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Alemtuzumab

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https://www.readbyqxmd.com/read/29352515/principles-of-alemtuzumab-immunoablation-in-hematopoietic-cell-transplantation-for-non-malignant-diseases-in-children-a-review
#1
REVIEW
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
https://www.readbyqxmd.com/read/29352101/activation-of-disease-during-therapy-with-alemtuzumab-in-3-patients-with-multiple-sclerosis
#2
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...
January 19, 2018: Neurology
https://www.readbyqxmd.com/read/29352097/defining-response-profiles-after-alemtuzumab-rare-paradoxical-disease-exacerbation
#3
EDITORIAL
Heinz Wiendl, Peter A Calabresi, Sven G Meuth
No abstract text is available yet for this article.
January 19, 2018: Neurology
https://www.readbyqxmd.com/read/29334337/durable-responses-in-refractory-autoimmune-hemolytic-anemia-with-alemtuzumab
#4
Renee K McAlister, Mahsa S Talbott, Nishitha M Reddy
Autoimmune hemolytic anemia occurs due to an interaction of IgG antibodies with protein antigens expressed on red blood corpuscles. Glucocorticoids are the mainstay of treatment for autoimmune hemolytic anemia. For patients not responding to initial therapy, other agents such as rituximab, immunosuppressive therapy, or splenectomy are considered. When refractory to these treatment options, alemtuzumab is an alternative agent. However, long-term outcomes of patients supporting its use are lacking. We present three patients with refractory autoimmune hemolytic anemia treated with alemtuzumab...
January 1, 2018: Journal of Oncology Pharmacy Practice
https://www.readbyqxmd.com/read/29317954/a-multiple-treatment-comparison-of-eleven-disease-modifying-drugs-used-for-multiple-sclerosis
#5
Vida Hamidi, Elisabeth Couto, Tove Ringerike, Marianne Klemp
Background: Several disease-modifying drug therapies are available for the treatment of multiple sclerosis (MS). To ensure the most appropriate MS management, we assessed the effectiveness and cost-effectiveness of the disease-modifying medicines used for MS. Methods: We conducted a systematic review including 11 disease-modifying drugs used for treatment of adult patients diagnosed with relapsing-remitting MS. We performed a network meta-analysis using both direct and indirect evidence...
February 2018: Journal of Clinical Medicine Research
https://www.readbyqxmd.com/read/29296707/cyclophosphamide-improves-engraftment-in-patients-with-scd-and-severe-organ-damage-who-undergo-haploidentical-pbsct
#6
Courtney D Fitzhugh, Matthew M Hsieh, Tiffani Taylor, Wynona Coles, Katherine Roskom, Delon Wilson, Elizabeth Wright, Neal Jeffries, Christopher J Gamper, Jonathan Powell, Leo Luznik, John F Tisdale
Peripheral blood stem cell transplantation (PBSCT) offers a curative option for sickle cell disease (SCD). Although HLA-matched sibling transplantation is promising, the vast majority of patients lack such a donor. We sought to develop a novel nonmyeloablative HLA-haploidentical PBSCT approach that could safely be used for patients with severe organ damage. Based on findings in our preclinical model, we developed a phase 1/2 trial using alemtuzumab, 400 cGy total body irradiation, and escalating doses of posttransplant cyclophosphamide (PT-Cy): 0 mg/kg in cohort 1, 50 mg/kg in cohort 2, and 100 mg/kg in cohort 3...
April 25, 2017: Blood Advances
https://www.readbyqxmd.com/read/29279357/successful-outcome-following-allogeneic-hematopoietic-stem-cell-transplantation-in-adults-with-primary-immunodeficiency
#7
Thomas A Fox, Ronjon Chakraverty, Siobhan Burns, Benjamin Carpenter, Kirsty Thomson, David Lowe, Adele Fielding, Karl Peggs, Panagiotis Kottaridis, Benjamin Uttenthal, Venetia Bigley, Matthew Buckland, Victoria Grandage, Shari Denovan, Sarah Grace, Julia Dahlstrom, Sarita Workman, Andrew Symes, Stephen Mackinnon, Rachael Hough, Emma Morris
INTRODUCTION: The primary immunodeficiencies (PID), rare inherited diseases characterised by severe dysfunction of immunity have been successfully treated by allogeneic hematopoietic stem cell transplantation (Allo-HSCT) in childhood. Controversy exists regarding optimal timing and use of Allo-HSCT in adults, due to lack of experience and previous poor outcomes. MATERIALS AND METHODS: 29 consecutive adult patients, with a mean age at transplant of 24 years (range 17-50) underwent Allo-HSCT...
December 26, 2017: Blood
https://www.readbyqxmd.com/read/29277513/risk-factors-treatment-and-immune-dysregulation-in-autoimmune-cytopenia-following-allogeneic-hematopoietic-stem-cell-transplantation-in-pediatric-patients
#8
Matthijs D Kruizinga, Maarten J D van Tol, Vincent Bekker, Tanja Netelenbos, Frans J Smiers, Dorine Bresters, Anja M Jansen-Hoogendijk, Monique M van Ostaijen-Ten Dam, Wouter J W Kollen, Jaap J Zwaginga, Arjan C Lankester, Robbert G M Bredius
Auto- or alloimmune cytopenia (AIC) is a known rare complication of hematopoietic stem cell transplantation (SCT). AIC after SCT is considered difficult to treat and associated with high morbidity and mortality. In this retrospective study in pediatric patients we evaluated incidence, outcome, potential risk factors and current treatment strategies. A nested matched case-control study was performed to search for biomarkers associated with AIC. Of 531 consecutive SCTs at our center between 2000 and 2016, 26 were complicated by the development of AIC (cumulative incidence 5...
December 19, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/29259997/evidence-of-b-cell-dysregulation-in-severe-cns-inflammation-after-alemtuzumab-therapy
#9
Francesca Rinaldi, Lisa Federle, Marco Puthenparampil, Paola Perini, Francesca Grassivaro, Paolo Gallo
No abstract text is available yet for this article.
January 2018: Neurology® Neuroimmunology & Neuroinflammation
https://www.readbyqxmd.com/read/29247512/alemtuzumab-depletion-failure-can-occur-in-multiple-sclerosis
#10
Nicolas Dubuisson, David Baker, Angray S Kang, Gareth Pryce, Monica Marta, Leo H Visser, Werner E Hofmann, Sharmilee Gnanapavan, Gavin Giovannoni, Klaus Schmierer
Alemtuzumab is a lymphocyte-depleting antibody and one of the most effective treatments for relapsing multiple sclerosis. However, it also causes loss of immune-tolerance leading to secondary autoimmunity and marked anti-drug antibody responses. Whilst these anti-drug responses have been reported to be of no significance, we hypothesised that they will affect the depleting-capacity and treatment-response in some individuals. This was found following analysis of the regulatory submission of the pivotal phase III trials, which was obtained from the European Medicines Agency...
December 16, 2017: Immunology
https://www.readbyqxmd.com/read/29226570/campath-calcineurin-inhibitor-reduction-and-chronic-allograft-nephropathy-the-3c-study-results-of-a-randomized-controlled-clinical-trial
#11
Richard Haynes, Lisa Blackwell, Natalie Staplin, William G Herrington, Jonathan Emberson, Parminder K Judge, Benjamin C Storey, Martin J Landray, Paul N Harden, Colin Baigent, Peter Friend
Calcineurin inhibitors (CNI e.g. tacrolimus) reduce short-term kidney transplant failure, but chronic nephrotoxicity may contribute to late transplant loss. Elective conversion to inhibitors of the mammalian target of rapamycin pathway (mTOR e.g. sirolimus) might avoid long-term CNI renal damage and improve outcomes. The 3C Study was a pragmatic randomized controlled trial comprising sequential randomizations between alemtuzumab and basiliximab induction therapy (at the time of surgery) and between tacrolimus and sirolimus maintenance therapy at 6-months post-transplant...
December 11, 2017: American Journal of Transplantation
https://www.readbyqxmd.com/read/29217782/rational-management-approach-to-pure-red-cell-aplasia
#12
Suresh Kumar Balasubramanian, Meena Sadaps, Swapna Thota, Mai Aly, Bartlomiej P Przychodzen, Cassandra M Hirsch, Valeria Visconte, Tomas Radivoyevitch, Jaroslaw P Maciejewski
Pure red cell aplasia is an orphan disease without rationally established standard therapies. Most cases are idiopathic; a subset is antibody-mediated. There is overlap between idiopathic cases and those with T-large granular lymphocytic leukemia, hypogammaglobulinemia, and low-grade lymphomas. In all these, the pathogenetic mechanisms may involve autoreactive cytotoxic responses. We selected 62 uniformly diagnosed pure red cell aplasia patients and analyzed their pathophysiologic features and responsiveness to rationally applied first-line and salvage therapies to propose diagnostic and therapeutic algorithms that may help guide management of prospective patients...
December 7, 2017: Haematologica
https://www.readbyqxmd.com/read/29212866/acquired-haemophilia-a-complicating-alemtuzumab-therapy-for-multiple-sclerosis
#13
Georgia McCaughan, Jennifer Massey, Ian Sutton, Jennifer Curnow
Alemtuzumab is a highly efficacious therapy used in the treatment of multiple sclerosis (MS), but uncoupling of T and B cell repopulation during immune reconstitution associates with an increasing range of secondary B cell-mediated autoimmune complications. A 34-year-old woman developed Graves' disease 11 months following an initial course of alemtuzumab treatment for MS. Nine months following the second treatment with alemtuzumab, the patient presented with spontaneous intramuscular and subcutaneous haemorrhage due to development of an inhibitory autoantibody to coagulation factor VIII...
December 5, 2017: BMJ Case Reports
https://www.readbyqxmd.com/read/29206087/alemtuzumab-induction-is-associated-with-an-equalization-of-outcomes-between-white-and-african-american-kidney-transplant-recipients
#14
Joseph T Brooks, Graham Mitro, Anthony DeLeonibus, Weikai Qu, Michael Rees, Munier Nazzal, Jorge Ortiz
OBJECTIVES: Our aim was to assess outcomes in White and African American kidney transplant recipients after induction with alemtuzumab. MATERIALS AND METHODS: We performed a retrospective study of 464 patients who received deceased-donor kidney transplants and were induced with alem-tuzumab between March 2006 and May 2015. We evaluated ethnic influences on patient and graft survival, delayed graft function, allograft failure, and rejection. RESULTS: There were 337 White (67...
December 5, 2017: Experimental and Clinical Transplantation
https://www.readbyqxmd.com/read/29189966/management-of-adverse-renal-events-related-to-alemtuzumab-treatment-in-multiple-sclerosis-a-belgian-consensus
#15
Ben Sprangers, D Decoo, D Dive, A Lysandropoulos, L Vanopdenbosch, C Bovy
Alemtuzumab is a humanized monoclonal antibody indicated for the treatment of adult patients with relapsing-remitting multiple sclerosis with active disease. Multiple sclerosis (MS) patients treated with alemtuzumab are at increased risk for autoimmune adverse events (thyroid disorders, immune thrombocytopenia, and renal disease). The use of alemtuzumab has been associated with the development of renal immune-mediated adverse events in 0.3% of patients in clinical trials in MS, which generally occurred within 39 months of the last administration...
November 30, 2017: Acta Neurologica Belgica
https://www.readbyqxmd.com/read/29186076/the-role-of-anti-thymocyte-globulin-or-alemtuzumab-based-serotherapy-in-the-prophylaxis-and-management-of-graft-versus-host-disease
#16
REVIEW
Robert Ali, Jeremy Ramdial, Sandra Algaze, Amer Beitinjaneh
Allogeneic hematopoietic stem cell transplant is an established treatment modality for hematologic and non-hematologic diseases. However, it is associated with acute and long-term sequelae which can translate into mortality. Graft-versus-host disease (GVHD) remains a glaring obstacle, especially with the advent of reduced-intensity conditioning. Serotherapy capitalizes on antibodies which target T cells and other immune cells to mitigate this effect. This article focuses on the utility of two such agents: anti-thymocyte globulin (ATG) and alemtuzumab...
November 29, 2017: Biomedicines
https://www.readbyqxmd.com/read/29178444/alemtuzumab-versus-interferon-beta-1a-for-relapsing-remitting-multiple-sclerosis
#17
REVIEW
Jian Zhang, Shengliang Shi, Yueling Zhang, Jiefeng Luo, Yousheng Xiao, Lian Meng, Xiaobo Yang
BACKGROUND: Alemtuzumab is a humanised monoclonal antibody that alters the circulating lymphocyte pool, causing prolonged lymphopenia, thus remoulding the immune repertoire that accompanies homeostatic lymphocyte reconstitution. It has been proved more effective than interferon (IFN) 1a for the treatment of relapsing-remitting multiple sclerosis (RRMS). OBJECTIVES: To compare the efficacy, tolerability and safety of alemtuzumab versus interferon beta 1a in the treatment of people with RRMS to prevent disease activity...
November 27, 2017: Cochrane Database of Systematic Reviews
https://www.readbyqxmd.com/read/29178248/no-indication-of-increased-infection-rates-using-low-dose-alemtuzumab-instead-of-anti-thymocyte-globulin-as-graft-versus-host-disease-prophylaxis-before-allogeneic-stem-cell-transplantation
#18
Thomas Neumann, Laila Schneidewind, Thomas Thiele, Daniel Pink, Meike Schulze, Christian Schmidt, William Krüger
BACKGROUND: Alemtuzumab as part of the conditioning protocol is effective in reducing graft-versus-host disease (GvHD), but may be associated with increased infection rates, especially when using high doses (ie, 100 mg). METHODS: We performed a retrospective, single-centre, case-control study analysing the rates of neutropenic fever, cytomegalovirus (CMV) reactivation, Epstein-Barr virus (EBV) reactivation, clinical manifest toxoplasmosis, and clinical manifest human herpesvirus-6 (HHV6) infection using low-dose alemtuzumab in comparison with anti-thymocyte globulin (ATG) as GvHD prophylaxis before allogeneic stem cell transplantation...
November 27, 2017: Transplant Infectious Disease: An Official Journal of the Transplantation Society
https://www.readbyqxmd.com/read/29163335/alopecia-universalis-following-alemtuzumab-treatment-in-multiple-sclerosis-a-barely-recognized-manifestation-of-secondary-autoimmunity-report-of-a-case-and-review-of-the-literature
#19
Julian Zimmermann, Timo Buhl, Marcus Müller
Secondary autoimmunity is the most frequent adverse event occurring in almost every other alemtuzumab-treated multiple sclerosis patient. We report a case of a patient with relapsing-remitting multiple sclerosis who reported smooth, circular areas of complete hair loss on both thighs 6 months after the second treatment cycle with alemtuzumab. The patient was diagnosed as having alopecia areata (AA). Within 3 months, AA progressed to complete loss of all body hair (alopecia universalis). Current literature rarely connects alemtuzumab with the onset of alopecia of autoimmune origin...
2017: Frontiers in Neurology
https://www.readbyqxmd.com/read/29158120/management-of-ms-relapse-during-alemtuzumab-therapy-is-it-really-b-cell-mediated
#20
Philipp Schwenkenbecher, Julian Deppe, Martin W Hümmert, Roland Jacobs, Paul Bronzlik, Martin Stangel, Thomas Skripuletz
No abstract text is available yet for this article.
October 22, 2017: Multiple Sclerosis and related Disorders
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