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Pierre Feugier, Thérèse Aurran, Béatrice Mahé, Remi Letestu, Florence Nguyen-Khac, Bruno Cazin, Olivier Tournilhac, Hervé Maisonneuve, Olivier Casasnovas, Alain Delmer, Véronique Leblond, Bruno Royer, Bernadette Corront, Sylvie Chevret, Roselyne Delépine, Sandrine Vaudaux, Eric Van den Neste, Marie Christine Béné, Florence Cymbalista, Damien Roosweil, Stéphane Leprêtre
March 15, 2018: Haematologica
Virginia Devonshire, Richard Phillips, Hilary Wass, Gerald Da Roza, Peter Senior
Alemtuzumab is a humanized anti-CD52 monoclonal antibody approved in more than 65 countries for the treatment of relapsing-remitting multiple sclerosis (RRMS). Compared with subcutaneous interferon-beta-1a, alemtuzumab significantly reduced clinical disease activity and the rate of brain volume loss, and improved disability outcomes in patients with active RRMS who were either treatment naive (CARE-MS I study) or who had an inadequate response (≥ 1 relapse after ≥ 6 months of treatment) to prior therapy (CARE-MS II study)...
March 10, 2018: Journal of Neurology
Jessica C Petrov, Masayuki Wada, Kevin G Pinz, Lulu E Yan, Kevin H Chen, Xiao Shuai, Hua Liu, Xi Chen, Lai-Han Leung, Huda Salman, Nabil Hagag, Fang Liu, Xun Jiang, Yupo Ma
Acute myeloid leukemia (AML) bears heterogeneous cells that can consequently offset killing by single-CAR-based therapy, which results in disease relapse. Leukemic stem cells (LSCs) associated with CD123 expression comprise a rare population that also plays an important role in disease progression and relapse. Here, we report on the robust anti-tumor activity of a compound CAR (cCAR) T-cell possessing discrete scFv domains targeting two different AML antigens, CD123, and CD33, simultaneously. We determined that the resulting cCAR T-cells possessed consistent, potent, and directed cytotoxicity against each target antigen population...
February 25, 2018: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
Catherine Lambert, Benedicte Dubois, Dominique Dive, Andreas Lysandropoulos, Dominik Selleslag, Ludo Vanopdenbosch, Vincent Van Pesch, Bart Vanwijmeersch, Ann Janssens
The article Management of immune thrombocytopenia in multiple sclerosis patients treated with alemtuzumab: a Belgian consensus, written by Lambert et al., was originally published electronically on the publisher's internet portal on 27 January 2018 without open access.
March 3, 2018: Acta Neurologica Belgica
Serafeim Katsavos, Alasdair Coles
Alemtuzumab, the first monoclonal antibody to be used as a therapy and the first to be humanized, was introduced into the treatment of multiple sclerosis in 1991 after its successful use in hematology, oncology, and transplantation medicine. One phase 2 and two phase 3 trials of this lymphocyte-depleting agent have established alemtuzumab's superior efficacy to interferon β-1a over the short term (2-3 years) with greater relapse rate reduction, reduced accumulation of disability, and more frequent sustained improvement in disability...
March 2, 2018: Cold Spring Harbor Perspectives in Medicine
Li Wang, Chun-Hui Qi, Ren Zhong, Chao Yuan, Qiu-Yue Zhong
BACKGROUND: Multiple sclerosis (MS) is an autoimmune disease, in which the insulating covers of nerve cells in the brain and spinal cord are demyelinated. This study was conducted to compare the efficacy of alemtuzumab and natalizumab in the treatment of different stages of MS patients. METHODS: A total of 585 patients diagnosed with MS and hospitalized were included and analyzed after which they were divided into the primary progressive MS A and B groups, the relapsing-remitting MS (RRMS) C and D groups, and the secondary progressive MS E and F groups...
February 2018: Medicine (Baltimore)
Małgorzata Mikulska, Simone Lanini, Carlota Gudiol, Lubos Drgona, Giuseppe Ippolito, Mario Fernández-Ruiz, Bernd Salzberger
BACKGROUND: The present review is part of the ESCMID Study Group for Infections in Compromised Hosts (ESGICH) Consensus Document on the safety of targeted and biological therapies. AIMS: To review, from an Infectious Diseases perspective, the safety profile of agents targeting CD19, CD20 and CD52 and to suggest preventive recommendations. SOURCES: Computer-based MEDLINE searches with MeSH terms pertaining to each agent or therapeutic family...
February 12, 2018: Clinical Microbiology and Infection
Irene Eriksson, Joris Komen, Fredrik Piehl, Rickard E Malmström, Björn Wettermark, Mia von Euler
PURPOSE: The purpose of this study is to describe the utilization of disease-modifying treatments (DMTs) in relapsing-remitting multiple sclerosis (MS) and assess the impact of both the introduction of new drugs and treatment recommendations (local recommendation on rituximab use issued at the largest MS clinic in Stockholm and regional Drug and Therapeutics Committee (DTC) recommendation on how dimethyl fumarate should be used). METHODS: Interrupted time series analyses using monthly data on all MS patients treated with DMTs in the Stockholm County, Sweden, from January 2011 to December 2017...
February 10, 2018: European Journal of Clinical Pharmacology
Floris C Loeff, J H Frederik Falkenburg, Lois Hageman, Wesley Huisman, Sabrina A J Veld, H M Esther van Egmond, Marian van de Meent, Peter A von dem Borne, Hendrik Veelken, Constantijn J M Halkes, Inge Jedema
Alemtuzumab (ALM) is used for T cell depletion in the context of allogeneic hematopoietic stem cell transplantation (alloSCT) to prevent acute graft-versus-host disease and graft rejection. Following ALM-based T cell-depleted alloSCT, relatively rapid recovery of circulating T cells has been described, including T cells that lack membrane expression of the GPI-anchored ALM target Ag CD52. We show, in a cohort of 89 human recipients of an ALM-based T cell-depleted alloSCT graft, that early lymphocyte reconstitution always coincided with the presence of large populations of T cells lacking CD52 membrane expression...
March 15, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
Bhagirathbhai R Dholaria, Ernesto Ayala, Lubomir Sokol, Taiga Nishihori, Julio C Chavez, Mohammad Hussaini, Ambuj Kumar, Mohamed A Kharfan-Dabaja
BACKGROUND: T- cell prolymphocytic leukemia (T- PLL) is a rare aggressive hematological malignancy. Alemtuzumab, an anti-CD52 humanized monoclonal antibody, is the treatment of choice for remission induction. Allogeneic hematopoietic cell transplantation (allo-HCT) has been described to induce durable remissions and improve survival, but data is limited. PATIENTS AND METHODS: We evaluated clinical outcomes of 11 patients, median age of 56 (range, 43-71) years who underwent allo-HCT for T-PLL...
January 29, 2018: Leukemia Research
Chandrashekhar A Kubal, Catherine Pennington, Jonathan Fridell, Burcin Ekser, Plamen Muhaylov, Richard Mangus
BACKGROUND Patients undergoing re-transplantation often receive high doses of immunosuppression, which may lead to an immunocompromised status of the recipient. This study investigates the outcomes after intestine/multivisceral re-transplantation. MATERIAL AND METHODS Clinical outcomes of 23 patients undergoing 24 re-transplantations at a single intestine transplant center were reviewed. Bone marrow suppression was used as a surrogate marker of immunocompromised status, and was defined as platelet count <50 k/mm3 and absolute lymphocyte count <200/mm³...
February 6, 2018: Annals of Transplantation: Quarterly of the Polish Transplantation Society
Marco Puthenparampil, Francesca Rinaldi, Lisa Federle, Chiara Cazzola, Paola Perini, Paolo Gallo
Background: The cause and clinical significance of the transient decrease in platelet (PLT) count observed in relapsing remitting multiple sclerosis (RRMS) during alemtuzumab administration remain undefined. The aim of this study was to analyse the kinetics and clinical relevance of early onset thrombocytopaenia in alemtuzumab-treated RRMS. Methods: A total of 26 patients with RRMS were included in a longitudinal study. Blood samples were collected immediately before the first alemtuzumab infusion (D0), and after 3 days (D3), 28 days (D28) and 49 days (D49)...
2018: Therapeutic Advances in Neurological Disorders
Catherine Lambert, Benedicte Dubois, Dominique Dive, Andreas Lysandropoulos, Dominik Selleslag, Ludo Vanopdenbosch, Vincent Van Pesch, Bart Vanwijmeersch, Ann Janssens
Alemtuzumab (Lemtrada® ) is a humanized monoclonal antibody indicated for the treatment of adult patients with relapsing-remitting multiple sclerosis with active disease defined by clinical or imaging features. Alemtuzumab demonstrated superior efficacy over active comparator in both treatment naive patients and those with inadequate response to prior therapy. Alemtuzumab is associated with a consistent and manageable safety and tolerability profile. Treatment with alemtuzumab for multiple sclerosis increases the risk for autoimmune adverse events including immune thrombocytopenia (ITP)...
January 27, 2018: Acta Neurologica Belgica
Michael Kaabak, Nadeen Babenko, Ron Shapiro, Allan Zokoyev, Olga Dymova, Edward Kim
Ischemia-reperfusion injury has multiple effects on a transplanted allograft, including delayed or impaired graft function, compromised long-term survival, and an association with an increased incidence of rejection. Eculizumab, a monoclonal antibody blocking terminal complement activation, has been postulated to be an effective agent in the prevention or amelioration of IRI. We performed a single-center prospective, randomized controlled trial involving 57 pediatric kidney transplant recipients between 2012 and 2016...
January 29, 2018: Pediatric Transplantation
Brigitte Decallonne, Emmanuel Bartholomé, Valérie Delvaux, Miguel D'haeseleer, Souraya El Sankari, Pierrette Seeldrayers, Bart Van Wijmeersch, Chantal Daumerie
This paper deals with thyroid disease that can occur after treatment with alemtuzumab (humanized monoclonal anti-CD52) for relapsing-remitting multiple sclerosis (MS). The 5-year incidence of thyroid adverse events in phase 3 clinical trials is up to 40.7%. In most cases, the thyroid dysfunction is mild and easily manageable and only few serious thyroid adverse events have been reported. The need for patient education on the risk of thyroid dysfunction, as well as regular clinical and biochemical thyroid function screening is well described...
January 25, 2018: Acta Neurologica Belgica
Madeleine Oliver, Graham Mitro, Patrick Tenbrink, Samer Alharthi, Nastassja Bedford, Jinling Wu, Amira Gohara, Matthew Jordan, Cassandra Zaremba, Michael Rees, Jorge Ortiz
OBJECTIVES: Posttransplant lymphoproliferative disorder is a known complication of solid-organ transplant. The use of depleting induction agents has demonstrated varying associations with incidence of posttransplant lymphoproliferative disorder. Alemtuzumab, a depleting induction agent for kidney transplant patients, has shown promising results in reducing the risk of acute rejection and graft loss in the first year. Its unique mechanism of depleting both T-cell and B-cell populations may be beneficial in preventing the occurrence of posttransplant lymphoproliferative disorder...
January 22, 2018: Experimental and Clinical Transplantation
Maria di Ioia, Deborah Farina, Valeria di Tommaso, Daniela Travaglini, Erika Pietrolongo, Marco Onofrj, Giovanna de Luca
BACKGROUND: Alemtuzumab, approved for multiple sclerosis (MS), can cause secondary autoimmune adverse events including thyroid disorders, immune thrombocytopenia (ITP), and glomerular nephropathies. Non-ITP autoimmune cytopenias are rarely reported. OBJECTIVE: To report a case of autoimmune hemolytic anemia (AIHA) and nephropathy in a MS patient treated with alemtuzumab. CASE REPORT: A 34-year-old man with MS developed albuminuria and AIHA after the first and only alemtuzumab treatment, with positive Coombs' direct and indirect tests and IgG autoantibodies...
January 1, 2018: Multiple Sclerosis: Clinical and Laboratory Research
Benoit Meunier, Audrey Rico, Julie Seguier, Clemence Boutiere, Mikael Ebbo, Jean Robert Harle, Nicolas Schleinitz, Jean Pelletier
BACKGROUND: Alemtuzumab is a humanized monoclonal antibody directed at CD52 approved as a disease-modifying therapy for relapsing forms of multiple sclerosis (MS). OBJECTIVE: To describe a case of a life-threatening autoimmune anemia occurring after a first course of alemtuzumab for relapsing-remitting MS in a 28-year-old male. METHODS: Case report. RESULTS: A 28-year-old male developed a life-threatening autoimmune anemia occurring 11 months after first alemtuzumab course...
January 1, 2018: Multiple Sclerosis: Clinical and Laboratory Research
Gregory M T Guilcher, Ravi Shah, Shalini Shenoy
Alemtuzumab is a humanized mAb targeted to CD52. Alemtuzumab is highly immunosuppressive with the ability to deplete T and B cells (in addition to other immune cell lines). A growing understanding of the PKs, dosing, and timing of administration of alemtuzumab has allowed for the study of its use as a conditioning agent for allogeneic HCT. The highly immunosuppressive properties of the drug are particularly appealing in the setting of non-malignant HCT, where GVHD provides no clinical benefit and relapse of malignancy is not applicable...
January 19, 2018: Pediatric Transplantation
Thomas Wehrum, Lena-Alexandra Beume, Oliver Stich, Irina Mader, Mathias Mäurer, Adam Czaplinski, Cornelius Weiller, Sebastian Rauer
OBJECTIVE: To report 3 patients with multiple sclerosis showing severe activation of disease during immunotherapy with alemtuzumab. METHODS: Retrospective case series. RESULTS: Patient 1, a 21-year-old woman, developed severe cognitive impairment, sight deterioration, severe gait ataxia, urinary retention, and extensive progression of cerebral lesion load, including new lesions that exhibited gadolinium ring enhancement and dominance of CD19/20-positive B lymphocytes, 6 months after induction of alemtuzumab...
February 13, 2018: Neurology
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