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https://www.readbyqxmd.com/read/29780793/an-exponential-regression-model-reveals-the-continuous-development-of-b-cell-subpopulations-used-as-reference-values-in-children
#1
Christoph Königs, Stephan Schultze-Strasser, Andrea Quaiser, Konrad Bochennek, Dirk Schwabe, Thomas E Klingebiel, Ulrike Koehl, Claudia Cappel, Udo Rolle, Peter Bader, Melanie Bremm, Sabine Huenecke, Shahrzad Bakhtiar
B lymphocytes are key players in humoral immunity, expressing diverse surface immunoglobulin receptors directed against specific antigenic epitopes. The development and profile of distinct subpopulations have gained awareness in the setting of primary immunodeficiency disorders, primary or secondary autoimmunity and as therapeutic targets of specific antibodies in various diseases. The major B cell subpopulations in peripheral blood include naïve (CD19+ or CD20+ IgD+ CD27- ), non-switched memory (CD19+ or CD20+ IgD+ CD27+ ) and switched memory B cells (CD19+ or CD20+ IgD- CD27+ )...
2018: Frontiers in Pediatrics
https://www.readbyqxmd.com/read/29780387/cd32-expressing-cd4-t-cells-are-phenotypically-diverse-and-can-contain-proviral-hiv-dna
#2
Genevieve E Martin, Matthew Pace, John P Thornhill, Chansavath Phetsouphanh, Jodi Meyerowitz, Morgane Gossez, Helen Brown, Natalia Olejniczak, Julianne Lwanga, Gita Ramjee, Pontiano Kaleebu, Kholoud Porter, Christian B Willberg, Paul Klenerman, Nneka Nwokolo, Julie Fox, Sarah Fidler, John Frater
Efforts to both characterize and eradicate the HIV reservoir have been limited by the rarity of latently infected cells and the absence of a specific denoting biomarker. CD32a (FcγRIIa) has been proposed to be a marker for an enriched CD4 T cell HIV reservoir, but this finding remains controversial. Here, we explore the expression of CD32 on CD3+ CD4+ cells in participants from two primary HIV infection studies and identify at least three distinct phenotypes (CD32low , CD32+ CD14+ , and CD32high ). Of note, CD4 negative enrichment kits remove the majority of CD4+ CD32+ T cells, potentially skewing subsequent analyses if used...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29779330/-tolerance-and-pharmacodynamics-phase-%C3%A2-clinical-trial-study-of-chimeric-anti-cd20-monoclonal-antibody-ibi301-in-chinese-patients-with-cd20-positive-non-hodgkin-s-lymphoma
#3
B Jiang, J Y Qi, M Y Sun, Z J Li, W Liu, L J Liu, F K Zhang, L G Qiu
Objective: To evaluate the tolerance and safety of a human-mouse chimeric anti-CD20 monoclonal antibody IBI301 in Chinese patients achieved objective response with CD20(+) B-cell non-Hodgkin's lymphoma (NHL). Methods: Nine patients with CD20(+) B-cell NHL received dose-escalating IBI301 infusions (250 mg/m(2), n =3; 375 mg/m(2), n =3; 500 mg/m(2), n =3, respectively). The data of all patients were collected for safety analyses. The median exposures of 125 mg/m(2), 375 mg/m(2), 500 mg/m(2) dose groups were 243, 690 and 980 mg, respectively...
April 14, 2018: Zhonghua Xue Ye Xue za Zhi, Zhonghua Xueyexue Zazhi
https://www.readbyqxmd.com/read/29777163/evolution-of-cll-treatment-from-chemoimmunotherapy-to-targeted-and-individualized-therapy
#4
REVIEW
Jan A Burger, Susan O'Brien
During the past 5 years, a number of highly active novel agents, including kinase inhibitors targeting BTK or PI3Kδ, an antagonist of the antiapoptotic protein BCL-2, and new anti-CD20 monoclonal antibodies, have been added to the therapeutic armamentarium for patients with chronic lymphocytic leukaemia (CLL). In these exciting times, care is needed to optimally integrate these novel agents into the traditional treatment algorithm without overlooking or compromising the benefits of established treatments, especially chemoimmunotherapy...
May 18, 2018: Nature Reviews. Clinical Oncology
https://www.readbyqxmd.com/read/29777009/feasibility-of-cxcr4-directed-radioligand-therapy-in-advanced-diffuse-large-b-cell-lymphoma
#5
Constantin Lapa, Heribert Hänscheid, Malte Kircher, Andreas Schirbel, Gerd Wunderlich, Rudolf Werner, Samuel Samnick, Jörg Kotzerke, Hermann Einsele, Andreas Buck, Hans-Jürgen Wester, Götz Ulrich Grigoleit
We have recently reported on our experience with C-X-C-motif chemokine receptor 4- (CXCR4-) directed radioligand therapy (RLT) in multiple myeloma and acute leukemia. Methods: Six patients with heavily pre-treated relapsed diffuse large B cell lymphoma (DLBCL) (3 males, 3 females; aged, 54±8 years) underwent CXCR4-directed RLT in combination with conditioning chemotherapy and allogeneic stem cell transplantation (SCT). In 2 patients, radioimmunotherapy (RIT) targeting CD20 or CD66 was added to enhance anti-lymphoma activity...
May 18, 2018: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
https://www.readbyqxmd.com/read/29774057/ocrelizumab-a-new-milestone-in-multiple-sclerosis-therapy
#6
REVIEW
Patricia Mulero, Luciana Midaglia, Xavier Montalban
B cells play a central role in the pathogenesis of multiple sclerosis (MS): they are involved in the activation of pro-inflammatory T cells, secretion of pro-inflammatory cytokines and production of autoantibodies directed against myelin. Hence, the use of B cell-depleting monoclonal antibodies as therapy for autoimmune diseases, including MS, has increased in recent years. Previous results with rituximab, the first therapeutic B cell-depleting chimeric monoclonal antibody that showed efficacy in MS clinical trials, encouraged researchers to evaluate the efficacy of a humanized anti-CD20 antibody, ocrelizumab, in MS...
2018: Therapeutic Advances in Neurological Disorders
https://www.readbyqxmd.com/read/29774030/changes-in-the-tcr%C3%AE-repertoire-and-tumor-immune-signature-from-a-cutaneous-melanoma-patient-immunized-with-the-csf-470-vaccine-a-case-report
#7
Mariana Aris, Alicia Inés Bravo, María Betina Pampena, Paula Alejandra Blanco, Ibel Carri, Daniel Koile, Patricio Yankilevich, Estrella Mariel Levy, María Marcela Barrio, José Mordoh
The allogeneic therapeutic vaccine CSF-470 has demonstrated a significant benefit over medium-dose IFNα2b in the distant metastasis-free survival for stages IIB-IIC-III cutaneous melanoma patients in a randomized phase II/III clinical trial (CASVAC-0401, NCT01729663). At the end of the 2-year CSF-470 immunization protocol, patient #006 developed several lung and one subcutaneous melanoma metastases; this later was excised. In this report, we analyzed the changes throughout vaccination of immune populations in blood and in the tumor tissue, with special focus on the T-cell repertoire...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29772458/phenotyping-and-target-expression-profiling-of-cd34-cd38-and-cd34-cd38-stem-and-progenitor-cells-in-acute-lymphoblastic-leukemia
#8
Katharina Blatt, Ingeborg Menzl, Gregor Eisenwort, Sabine Cerny-Reiterer, Harald Herrmann, Susanne Herndlhofer, Gabriele Stefanzl, Irina Sadovnik, Daniela Berger, Alexandra Keller, Alexander Hauswirth, Gregor Hoermann, Michael Willmann, Thomas Rülicke, Heinz Sill, Wolfgang R Sperr, Christine Mannhalter, Junia V Melo, Ulrich Jäger, Veronika Sexl, Peter Valent
Leukemic stem cells (LSCs) are an emerging target of curative anti-leukemia therapy. In acute lymphoblastic leukemia (ALL), LSCs frequently express CD34 and often lack CD38. However, little is known about markers and targets expressed in ALL LSCs. We have examined marker- and target expression profiles in CD34+ /CD38- LSCs in patients with Ph+ ALL (n = 22) and Ph- ALL (n = 27) by multi-color flow cytometry and qPCR. ALL LSCs expressed CD19 (B4), CD44 (Pgp-1), CD123 (IL-3RA), and CD184 (CXCR4) in all patients tested...
May 14, 2018: Neoplasia: An International Journal for Oncology Research
https://www.readbyqxmd.com/read/29770496/long-term-survival-and-loss-in-expectancy-of-life-in-a-population-based-cohort-of-7114-patients-with-diffuse-large-b-cell-lymphoma
#9
Sara Ekberg, Mats Jerkeman, Per-Ola Andersson, Gunilla Enblad, Björn E Wahlin, Sverker Hasselblom, Therese M Andersson, Sandra Eloranta, Karin E Smedby
Survival has improved among patients with diffuse large B-cell lymphoma (DLBCL) with the addition of anti-CD20 antibody therapy. We aimed to quantify trends and remaining loss in expectation of life (LEL) due to DLBCL at a national population-based level. Patients diagnosed with DLBCL 2000-2013 (N=7114) were identified through the Swedish Lymphoma Registry and classified according to the age-adjusted International Prognostic Index (aaIPI).The novel measure LEL is the difference between remaining life years among patients and the general population and was predicted using flexible parametric models from diagnosis and among 2-year survivors, by age and sex...
May 17, 2018: American Journal of Hematology
https://www.readbyqxmd.com/read/29768934/a-safety-profile-of-medications-used-to-treat-waldenstr%C3%A3-m-s-macroglobulinemia
#10
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/29766466/concurrent-isolated-igg2-positive-membranous-nephropathy-and-malignant-b-cell-lymphoma
#11
Satoshi Shimada, Takashi Nakamichi, Gen Yamada, Kaori Narumi, Hajime Usubuchi, Tae Yamamoto, Satoshi Ichikawa, Noriko Fukuhara, Mariko Miyazaki, Hideo Harigae, Hiroshi Sato, Sadayoshi Ito
A recent systematic review showed that hematological malignancy is often complicated by membranous nephropathy (MN). Histologically, the deposition of IgG subclasses other than IgG4 may imply secondary MN, such as malignancy-associated MN (M-MN). We describe a very rare case of concurrent isolated IgG2-positive MN and B-cell lymphoma. An 83-year-old woman was hospitalized at our institute for facial and lower extremity edema persisting for 2 months. Laboratory tests showed urinary protein level of 10.8 g/day, serum albumin level of 1...
May 15, 2018: CEN Case Reports
https://www.readbyqxmd.com/read/29765543/igg4-related-kidney-disease-the-effects-of-a-rituximab-based-immunosuppressive-therapy
#12
Giacomo Quattrocchio, Antonella Barreca, Andrea Demarchi, Laura Solfietti, Giulietta Beltrame, Roberta Fenoglio, Michela Ferro, Paola Mesiano, Stefano Murgia, Giulio Del Vecchio, Carlo Massara, Cristiana Rollino, Dario Roccatello
IgG4-related disease (IgG4-RD) is a recently recognized disorder, characterized by elevated serum IgG4 concentrations, dense tissue infiltration of IgG4-positive plasma cells and storiform fibrosis. Treatment is usually based on steroids, however, relapses and long-term adverse effects are frequent. We prospectively studied 5 consecutive patients with histologically-proven IgG4-RD and renal involvement, treated with an extended Rituximab protocol combined with steroids. Two doses of intravenous cyclophosphamide were added in 4 patients...
April 20, 2018: Oncotarget
https://www.readbyqxmd.com/read/29763678/acute-aerobic-exercise-induces-a-preferential-mobilisation-of-plasmacytoid-dendritic-cells-into-the-peripheral-blood-in-man
#13
Frankie F Brown, John P Campbell, Alex J Wadley, James P Fisher, Sarah Aldred, James E Turner
Dendritic cells (DCs) are important sentinel cells of the immune system responsible for presenting antigen to T cells. Exercise is known to cause an acute and transient increase in the frequency of DCs in the bloodstream in humans, yet there are contradictory findings in the literature regarding the phenotypic composition of DCs mobilised during exercise, which may have implications for immune regulation and health. Accordingly, we sought to investigate the composition of DC sub-populations mobilised in response to acute aerobic exercise...
May 12, 2018: Physiology & Behavior
https://www.readbyqxmd.com/read/29755476/transitional-b-cells-and-tlr9-responses-are-defective-in-selective-iga-deficiency
#14
Andri L Lemarquis, Helga K Einarsdottir, Rakel N Kristjansdottir, Ingileif Jonsdottir, Bjorn R Ludviksson
Selective IgA deficiency (IgAD) is the most common primary antibody deficiency in the western world with affected individuals suffering from an increased burden of autoimmunity, atopic diseases and infections. It has been shown that IgAD B cells can be induced with germinal center mimicking reactions to produce IgA. However, IgA is the most prevalent antibody in mucosal sites, where antigen-independent responses are important. Much interest has recently focused on the role of TLR9 in both naïve and mature B cell differentiation into IgA secreting plasma cells...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29754509/-new-and-traditional-directions-in-the-biology-and-management-of-childhood-acute-lymphoblastic-leukemia
#15
Bálint Egyed, Gábor Kovács, Nóra Kutszegi, Andrea Rzepiel, Judit Csányiné Sági, Dániel János Erdélyi, Judit Müller, Ágnes Félné Semsei
Owing to clinical trials and improvement over the past few decades, the majority of children with acute lymphoblastic leukemia (ALL) survive by first-line chemotherapy and combat with the problems of returning to community. However, many patients may have severe acute or late therapeutic side effects, and the survival rate in some groups (e.g., patients with MLL rearrangements, hypodiploidy, IKZF1 mutation or early precursor T cell phenotype) is far behind the average. Innovative strategies in medical attendance provide better clinical outcomes for them: complete gene diagnostics, molecularly targeted anticancer treatment, immuno-oncology and immune cell therapy...
May 2018: Orvosi Hetilap
https://www.readbyqxmd.com/read/29754401/treatment-of-localized-stage-follicular-lymphoma
#16
REVIEW
Marc Sorigue, Victòria Tuset, Juan-Manuel Sancho
Follicular lymphoma (FL) is the most common indolent lymphoma and it most frequently presents in an advanced-stage. Therapeutic considerations for advanced-stage are different from those of localized-stage FL, in which radiotherapy (RT) is generally recommended. However, the available evidence suffers from shortcomings that are relatively specific to this clinical entity due to its rarity and long survival with all available treatment modalities, including that most of the existing evidence originated at a time when diagnostic classifications, staging procedures and radiotherapeutic standards were different from those available today and when anti-CD20 monoclonal antibodies were not available...
May 12, 2018: European Journal of Haematology
https://www.readbyqxmd.com/read/29752199/gemcitabine-oxaliplatin-plus-rituximab-r-gemox-as-first-line-treatment-in-elderly-patients-with-diffuse-large-b-cell-lymphoma-a-single-arm-open-label-phase-2-trial
#17
Qiu-Dan Shen, Hua-Yuan Zhu, Li Wang, Lei Fan, Jin-Hua Liang, Lei Cao, Wei Wu, Yi Xia, Jian-Yong Li, Wei Xu
BACKGROUND: The combination of rituximab, gemcitabine, and oxaliplatin (R-GemOx) has shown high efficacy with a low toxicity profile in elderly patients with relapsed and refractory diffuse large B-cell lymphoma. We aimed to evaluate the efficacy, safety, and feasibility of the R-GemOx regimen as a first-line treatment in elderly patients with diffuse large B-cell lymphoma. METHODS: In this single-arm, open-label, phase 2 clinical trial, we enrolled patients with previously untreated, histologically confirmed, CD20-positive diffuse large B-cell lymphoma, aged 70 years or older, or aged 60-69 years with an Eastern Cooperative Oncology Group (ECOG) performance status score of 2 or greater...
May 8, 2018: Lancet Haematology
https://www.readbyqxmd.com/read/29750632/positron-emission-tomography-guided-therapy-of-aggressive-non-hodgkin-lymphomas-petal-a-multicenter-randomized-phase-iii-trial
#18
Ulrich Dührsen, Stefan Müller, Bernd Hertenstein, Henrike Thomssen, Jörg Kotzerke, Rolf Mesters, Wolfgang E Berdel, Christiane Franzius, Frank Kroschinsky, Matthias Weckesser, Dorothea Kofahl-Krause, Frank M Bengel, Jan Dürig, Johannes Matschke, Christine Schmitz, Thorsten Pöppel, Claudia Ose, Marcus Brinkmann, Paul La Rosée, Martin Freesmeyer, Andreas Hertel, Heinz-Gert Höffkes, Dirk Behringer, Gabriele Prange-Krex, Stefan Wilop, Thomas Krohn, Jens Holzinger, Martin Griesshammer, Aristoteles Giagounidis, Aruna Raghavachar, Georg Maschmeyer, Ingo Brink, Helga Bernhard, Uwe Haberkorn, Tobias Gaska, Lars Kurch, Daniëlle M E van Assema, Wolfram Klapper, Dieter Hoelzer, Lilli Geworski, Karl-Heinz Jöckel, André Scherag, Andreas Bockisch, Jan Rekowski, Andreas Hüttmann
Purpose Interim positron emission tomography (PET) using the tracer, [18 F]fluorodeoxyglucose, may predict outcomes in patients with aggressive non-Hodgkin lymphomas. We assessed whether PET can guide therapy in patients who are treated with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP). Patients and Methods Newly diagnosed patients received two cycles of CHOP-plus rituximab (R-CHOP) in CD20-positive lymphomas-followed by a PET scan that was evaluated using the ΔSUVmax method. PET-positive patients were randomly assigned to receive six additional cycles of R-CHOP or six blocks of an intensive Burkitt's lymphoma protocol...
May 11, 2018: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/29750146/sensitive-detection-of-the-natural-killer-cell-mediated-cytotoxicity-of-anti-cd20-antibodies-and-its-impairment-by-b-cell-receptor-pathway-inhibitors
#19
Floyd Hassenrück, Eva Knödgen, Elisa Göckeritz, Safi Hasan Midda, Verena Vondey, Lars Neumann, Sylvia Herter, Christian Klein, Michael Hallek, Günter Krause
The antibody-dependent cell-mediated cytotoxicity (ADCC) of the anti-CD20 monoclonal antibodies (mAbs) rituximab and obinutuzumab against the cell line Raji and isolated CLL cells and its potential impairment by kinase inhibitors (KI) was determined via lactate dehydrogenase release or calcein retention, respectively, using genetically modified NK92 cells expressing CD16-176V as effector cells. Compared to peripheral blood mononuclear cells, recombinant effector cell lines showed substantial alloreactivity-related cytotoxicity without addition of mAbs but afforded determination of ADCC with reduced interassay variability...
2018: BioMed Research International
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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