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Immunosuppression withdrawal

Kim Heang Ly, François Dalmay, Guillaume Gondran, Sylvain Palat, Holy Bezanahary, Anne Cypierre, Anne-Laure Fauchais, Eric Liozon
Although a glucocorticoid (GC)-sparing strategy is needed for patients with giant cell arteritis (GCA) suffering from refractory disease or serious treatment-related complications, evidence of efficacy in this setting of immunosuppressive drugs and biotherapies is lacking. Herein, we evaluated the GC-sparing effects and tolerability of addition of dapsone (DDS) to prednisone therapy in patients with GCA. We retrospectively assessed data on 18 GCA patients who received DDS as a first-line treatment (DDS-1 group) and 52 patients who received it as a second- or third-line treatment for refractory GCA, with or without excessive GC-related toxicity (DDS-2 group)...
October 2016: Medicine (Baltimore)
Oleg O Rummo, Mario Carmellini, Lionel Rostaing, Rainer Oberbauer, Maarten H L Christiaans, Christiane Mousson, Robert M Langer, Franco Citterio, Bernard Charpentier, Malcolm Brown, Gbenga Kazeem, Frank Lehner
ADHERE was a randomized, open-label, Phase IV study comparing renal function at Week 52 post-kidney transplant, in patients who received prolonged-release tacrolimus-based immunosuppressive regimens. On days 0-27, patients received prolonged-release tacrolimus (initially 0.2mg/kg/day), corticosteroids and mycophenolate mofetil (MMF). Patients were randomized on Day 28 to receive either prolonged-release tacrolimus plus MMF (Arm 1) or prolonged-release tacrolimus (≥25% dose-reduction on Day 42) plus sirolimus (Arm 2)...
October 18, 2016: Transplant International: Official Journal of the European Society for Organ Transplantation
Yan-Ni Li, Huan Ma, Lu Zhou, Jie Zhang, Li-Ping Guo, Shu-Qian Li, Yi-Qi Qian, Bang-Mao Wang
BACKGROUND: The long-term outcomes of patients with autoimmune hepatitis (AIH) given the immunosuppressive treatment are considered to be preferable. However, little is known about the response of AIH patients with cirrhosis to immunosuppressive treatment. We assessed the effects of immunosuppressive therapy in Chinese AIH patients with cirrhosis from a tertiary hospital. METHODS: Patients with a clinical diagnosis of AIH January 2000 and December 2015 were retrospectively reviewed...
2016: Chinese Medical Journal
Umberto Maggiore, Julio Pascual
Cancer immunotherapy, especially the use of checkpoint inhibitors, is expanding and can be efficacious in organ transplant recipients with malignant neoplasia. In this review, we summarize clinical findings and evolution of several patients treated with CTL4-4 or PD-1 inhibitors reported in the literature. The CTL-4 inhibitor ipilimumab has been safely used in several liver and kidney allograft recipients. PD1-inhibitors look promising for tumor shrinking, but acute rejection is the rule, so they should be avoided in recipients of life-saving organs...
September 2016: Advances in Chronic Kidney Disease
Joshua Augustine, Donald E Hricik
Although calcineurin inhibitor drugs have been the mostly used therapy in modern immunosuppression in kidney transplantation, their effect on kidney allograft dysfunction has been suboptimal as far as preservation of kidney function is concerned. Additionally, there are metabolic and other nonmetabolic effects including increased risk of malignancy that has necessitated the use of mammalian target of rapamycin inhibitors to reduce exposure to calcineurin inhibitors. Mammalian target of rapamycin inhibitors, both sirolimus and everolimus, have been studied in several trials to facilitate preservation of kidney function with variable effects on kidney allograft function and immunogenicity...
September 2016: Advances in Chronic Kidney Disease
Rohini Prashar, K K Venkat
Kidney transplantation is well established as the best treatment option for end-stage kidney disease. It confers not only a better quality of life but also a significant survival advantage compared to dialysis. However, despite significant improvement in short-term kidney transplant graft survival over the past three decades, long-term graft survival remains suboptimal. Concerns about the possible contribution of chronic calcineurin inhibitor (CNI) nephrotoxicity to late allograft failure and other serious adverse effects of currently used immunosuppressive agents (especially corticosteroids) have led to increasing interest in developing regimens which may better preserve kidney allograft function and minimize other immunosuppression-related problems without increasing the risk of rejection...
September 2016: Advances in Chronic Kidney Disease
C M Cruz, S Pereira, J Gandara, S Ferreira, V Lopes, J Daniel, H P Miranda
Calcineurin inhibitors (CNI) are the base of immunosuppressive regimens in liver transplantation but they are associated with significant side effects, namely nephrotoxicity, which leads to increased morbidity and mortality. Through time, mycophenolate mofetil (MMF) as monotherapy has been suggested as an alternative in patients with CNI-related toxicity, but still no consensus has been reached as to its efficacy. We have evaluated the safety, efficacy, and tolerability of MMF monotherapy in selected patients, developing CNI-associated events, focusing primarily on kidney dysfunction...
September 2016: Transplantation Proceedings
Claire S Allen, James Hs Yeung, Ben Vandermeer, Joanne Homik
BACKGROUND: This is an update of a Cochrane Review first published in 1999. Corticosteroids are widely used in inflammatory conditions as an immunosuppressive agent. Bone loss is a serious side effect of this therapy. Several studies have examined the use of bisphosphonates in the prevention and treatment of glucocorticosteroid-induced osteoporosis (GIOP) and have reported varying magnitudes of effect. OBJECTIVES: To assess the benefits and harms of bisphosphonates for the prevention and treatment of GIOP in adults...
October 5, 2016: Cochrane Database of Systematic Reviews
Jun-Ying Du, Yi Liang, Jun-Fan Fang, Yong-Liang Jiang, Xiao-Mei Shao, Xiao-Fen He, Jian-Qiao Fang
Exogenous and endogenous opioids have been shown to modulate the immune system. Morphine-induced immunosuppression has been investigated extensively. However, the immune-regulating function of endogenous opioid peptides is unclear. The present study aimed to evaluate the difference in effects on cellular immune function between recombinant rat β-endorphin (β-EP; 50 µg/kg) and plant source morphine (10 mg/kg) via intraperitoneal injection treatment in a rat model of bone cancer pain. Walker 256 cells were injected into a tibial cavity injection to establish the bone cancer pain model...
October 2016: Experimental and Therapeutic Medicine
Alberto Baroja-Mazo, Beatriz Revilla-Nuin, Pascual Parrilla, Laura Martínez-Alarcón, Pablo Ramírez, José Antonio Pons
Transplantation is the optimal treatment for end-stage organ failure, and modern immunosuppression has allowed important progress in short-term outcomes. However, immunosuppression poorly influences chronic rejection and elicits chronic toxicity in current clinical practice. Thus, a major goal in transplantation is to understand and induce tolerance. It is well established that human regulatory T cells expressing the transcription factor FoxP3 play important roles in the maintenance of immunological self-tolerance and immune homeostasis...
September 14, 2016: World Journal of Gastroenterology: WJG
Sindhu Chandran, Sandy Feng
PURPOSE OF REVIEW: The attainment of tolerance remains a highly desirable goal in recipients of kidney transplants. Achievement of this goal would extend graft survival and eradicate toxicities related to long-term immunosuppression. Understanding mechanisms of tolerance and strategies to induce tolerance - their risk/benefit profiles - is essential for future success. RECENT FINDINGS: Mechanistic studies of spontaneously tolerant kidney transplant recipients have uncovered potential roles for B or regulatory T cells, or both, in the maintenance of tolerance...
November 2016: Current Opinion in Nephrology and Hypertension
Nahid Tabibzadeh, François Glowacki, Marie Frimat, Vincent Elsermans, François Provôt, Arnaud Lionet, Viviane Gnemmi, Alexandre Hertig, Christian Noël, Marc Hazzan
BACKGROUND: Despite long-term side effects, calcineurin inhibitors (CNI) remain a cornerstone of immunosuppression in renal transplantation. Few trials assessed the long-term outcome after early CNI withdrawal. METHODS: This intention-to-treat study assessed the 10-year outcome of 108 patients randomly converted from a cyclosporine (CsA)-mycophenolate mofetil (MMF)-prednisone regimen to a dual therapy (CsA-prednisone or MMF-prednisone) at 3 months postgraft. RESULTS: At 10 years, 3...
September 13, 2016: Clinical Transplantation
G Ciancio, P Tryphonopoulos, J J Gaynor, G Guerra, J Sageshima, D Roth, L Chen, W Kupin, A Mattiazzi, L Tueros, S Flores, L Hanson, R H Powell, P Ruiz, R Vianna, G W Burke
BACKGROUND: Recent studies suggest that the combination of tacrolimus (TAC) and everolimus (EVL) could become a viable option for use as standard maintenance immunosuppression in non-highly sensitized kidney transplant recipients. METHODS: We conducted a single-center, open-label, randomized pilot trial comparing two maintenance immunosuppression regimens in non-highly sensitized, adult, primary kidney transplant recipients: (TAC/EVL, Group A) vs our standard maintenance regimen of TAC plus enteric-coated mycophenolate mofetil (TAC/EC-MPS, Group B)...
July 2016: Transplantation Proceedings
Johan W de Fijter
Malignancy is the second most common single cause of death observed in organ transplant recipients. The excess cancer risk is related to intensity and duration of immunosuppressive therapy and inversely to recipient age. Immunodeficiency and (chronic/oncogenic) viral infections together constitute a major risk. Nonmelanoma skin cancer, Kaposi sarcoma and posttransplant lymphoproliferative disease (PTLD) have standardized incidence ratios exceeding 10- or 50-fold. The mammalian target of rapamycin (mTOR) inhibitors, sirolimus and everolimus, are increasingly used after organ transplantation with potential advantages in virus-associated post-transplant malignancies as well as anti-cancer properties...
August 10, 2016: Transplantation
Quan Dong Nguyen, Pauline T Merrill, Glenn J Jaffe, Andrew D Dick, Shree Kumar Kurup, John Sheppard, Ariel Schlaen, Carlos Pavesio, Luca Cimino, Joachim Van Calster, Anne A Camez, Nisha V Kwatra, Alexandra P Song, Martina Kron, Samir Tari, Antoine P Brézin
BACKGROUND: Non-infectious uveitis is a potentially sight-threatening ocular disorder caused by chronic inflammation and its complications. Therapeutic success is limited by systemic adverse effects associated with long-term corticosteroid and immunomodulator use if topical medication is not sufficient to control the inflammation. We aimed to assess the efficacy and safety of adalimumab in patients with inactive, non-infectious uveitis controlled by systemic corticosteroids. METHODS: We did this multicentre, double-masked, randomised, placebo-controlled phase 3 trial at 62 study sites in 21 countries in the USA, Canada, Europe, Israel, Australia, and Latin America...
September 17, 2016: Lancet
Abraham Shaked, Bao-Li Chang, Michael R Barnes, Peter Sayre, Yun R Li, Smita Asare, Michele DesMarais, Michael V Holmes, Toumy Guettouche, Brendan J Keating
: The ability to noninvasively diagnose acute cellular rejection (ACR) with high specificity and sensitivity would significantly advance personalized liver transplant recipient care and management of immunosuppression. We performed microRNA (miRNA) profiling in 318 serum samples from 69 liver transplant recipients enrolled in the Immune Tolerance Network immunosuppression withdrawal (ITN030ST) and Clinical Trials in Organ Transplantation (CTOT-03) studies. We quantified serum miRNA at clinically indicated and/or protocol biopsy events (n = 130)...
August 17, 2016: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
Xiao-Yan Shu, Xia-Fang Yan, Lei Dong, Li Ding, Dong-Mei Han, Mei Xue, Zhi-Dong Wang, Hong-Min Yan, Heng-Xiang Wang, Lian-Ning Duan
OBJECTIVE: To analyze the risk factors of patients with relapsed leukemia after allogeneic hematopoietic stem cell transplantation, and to explore the therapeutic strategies for recurrence. METHODS: The Cox proportional hazard regression model was used for univariate and multivariate analysis of transplantation-related index, a single center retrospective study of clinical data of 202 cases of leukemia received allo-HSCT from March 2004 to October 2014 had been conducted to screen the risk factors for recurrence after transplantation...
August 2016: Zhongguo Shi Yan Xue Ye Xue za Zhi
Jingli Lu, Xiaojian Zhang
Establishing allograft tolerance is a highly desirable therapeutic goal in kidney transplantation, from which recipients would greatly benefit by withdrawing or minimizing immunosuppression. Identifying biomarkers in predicting tolerance or early diagnosing rejection is essential to direct personalized management. Recent findings have revealed that multiple populations of immune cells have involved in promoting long-term graft function or inducing rejection in renal transplant recipients. Thus, roles of immune cells add another level to predict the renal tolerant state; tailoring their functional and/or phenotypic characteristics would provide insights into mechanism involved in transplant tolerance that may aid in designing new therapies...
September 2016: Molecular Immunology
Antônio Tonete Bafi, Daniere Yurie Vieira Tomotani, Flávio Geraldo Rezende de Freitas
The growing population of solid organ transplant (SOT) recipients is at a significantly increased risk for developing infections. In some patients, the infection can lead to a dysregulated systemic inflammatory response with acute organ dysfunction. SOT recipients with sepsis tend to have less fever and leukocytosis instances. Moreover, they have diminished symptoms and attenuated clinical and radiologic findings. The current management of sepsis is similar to general patients. It relies mainly on early recognition and treatment, including appropriate administration of antibiotics and resuscitation with intravenous fluids and vasoactive drugs when needed...
July 21, 2016: Shock
Emilie Dugast, Jean-Paul Soulillou, Yohann Foucher, Emmanuelle Papuchon, Pierrick Guerif, Chloé Paul, David Riochet, Mélanie Chesneau, Anne Cesbron, Karine Renaudin, Magali Giral, Sophie Brouard
Long-term renal transplant outcome is limited by side effects of immunosuppressive drugs, particularly CNI. We assumed that some patients selected for a "low immunological risk of rejection" could be eligible and benefit from a CNI weaning strategy. We designed a prospective, randomized, multicenter, double-blind placebo-controlled clinical study (Eudract: 2010-019574-33) to analyse the benefit-risk ratio of tacrolimus weaning on highly selected patients (>= 4 years of transplantation, normal histology, stable graft function, no anti-HLA immunization)...
July 1, 2016: American Journal of Transplantation
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