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Transplant tolerance

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https://www.readbyqxmd.com/read/29229594/interim-results-of-brentuximab-vedotin-in-combination-with-nivolumab-in-patients-with-relapsed-or-refractory-hodgkin-lymphoma
#1
Alex F Herrera, Alison J Moskowitz, Nancy L Bartlett, Julie M Vose, Radhakrishnan Ramchandren, Tatyana A Feldman, Ann S LaCasce, Stephen M Ansell, Craig H Moskowitz, Keenan Fenton, Carol Anne Ogden, David Taft, Qu Zhang, Kazunobu Kato, Mary Campbell, Ranjana H Advani
In this phase 1/2 study, brentuximab vedotin (BV) and nivolumab (Nivo) administered in combination were evaluated as initial salvage therapy in patients with relapsed or refractory (R/R) classical Hodgkin lymphoma (HL) (ClinicalTrials.gov #NCT02572167). Patients received up to 4 cycles of combination treatment, with BV administered on Day 1 and Nivo on Day 8 of the first cycle. For Cycles 2-4, BV and Nivo were both administered on Day 1. Following study treatment, responses were evaluated by investigators per the 2014 Lugano classification, and patients could proceed to autologous stem cell transplantation (ASCT)...
December 11, 2017: Blood
https://www.readbyqxmd.com/read/29226102/timing-of-hepatitis-c-virus-treatment-in-liver-transplant-candidates-in-the-era-of-direct-acting-antiviral-agents
#2
REVIEW
George Cholankeril, Mairin Joseph-Talreja, Brandon J Perumpail, Andy Liu, Eric R Yoo, Aijaz Ahmed, Aparna Goel
Chronic hepatitis C virus (HCV) infection remains the leading indication for liver transplantation (LT) in the United States. While most patients with chronic HCV infection remain asymptomatic, up to one-third develop progressive liver disease resulting in cirrhosis. LT is often the only curative treatment once significant hepatic decompensation develops. However, antiviral therapy for HCV infection has advanced markedly in the past 5 years with the discovery and approval of direct-acting antiviral agents. These new regimens are well tolerated, of short duration and highly effective, unlike the traditional treatment with pegylated-interferon and ribavirin...
December 28, 2017: Journal of Clinical and Translational Hepatology
https://www.readbyqxmd.com/read/29225150/decellularised-conjunctiva-for-ocular-surface-reconstruction
#3
Joana Witt, Sonja Mertsch, Maria Borrelli, Jana Dietrich, Gerd Geerling, Stefan Schrader, Kristina Spaniol
Conjunctival reconstruction is an integral component of ocular surface restoration. Decellularised tissues are frequently used clinically for tissue engineering. This study identifies porcine decellularised conjunctiva (PDC) and human decellularised conjunctiva (HDC) as promising substitutes for conjunctival reconstruction. PDC and HDC were nearly DNA-free, structurally intact and showed no cytotoxic effects in vitro, which was confirmed by DNA quantification, histology, transmission electron microscopy, collagen quantification and cytotoxicity assay...
December 7, 2017: Acta Biomaterialia
https://www.readbyqxmd.com/read/29222360/antiviral-treatment-of-bk-virus-viremia-after-kidney-transplantation
#4
REVIEW
Andrew D Santeusanio, Benjamin E Lukens, Judy Eun
PURPOSE: The various antiviral treatment options in the management of BK virus (BKV) viremia and BKV-associated nephropathy (BKVAN) are reviewed. SUMMARY: Review of the PubMed database from 1990 to 2016 for all English language case series, cohort studies, and randomized controlled trials detailing antiviral treatment of BKV viremia or BKVAN in kidney transplant recipients returned only 16 published reports. The majority of these reports were based on small case series or protocol-based cohort studies, with no prospective head-to-head data and only modest benefit reported for cidofovir, leflunomide, i...
December 15, 2017: American Journal of Health-system Pharmacy: AJHP
https://www.readbyqxmd.com/read/29222315/extracorporeal-photopheresis-cellular-therapy-for-the-treatment-of-acute-and-chronic-graft-versus-host-disease
#5
REVIEW
Jennifer Schneiderman
Allogeneic hematopoietic stem cell transplantation (HSCT) is a potentially curative option for many disease states. Despite significant improvements in strategies used to prevent and treat acute and chronic graft-versus-host disease (a/cGVHD), they continue to negatively affect outcomes of HSCT significantly. Standard, first-line treatment consists of corticosteroids; beyond this, there is little consistency in therapeutic regimens. Current options include the addition of various immunosuppressive agents, the use of which puts patients at even higher risks for infection and other morbidities...
December 8, 2017: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/29218834/comparative-evaluation-of-simple-indices-using-a-single-fasting-blood-sample-to-estimate-beta-cell-function-after-islet-transplantation
#6
Justyna E Gołębiewska, Julia Solomina, Celeste Thomas, Mark Kijek, Piotr Bachul, Lindsay Basto, Karolina Golab, Ling-Jia Wang, Natalie Fillman, Martin Tibudan, Kamil Cieply, Luis Philipson, Alicja Dębska-Ślizień, J Michael Millis, John Fung, Piotr Witkowski
Six single fasting blood sample based indices: Secretory Unit of Islet Transplant Objects (SUITO), Transplant Estimated Function (TEF), Homeostasis Model Assessment (HOMA)2-B%, C-peptide/glucose ratio (CP/G), C-peptide/glucose creatinine ratio (CP/GCr) and BETA-2 score, were compared against commonly used 90-min mixed meal tolerance test (MMTT) serum glucose and beta-score to assess which of them best recognizes the state of acceptable blood glucose control without insulin supplementation after islet allotransplantation (ITx)...
December 8, 2017: American Journal of Transplantation
https://www.readbyqxmd.com/read/29218052/spoiling-for-a-fight-b-lymphocytes-as-initiator-and-effector-populations-within-tertiary-lymphoid-organs-in-autoimmunity-and-transplantation
#7
REVIEW
Jawaher Alsughayyir, Gavin J Pettigrew, Reza Motallebzadeh
Tertiary lymphoid organs (TLOs) develop at ectopic sites within chronically inflamed tissues, such as in autoimmunity and rejecting organ allografts. TLOs differ structurally from canonical secondary lymphoid organs (SLOs), in that they lack a mantle zone and are not encapsulated, suggesting that they may provide unique immune function. A notable feature of TLOs is the frequent presence of structures typical of germinal centers (GCs). However, little is known about the role of such GCs, and in particular, it is not clear if the B cell response within is autonomous, or whether it synergizes with concurrent responses in SLOs...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29217776/melphalan-140mg-m2-or-200mg-m2-for-autologous-transplantation-in-myeloma-results-from-the-collaboration-to-collect-autologous-transplant-outcomes-in-lymphoma-and-myeloma-calm-study-a-report-by-the-ebmt-chronic-malignancies-working-party
#8
Holger W Auner, Simona Iacobelli, Giulia Sbianchi, Cora Knol-Bout, Didier Blaise, Nigel H Russell, Jane F Apperley, David Pohlreich, Paul Browne, Guido Kobbe, Cecilia Isaksson, Stig Lenhoff, Christoph Scheid, Cyrille Touzeau, Esa Jantunen, Achilles Anagnostopoulos, Ibrahim Yakoub-Agha, Alina Tanase, Nicolaas Schaap, Wieslaw Wiktor-Jedrzejczak, Marta Krejci, Stefan O Schönland, Curly Morris, Laurent Garderet, Nicolaus Kröger
Melphalan at a dose of 200mg/m2 is standard conditioning prior to autologous haematopoietic stem cell transplantation for multiple myeloma, but a dose of 140mg/m2 is often used in clinical practice in patients perceived to be at risk of excess toxicity. To determine if melphalan 200 and melphalan 140 are equally effective and tolerable in clinically relevant patient subgroups we analysed 1964 first single autologous transplantation episodes using a series of Cox proportional-hazards models. Overall survival, progression-free survival, cumulative incidence of relapse, non-relapse mortality, haematopoietic recovery and second primary malignancy rates were not significantly different between the melphalan 140 (n=245) and melphalan 200 (n=1719) groups...
December 7, 2017: Haematologica
https://www.readbyqxmd.com/read/29217301/-gut-microbiota-what-impact-on-colorectal-carcinogenesis-and-treatment
#9
REVIEW
Antoine Bruneau, Minh-Tam Baylatry, Anne Christine Joly, Harry Sokol
The gut microbiota, composed of 1014 microorganisms, is now considered as a "hidden organ", regarding to its digestive, metabolic and immune functions, which are helpful to its host. For the last 15 years, advances in molecular biology have highlighted the association of gut microbiota dysbiosis with several diseases, including colorectal cancer. An increased abundance of some bacteria (including Fusobacterium nucleatum, Bacteroides fragilis, Escherichia coli) is associated with cancer, whereas others seem to be protective (Faecalibacterium prausnitzii)...
December 4, 2017: Bulletin du Cancer
https://www.readbyqxmd.com/read/29214523/haematopoietic-stem-cell-transplantation-arrests-the-progression-of-neurodegenerative-disease-in-late-onset-tay-sachs-disease
#10
Karolina M Stepien, Su Han Lum, J Edmond Wraith, Christian J Hendriksz, Heather J Church, David Priestman, Frances M Platt, Simon Jones, Ana Jovanovic, Robert Wynn
Tay-Sachs disease is a rare metabolic disease caused by a deficiency of hexosaminidase A that leads to accumulation of GM2 gangliosides predominantly in neural tissue. Late-onset Tay-Sachs disease variant is associated with a higher level of residual HexA activity. Treatment options are limited, and there are a few described cases who have undergone haematopoietic stem cell transplantation (HSCT) with variable outcome.We describe a case of a 23-year-old male patient who presented with a long-standing tremor since 7 years of age...
December 7, 2017: JIMD Reports
https://www.readbyqxmd.com/read/29214126/pharmacologic-complement-inhibition-in-clinical-transplantation
#11
REVIEW
Vasishta S Tatapudi, Robert A Montgomery
Purpose of Review: Over the past two decades, significant strides made in our understanding of the etiology of antibody-mediated rejection (AMR) in transplantation have put the complement system in the spotlight. Here, we review recent progress made in the field of pharmacologic complement inhibition in clinical transplantation and aim to understand the impact of this therapeutic approach on outcomes in transplant recipients. Recent Findings: Encouraged by the success of agents targeting the complement cascade in disorders of unrestrained complement activation like paroxysmal nocturnal hemoglobinuria (PNH) and atypical hemolytic uremic syndrome (aHUS), investigators are testing the safety and efficacy of pharmacologic complement blockade in mitigating allograft injury in conditions ranging from AMR to recurrent post-transplant aHUS, C3 glomerulopathies and antiphospholipid anti-body syndrome (APS)...
2017: Current Transplantation Reports
https://www.readbyqxmd.com/read/29212210/mir-21-silencing-ameliorates-experimental-autoimmune-encephalomyelitis-by-promoting-the-differentiation-of-il-10-producing-b-cells
#12
Hui Wang, Wenrong Xu, Qixiang Shao, Qing Ding
IL-10-producing regulatory B (IL-10+ Breg) cells promote tolerance in autoimmune diseases and transplantation. However, it remains unclear whether microRNAs are involved in the development of IL-10+ Breg cells. Here, we found that microRNA-21 (miR-21) acts as an upstream regulator of IL-10 by targeting the 3' untranslated region of IL-10 mRNA. We also demonstrated that IL-10+ Breg cells exhibit lower miR-21 expression than non-Breg cells and that miR-21 acts as a potent negative regulator of the differentiation of IL-10+ Breg cells...
November 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/29210728/are-donor-lymphocytes-a-barrier-to-transplantation-tolerance
#13
Jawaher Alsughayyir, Reza Motallebzadeh, Gavin J Pettigrew
PURPOSE OF REVIEW: Following solid organ transplantation (SOT), populations of donor lymphocytes are frequently found in the recipient circulation. Their impact on host alloimmunity has long been debated but remains unclear, and it has been suggested that transferred donor lymphocytes may either promote tolerance to the graft or hasten its rejection. We discuss possible mechanisms by which the interaction of donor passenger lymphocytes with recipient immune cells may either augment the host alloimmune response or inhibit it...
November 27, 2017: Current Opinion in Organ Transplantation
https://www.readbyqxmd.com/read/29207952/economic-burden-of-preemptive-treatment-of-cmv-infection-after-allogeneic-stem-cell-transplantation-a-retrospective-study-of-208-consecutive-patients
#14
Christine Robin, François Hémery, Christel Dindorf, Julien Thillard, Ludovic Cabanne, Rabah Redjoul, Florence Beckerich, Christophe Rodriguez, Cécile Pautas, Andrea Toma, Sébastien Maury, Isabelle Durand-Zaleski, Catherine Cordonnier
BACKGROUND: Cytomegalovirus (CMV) infection and disease (CMV episodes) are global concerns after allogeneic hematopoietic stem cell transplantation (HSCT). They affect survival, both by direct and indirect effects. Due to safety issues of current anti-CMV antivirals, long-term CMV prophylaxis is poorly tolerated and the most common strategy to decrease the incidence of CMV disease is preemptive. New, less toxic, molecules are currently being assessed for CMV prophylaxis which should replace or considerably decrease the preemptive approach...
December 5, 2017: BMC Infectious Diseases
https://www.readbyqxmd.com/read/29207679/italian-real-life-experience-with-brentuximab-vedotin-results-of-a-large-observational-study-on-234-relapsed-refractory-hodgkin-s-lymphoma
#15
Cinzia Pellegrini, Alessandro Broccoli, Alessandro Pulsoni, Luigi Rigacci, Caterina Patti, Guido Gini, Donato Mannina, Monica Tani, Chiara Rusconi, Alessandra Romano, Anna Vanazzi, Barbara Botto, Armando Santoro, Stefan Hoaus, Gian Matteo Rigolin, Pellegrino Musto, Patrizio Mazza, Stefano Molica, Paolo Corradini, Angelo Fama, Francesco Gaudio, Michele Merli, Fioravante Ronconi, Giuseppe Gritti, Daniele Vallisa, Patrizia Tosi, Anna Marina Liberati, Antonello Pinto, Vincenzo Pavone, Filippo Gherlinzoni, Maria Paola Bianchi, Stefano Volpetti, Livio Trentin, Maria Cecilia Goldaniga, Maurizio Bonfichi, Amalia De Renzo, Corrado Schiavotto, Michele Spina, Angelo Michele Carella, Vittorio Stefoni, Lisa Argnani, Pier Luigi Zinzani
A large Italian multicenter observational retrospective study was conducted on the use of brentuximab vedotin (BV) for patients with relapsed Hodgkin's lymphoma (HL) to check if clinical trial results are confirmed even in a real life context. 234 CD30+ HL patients were enrolled. Best response was observed after a median of 4 cycles in 140 patients (59.8%): 74 (31.6%) patients obtained a complete response (CR) and 66 (28.2%) achieved a partial response (PR); overall response rate at the end of the treatment was 48...
October 31, 2017: Oncotarget
https://www.readbyqxmd.com/read/29207601/dissecting-the-mechanisms-involved-in-anti-human-t-lymphocyte-immunoglobulin-atg-induced-tolerance-in-the-setting-of-allogeneic-stem-cell-transplantation-potential-implications-for-graft-versus-host-disease
#16
Katia Beider, David Naor, Valeria Voevoda, Olga Ostrovsky, Hanna Bitner, Evgenia Rosenberg, Nira Varda-Bloom, Victoria Marcu-Malina, Jonathan Canaani, Ivetta Danilesko, Avichai Shimoni, Arnon Nagler
Polyclonal anti-human thymocyte globulins (ATG) have been recently shown to significantly reduce the incidence of graft versus host disease (GVHD) post allogeneic stem cell transplantation (HSCT) from both sibling and unrelated donors. Induction of regulatory T cells has been suggested as one of the possible mechanisms. The aim of current study was to further characterize the T cell populations induced by ATG treatment and to delineate the mechanisms involved in ATG-induced tolerance. Phenotypic characterization revealed a significant increase in the expression of FoxP3, GITR, CD95, PD-1 and ICOS as well as the complement inhibitory molecules CD55, CD58 and CD59 on CD4+CD25+ T cells upon ATG treatment...
October 31, 2017: Oncotarget
https://www.readbyqxmd.com/read/29207227/first-case-report-of-using-ofatumumab-in-kidney-transplantation-ab0-incompatible
#17
Nicoletta Mancianti, Giulio Monaci, Fabio Rollo, Paola Buracchi, Andrea Guarnieri, Marina Di Luca, Mauro Martello, Guido Garosi
Modern methods for desensitization protocol rely heavily on combined apheresis therapy and Rituximab, a chimeric (murine and human) anti-CD20 antibody used in AB0 incompatible kidney transplants. Severe infusion related reactions due to the administration of Rituximab are reported in 10% of patients. These adverse reactions may hinder the completion of the desensitization protocol. Therefore, it's useful to test alternative B cell depleting therapies. Our clinical case focuses on a 41-year-old male who developed an adverse infusion reaction following the administration of Rituximab and was given Ofatumumab as an alternative treatment...
December 5, 2017: Giornale Italiano di Nefrologia: Organo Ufficiale Della Società Italiana di Nefrologia
https://www.readbyqxmd.com/read/29201790/therapy-targeting-stem-cell-in-patients-with-decompensated-cirrhosis-of-liver-in-a-tertiary-treatment-care-center-of-bangladesh
#18
Mamun Al Mahtab, Sheikh Mn Alam, Ahmed L Moben, Ruksana Raihan, Mohammad A Alam, Mohammad A Rahim, Mohammad H Uddin, Sheikh Mohammad Fazle Akbar
Introduction: Decompensated cirrhosis is associated with significantly high mortality resulting from hepatic failure, and liver transplantation seems to be the only viable indication for its management. The objective of this study is to assess if granulocyte colony-stimulating factor (G-CSF), a stimulatory of stem cell in vivo, may be of any benefit for patients with decompensated cirrhosis of liver. Materials and methods: Seventeen consecutive patients with decompensated cirrhosis of liver were recruited in this prospective study...
January 2017: Euroasian Journal of Hepato-Gastroenterology
https://www.readbyqxmd.com/read/29201599/combining-adoptive-treg-transfer-with-bone-marrow-transplantation-for-transplantation-tolerance
#19
REVIEW
Nina Pilat, Nicolas Granofszky, Thomas Wekerle
Purpose of Review: The mixed chimerism approach is an exceptionally potent strategy for the induction of donor-specific tolerance in organ transplantation and so far the only one that was demonstrated to work in the clinical setting. Regulatory T cells (Tregs) have been shown to improve chimerism induction in experimental animal models. This review summarizes the development of innovative BMT protocols using therapeutic Treg transfer for tolerance induction. Recent Findings: Treg cell therapy promotes BM engraftment in reduced conditioning protocols in both, mice and non-human primates...
2017: Current Transplantation Reports
https://www.readbyqxmd.com/read/29198928/lung-autoantibodies-ready-for-prime-time
#20
EDITORIAL
Luke Milross, Ramsey Hachem, Deborah Levine, Allan R Glanville
Despite advances in our understanding of the immunology of lung allograft tolerance and a reduction in the rate of acute allograft rejection using contemporary immunosuppressive protocols, the rate of chronic lung allograft dysfunction (CLAD), both obstructive and restrictive, remains unacceptably high. CLAD, particularly the restrictive phenotype, is a harbinger of a foreshortened survival. The development of a consensus approach to the diagnosis of antibody-mediated rejection by the International Society for Heart and Lung Transplantation has highlighted the need for a uniform approach toward the investigation, diagnosis, implications and management of both human leukocyte antigen (HLA) and non-HLA-related antibody formation...
November 8, 2017: Journal of Heart and Lung Transplantation
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