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Chronic lymphocytic leukemia

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https://www.readbyqxmd.com/read/29775689/biomarkers-for-checkpoint-inhibition-in-hematologic-malignancies
#1
REVIEW
Djordje Atanackovic, Tim Luetkens
In the past few years we have seen remarkable paradigm shifts in the treatment of many solid tumors due to the introduction of inhibitors targeting immune checkpoints such as PD-1/PD-L1 and CTLA-4. Recent results indicate that checkpoint inhibition also represents a very promising approach for certain types of hematologic malignancies. Unfortunately, treatment with checkpoint inhibitors is also associated with substantial toxicities and high costs and only a subset of patients appears to derive clinical benefit from these treatments...
May 15, 2018: Seminars in Cancer Biology
https://www.readbyqxmd.com/read/29771146/nanosized-ethanol-based-malleable-liposomes-of-cytarabine-to-accentuate-transdermal-delivery-formulation-optimization-in-vitro-skin-permeation-and-in-vivo-bioavailability
#2
Rakesh Raj, Pooja Mongia Raj, Alpana Ram
Cytarabine is a pyrimidine nucleoside analog used predominantly for acute myeloid leukemia (AML) and also for other indications, including acute lymphocytic leukemia, chronic myelogenous leukemia, and lymphoma by parenteral route due to its low oral bioavailability. Parenteral administration requires constant plasma level, monitoring for its fluctuation and poor patients compliances. Hence the objective of this work is to construct optimized nanosized malleable liposomes of cytarabine to accentuate transdermal delivery of drug to circumvent previously mentioned drawbacks...
May 17, 2018: Artificial Cells, Nanomedicine, and Biotechnology
https://www.readbyqxmd.com/read/29769184/explaining-resistance-to-car-t-cells
#3
(no author information available yet)
A new study reveals several attributes of T cells from patients with chronic lymphocytic leukemia who respond to CAR T-cell therapy. The patients' T cells show increased expression of memory-related genes and high activity of STAT3, which promotes memory cell differentiation. The researchers also found that patients who underwent complete remission have certain CD8+ T cells.
May 16, 2018: Cancer Discovery
https://www.readbyqxmd.com/read/29768934/a-safety-profile-of-medications-used-to-treat-waldenstr%C3%A3-m-s-macroglobulinemia
#4
Ramón García-Sanz, Cristina Jiménez, Verónica González de la Calle, María Eugenia Sarasquete
Waldenström's macroglobulinemia (WM) is a B-cell lymphoproliferative disease with serum IgM monoclonal component and bone marrow infiltration by lymphoplasmacytic lymphoma. Traditional therapy was based on that regimens used for closely related entities, such as chronic lymphocytic leukemia or multiple myeloma. This resulted in a lack of drugs specifically approved for WM, until the discovery of the BTK inhibitors. Areas covered. Two main therapeutic attitudes are possible: 1) conventional therapies based on combinations with alkylating agents or proteasome inhibitors with steroids and anti-CD20 monoclonal antibodies, or; 2) new approaches with BTK inhibitors, usually alone...
May 17, 2018: Expert Opinion on Drug Safety
https://www.readbyqxmd.com/read/29765537/stat3-activated-cd36-facilitates-fatty-acid-uptake-in-chronic-lymphocytic-leukemia-cells
#5
Uri Rozovski, David M Harris, Ping Li, Zhiming Liu, Preetesh Jain, Alessandra Ferrajoli, Jan Burger, Phillip Thompson, Nitin Jain, William Wierda, Michael J Keating, Zeev Estrov
Although several studies established that unlike normal B cells chronic lymphocytic leukemia (CLL) cells metabolize fatty acids (FA), how CLL cells internalize FA is poorly understood. Because in various cell types CD36 facilitates FA uptake, we wondered whether a similar mechanism is operative CLL. We found that CD36 levels are higher in CLL cells than in normal B cells, and that small interfering RNA, CD36 neutralizing antibodies or sulfosuccinimidyl oleate (SSO) that inhibits CD36 significantly reduced the oxygen consumption of CLL cells incubated with FA...
April 20, 2018: Oncotarget
https://www.readbyqxmd.com/read/29764250/immunological-changes-with-kinase-inhibitor-therapy-for-chronic-lymphocytic-leukemia
#6
Christopher Pleyer, Adrian Wiestner, Clare Sun
Ibrutinib and idelalisib are kinase inhibitors that have revolutionized the treatment of chronic lymphocytic leukemia (CLL). Capable of inducing durable remissions, these agents also modulate the immune system. Both ibrutinib and idelalisib abrogate the tumor-supporting microenvironment by disrupting cell-cell interactions, modulating the T-cell compartment, and altering the cytokine milieu. Ibrutinib also partially restores T-cell and myeloid defects associated with CLL. In contrast, immune-related adverse effects, including pneumonitis, colitis, hepatotoxicity, and infections are of particular concern with idelalisib...
May 15, 2018: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/29763855/identification-of-new-phosphorylation-sites-of-cd23-in-b-cells-of-patients-with-chronic-lymphocytic-leukemia
#7
Martina Maďarová, Rastislav Mucha, Stanislav Hresko, Zuzana Makarová, Zuzana Gdovinová, Jarmila Szilasiová, Marianna Vitková, Tomáš Guman, Natalia Štecová, Tomas Dobransky
B-cell chronic lymphocytic leukemia (B-CLL) is the most common lymphoproliferative disorder in adults. Patients with B-CLL strongly express the CD23 - C type of lectin (low affinity IgE receptor, Fc epsilon RII), which is linked to B cell activation and proliferation. Phosphorylation in lymphocytes is tightly associated with regulation of protein activities, functional regulation and cell signaling, and may thus affect initiation and/or progression of the disease. Here we report changes in the phosphorylation of CD23 on threonine (pThr314) and two serine residues (pSer254, pSer265) in B lymphocytes of B-CLL patients, using a flow cytometry approach...
May 9, 2018: Leukemia Research
https://www.readbyqxmd.com/read/29762141/pd-1-expression-in-chronic-lymphocytic-leukemia-small-lymphocytic-lymphoma-cll-sll-and-large-b-cell-richter-transformation-dlbcl-rt-a-characteristic-feature-of-dlbcl-rt-and-potential-surrogate-marker-for-clonal-relatedness
#8
Rong He, Wei Ding, David S Viswanatha, Dong Chen, Min Shi, Daniel Van Dyke, Shulan Tian, Linda N Dao, Sameer A Parikh, Tait D Shanafelt, Timothy G Call, Stephen M Ansell, Jose F Leis, Ming Mai, Curtis A Hanson, Karen L Rech
Chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) is a low-grade B-cell neoplasm and ∼2% to 9% patients develop an aggressive lymphoma, most commonly diffuse large B-cell lymphoma (Richter transformation, DLBCL-RT). Programmed death-1 (PD-1) pathway plays a crucial role in tumor host immunity evasion and its blockade has emerged as an effective anti-cancer immunotherapy. PD-L1 and PD-1 expression has shown predictive value in anti-PD cancer immunotherapy; however, it has not been well documented in CLL/SLL and DLBCL-RT...
May 14, 2018: American Journal of Surgical Pathology
https://www.readbyqxmd.com/read/29761374/the-prognostic-role-of-hbv-infection-in-chronic-lymphocytic-leukemia
#9
Jin-Hua Liang, Rui Gao, Jun-Cheng Dai, Robert Peter Gale, Wang Li, Lei Fan, Zhi-Bin Hu, Wei Xu, Jian-Yong Li
PURPOSE: We attempt to assess the impact of hepatis-B virus (HBV) status on the prognosis of chronic lymphocytic leukemia (CLL) using a Chinese case cohort. METHODS: Five hundred and one consecutive newly diagnosed subjects with CLL were enrolled in this case cohort. HBV infection was defined as hepatitis B surface antigen (HBsAg) positive or hepatitis-B core antibody (HBcAb) positive. Univariate and stepwise multivariate Cox regression analyses were used to screen the prognostic risk factors associated with the end point of time-to-treatment (TTT) or overall survival (OS)...
May 14, 2018: Journal of Cancer Research and Clinical Oncology
https://www.readbyqxmd.com/read/29760835/cutaneous-mucormycosis-following-a-bullous-pemphigoid-flare-in-a-chronic-lymphocytic-leukemia-patient-on-ibrutinib
#10
Matthew K Stein, Saradasri Karri, Jackson Reynolds, Jeff Owsley, Austin Wise, Mike G Martin, Fereshteh Zare
While the recent development of novel therapeutics in oncology, such as small molecule kinase inhibitors (SMKIs), has enabled our ability to target disease-specific molecular pathways, the prolonged impact of these agents on the immune system and infectious risk remains to be seen. We present a 68-year-old male with refractory chronic lymphocytic leukemia (CLL) on ibrutinib monotherapy for 3 years who developed extensive cutaneous mucormycosis following a severe bullous pemphigoid (BP) flare. He received amphotericin B for 4 weeks and was continued on posaconazole with resolution of his mucormycosis infection...
April 2018: World Journal of Oncology
https://www.readbyqxmd.com/read/29759975/restoring-the-switch-for-cancer-cell-death-targeting-the-apoptosis-signaling-pathway
#11
REVIEW
Clement Chung
PURPOSE: The relevance of apoptosis to cancer development and pharmacologic agents that target this pathway in selected malignancies are described. SUMMARY: Apoptosis is a tightly regulated biological process mediated by both proapoptotic (i.e., prodeath) and antiapoptotic (i.e., prosurvival) proteins. While apoptosis represents a well-established effector mechanism induced by conventional chemotherapy in many malignancies, the development of apoptosis-based targeted therapy is relatively new...
May 14, 2018: American Journal of Health-system Pharmacy: AJHP
https://www.readbyqxmd.com/read/29759563/targeting-the-tumor-promoting-effects-of-adenosine-in-chronic-lymphocytic-leukemia
#12
REVIEW
Yiqing Cai, Lili Feng, Xin Wang
Chronic lymphocytic leukemia (CLL) is a hematological malignancy which is characterized by progressive accumulation of functionally deficient B cells in blood, bone marrow, and lymphatic tissue. The tumor microenvironment (TME) appears to play a critical role in genesis and progression of CLL. High levels of extracellular adenosine (ADO) are detected in CLL as a consequence of expression of ecto-enzymes, such as CD39 and CD73. Extracellular ADO exhibits a broad range of effects on cell cycle control, immunoregulation, angiogenesis and cytokine regulation through both direct and indirect mechanisms...
June 2018: Critical Reviews in Oncology/hematology
https://www.readbyqxmd.com/read/29757455/cells-cytokines-chemokines-and-cancer-stress-a-biobehavioral-study-of-patients-with-chronic-lymphocytic-leukemia
#13
Barbara L Andersen, Neha Godiwala Goyal, David M Weiss, Travis D Westbrook, Kami J Maddocks, John C Byrd, Amy J Johnson
BACKGROUND: Chronic lymphocytic leukemia (CLL) is the most prevalent adult leukemia, with profound disease-related cellular, humoral, and innate immune suppression. The objective of this study was to study the correlations between stress and disease-specific, negative prognostic cellular, cytokine, and chemokine markers in patients with CLL. METHODS: A single-group, observational design was used. Patients with relapsed/refractory CLL (N = 96) who were entering a phase 2 trial of an experimental therapy (ibrutinib) were studied...
May 14, 2018: Cancer
https://www.readbyqxmd.com/read/29756258/a-prospective-analysis-of-circulating-saturated-and-monounsaturated-fatty-acids-and-risk-of-non-hodgkin-lymphoma
#14
Yu-Han Chiu, Kimberly A Bertrand, Shumin Zhang, Francine Laden, Mara M Epstein, Bernard A Rosner, Stephanie Chiuve, Hannia Campos, Edward L Giovannucci, Jorge E Chavarro, Brenda M Birmann
Circulating saturated (SFA) and monounsaturated fatty acids (MUFA), which are predominantly derived from endogenous metabolism, may influence non-Hodgkin lymphoma (NHL) risk by modulating inflammation or lymphocyte membrane stability. However, few biomarker studies have evaluated NHL risk associated with these fats. We conducted a prospective study of 583 incident NHL cases and 583 individually matched controls with archived pre-diagnosis red blood cell (RBC) specimens in the Nurses' Health Study (NHS) and Health Professionals Follow-up Study (HPFS)...
May 14, 2018: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/29754984/donor-lymphocyte-infusion-in-myeloid-disorders
#15
REVIEW
Selami Koçak Toprak
A number of modalities including both pharmaceutical and cell-based treatments have long been tested and developed to prevent and treat relapses after allogeneic stem cell transplantation (allo-HSCT). The ability of donor T cells to recognize antigenic structures on leukemic cell surfaces and destroy them is a well-known fact. Based on this fact, the idea of using donor T cells to contribute to the development of adoptive immunotherapy has emerged. Donor lymphocytes are easy to obtain and donor lymphocyte infusions (DLI) have a simple rational while this treatment modality is an effective example of cellular therapy...
April 18, 2018: Transfusion and Apheresis Science
https://www.readbyqxmd.com/read/29752258/how-and-when-i-do-allogeneic-transplant-in-cll
#16
John G Gribben
Allogenic stem cell transplantation (allo-SCT) has been considered the treatment of choice for high-risk patients with chronic lymphocytic leukemia (CLL) and the only approach offered with curative intent in this disease. The availability novel agents including the B cell receptor inhibitors (BCRi) ibrutinib, acalabrutinib and idelalisib, as well as venetoclax which targets the BCL2 pathway and the success of these agents in treating high-risk disease patients has made it more difficult to assess who and when in their treatment course allo-SCT should be considered...
May 11, 2018: Blood
https://www.readbyqxmd.com/read/29750316/elevated-soluble-cd23-level-indicates-increased-risk-of-b-cell-non-hodgkin-s-lymphomas-evidence-from-a-meta-analysis
#17
REVIEW
Yi-Shu Huang, Xiang Zhou, Zhi-Fang Yang, Zheng-Tao Lv
The aim of the present study was to determine whether circulating soluble CD23 (sCD23) was associated with B cells non-Hodgkin's lymphomas (B-NHL). PubMed, EMBASE, and ISI Web of Science were extensively searched without language restriction. Data was extracted in a standardized data collection sheet after two reviewers scanned studies independently. The association between sCD23 and NHL was indicated as odds ratio (OR) along with its related 95% confidence interval (95% CI). Meta-analysis was conducted via RevMan 5...
May 11, 2018: Annals of Hematology
https://www.readbyqxmd.com/read/29749403/obinutuzumab-plus-bendamustine-in-previously-untreated-patients-with-cll-a-subgroup-analysis-of-the-green-study
#18
Stephan Stilgenbauer, Veronique Leblond, Robin Foà, Sebastian Böttcher, Osman Ilhan, Wolfgang Knauf, Eva Mikuskova, Christoph Renner, Eugen Tausch, Dariusz Woszczyk, Ekaterina Gresko, Linda Lundberg, Tom Moore, Thea Morris, Susan Robson, Francesc Bosch
GREEN (NCT01905943) is a non-randomized, open-label phase IIIb study investigating obinutuzumab alone or plus chemotherapy in chronic lymphocytic leukemia (CLL). We report a preplanned subgroup analysis of 158 previously untreated CLL patients receiving obinutuzumab-bendamustine (G-B). Patients received six 28-day cycles (C) of G-B: obinutuzumab day (D)1/D2 of C1 (25 mg D1/975 mg D2), 1000 mg D8 and D15 of C1, and D1 of C2-6; and bendamustine 70/90 mg/m2 D1 and D2 of C1-6. The primary endpoint was safety/tolerability...
April 27, 2018: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/29749344/usefulness-of-cancer-free-survival-in-estimating-the-lifetime-attributable-risk-of-cancer-incidence-from-radiation-exposure
#19
Songwon Seo, Dal Nim Lee, Young-Woo Jin, Won Jin Lee, Sunhoo Park
Risk projection models estimating the lifetime cancer risk from radiation exposure are generally based on exposure dose, age at exposure, attained age, gender, and study population-specific factors, such as baseline cancer risks and survival rates. Because such models have been mostly based on the Life Span Study cohort of Japanese atomic bomb survivors, the baseline risks and survival rates in the target population should be considered when applying the cancer risk from Japanese atomic bomb survivors. The survival function used in risk projection models that are commonly used in radiological protection field to estimate cancer risk from medical or occupational exposure is based on all-cause mortality...
May 11, 2018: Journal of Radiological Protection: Official Journal of the Society for Radiological Protection
https://www.readbyqxmd.com/read/29748447/morphologic-immunophenotypic-and-genetic-features-of-chronic-lymphocytic-leukemia-with-trisomy-12-a-comprehensive-review
#20
Francesco Autore, Paolo Strati, Luca Laurenti, Alessandra Ferrajoli
Chronic lymphocytic leukemia is an extremely heterogeneous disease and prognostic factors such as chromosomal abnormalities are important predictors of time to first treatment and survival. Trisomy 12 is the second most frequent aberration detected by fluorescence in situ hybridization at the time of diagnosis (10% to 25%), and it confers an intermediate prognostic risk, with a median time to first treatment of 33 months and a median overall survival of 114 months. Here, we review the unique morphologic, immunophenotypic, and genetic characteristics of patients with chronic lymphocytic leukemia and trisomy 12...
May 10, 2018: Haematologica
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