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Katelyn Paz, Ryan Flynn, Jing Du, Stacey Tannheimer, Amy J Johnson, Shuai Dong, Anne-Katrien Stark, Klaus Okkenhaug, Angela Panoskaltsis-Mortari, Peter T Sage, Arlene H Sharpe, Leo Luznik, Jerome Ritz, Robert J Soiffer, Corey S Cutler, John Koreth, Joseph H Antin, David B Miklos, Kelli P MacDonald, Geoffrey R Hill, Ivan Maillard, Jonathan S Serody, William J Murphy, David H Munn, Colby Feser, Michael Zaiken, Bart Vanhaesebroeck, Laurence A Turka, John C Byrd, Bruce R Blazar
Chronic graft-versus-host disease is a leading cause of morbidity and mortality following allotransplant. Activated donor effector T-cells can differentiate into pathogenic T helper (Th)-17 cells and germinal center -promoting Tfollicular helper cells, resulting in cGVHD. Phosphoinositide-3-kinase-δ, a lipid kinase, is critical for activated T-cell survival, proliferation, differentiation, and metabolism. We demonstrate PI3Kδ activity in donor T-cells that become Tfhs is required for cGVHD in a non-sclerodermatous multi-organ system disease model that includes bronchiolitis obliterans, dependent upon GC B-cells, Tfhs, and counterbalanced by Tfollicular regulatory cells, each requiring PI3Kδ signaling for function and survival...
February 12, 2019: American Journal of Transplantation
Jun Li, Julia Koerner, Michael Basler, Thomas Brunner, Christopher J Kirk, Marcus Groettrup
Chronic antibody-mediated rejection is the leading cause of allograft dysfunction and loss after kidney transplantation, and current immunosuppressive regimens fail to target the plasma cells that produce alloantibodies. We previously showed that treatment with the immunoproteasome inhibitor ONX 0914 prevented the expansion of plasma cells and prevented chronic allograft nephropathy and organ failure after kidney transplantation in rats, but the mechanism has remained elusive. In the current study, we confirmed a long-term reduction in alloantibody production and improvements in allograft histology in rats treated with ONX 0914 or with the broad-spectrum proteasome inhibitor bortezomib...
January 22, 2019: Kidney International
Boglarka Gyurkocza, Rainer Storb, Thomas R Chauncey, David G Maloney, Barry E Storer, Brenda M Sandmaier
We analyzed outcomes of 126 patients with hematologic malignancies, who relapsed after first allogeneic hematopoietic cell transplantation (HCT) and received subsequent allografts. In 17 cases, the original donors were utilized, while in 109 cases different donors were identified. The 2-year overall survival (OS), relapse, and non-relapse mortality (NRM) rates were 33%, 42%, and 33%, respectively. Patients with early relapse after first allogeneic HCT (within 100 days vs. 100 days to 12 months vs. >12 months) had higher relapse rates (50% vs...
January 22, 2019: Leukemia & Lymphoma
Christine Giraud, Jean-Baptiste Thibert, Yohan Desbrosses, Bénédicte Debiol, Tamim Alsuliman, Laurent Bardiaux, Frédéric Garban, Thi Ngoc Phuong Huynh, Olga Samsonova, Ibrahim Yakoub-Agha, Bénédicte Bruno
The recommendations of the French Health and Drug Safety Authorities (HAS/ANSM-Haute Autorité de santé/Agence nationale de sécurité du médicament) are known, but there are always new developments underway. With regards to CMV suppression, there is the introduction of platelet glycoprotein Ia and the Intercept (Amotosalem+UVA) inactivation method which addresses bacterial risk. The irradiation of platelets is included in the recommendations to ensure HEV-negative plasma post allograft. In terms of blood transfusion safety, these measures as well as the broader spectrum of Ia, particularly for arboviruses, are a real breakthrough...
January 18, 2019: Bulletin du Cancer
C Anton Fries, Sharon D Lawson, Lin C Wang, Jerry R Spencer, Mark Roth, Rory F Rickard, Vijay S Gorantla, Michael R Davis
INTRODUCTION: Vascularized composite allotransplantation can reconstruct devastating tissue loss by replacing like-with-like tissues, most commonly in the form of hand or face transplantation. Unresolved technical and ethical challenges have meant that such transplants remain experimental treatments. The most significant barrier to expansion of this field is the requirement for systemic immunosuppression, its toxicity and effect on longevity.Hydrogen sulfide (H2S) has been shown experimentally to ameliorate the ischemia reperfusion injury associated with composite tissue autotransplantation, which has been linked to acute rejection in solid organ transplantation...
January 9, 2019: Annals of Plastic Surgery
Nicholas L Robbins, Matthew J Wordsworth, Bijaya K Parida, Bruce Kaplan, Vijay S Gorantla, Col Erik K Weitzel, Warren C Breidenbach
BACKGROUND: From 1996 to 2000 Diefenbeck et al. carried out 6 knee vascularized composite allotransplants(VCA). The VCAs were composed of bone, soft tissue, and the femoral vascular pedicle (25-40 cm total length). All rejected between 14 to 56 months. The failures were attributed to chronic rejection (CR). In 2008 the Louisville team lost their fourth patient's hand transplant at 8 months. During the rejection workup the senior surgeon's intra-operative findings noted a thickened arterial pedicle attributed to intimal hyperplasia (IH) with significant fibrotic perivascular tissue and a near 'no flow phenomenon'...
December 28, 2018: Plastic and Reconstructive Surgery
Philippe Lewalle, Cécile Pochon, Mauricette Michallet, Pascal Turlure, Eolia Brissot, Catherine Paillard, Mathieu Puyade, Gabrielle Roth-Guepin, Ibrahim Yakoub-Agha, Sylvain Chantepie
Allogeneic hematopoietic stem cell transplantation is a curative treatment for many hematological diseases. However, this procedure causes the patient to be susceptible to infection. Prophylactic treatments are administered in clinical practice even thought the level of evidence of their effectiveness is not always high. In addition, changes in the transplantation procedures - use of reduced intensity conditioning, development of alternative graft sources - must lead to a rethinking of attitudes towards prophylaxis...
January 4, 2019: Bulletin du Cancer
Raymund R Razonable, Hatem Amer, Samir Mardini
The optimal approach to preventing cytomegalovirus (CMV) disease after face transplant is unknown. We report an individualized hybrid approach, initially using valganciclovir prophylaxis followed by surveillance and preemptive therapy guided by viral and immunologic markers. A 31-year-old man received a near-total face allotransplant for gunshot injury-related severe facial deformities. He was CMV seronegative, and the donor was CMV seropositive (D+/R- mismatch), and he received intravenous ganciclovir followed by oral valganciclovir prophylaxis...
January 2019: Mayo Clinic Proceedings
Y Ding, J Shao, K Hua, X Wang
OBJECTIVE: A rat model of right whole ovary transplantation is difficult to establish because of an unfit location or absence of the right ovarian artery. The purpose of this study is to develop a rat model of left whole ovary transplantation. METHODS: Two methods of whole ovary transplantation were performed. In Group A (n = 40), the rats underwent right whole ovary grafting via conventional orthotopic allotransplant, with donor abdominal aorta and inferior vena cava end-to-side anastomoses to the recipient abdominal aorta and inferior vena cava...
December 2018: Transplantation Proceedings
Bin Pan, Fan Zhang, Zhenzhen Lu, Lingling Li, Longmei Shang, Fan Xia, Ruixue Fu, Mengdi Xu, Lingyu Zeng, Kailin Xu
Defect of thymus results in poor posttransplant immune recovery and dysfunction of immune tolerance after allogeneic hematopoietic cell transplants (allo-HCT). Improving thymus regeneration represents a potential strategy to accelerate recovery of T-cell immunity. IL-22 was reported to mediate thymus regeneration after injury. In this study, we found donor T-cell is a major source of IL-22 in allotransplant recipient. Through applying IL-22 knock out (IL-22KO) mice in allo-HCT, we found donor T-cell derived IL-22 promotes thymus regeneration in association with increased level of intra-thymic IL-22...
December 14, 2018: International Immunopharmacology
Hiroki Oda, Ryosuke Ikeguchi, Tomoki Aoyama, Souichi Ohta, Takashi Noguchi, Yukitoshi Kaizawa, Hirofumi Yurie, Hisataka Takeuchi, Sadaki Mitsuzawa, Koji Yamamoto, Shuichi Matsuda
BACKGROUND: Skin is considered to be the most antigenic component of all vascularized composite allotransplantation tissues. However, no studies have used methods other than histological assessment to analyze the relative antigenicity of various components. In this study, we analyzed gene expression to investigate the relative antigenicity of each component in the transplanted limb. METHODS: Seven Brown Norway rats and 31 Lewis rats were assigned to two groups: an allograft group and a syngeneic (control) group...
December 17, 2018: Microsurgery
Jaroslaw Pieróg, Kleanthis Fytianos, Luca Tamò, Cedric Simillion, Adriano Taddeo, Gregor Kocher, Mathias Gugger, Tomasz Grodzki, Manfred Heller, Fabian Blank, Thomas Geiser, Ralph A Schmid, Amiq Gazdhar
OBJECTIVES: Stem cells secrete significant amounts of bioactive factors in their secretome that can be immunosuppressive. We studied the effect of the secretome obtained from bone marrow-derived mesenchymal stem cells (BMSC-sec) in combination with cyclosporine A following acute rejection of lung allografts in the rat. METHODS: Lung allotransplants were performed from male Brown Norway donor rats to recipient male Fisher 344 rats. Rat BMSC-sec was introduced intratracheally in the recipient every day after the transplant until the day the animal was sacrificed...
December 1, 2018: Interactive Cardiovascular and Thoracic Surgery
Louise Bouard, Caroline Bodet-Milin, Clément Bailly, Thierry Guillaume, Pierre Peterlin, Alice Garnier, Amandine Le Bourgeois, Béatrice Mahé, Viviane Dubruille, Nicolas Blin, Cyrille Touzeau, Thomas Gastinne, Anne Lok, Antoine Bonnet, Marie C Béné, Steven Le Gouill, Philippe Moreau, Franéoise Kraeber-Bodéré, Patrice Chevallier
The impact of early fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET-CT) status on survival after allogeneic transplantation for lymphoma is poorly reported. This retrospective study included all adult Hodgkin lymphoma (HL) or non-Hodgkin lymphoma(NHL) patients (>18 years old) who benefited from FDG PET-CT before (within 1 month) and/or early (+3 months and within +6 to 9 months) after allogeneic stem cell transplantation in our institution between 2005 and 2015 and who were still without documented progression or relapse at the time of the FDG PET-CT...
November 24, 2018: Biology of Blood and Marrow Transplantation
Ying-Jun Chang, Lan-Ping Xu, Yu Wang, Xiao-Hui Zhang, Huan Chen, Yu-Hong Chen, Feng-Rong Wang, Wei Han, Yu-Qian Sun, Chen-Han Yan, Fei-Fei Tang, Xiao-Dong Mo, Kai-Yan Liu, Xiao-Jun Huang
This long-term follow-up study evaluated the effects of corticosteroid prophylaxis on graft-versus-host disease (GVHD)-free, relapse-free survival (GRFS) based on a controlled open-label randomized trial in which 228 allotransplant recipients were categorized as low risk (n = 83, group A) or high risk; patients at high risk were randomly assigned to receive (n = 72, group B) or not receive (n = 73, group C) low-dose methylprednisolone prophylaxis. The cumulative incidences of chronic GVHD, relapse, nonrelapse mortality, leukemia-free survival, overall survival, and GRFS were 60%, 19%, 16%, 68%, 73%, and 46%, respectively, in all cases...
November 24, 2018: Biology of Blood and Marrow Transplantation
Abhijit Jagdale, Hayato Iwase, Edwin Klein, David K C Cooper
There is an increased incidence of certain tumors and other neoplastic disease in organ allotransplant recipients receiving immunosuppressive therapy. Following clinical pig organ xenotransplantation, will there be a risk of the development of neoplasia in the pig graft or in other tissues transplanted with it, eg, lymph nodes? The incidence of neoplasia in young slaughterhouse pigs is very low (<0.005%), but in older pigs is largely unknown (as most pigs are killed within the first six months of life). However, lymphosarcoma, nephroblastoma, and melanoma have been reported in pigs...
November 9, 2018: Xenotransplantation
I S Mukhamadeev, K V Prokhorov, A A Oborin
We present a clinical case of successful correction of aneurismatic dilatation of the anastomosis zone after allotransplant implantation. In 2004 this patient underwent implantation of an arterial allotransplant of "complex architectonics" because of trauma of the iliofemoral arterial segment. After 12 years he reported appearance of discomfort in the left side of the abdomen. Duplex ultrasound scanning revealed aneurism at the site of anastomosis of the prosthesis with internal iliac artery. Therefore, we performed endovascular isolation of the aneurism with the use of a stent-graft and restoration of blood flow down to the extremity periphery has been performed...
June 2018: Kardiologiia
Lauren Veltri, Katayoun Rezvani, Betul Oran, Rohtesh Mehta, Gabriela Rondon, Partow Kebriaei, Uday Popat, Yago Nieto, Chitra Hosing, Muzaffar Qazilbash, Issa Khouri, Elizabeth Shpall, Richard Champlin, David Marin
The outcome of persons > 65 years with acute myeloid leukemia (AML) is poor. A transplant from an HLA-identical sibling or an HLA-matched unrelated donor can cure some of these patients but is associated with a substantial transplant-related mortality and a high relapse risk. We analyzed 185 subjects > 65 years with high-risk AML receiving conventional (n = 42) or reduced-intensity (n = 143) pretransplant conditioning and a transplant from an HLA-identical sibling (n = 66) or a 10/10 loci HLA-matched unrelated donor (n = 119)...
October 9, 2018: Biology of Blood and Marrow Transplantation
Shaun D Mendenhall, Michael T Ginnetti, Justin D Sawyer, Steven J Verhulst, Bradford L West, L Scott Levin, Michael W Neumeister
Background: Vascularized composite allotransplantation (VCA) is an emerging and growing field. Little is known about the prevalence and distribution of the adult potential donor population in the United States now that it falls under the oversight of the United Network for Organ Sharing (UNOS). Methods: We assessed the UNOS database from 2008 to 2015 to estimate the prevalence and distribution of adult potential vascularized composite allograft donors. Donor inclusion and exclusion criteria were developed in a way to minimize risk to recipients and were applied to the dataset...
June 2018: Plastic and Reconstructive Surgery. Global Open
Anoma Nellore, Jay A Fishman
Post-transplantation infections are common in allograft recipients and should be expected in all immunocompromised hosts. Based on the need for immunosuppression in xenotransplantation, procedures developed to enhance safety in allotransplantation can be applied in future xenotransplantation clinical trials. Standardized approaches can be developed to guide the evaluation of common infectious syndromes in xenograft recipients. The opportunity created by screening of swine intended as xenograft donors has equal applicability to allotransplantation-notably broader screening strategies for allograft donors such as use of advanced sequencing modalities including broad-range molecular probes, microarrays, and high-throughput pyrosequencing...
July 2018: Xenotransplantation
Sara Salehi, Kenny Tran, Warren L Grayson
In the past, a diagnosis of organ failure would essentially be a death sentence for patients. With improved techniques for organ procurement and surgical procedures, transplantations to treat organ failure have become standard medical practice. However, while the demand for organs has skyrocketed, the donor pool has not kept pace leading to long recipient waiting lists. Organ preservation provides a means to increase the number of available transplantable organs. However, there are significant drawbacks associated with cold storage, the current gold standard...
September 2018: Yale Journal of Biology and Medicine
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