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Immunosuppression withdrawal

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https://www.readbyqxmd.com/read/28729300/rapamycin-is-highly-effective-in-murine-models-of-immune-mediated-bone-marrow-failure
#1
Xingmin Feng, Zenghua Lin, Wanling Sun, Maile K Hollinger, Marie J Desierto, Keyvan Keyvanfar, Daniela Malide, Pawel Muranski, Jichun Chen, Neal S Young
Acquired aplastic anemia, the prototypical bone marrow failure disease, is characterized by pancytopenia and marrow hypoplasia. Most aplastic anemia patients respond to immunosuppressive therapy, usually as anti-thymocyte globulin and cyclosporine, but some relapse on cyclosporine withdrawal or require long-term administration of cyclosporine to maintain blood counts. In the current study, we tested efficacy of rapamycin as a new or alternative treatment in mouse models of immune-mediated bone marrow failure...
July 20, 2017: Haematologica
https://www.readbyqxmd.com/read/28729151/standard-dose-pembrolizumab-in-combination-with-reduced-dose-ipilimumab-for-patients-with-advanced-melanoma-keynote-029-an-open-label-phase-1b-trial
#2
Georgina V Long, Victoria Atkinson, Jonathan S Cebon, Michael B Jameson, Bernie M Fitzharris, Catriona M McNeil, Andrew G Hill, Antoni Ribas, Michael B Atkins, John A Thompson, Wen-Jen Hwu, F Stephen Hodi, Alexander M Menzies, Alexander D Guminski, Richard Kefford, Benjamin Y Kong, Babak Tamjid, Archana Srivastava, Anna J Lomax, Mohammed Islam, Xinxin Shu, Scot Ebbinghaus, Nageatte Ibrahim, Matteo S Carlino
BACKGROUND: Reduced-dose nivolumab in combination with standard-dose ipilimumab improves objective response and progression-free survival compared with standard-dose ipilimumab alone, but increases toxicity. We assessed the safety and anti-tumour activity of standard-dose pembrolizumab in combination with reduced-dose ipilimumab. METHODS: In this open-label, phase 1b trial, we recruited patients from 12 medical centres in Australia, New Zealand, and the USA. Eligible patients were aged at least 18 years, had advanced melanoma, had an Eastern Coooperative Oncology Group performance status of 0 or 1, had measurable disease according to the Response Evaluation Criteria in Solid Tumors (RECIST) version 1...
July 17, 2017: Lancet Oncology
https://www.readbyqxmd.com/read/28675117/peripheral-immune-system-suppression-in-early-abstinent-alcohol-dependent-individuals-links-to-stress-and-cue-related-craving
#3
Helen C Fox, Verica Milivojevic, Gustavo A Angarita, Raymond Stowe, Rajita Sinha
BACKGROUND: Peripheral immune system cytokines may play an integral role in the underlying sensitized stress response and alcohol craving during early alcohol withdrawal. To date, the nature of these immune changes during early abstinence have not been examined. METHODS: A total of 39 early abstinent, treatment-seeking, alcohol-dependent individuals and 46 socially drinking controls were exposed to three guided imageries: stress, alcohol cue and neutral. These were presented randomly across consecutive days...
July 2017: Journal of Psychopharmacology
https://www.readbyqxmd.com/read/28669992/treatment-of-membranous-nephropathy-time-for-a-paradigm-shift
#4
REVIEW
Piero Ruggenenti, Fernando C Fervenza, Giuseppe Remuzzi
In patients with membranous nephropathy, alkylating agents (cyclophosphamide or chlorambucil) alone or in combination with steroids achieve remission of nephrotic syndrome more effectively than conservative treatment or steroids alone, but can cause myelotoxicity, infections, and cancer. Calcineurin inhibitors can improve proteinuria, but are nephrotoxic. Most patients relapse after treatment withdrawal and can become treatment dependent, which increases the risk of nephrotoxicity. The discovery of nephritogenic autoantibodies against podocyte M-type phospholipase A2 receptor (PLA2R) and thrombospondin type-1 domain- containing protein 7A (THSD7A) antigens provides a clear pathophysiological rationale for interventions that specifically target B-cell lineages to prevent antibody production and subepithelial deposition...
July 3, 2017: Nature Reviews. Nephrology
https://www.readbyqxmd.com/read/28656563/cutaneous-graft-versus-host-disease-diagnosis-and-treatment
#5
REVIEW
Karla Strong Rodrigues, Carla Oliveira-Ribeiro, Silvia de Abreu Fiuza Gomes, Robert Knobler
Graft-versus-host disease (GVHD) is an immunological reaction and a frequent complication following allogeneic hematopoietic stem cell transplantation. It is associated with high mortality rates and may have a significant negative impact on the patient's quality of life, particularly in the chronic-stage setting. Many different organs can be involved, which leads to a wide range of clinical manifestations. In this context, dermatologists play a key role by diagnosing and treating GVHD from the outset since cutaneous features are not just the most common but are also usually the presenting sign...
June 27, 2017: American Journal of Clinical Dermatology
https://www.readbyqxmd.com/read/28655795/first-in-human-study-of-amg%C3%A2-820-a-monoclonal-anti-colony-stimulating-factor-1-receptor-antibody-in-patients-with-advanced-solid-tumors
#6
Kyriakos P Papadopoulos, Larry Gluck, Lainie P Martin, Anthony J Olszanski, Anthony W Tolcher, Gataree Ngarmchamnanrith, Erik Rasmussen, Benny Amore, Dirk Nagorsen, John S Hill, Joe Stephenson
Binding of colony-stimulating factor 1 (CSF1) ligand to the CSF1 receptor (CSF1R) regulates survival of tumor-associated macrophages, which generally promote an immunosuppressive tumor microenvironment. AMG 820 is an investigational, fully human CSF1R antibody that inhibits binding of the ligands CSF1 and interleukin-34 and subsequent ligand-mediated receptor activation. This first-in-human phase I study evaluated the safety, pharmacokinetics, pharmacodynamics, and antitumor activity of AMG 820.<br /><br />Experimental Design: Adult patients with relapsed or refractory advanced solid tumors received intravenous AMG 820 0...
June 27, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28632810/hydralazine-associated-cutaneous-casculitis-presenting-with-aerodigestive-tract-involvement
#7
Laura E Levin, Cynthia Magro, James Horowitz, Joanna Harp
Hydralazine-induced small vessel vasculitis is a rare entity with a limited number of cases reported in the dermatologic literature. A characteristic pattern of acral pseudoembolic vesiculopustules with necrosis and ulceration has been suggested along with involvement of the aerodigestive tract, indicating mucosal involvement is an important feature of this disease. We report the case of a patient with hydralazine-induced vasculitis who exemplified this characteristic presentation associated with severe involvement of the aerodigestive tract and gastrointestinal tract bleeding...
May 2017: Cutis; Cutaneous Medicine for the Practitioner
https://www.readbyqxmd.com/read/28624108/modification-of-immunosuppressive-therapy-as-risk-factor-for-complications-after-liver-transplantation
#8
REVIEW
Paolo De Simone, Paola Carrai, Laura Coletti, Davide Ghinolfi, Stefania Petruccelli, Franco Filipponi
Management of complications post-liver transplantation (LT) includes immunosuppressive manipulations with the aim to reduce the overall burden of immunologic suppression and compensate for renal, cardiovascular, metabolic toxicities, and for the increased oncologic risk. Two approaches can be implemented to reduce immunosuppression-related adverse events: upfront schedules tailored to the pretransplant individual patient's risk profile versus downstream modifications in the event of immunosuppression-related complications...
April 2017: Best Practice & Research. Clinical Gastroenterology
https://www.readbyqxmd.com/read/28610760/iatrogenic-kaposi-s-sarcoma-a-retrospective-cohort-study-in-an-italian-tertiary-care-centre
#9
L Brambilla, A Tourlaki, G Genovese
AIMS: Kaposi's sarcoma (KS) is a lymphoangioproliferative multicentric disorder. Among its four distinct clinical variants, iatrogenic KS (iKS) typically affects patients who have received immunosuppressant regimens for organ transplants, proliferative disorders, or immune-mediated diseases. The aim of the current study was to examine the characteristics of a cohort of patients with iKS, evaluating the differences in terms of epidemiological and clinical features, management and outcomes between organ transplant recipients (OTR) and patients immunosuppressed for other medical conditions...
June 10, 2017: Clinical Oncology: a Journal of the Royal College of Radiologists
https://www.readbyqxmd.com/read/28608637/regulatory-t-cell-therapy-in-liver-transplantation
#10
REVIEW
Gavin P Whitehouse, Andrew Hope, Alberto Sanchez-Fueyo
Modern immunosuppression drug regimens have produced excellent short-term survival after liver transplantation but it is generally accepted that the side effects of these medications remain a significant contributing factor for less satisfactory long term outcomes. The liver has unique tolerogenic properties as evidenced by the higher rates of operational tolerance seen in liver transplant recipients compared to other solid organ transplants, and therefore, liver transplantation offers an attractive setting in which to study tolerizing therapies...
August 2017: Transplant International: Official Journal of the European Society for Organ Transplantation
https://www.readbyqxmd.com/read/28608031/adalimumab-in-refractory-cystoid-macular-edema-associated-with-birdshot-chorioretinopathy
#11
Laura R Steeples, Paul Spry, Richard W J Lee, Ester Carreño
PURPOSE: To report the clinical outcomes of adalimumab therapy in cases of birdshot chorioretinitis (BCR) with cystoid macular edema (CME) refractory to conventional immunotherapy. METHODS: This is a retrospective case series of three BCR patients treated with adalimumab for refractory CME. The main outcome measure was central subfield thickness (CST) on optical coherence tomography. Any patients treated with local steroids and/or receiving systemic steroids higher than 40 mg prednisolone daily during adalimumab therapy were excluded...
June 12, 2017: International Ophthalmology
https://www.readbyqxmd.com/read/28606879/can-immunosuppression-be-stopped-after-liver-transplantation
#12
REVIEW
Pierre-Alain Clavien, Xavier Muller, Michelle L de Oliveira, Philipp Dutkowski, Alberto Sanchez-Fueyo
Liver transplantation has improved dramatically over the past three decades, mainly as a result of advances in surgical techniques and management of post-transplant complications. The focus has now turned towards rescuing additional organs in the face of scarce organ supply, or prevention of long-term toxicity associated with immunosuppression. The liver appears to be privileged in terms of immune tolerance, with a low incidence of antibody-mediated rejection, which is in sharp contrast to other solid organ transplants, such as kidney, lung, and heart transplants...
July 2017: Lancet. Gastroenterology & Hepatology
https://www.readbyqxmd.com/read/28605781/everolimus-with-cyclosporine-withdrawal-or-low-exposure-cyclosporine-in-kidney-transplantation-from-month-3-a-multicentre-randomized-trial
#13
Klemens Budde, Martin Zeier, Oliver Witzke, Wolfgang Arns, Frank Lehner, Markus Guba, Johannes Jacobi, Volker Kliem, Petra Reinke, Ingeborg A Hauser, Bruno Vogt, Rolf Stahl, Thomas Rath, Michael Duerr, Eva-Maria Paulus, Christoph May, Martina Porstner, Claudia Sommerer
Background.: Randomized trials have shown that early adoption of everolimus-based immunosuppressive regimens without a calcineurin inhibitor (CNI) improves long-term kidney graft function, but the optimal strategy for CNI minimization remains uncertain. Methods.: In a prospective, randomized, multicentre, 12-month trial, 499 de novo kidney transplant patients were randomized at Month 3 to (i) remain on standard CNI (cyclosporine) therapy with mycophenolic acid, (ii) convert to everolimus with mycophenolic acid or (iii) start everolimus with reduced CNI and no mycophenolic acid (clinical trials registry: ClinicalTrials...
June 1, 2017: Nephrology, Dialysis, Transplantation
https://www.readbyqxmd.com/read/28592129/allogeneic-stem-cell-transplantation-after-fludarabine-melphalan-and-thymoglobulin-followed-by-early-withdrawal-of-prophylactic-immunosuppression-in-patients-with-acute-lymphoblastic-leukemia-update-of-single-center-study
#14
L Raida, A Kuba, Z Rusinakova, R Szotkowska, I Skoumalova, E Faber, T Szotkowski, P Rohon, J Hubacek, K Indrak, Z Pikalova, M Jarosova, M Divoka, K Langova, T Papajik
Presented are updated results of allogeneic hematopoietic stem cell transplantations (HSCTs) in 25 adult patients with acute lymphoblastic leukemia (ALL) in complete remission (CR) after a reduced intensity conditioning (RIC) combining fludarabine (150 mg/m2) and melphalan (140 mg/m2) with thymoglobulin (4.5 mg/kg or recently 4.0 mg/kg) followed by early initiation of reduction and withdrawal of prophylactic posttransplant immunosuppression. The median post-transplant follow-up was 32 (range, 4-87) months. Stable engraftment of donor's hematopoiesis was achieved in all patients...
June 8, 2017: Neoplasma
https://www.readbyqxmd.com/read/28577733/-transplant-tolerance-through-mixed-chimerism
#15
Julien Zuber
Three pilot studies have offered proof-of-concept that operational tolerance can be induced through mixed chimerism in recipients of combined kidney and hematopoietic cell transplants from the same donor. In two studies, sustained mixed chimerism was induced allowing safe and rejection-free immunosuppression withdrawal. However, this success came at heavy toll, requiring harsh cytoreductive regimen and a balance tipped toward graft-versus-host reactivity. Hence, achievement of durable chimerism in humans is not devoid of a significant risk of graft-versus-host disease...
April 2017: Néphrologie & Thérapeutique
https://www.readbyqxmd.com/read/28546260/randomised-controlled-trial-of-prolonged-treatment-in-the-remission-phase-of-anca-associated-vasculitis
#16
Alexandre Karras, Christian Pagnoux, Marion Haubitz, Kirsten de Groot, Xavier Puechal, Jan Willem Cohen Tervaert, Mårten Segelmark, Loic Guillevin, David Jayne
OBJECTIVES: A prospective randomised trial to compare two different durations of maintenance immunosuppressive therapy for the prevention of relapse in anti-neutrophil cytoplasmic antibodies (ANCA)-associated vasculitis (AAV). METHODS: Patients with AAV were recruited 18-24 months after diagnosis if they were in stable remission after cyclophosphamide/prednisolone-based induction followed by azathioprine/prednisolone maintenance therapy. They were randomised (1:1) to receive continued azathioprine/prednisolone to 48 months from diagnosis (continuation group) or to withdraw azathioprine/prednisolone by 24 months (withdrawal group)...
May 25, 2017: Annals of the Rheumatic Diseases
https://www.readbyqxmd.com/read/28537473/anakinra-in-the-treatment-of-patients-with-refractory-scleritis-a-pilot-study
#17
C Bottin, A Fel, N Butel, F Domont, A L Remond, L Savey, V Touitou, J F Alexandra, P LeHoang, P Cacoub, B Bodaghi, D Saadoun
PURPOSE: This study aimed to evaluate the safety and efficacy of anakinra for severe and refractory scleritis. METHODS: Ten patients with severe (i.e. at least 2 ocular relapses per year despite treatment) and refractory [i.e. at least to one disease modifying antirheumatic drugs (DMARDS)] scleritis were treated with anakinra (100 mg/day subcutaneously). Scleritis was associated with inflammatory systemic diseases in 60% of cases. The remission rate defined the primary outcome...
May 24, 2017: Ocular Immunology and Inflammation
https://www.readbyqxmd.com/read/28529524/antithyroid-drug-therapy-for-graves-disease-and-implications-for-recurrence
#18
REVIEW
Jia Liu, Jing Fu, Yuan Xu, Guang Wang
Graves' disease (GD) is the most common cause of hyperthyroidism worldwide. Current therapeutic options for GD include antithyroid drugs (ATD), radioactive iodine, and thyroidectomy. ATD treatment is generally well accepted by patients and clinicians due to some advantages including normalizing thyroid function in a short time, hardly causing hypothyroidism, and ameliorating immune disorder while avoiding radiation exposure and invasive procedures. However, the relatively high recurrence rate is a major concern for ATD treatment, which is associated with multiple influencing factors like clinical characteristics, treatment strategies, and genetic and environmental factors...
2017: International Journal of Endocrinology
https://www.readbyqxmd.com/read/28521707/biologic-agents-in-systemic-dermatotherapy-cutaneous-and-systemic-side-effects
#19
George Badavanis, Efstathia Pasmatzi, Alexandra Monastirli, Dionysios Tsambaos
The recent significant breakthroughs in the understanding of the pathogenetic mechanisms of psoriasis and other immune-mediated inflammatory disorders, have led to the emergence of a wide array of biologic agents or biologics, that are especially designed to target selective intracellular or extracellular components and pathways of the dysregulated immune response. These targeted biologic agents have altered the landscape in dermatotherapy aiming to offer higher therapeutic efficacy and an alternative in patients who either failed on conventional systemic regimens or have no other therapeutic options...
May 18, 2017: Current Drug Safety
https://www.readbyqxmd.com/read/28518214/immune-monitoring-as-prerequisite-for-transplantation-tolerance-trials
#20
REVIEW
K Behnam Sani, B Sawitzki
Ever since its first application in clinical medicine, scientists have been urged to induce tolerance towards foreign allogeneic transplants and thus avoid rejection by the recipient's immune system. This would circumvent chronic use of immunosuppressive drugs (IS) and thus avoid development of IS-induced side effects, which are contributing to the still unsatisfactory long-term graft and patient survival after solid organ transplantation. Although manifold strategies of tolerance induction have been described in preclinical models, only three therapeutic approaches have been utilized successfully in a still small number of patients...
August 2017: Clinical and Experimental Immunology
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