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Alemtuzumab

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https://www.readbyqxmd.com/read/29136317/il-7-receptor-heterogeneity-as-a-mechanism-for-repertoire-change-during-post-depletional-homeostatic-proliferation-and-its-relation-to-costimulation-blockade-resistant-rejection
#1
He Xu, Victoria A Bendersky, Todd V Brennan, Jaclyn R Espinosa, Allan D Kirk
Kidney transplant patients treated with belatacept without depletional induction experience higher rates of acute rejection compared to patients treated with conventional immunosuppression. Costimulation blockade-resistant rejection (CoBRR) is associated with terminally differentiated T cells. Alemtuzumab induction and belatacept/sirolimus immunotherapy effectively prevents CoBRR. We hypothesized that cells in late phases of differentiation would be selectively less capable of repopulating post-depletion than more naïve phenotypes, providing a potential mechanism by which lymphocyte depletion and repopulation could reduce the risk of CoBRR...
November 14, 2017: American Journal of Transplantation
https://www.readbyqxmd.com/read/29136299/malignancy-in-renal-transplant-recipients-exposed-to-cyclophosphamide-prior-to-transplantation-for-the-treatment-of-native-glomerular-disease
#2
M R Jorgenson, J L Descourouez, T Singh, Brad C Astor, Sarah E Panzer
STUDY OBJECTIVE: To evaluate the risk of post-transplantation malignancy in renal transplant recipients exposed to pre-transplantation cyclophosphamide for treatment of glomerular nephropathy (GN). DESIGN: Retrospective cohort study. SETTING: Tertiary academic medical center. PATIENTS: Six hundred adult renal transplant recipients transplanted between 1993 and 2014; 54 patients were exposed to pre-transplantation cyclophosphamide for treatment of GN (GN-CYC group), and 546 patients with polycystic kidney disease were not exposed to pre-transplantation cyclophosphamide (PKD group)...
November 14, 2017: Pharmacotherapy
https://www.readbyqxmd.com/read/29131039/adverse-reactions-of-antibody-therapy-for-primary-cutaneous-lymphomas-rituximab-brentuximab-vedotin-alemtuzumab-and-mogamulizumab
#3
I Saulite, E Guenova, W Hoetzenecker
Treatment of advanced PCLs is limited and rarely reaches complete remission despite aggressive treatment modalities, such as polychemotherapy with various adverse effects. However, several monoclonal antibodies drug agents in patients with advanced primary cutaneous lymphomas demonstrate promising efficacy and manageable safety profiles. The monoclonal antibodies drug agents have favourable tolerability compared with multi-agent cytotoxic chemotherapy. However, adverse effects manifest with a broad clinical spectrum, hence the markers of targeted therapies are not limited to tumour cells but found on tumour cells and also on benign T and/or B cells...
2018: Current Problems in Dermatology
https://www.readbyqxmd.com/read/29100032/extracorporeal-human-whole-blood-in-motion-as-a-tool-to-predict-first-infusion-reactions-and-mechanism-of-action-of-immunotherapeutics
#4
Erika A K Fletcher, Mohamed Eltahir, Frida Lindqvist, Jonas Rieth, Gunilla Törnqvist, Justyna Leja-Jarblad, Sara M Mangsbo
First infusion reactions along with severe anaphylactic responses can occur as a result of systemic administration of therapeutic antibodies. The underlying mechanisms by which monoclonal antibodies induce cytokine release syndrome (CRS) can involve direct agonistic effects via the drug target, or a combination of target-engagement along with innate receptor interactions. Despite the wide variety of pathways and cells that can play a role in CRS, many currently used assays are devoid of one or more components that must be present for these responses to occur...
October 27, 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/29081658/understanding-the-positive-benefit-risk-profile-of-alemtuzumab-in-relapsing-multiple-sclerosis-perspectives-from-the-alemtuzumab-clinical-development-program
#5
REVIEW
Eva Havrdova, Jeffrey A Cohen, Dana Horakova, Ivana Kovarova, Eva Meluzinova
The introduction of high-efficacy therapies for relapsing-remitting multiple sclerosis has driven re-evaluation of treatment goals and benefit:risk considerations in treatment choice. In the alemtuzumab Phase II and III clinical trials, patients treated with alemtuzumab 12 mg versus subcutaneous interferon beta-1a demonstrated significantly reduced annualized relapse rates and improved magnetic resonance imaging outcomes, and were significantly more likely to achieve no evidence of disease activity and reduction in brain volume loss...
2017: Therapeutics and Clinical Risk Management
https://www.readbyqxmd.com/read/29063805/telomere-length-in-poor-risk-chronic-lymphocytic-leukemia-associations-with-disease-characteristics-and-outcome
#6
Daniela Steinbrecher, Billy Michael Chelliah Jebaraj, Christof Schneider, Jennifer Edelmann, Florence Cymbalista, Véronique Leblond, Alain Delmer, Stefan Ibach, Eugen Tausch, Annika Scheffold, Johannes Bloehdorn, Michael Hallek, Peter Dreger, Hartmut Döhner, Stephan Stilgenbauer
Telomere length in chronic lymphocytic leukemia (CLL) is described as an independent prognostic factor based largely on previously untreated patients from chemotherapy based trials. Here, we studied telomere length associations in high-risk, relapsed/refractory CLL treated with alemtuzumab in the CLL2O study (n = 110) of German and French CLL study groups. Telomere length (median 3.28 kb, range 2.52-7.24 kb) was relatively short, since 84.4% of patients had 17p- which is generally associated with short telomeres...
October 24, 2017: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/29055482/a-case-of-acute-fulminant-multiple-sclerosis-treated-with-alemtuzumab
#7
F Gobbin, A Marangi, R Orlandi, S Richelli, M Turatti, M Calabrese, A Forgione, F Alessandrini, M D Benedetti, S Monaco, A Gajofatto
We describe the case of a woman who came to our attention for acute onset and very rapidly worsening left hemiplegia, vision loss and cognitive impairment. MRI, laboratory and clinical investigations were highly suggestive of an active inflammatory demyelinating disease. Following exclusion of other possible etiologies, a diagnosis of Marburg's variant multiple sclerosis was made. After repeated high-dose steroids and plasma-exchange, the patient was treated with a first course of alemtuzumab followed by improvement of the clinical and MRI picture...
October 2017: Multiple Sclerosis and related Disorders
https://www.readbyqxmd.com/read/29055479/is-there-a-change-of-paradigm-towards-more-effective-treatment-early-in-the-course-of-apparent-high-risk-ms
#8
REVIEW
Óscar Fernández
BACKGROUND: Aggressive, highly active, or rapidly evolving severe relapsing-remitting multiple sclerosis (RRMS) is characterized by frequent relapses and active disease on magnetic resonance imaging, ultimately leading to a high risk for rapid disability accumulation. The treatment approach for high-risk patients is evolving into a model of individualized therapy in which early initiation of high-efficacy disease-modifying therapy (DMT), which I refer to as "early and strong" therapy, is viewed as a rational strategy to prevent the irreversible damage that occurs at disease onset and early in the disease course...
October 2017: Multiple Sclerosis and related Disorders
https://www.readbyqxmd.com/read/29055450/management-of-infusion-related-reactions-associated-with-alemtuzumab-in-patients-with-multiple-sclerosis
#9
Saša Šega-Jazbec, Barbara Barun, Alenka Horvat Ledinek, Višnja Fabekovac, Magdalena Krbot Skorić, Mario Habek
OBJECTIVE: Infusion-associated reactions (IARs) occur in >90% patients with multiple sclerosis (MS) treated with alemtuzumab. We aimed to study the frequency of IARs at 2 sites using 5 days of steroids (1g/day of IV methylprednisolone), but otherwise distinct protocols. METHODS: This was retrospective chart review of 38 consecutive MS patients who were treated with alemtuzumab from June 2015 till February 2017 at Department of Neurology, University Hospital Center Zagreb, Croatia and Department of Neurology, University Medical Center Ljubljana, Slovenia...
October 2017: Multiple Sclerosis and related Disorders
https://www.readbyqxmd.com/read/29044676/world-health-organization-defined-eosinophilic-disorders-2017-update-on-diagnosis-risk-stratification-and-management
#10
REVIEW
Jason Gotlib
DISEASE OVERVIEW: The eosinophilias encompass a broad range of nonhematologic (secondary or reactive) and hematologic (primary, clonal) disorders with potential for end-organ damage. DIAGNOSIS: Hypereosinophilia has generally been defined as a peripheral blood eosinophil count greater than 1500/mm(3) and may be associated with tissue damage. After exclusion of secondary causes of eosinophilia, diagnostic evaluation of primary eosinophilias relies on a combination of morphologic review of the blood and marrow, standard cytogenetics, fluorescent in situ-hybridization, flow immunocytometry, and T-cell clonality assessment to detect histopathologic or clonal evidence for an acute or chronic myeloid or lymphoproliferative disorder...
November 2017: American Journal of Hematology
https://www.readbyqxmd.com/read/29033895/autoimmune-thyroid-diseases-in-patients-treated-with-alemtuzumab-for-multiple-sclerosis-an-example-of-selective-anti-tsh-receptor-immune-response
#11
REVIEW
Mario Rotondi, Martina Molteni, Paola Leporati, Valentina Capelli, Michele Marinò, Luca Chiovato
Alemtuzumab, a humanized anti-CD52 monoclonal antibody, is approved for the treatment of active relapsing-remitting multiple sclerosis (MS). Alemtuzumab induces a rapid and prolonged depletion of lymphocytes from the circulation, which results in a profound immuno-suppression status followed by an immune reconstitution phase. Secondary to reconstitution autoimmune diseases represent the most common side effect of Alemtuzumab treatment. Among them, Graves' disease (GD) is the most frequent one with an estimated prevalence ranging from 16...
2017: Frontiers in Endocrinology
https://www.readbyqxmd.com/read/29029524/comparative-efficacy-and-safety-of-antibody-induction-therapy-for-the-treatment-of-kidney-a-network-meta-analysis
#12
Mingjie Shao, Tingting Tian, Xinyan Zhu, Yingzi Ming, Yasuko Iwakiri, Shaojun Ye, Qifa Ye
To evaluate the efficacy and safety of antibody induction therapies in kidney transplantation. Systematic literature searches were undertaken using MEDLINE, Embase, and Cochrane Library database from 1980 to 2016. Randomized controlled trials (RCTs) comparing three antibody induction therapies (alemtuzumab, interleukin-2 receptor antibodies and antithymocyte globulin) between each other were identified. Bayesian network meta-analysis was used to combine both the direct and indirect evidence on treatment efficacy and its safety...
September 12, 2017: Oncotarget
https://www.readbyqxmd.com/read/28987015/center-practice-drives-variation-in-choice-of-u-s-kidney-transplant-induction-therapy-a-retrospective-analysis-of-contemporary-practice
#13
V R Dharnidharka, A S Naik, D A Axelrod, M A Schnitzler, Z Zhang, S Bae, D L Segev, D C Brennan, T Alhamad, R Ouseph, N N Lam, M Nazzal, H Randall, B L Kasiske, M McAdams-Demarco, K L Lentine
To assess factors that influence the choice of induction regimen in contemporary kidney transplantation, we examined center-identified, national transplant registry data for 166,776 US recipients (2005-2014). Bi-level hierarchical models were constructed, wherein use of each regimen was compared pairwise with use of interleukin-2 receptor blocking antibodies (IL2rAb). Overall, 81.8% of patients received induction, including thymoglobulin (TMG, 46.0%), IL2rAb (21.9%), alemtuzumab (ALEM, 12.5%), and other agents (1...
October 7, 2017: Transplant International: Official Journal of the European Society for Organ Transplantation
https://www.readbyqxmd.com/read/28975400/disease-reactivation-after-switching-from-natalizumab-to-daclizumab
#14
Timo Uphaus, Christoph Oberwittler, Sergiu Groppa, Frauke Zipp, Stefan Bittner
Discontinuation of natalizumab can lead to severe rebound of disease activity in patients with relapsing-remitting multiple sclerosis (RRMS); nevertheless, the treatment regimen in this clinical situation remains controversial. We report the case of a 25-year-old male patient with RRMS who was clinically stable under 3 years of natalizumab before treatment was stopped due to progressive multifocal leucencephalopathy (PML) safety concerns. After initiation of daclizumab, the patient suffered from disease reactivation, which was ultimately controlled by intravenous methylprednisolone and alemtuzumab treatment...
October 3, 2017: Journal of Neurology
https://www.readbyqxmd.com/read/28972490/phagocytosis-and-expression-of-fcg-receptors-and-cd180-on-monocytes-in-chronic-lymphocytic-leukemia
#15
T Tsertsvadze, N Mitskevich, A Bilanishvili, D Girdaladze, N Porakishvili
Chronic lymphocytic leukaemia (CLL) is a lymphoproliferative disease characterised by accumulation of monoclonal CD19+CD5+CD23+ lymphocytes in the peripheral blood and bone marrow. CLL is the most common type of the adult leukemia in the Western world. The disease is incurable, albeit there are new molecular and immunotherapy methods currently available in conjunction with chemotherapy, leading to the "precision therapy". The majority of immunotherapeutic approaches are based on the ability of therapeutic antibodies (Rituximab, Alemtuzumab) to mobilize anti-tumour potential of the Natural Killer cells and macrophages/monocytes through their Fcg-receptors (FcγR)...
September 2017: Georgian Medical News
https://www.readbyqxmd.com/read/28966663/alemtuzumab-in-the-long-term-treatment-of-relapsing-remitting-multiple-sclerosis-an-update-on-the-clinical-trial-evidence-and-data-from-the-real-world
#16
Tjalf Ziemssen, Katja Thomas
Alemtuzumab is a humanized monoclonal antibody approved for the treatment of relapsing-remitting multiple sclerosis (RRMS), given as two annual courses on five consecutive days at baseline and on three consecutive days 12 months later. Here we provide an update on the long-term efficacy and safety of alemtuzumab in RRMS, including real-world experience, and advances in our understanding of its mechanism of action. Recent data from the phase II/III extension study have demonstrated that alemtuzumab reduces relapse rates, disability worsening, and the rate of brain volume loss over the long term, with many patients achieving no evidence of disease activity...
October 2017: Therapeutic Advances in Neurological Disorders
https://www.readbyqxmd.com/read/28958469/lenalidomide-maintenance-therapy-in-previously-treated-chronic-lymphocytic-leukaemia-continuum-a-randomised-double-blind-placebo-controlled-phase-3-trial
#17
Asher A Chanan-Khan, Andrey Zaritskey, Miklos Egyed, Samuel Vokurka, Sergey Semochkin, Anna Schuh, Jeannine Kassis, David Simpson, Jennie Zhang, Brendan Purse, Robin Foà
BACKGROUND: The efficacy and safety of lenalidomide as maintenance therapy after chemotherapy-based second-line therapy in patients with chronic lymphocytic leukaemia is unknown. Although kinase inhibitors can improve outcomes for some patients with relapsed and refractory disease, not all patients have access to these novel drugs. In this study, we aimed to assess the efficacy and safety of lenalidomide as maintenance therapy in patients with previously treated chronic lymphocytic leukaemia...
September 25, 2017: Lancet Haematology
https://www.readbyqxmd.com/read/28937435/immunophenotype-expression-change-from-cd52-to-cd52-on-erythrodermic-peripheral-t-cell-lymphoma-not-otherwise-specified-after-treatment-with-alemtuzumab
#18
Maulik M Dhandha, Kari E Sufficool, Claudia I Vidal, Katherine J Robbins, Mark J Fesler, Jacqueline R Batanian, Maria Yadira Hurley
No abstract text is available yet for this article.
September 11, 2017: American Journal of Dermatopathology
https://www.readbyqxmd.com/read/28918995/cutaneous-adverse-events-of-targeted-therapies-for-hematolymphoid-malignancies
#19
REVIEW
Julia D Ransohoff, Bernice Y Kwong
The identification of oncogenic drivers of liquid tumors has led to the rapid development of targeted agents with distinct cutaneous adverse event (AE) profiles. The diagnosis and management of these skin toxicities has motivated a novel partnership between dermatologists and oncologists in developing supportive oncodermatology clinics. In this article we review the current state of knowledge of clinical presentation, mechanisms, and management of the most common and significant cutaneous AEs observed during treatment with targeted therapies for hematologic and lymphoid malignancies...
July 14, 2017: Clinical Lymphoma, Myeloma & Leukemia
https://www.readbyqxmd.com/read/28910968/efficiency-of-antibody-therapy-in-demyelinating-diseases
#20
Tetsuya Akaishi, Ichiro Nakashima
Monoclonal antibody therapy is a new treatment strategy for many types of diseases including cancers and autoimmune diseases, realizing a high efficacy and tolerability. In multiple sclerosis (MS) and neuromyelitis optica (NMO) spectrum disorders, several monoclonal antibodies have been suggested to decrease the incidence of clinical relapse and the disease activity. In MS, anti-α4 integrin (natalizumab), anti-CD52 (alemtuzumab), anti-CD25 (daclizumab) and anti-CD20 (ocrelizumab) have been shown to effectively reduce the relapses in randomized controlled trials and have been approved by the Food and Drug Administration...
July 1, 2017: International Immunology
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