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Alemtuzumab

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https://www.readbyqxmd.com/read/28635362/costs-and-effectiveness-of-fingolimod-versus-alemtuzumab-in-the-treatment-of-highly-active-relapsing-remitting-multiple-sclerosis-in-the-uk-retreatment-discount-and-disutility
#1
Stephen M Montgomery, Jeanette Kusel, Richard Nicholas, Nicholas Adlard
OBJECTIVE: Patients with relapsing-remitting multiple sclerosis (RRMS) treated with disease modifying therapies (DMTs) who continue to experience disease activity may be considered for escalation therapies such as fingolimod or may be considered for alemtuzumab. Previous economic modelling used Markov models; applying one alternative technique, discrete event simulation (DES) modelling, allows retreatment and long-term adverse events (AEs) to be included in the analysis. METHODS: A DES was adapted to model relapse-triggered retreatment with alemtuzumab and the effect of including ongoing quality-adjusted life year (QALY) decrements for AEs that extend beyond previous one year Markov cycles...
June 21, 2017: Journal of Medical Economics
https://www.readbyqxmd.com/read/28632322/reduced-intensity-conditioning-allogeneic-transplantation-after-salvage-treatment-with-dt-pace-in-myeloma-patients-relapsing-early-after-autologous-transplant
#2
K Randall, M Kaparou, E Xenou, S Paneesha, B Kishore, A Kanellopoulos, R Lovell, K Holder, J Suhr, L Baker, L Ryan, E Nikolousis
OBJECTIVE: In this retrospective single center study we have looked into the transplant outcomes(overall survival OS, progression free survival PFS,GvHD) and the role of chimerism, DLI and pre-transplant characteristics in patients who had a suboptimal response (<12 months)to an autologous stem cell transplant for myeloma and underwent an Alemtuzumab T-cell depleted reduced intensity allograft(RIC). METHODS: 24 patients were salvaged with 2 cycles of DT-PACE and received a RIC transplant with Fludarabine, Melphalan and Alemtuzumab...
June 20, 2017: European Journal of Haematology
https://www.readbyqxmd.com/read/28626781/both-cladribine-and-alemtuzumab-may-effect-ms-via-b-cell-depletion
#3
David Baker, Samuel S Herrod, Cesar Alvarez-Gonzalez, Lukasz Zalewski, Christo Albor, Klaus Schmierer
OBJECTIVE: To understand the efficacy of cladribine (CLAD) treatment in MS through analysis of lymphocyte subsets collected, but not reported, in the pivotal phase III trials of cladribine and alemtuzumab induction therapies. METHODS: The regulatory submissions of the CLAD Tablets Treating Multiple Sclerosis Orally (CLARITY) (NCT00213135) cladribine and Comparison of Alemtuzumab and Rebif Efficacy in Multiple Sclerosis, study one (CARE-MS I) (NCT00530348) alemtuzumab trials were obtained from the European Medicine Agency through Freedom of Information requests...
July 2017: Neurology® Neuroimmunology & Neuroinflammation
https://www.readbyqxmd.com/read/28619423/acute-respiratory-distress-syndrome-following-alemtuzumab-therapy-for-relapsing-multiple-sclerosis
#4
Keh Yann, Fran Jackson, Nazar Sharaf, Tatiana Mihalova, Paul Talbot, David Rog, Adrian Pace
We present the case of a 54 year old woman with known relapsing-remitting multiple sclerosis who presented with acute respiratory deterioration five weeks after a first course of alemtuzumab. Imaging showed bilateral ground glass changes and extensive investigations confirmed chest infection with dual pathogens - Pneumocystis jirovecii and Cytomegalovirus. She responded to standard anti-PJP and CMV therapy and was discharged on oral prophylaxis. Opportunistic infections in the weeks immediately following alemtuzumab therapy remain an uncommon complication but one that requires clinical vigilance, careful monitoring and appropriate prophylactic therapy...
May 2017: Multiple Sclerosis and related Disorders
https://www.readbyqxmd.com/read/28617370/-clinical-recommendations-on-the-use-of-alemtuzumab-lemtrada
#5
V M Alifirova, G N Bisaga, A N Boyko, V V Bryukhov, M V Davydovskay, M N Zakharova, E V Zakharova, N A Malkova, E V Popova, G N Salogub, S A Sivertseva, E A Troshina, N V Khachanova, T E Schmidt
No abstract text is available yet for this article.
2017: Zhurnal Nevrologii i Psikhiatrii Imeni S.S. Korsakova
https://www.readbyqxmd.com/read/28604941/induction-of-new-autoimmune-diseases-after-alemtuzumab-therapy-for-multiple-sclerosis-learning-from-adversity
#6
Lawrence Steinman
No abstract text is available yet for this article.
June 12, 2017: JAMA Neurology
https://www.readbyqxmd.com/read/28604916/interpreting-lymphocyte-reconstitution-data-from-the-pivotal-phase-3-trials-of-alemtuzumab
#7
David Baker, Samuel S Herrod, Cesar Alvarez-Gonzalez, Gavin Giovannoni, Klaus Schmierer
Importance: Alemtuzumab, a CD52-depleting monoclonal antibody, effectively inhibits relapsing multiple sclerosis (MS) but is associated with a high incidence of secondary B-cell autoimmunities that limit use. These effects may be avoided through control of B-cell hyperproliferation. Objective: To investigate whether the data describing the effect of alemtuzumab on lymphocyte subsets collected during the phase 3 trial program reveal mechanisms explaining efficacy and the risk for secondary autoimmunity with treatment of MS...
June 12, 2017: JAMA Neurology
https://www.readbyqxmd.com/read/28600850/eight-year-follow-up-in-pediatric-living-donor-kidney-recipients-receiving-alemtuzumab-induction
#8
Michael M Kaabak, Nadeen N Babenko, Ron Shapiro, Alexey A Maschan, Allan K Zokoev, Stanislav V Schekaturov, Julia N Vyunkova, Olga V Dymova
Recipient lymphocytes are crucial for direct and indirect pathways of allorecognition. We proposed that the administration of alemtuzumab several weeks pretransplantation could eradicate peripheral lymphatic cells and promote donor-specific acceptance. This was a single-center, retrospective review of 101 consecutive living donor kidney transplantations in pediatric patients (age 7 months-18 years), performed between September 2006 and April 2010. IS protocol included two 30 mg doses of alemtuzumab: The first was given 12-29 days prior to transplantation, and the second at the time of transplantation...
June 10, 2017: Pediatric Transplantation
https://www.readbyqxmd.com/read/28600462/failure-of-alemtuzumab-therapy-to-control-mog-encephalomyelitis
#9
Brigitte Wildemann, Sven Jarius, Alexander Schwarz, Ricarda Diem, Andrea Viehöver, Stefan Hähnel, Markus Reindl, Mirjam Korporal-Kuhnke
No abstract text is available yet for this article.
June 9, 2017: Neurology
https://www.readbyqxmd.com/read/28597710/comparing-treatment-options-for-chronic-inflammatory-neuropathies-and-choosing-the-right-treatment-plan
#10
Eduardo Nobile-Orazio, Francesca Gallia, Fabrizia Terenghi, Mariangela Bianco
Chronic inflammatory neuropathies are disorders caused by an immune response to peripheral nerve. They include chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), multifocal motor neuropathy (MMN) and neuropathy associated with anti-MAG IgM monoclonal gammopathy and other less frequent neuropathies. Several immune therapies have been proven to be effective in these neuropathies even if the best therapeutic option is still unsettled. Areas covered: The authors reviewed the literature to compare the efficacy and safety of currently used immune therapies in these neuropathies...
June 9, 2017: Expert Review of Neurotherapeutics
https://www.readbyqxmd.com/read/28592744/treatment-advances-and-prognosis-for-patients-with-adult-t-cell-leukemia-lymphoma
#11
Hiroo Katsuya, Kenji Ishitsuka
A classification for adult T-cell leukemia-lymphoma (ATL) based on clinical features was proposed in 1991: acute, lymphoma, chronic, and smoldering types, and their median survival times (MSTs) were reported to be 6.2, 10.2, 24.3 months, and not reached, respectively. Several new therapies for ATL have since been developed, i.e. dose-intensity multi-agent chemotherapies, allogeneic hematopoietic stem cell transplantation (allo-HSCT), monoclonal antibodies, and anti-viral therapy. The monoclonal antibody to CCR4, mogamulizumab, clearly improved response rates in patients with treatment-naïve and relapsed aggressive ATL, and has the potential to provide a survival advantage...
June 8, 2017: Journal of Clinical and Experimental Hematopathology: JCEH
https://www.readbyqxmd.com/read/28591758/are-the-polyomaviruses-bk-and-jc-associated-with-opportunistic-infections-graft-versus-host-disease-or-worse-outcomes-in-adult-patients-receiving-their-first-allogeneic-stem-cell-transplantation-with-low-dose-alemtuzumab
#12
Laila Schneidewind, Thomas Neumann, Florian Knoll, Kathrin Zimmermann, Sigrun Smola, Christian Andreas Schmidt, William Krüger
BACKGROUND: The association of polyomaviruses BK and JC with other opportunistic infections and graft-versus-host disease (GvHD) in allogeneic stem cell transplantation is controversially discussed. METHODS: We conducted a retrospective study of 64 adult patients who received their first allogeneic stem cell transplantation between March 2010 and December 2014; the follow-up time was 2 years. RESULTS: Acute leukemia was the most frequent underlying disease (45...
June 8, 2017: Acta Haematologica
https://www.readbyqxmd.com/read/28589551/centre-characteristics-and-procedure-related-factors-have-an-impact-on-outcomes-of-allogeneic-transplantation-for-patients-with-cll-a-retrospective-analysis-from-the-european-society-for-blood-and-marrow-transplantation-ebmt
#13
Johannes Schetelig, Liesbeth C de Wreede, Niels S Andersen, Carol Moreno, Michel van Gelder, Antonin Vitek, Michal Karas, Mauricette Michallet, Maciej Machaczka, Martin Gramatzki, Dietrich Beelen, Jürgen Finke, Julio Delgado, Liisa Volin, Jakob Passweg, Peter Dreger, Nicolaas Schaap, Eva Wagner, Anja Henseler, Anja van Biezen, Martin Bornhäuser, Simona Iacobelli, Hein Putter, Stefan O Schönland, Nicolaus Kröger
The best approach for allogeneic haematopoietic stem cell transplantations (alloHCT) in patients with chronic lymphocytic leukaemia (CLL) is unknown. We therefore analysed the impact of procedure- and centre-related factors on 5-year event-free survival (EFS) in a large retrospective study. Data of 684 CLL patients who received a first alloHCT between 2000 and 2011 were analysed by multivariable Cox proportional hazards models with a frailty component to investigate unexplained centre heterogeneity. Five-year EFS of the whole cohort was 37% (95% confidence interval [CI], 34-42%)...
June 7, 2017: British Journal of Haematology
https://www.readbyqxmd.com/read/28578010/unrelated-umbilical-cord-blood-transplantation-for-sickle-cell-disease-following-reduced-intensity-conditioning-results-of-a-phase-i-trial
#14
Allistair Abraham, Andrew Cluster, David Jacobsohn, David Delgado, Monica L Hulbert, Divyesh Kukadiya, Lisa Murray, Shalini Shenoy
Hematopoietic stem cell transplantation from HLA-matched sibling donors results in disease free survival of >90% in patients with sickle cell disease (SCD) but only about 18% have suitable donors. Unrelated cord blood transplantation (UCBT) is one way to expand donor options for patients with severe SCD but historically has been associated with high graft rejection rates (50-62%). We hypothesized that the addition of thiotepa to a previously tested reduced intensity conditioning (RIC) regimen would support engraftment after UCBT in SCD patients...
May 31, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/28573314/reduced-toxicity-myeloablative-hla-haploidentical-hematopoietic-stem-cell-transplantation-with-post-transplantation-cyclophosphamide-for-sickle-cell-disease
#15
Volker Wiebking, Sebastian Hütker, Irene Schmid, Stefanie Immler, Tobias Feuchtinger, Michael H Albert
Allogeneic hematopoietic stem cell transplantation (HSCT) offers the possibility of cure for sickle cell disease (SCD) patients. Unfortunately, the probability of finding an HLA-matched donor for SCD patients is low. HSCT from HLA-haploidentical donors using reduced intensity conditioning, unmanipulated bone marrow and post-transplantation cyclophosphamide (ptCy) has resulted in negligible toxicity but high rates of graft rejection. We hypothesized that combining ptCy with a myeloablative reduced toxicity conditioning including serotherapy to increase immune ablation would allow for better engraftment...
June 1, 2017: Annals of Hematology
https://www.readbyqxmd.com/read/28559746/estimating-outcomes-and-cost-effectiveness-using-a-single-arm-clinical-trial-ofatumumab-for-double-refractory-chronic-lymphocytic-leukemia
#16
Anthony J Hatswell, Gwilym J Thompson, Penny A Maroudas, Oleg Sofrygin, Thomas E Delea
BACKGROUND: Ofatumumab (Arzerra(®), Novartis) is a treatment for chronic lymphocytic leukemia refractory to fludarabine and alemtuzumab [double refractory (DR-CLL)]. Ofatumumab was licensed on the basis of an uncontrolled Phase II study, Hx-CD20-406, in which patients receiving ofatumumab survived for a median of 13.9 months. However, the lack of an internal control arm presents an obstacle for the estimation of comparative effectiveness. METHODS: The objective of the study was to present a method to estimate the cost effectiveness of ofatumumab in the treatment of DR-CLL...
2017: Cost Effectiveness and Resource Allocation: C/E
https://www.readbyqxmd.com/read/28556989/weight-based-dosing-of-alemtuzumab-an-ounce-of-prevention
#17
Joshua J Augustine
Alemtuzumab is a lymphocyte-depleting humanized monoclonal antibody that targets CD52 and binds to T and B lymphocytes, macrophages, monocytes and natural killer cells.(1) It was approved decades ago for the treatment of B-cell chronic lymphocytic leukemia (CLL), and the use of alemtuzumab in kidney transplantation was first described in the late 1990s as a drug that could promote tolerance and allow for maintenance drug minimization.(2) Although there has been variability in dosing in renal transplantation(3-5) , alemtuzumab is typically administered at a dosage of 30 mg intravenously once or twice in the perioperative transplant period, which is a fraction the cumulative dosage used for CLL...
May 30, 2017: Transplant International: Official Journal of the European Society for Organ Transplantation
https://www.readbyqxmd.com/read/28556519/lessons-learned-early-termination-of-a-randomized-trial-of-calcineurin-inhibitor-and-corticosteroid-avoidance-using-belatacept
#18
Kenneth A Newell, Aneesh K Mehta, Christian P Larsen, Peter G Stock, A Bradley Farris, Shikha G Mehta, David Ikle, Brian Armstrong, Yvonne Morrison, Nancy Bridges, Mark Robien, Roslyn B Mannon
The intent of this NIH-sponsored study was to compare a belatacept-based immunosuppressive regimen with a maintenance regimen of tacrolimus and mycophenolate (MMF). Nineteen primary, EBV-immune renal transplant recipients with a negative cross-match were randomized to one of three groups. All patient groups received perioperative steroids and maintenance MMF. Patients in groups 1 and 2 were induced with alemtuzumab and maintained on tacrolimus or belatacept, respectively. Patients in group 3 were induced with basiliximab, received 3 months of tacrolimus, and maintained on belatacept...
May 28, 2017: American Journal of Transplantation
https://www.readbyqxmd.com/read/28550802/mechanism-of-action-of-three-newly-registered-drugs-for-multiple-sclerosis-treatment
#19
REVIEW
Kaja Kasarełło, Agnieszka Cudnoch-Jędrzejewska, Andrzej Członkowski, Dagmara Mirowska-Guzel
Multiple sclerosis (MS) is a disease of suspected autoimmune origin leading to neurodegeneration. The disease pathomechanism is considered to be primarily based on neuroinflammation directed against myelin antigens caused by autoreactive T cells. MS etiology remains still unknown, which makes it difficult to create an efficient therapy, therefore, MS treatment targets mechanisms involved in disease pathology. In this review, we present the mechanism of action of three newly registered drugs for MS. Dimethyl fumarate (DMF) is an agent presenting a broad spectrum of action...
February 22, 2017: Pharmacological Reports: PR
https://www.readbyqxmd.com/read/28536356/hla-c-kir-ligands-determine-the-impact-of-anti-thymocyte-globulin-atg-on-graft-versus-host-and-graft-versus-leukemia-effects-following-hematopoietic-stem-cell-transplantation
#20
Johannes Clausen, Alexandra Böhm, Irene Straßl, Olga Stiefel, Veronika Buxhofer-Ausch, Sigrid Machherndl-Spandl, Josef König, Stefan Schmidt, Hansjörg Steitzer, Martin Danzer, Hedwig Kasparu, Ansgar Weltermann, David Nachbaur
Rabbit anti-thymocyte globulins (ATGs) are widely used for the prevention of acute and chronic graft versus host disease (aGVHD, cGVHD) following allogeneic hematopoietic stem cell transplantation (HSCT). However, most prospective and retrospective studies did not reveal an overall survival (OS) benefit associated with ATG. Homozygosity for human leukocyte antigen (HLA)-C group 1 killer-cell immunoglobulin-like receptor ligands (KIR-L), i.e. C1/1 KIR-L status, was recently shown to be a risk factor for severe aGVHD...
March 28, 2017: Biomedicines
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