https://www.readbyqxmd.com/read/28670499/wnt-signaling-pathway-protein-lef1-in-cancer-as-a-biomarker-for-prognosis-and-a-target-for-treatment
#13
REVIEW
Larion Santiago, Garrett Daniels, Dongwen Wang, Fang-Ming Deng, Peng Lee
Transcription factors are regulatory proteins that either activate or repress the transcription of genes via binding to DNA regulatory sequences and regulating recruitment of transcriptional complexes. Lymphoid enhancer-binding factor 1 (LEF1), a member of the T-cell Factor (TCF)/LEF1 family of high-mobility group transcription factors, is a downstream mediator of the Wnt/β-catenin signaling pathway, but can also modulate gene transcription independently. LEF1 is essential in stem cell maintenance and organ development, especially in its role in epithelial-mesenchymal transition (EMT) by activating the transcription of hallmark EMT effectors including N-Cadherin, Vimentin, and Snail...
2017: American Journal of Cancer Research
https://www.readbyqxmd.com/read/28669130/review-of-the-clinical-pharmacokinetics-and-pharmacodynamics-of-alemtuzumab-and-its-use-in-kidney-transplantation
#14
REVIEW
Marieke van der Zwan, Carla C Baan, Teun van Gelder, Dennis A Hesselink
Alemtuzumab is a humanized monoclonal antibody against CD52 and causes depletion of T and B lymphocytes, monocytes, and NK cells. Alemtuzumab is registered for the treatment of multiple sclerosis (MS) and is also used in chronic lymphocytic leukemia (CLL). Alemtuzumab is used off-label in kidney transplantation as induction and anti-rejection therapy. The objective of this review is to present a review of the pharmacokinetics, pharmacodynamics, and use of alemtuzumab in kidney transplantation. A systematic literature search was conducted using Ovid Medline, Embase, and Cochrane Central Register of controlled trials...
July 1, 2017: Clinical Pharmacokinetics
https://www.readbyqxmd.com/read/28664772/bendamustine-hydrochloride-in-patients-with-b-cell-malignancies-who-have-comorbidities-is-there-an-optimal-dose
#15
Max J Gordon, Lionel D Lewis, Jennifer R Brown, Alexey V Danilov
The majority of patients with non-Hodgkin lymphoma (NHL) and chronic lymphocytic leukemia (CLL) present with comorbidities. Many of them are poor candidates for intensive chemo-immunotherapy regimens, such as FCR (fludarabine, cyclophosphamide, rituximab). Still, most clinical trials aim to enroll 'fit' patients, who poorly represent the community oncology population. Areas covered: In the past decade, bendamustine hydrochloride, a cytotoxic agent with structural similarities to both alkylating agents and purine analogs, has received widespread use in therapy of NHL and CLL, and has demonstrated a relatively favorable toxicity profile...
July 10, 2017: Expert Review of Hematology
https://www.readbyqxmd.com/read/28661188/bruton-s-tyrosine-kinase-inhibitors-in-b-cell-lymphoma-current-experience-and-future-perspectives
#16
T Seiler, M Dreyling
The Bruton tyrosine kinase (BTK) is a central hub in the B cell receptor (BCR) pathway and strongly influences B cell maturation, differentiation and proliferation. Not surprisingly, BTK plays an essential role in the pathogenesis of various B cell lymphomas. Inhibitors of BTK have broadened our therapeutic options in several B cell lymphomas and already are an integral element in the treatment of Mantle Cell Lymphoma (MCL), chronic lymphocytic leukemia (CLL) and Waldenström's marcoglobulinemia. Several second generation BTK inhibitors are in clinical development and might further improve tolerability and efficacy of therapy in advanced stage CLL and MCL...
July 10, 2017: Expert Opinion on Investigational Drugs
https://www.readbyqxmd.com/read/28659152/idelalisib-may-have-the-potential-to-increase-radiotherapy-side-effects
#17
Thomas Gryc, Florian Putz, Nicole Goerig, Sonia Ziegler, Rainer Fietkau, Luitpold V Distel, Barbara Schuster
INTRODUCTION: Idelalisib is approved for the treatment of relapsed chronic lymphocytic leukemia together with Rituximab and for monotherapy of follicular B-cell non-Hodgkin's lymphoma and small lymphocytic lymphoma. It is a potent and selective phosphatidylinositol 3-kinase-δ (PI3K-δ) inhibitor. PI3K-δ primarily is expressed in B-cells and prevents effectively proliferation in malignant B-cells. METHODS: We provide a detailed report on treatment history and photo documentation of acute adverse effects of radiation therapy with simultaneous Idelalisib medication in one case of B-CLL...
June 28, 2017: Radiation Oncology
https://www.readbyqxmd.com/read/28658265/enhanced-cdc-of-b-cell-chronic-lymphocytic-leukemia-cells-mediated-by-rituximab-combined-with-a-novel-anti-complement-factor-h-antibody
#18
Mark T Winkler, Ryan T Bushey, Elizabeth B Gottlin, Michael J Campa, Eross S Guadalupe, Alicia D Volkheimer, J Brice Weinberg, Edward F Patz
Rituximab therapy for B cell chronic lymphocytic leukemia (B-CLL) has met with mixed success. Among several factors to which resistance can be attributed is failure to activate complement dependent cytotoxicity (CDC) due to protective complement regulatory proteins, including the soluble regulator complement factor H (CFH). We hypothesized that rituximab killing of non-responsive B-CLL cells could be augmented by a novel human monoclonal antibody against CFH. The B cells from 11 patients with B-CLL were tested ex vivo in CDC assays with combinations of CFH monoclonal antibody, rituximab, and a negative control antibody...
2017: PloS One
https://www.readbyqxmd.com/read/28645939/combined-btk-and-pi3k%C3%AE-inhibition-with-acalabrutinib-and-acp-319-improves-survival-and-tumor-control-in-cll-mouse-model
#19
Carsten U Niemann, Helena I Mora-Jensen, Eman L Dadashian, Fanny Krantz, Todd Covey, Shih-Shih Chen, Nicholas- Chiorazzi, Raquel Izumi, Roger Ulrich, Brian J Lannutti, Adrian Wiestner, Sarah E M Herman
Purpose: Targeting the B-cell receptor (BCR) pathway with inhibitors of BTK and PI3K-delta is highly effective for the treatment of chronic lymphocytic leukemia (CLL). However, deep remissions are uncommon and drug resistance with single-agent therapy can occur. In vitro studies support the effectiveness of combing PI3K-delta and BTK inhibitors. <p>Experimental design: As CLL proliferation and survival depends on the microenvironment, we used murine models to assess the efficacy of the BTK inhibitor acalabrutinib combined with the PI3K-delta inhibitor ACP-319 in vivo We compared single-agent with combination therapy in TCL1-192 cell-injected mice, a model of aggressive CLL...
June 23, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28644154/acute-promyelocytic-leukemia-and-chronic-lymphocytic-leukemia-concomitant-presentation-of-two-molecularly-distinct-entities
#20
Jingdong Su, Diana Veillon, Rodney Shackelford, James Cotelingam, Hazem El-Osta, Glenn Mills, Reinhold Munker, Srinivas Devarakonda
Acute myeloid leukemia (AML) developing in patients with chronic lymphocytic leukemia (CLL) is very uncommon and usually associated with prior treatment. Acute promyelocytic leukemia (APL) accounts for a very small proportion of treatment-associated AML. So far, there has been only one reported case of APL occurring post radiation for prostate cancer in a patient with CLL. We report herein the first case of APL and CLL presenting concomitantly in an untreated patient. Evaluation of peripheral blood and bone marrow aspirate with immunohistochemistry, flow cytometry, and FISH to confirm two morphologically, molecularly and genetically distinct leukemic populations characteristic of APL and CLL is required...
May 2017: Journal of the Louisiana State Medical Society: Official Organ of the Louisiana State Medical Society
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