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American Journal of Transplantation

Robert C Harland, Goran Klintmalm, Stephen Jensik, Harold Yang, Jonathan Bromberg, John Holman, Mysore S Anil Kumar, Vicki Santos, Tami Jo Larson, Xuegong Wang
This study assessed the efficacy and safety of the anti-CD40 monoclonal antibody bleselumab (ASKP1240) in de novo kidney transplant recipients over 36 months post-transplant. Transplant recipients were randomized (1:1:1) to standard of care (SoC: 0.1 mg/kg/day immediate-release tacrolimus [IR-TAC]; target minimum blood concentration (Ctrough ) 4-11 ng/mL] plus 1 g mycophenolate mofetil [MMF] twice daily), or bleselumab (200 mg on days 0/7/14/28/42/56/70/90, and monthly thereafter) plus either MMF or IR-TAC (0...
September 11, 2019: American Journal of Transplantation
Thomas M Savage, Brittany A Shonts, Saiping Lau, Aleksandar Obradovic, Harlan Robins, Abraham Shaked, Yufeng Shen, Megan Sykes
We recently developed a high throughput T cell receptor β chain (TCRβ) sequencing-based approach to identifying and tracking donor-reactive T cells. To address the role of clonal deletion in liver allograft tolerance, we applied this method in samples from a recent randomized study, ITN030ST, in which immunosuppression withdrawal was attempted within 2 years of liver transplantation. We identified donor-reactive T cell clones via TCRβ sequencing following a pre-transplant mixed lymphocyte reaction and tracked these clones in the circulation following transplantation in 3 tolerant and 5 non-tolerant subjects...
September 11, 2019: American Journal of Transplantation
Julie Boucquemont, Ahna L H Pai, Vikas R Dharnidharka, Diane Hebert, Nataliya Zelikovsky, Sandra Amaral, Susan L Furth, Bethany J Foster
Disruption of usual routines may hinder adherence, increasing the risk of rejection. We aimed to compare weekend versus weekday medication adherence among adolescent and young adult kidney transplant recipients, hypothesizing poorer adherence on weekends. We examined data from the Teen Adherence in Kidney transplant Effectiveness of Intervention Trial (TAKE-IT). We assessed the 3-month run-in period (no intervention) and the 12-month intervention interval, considering a potential interaction between weekend/weekday and treatment group...
September 10, 2019: American Journal of Transplantation
Ronald F Parsons, Arslan Zahid, Shalini Bumb, Hannah Decker, H Clifford Sullivan, F Eun-Hyung Lee, I Raul Badell, Mandy L Ford, Christian P Larsen, Thomas C Pearson, Annette M Jackson, Dong-Feng Chen, Matthew Levine, Malek Kamoun, Robert A Bray, Howard M Gebel
Recent evidence suggests that belatacept reduces the durability of pre-existing antibodies to class I and class II HLA antigens. In this case series of 163 highly-sensitized kidney transplant candidates whose calculated panel reactive antibody (cPRA) activity was ≥98-100%, the impact of belatacept on pre-existing HLA antibodies was assessed. Of the 163 candidates, 72 underwent transplantation between 12/4/2014 and 4/15/2017; 60 of these transplanted patients remained on belatacept consecutively for at least six months...
August 27, 2019: American Journal of Transplantation
Manon Launay, Joelle Guitard, Richard Dorent, Yoann Prevot, Florent Prion, Laurence Beaumont, Benjamin Kably, Lucien Lecuyer, Eliane M Billaud, Romain Guillemain
Belatacept (BTC) is indicated for prophylaxis of graft rejection in adults receiving a renal transplant (Tx). This retrospective observational study (3 centers) included all heart-transplant recipients receiving BTC between 01/2014 and 10/2018. Forty EBV+ patients mean GFR 35±20mL/min/m² were identified, among whom belatacept was initiated during the first 3 months after transplantation in 12 patients, and later in 28 patients. Several patients were multi-organ-transplant recipients. Study outcomes were GFR, safety and changes in immunosuppressive therapy...
August 26, 2019: American Journal of Transplantation
Bernd Schröppel, Enver Akalin, Mukta Baweja, Roy D Bloom, Sander Florman, Michael Goldstein, Brandy Haydel, Donald E Hricik, Sanjay Kulkarni, Matthew Levine, Anita Mehrotra, Anup Patel, Emilio D Poggio, Lloyd Ratner, Ron Shapiro, Peter S Heeger
Animal models and observational human data indicate that complement, including C5a, pathogenically participates in ischemia reperfusion (IR) injury that manifests as delayed graft function (DGF) following deceased donor kidney transplantation. We report on the safety/efficacy of anti-C5 monoclonal antibody eculizumab (ECU) administered in the operating room prior to reperfusion, to prevent DGF in recipients of deceased donor kidney transplants in two related, investigator-sponsored, randomized controlled trials...
August 26, 2019: American Journal of Transplantation
Laneshia K Tague, Davide Scozzi, Michael Wallendorf, Brian F Gage, Alexander S Krupnick, Daniel Kreisel, Derek Byers, Ramsey Hachem, Andrew E Gelman
Although neutropenia is a common complication following lung transplantation, its relationship to recipient outcomes remains understudied. We evaluated a retrospective cohort of 228 adult lung transplant recipients between 2008 and 2013 to assess the association of neutropenia and Granulocyte Colony Stimulating Factor (GCSF) treatment with outcomes. Neutropenia was categorized as mild (ANC 1000-1499), moderate (500-999) or severe (<500) and also as a time-varying continuous variable. Association with survival, acute rejection (ACR) and chronic lung allograft dysfunction (CLAD) were assessed by Cox proportional hazards regression...
August 26, 2019: American Journal of Transplantation
Nikhil Kapila, Kawtar Al-Khalloufi, Pablo A Bejarano, Jason M Vanatta, Xaralambos B Zervos
Fibrosing cholestatic hepatitis (FCH) post transplantation can lead to graft failure and death. In the era of direct acting antiviral therapy (DAA), several studies have demonstrated the efficacy and safety of transplanting hepatitis C virus (HCV) positive allografts into HCV negative recipients. In this case series, we present two cases of HCV negative recipients who underwent kidney transplantation from viremic donors and developed FCH. Both patients presented after transplant with abnormal liver function tests and HCV viral loads of greater than 100,000,000 IU/mL...
August 26, 2019: American Journal of Transplantation
Annie J Tsay, Howard J Eisen
Approximately 50 years after the first human-to-human heart transplant, we do not have an optimal post-heart transplantation regimen. The current standard of care includes calcineurin inhibitors (CNI) (tacrolimus, cyclosporine (CsA)), anti-metabolites (mycophenolic acid (MPA)), and steroids. This article is protected by copyright. All rights reserved.
August 26, 2019: American Journal of Transplantation
Zoltan Czigany, Wiebke Kramp, Jan Bednarsch, Gregory van der Kroft, Joerg Boecker, Pavel Strnad, Markus Zimmermann, Ger Koek, Ulf Peter Neumann, Georg Lurje
Muscle wasting, and alterations of body composition (BC) are linked to clinical outcomes in numerous medical conditions. The role of myosteatosis in post-transplant outcomes remains to be determined. Here we investigated skeletal muscle mass and myosteatosis as prognostic factors in patients undergoing orthotopic liver transplantation (OLT). The data of 225 consecutive OLT-recipients from a prospective database were retrospectively analysed (05/2010-12/2017). Computed-tomography-based skeletal-muscle-index/SMI (muscle mass), visceral-fat-area/VFA (visceral adiposity) and mean skeletal-muscle-radiation-attenuation/SM-RA (myosteatosis) were calculated using a segmentation tool...
August 26, 2019: American Journal of Transplantation
Christine M Durand, Michael A Chattergoon, Niraj M Desai
Organs from hepatitis C virus-infected (HCV+) deceased donors are a growing resource, primarily due to the unrelenting epidemic of opioid overdose deaths. Direct-acting antivirals (DAAs), which can readily cure HCV, have opened the door to transplanting HCV+ donor organs into HCV-naïve recipients. This article is protected by copyright. All rights reserved.
August 25, 2019: American Journal of Transplantation
Miriam T Jacobs, Marissa Olson, Bruna Pellini Ferreira, Ramon Jin, Ramsey Hachem, Derek Byers, Chad Witt, Armin Ghobadi, John F DiPersio, Iskra Pusic
Development of graft-versus-host disease (GvHD) is a rare complication after transfusions or solid organ transplantation. Patients typically present with a skin rash, diarrhea, liver failure, and bone marrow aplasia. A diagnosis of transfusion/transplantation associated-GvHD is made based on the clinical and histologic evidence, yet it is often delayed due to the nonspecific symptoms attributed to the patient's underlying illness. Several therapeutic approaches are being used including both increasing and withdrawing immunosuppression, and the use of cellular therapies...
August 25, 2019: American Journal of Transplantation
Marc Puigvehí, Dana Hashim, Philipp K Haber, Amreen Dinani, Thomas D Schiano, Amon Asgharpour, Tatyana Kushner, Gaurav Kakked, Parissa Tabrizian, Myron Schwartz, Ahmet Gurakar, Douglas Dieterich, Paolo Boffetta, Scott L Friedman, Josep M Llovet, Behnam Saberi
HCV infection has been the most common etiology in HCC-related liver transplantation (LT). Since 2014, direct-acting antivirals (DAAs) have dramatically improved HCV cure. We aimed to study the changing pattern of etiologies and impact in outcome in HCC-related LT according to HCV treatment-era through retrospective analysis of the Scientific Registry of Transplant Recipients (SRTR) database (1987-2017). A total of 27,855 HCC-related LT were performed (median age 59 years, 77% male). In the DAA-era (2014-2017) there has been a 14...
August 22, 2019: American Journal of Transplantation
Anthony J Michaels, Matteo Stoppato, Walter J Flores, Keith A Reimann, Kathleen D Engelman
The antagonistic anti-CD40 antibody, 2C10, and its recombinant primate derivative, 2C10R4, are potent immunosuppressive antibodies whose utility in allo- and xenotransplantation have been demonstrated in nonhuman primate studies. In this study, we defined the 2C10 binding epitope and found only slight differences in affinity of 2C10 for CD40 derived from four primate species. Staining of truncation mutants mapped the 2C10 binding epitope to the N-terminal portion of CD40. Alanine scanning mutagenesis of the first 60 residues in the CD40 ectodomain highlighted key amino acids important for binding of 2C10, and for binding of the noncross-blocking anti-CD40 antibodies 3A8 and 5D12...
August 20, 2019: American Journal of Transplantation
Melissa G Kaltenbach, Michael O Harhay, Peter L Abt, David S Goldberg
We sought to characterize the trend in alanine aminotransferase elevations prior to transplant and the impact on the pattern of enzyme elevations on organ utilization and graft function. We performed a retrospective cohort study of UNOS data on all deceased donors between 2007 and 2016. Serum alanine aminotransferase (ALT) was categorized into six study groups with peak ALT <499, 500-749, 750-999, 1000-1999, 2000-2999, and >3000 IU/L. The change from peak ALT to terminal ALT prior to transplant was categorized as no change/increasing at time transplant, 0...
August 17, 2019: American Journal of Transplantation
Max T Buchko, Catherine J Stewart, Sanaz Hatami, Sayed Himmat, Darren H Freed, Jayan Nagendran
Ex vivo lung perfusion (EVLP) protocols generally limit metabolic supplementation to insulin and glucose. We sought to determine whether the addition of total parenteral nutrition (TPN) would improve lung function in EVLP. Ten porcine lungs were perfused using EVLP for 24 hours and supplemented with insulin and glucose. In the treatment group (n=5), the perfusate was also supplemented with a continuous infusion of TPN containing lipids, amino acids, essential vitamins and cofactors. Physiologic parameters and perfusate electrolytes were continuously evaluated...
August 16, 2019: American Journal of Transplantation
Qingyong Xu, Vivian C McAlister, Steve Leckie, Andrew A House, Anton Skaro, Paul Marotta
Angiotensin II type I receptor (AT1R) agonistic autoantibodies (AT1R-AA) are detrimental to kidney transplantation. Early studies suggested a similar negative effect in primary liver transplantation. Here, we studied AT1R-AA in a retrospective cohort of 94 patients who received a second liver transplant to determine their prevalence and effects. The concentrations of preformed AT1R-AA before transplantation were higher (P = .019) in the 48 patients who lost their liver grafts than in the 46 patients whose grafts survived...
August 16, 2019: American Journal of Transplantation
Melena D Bellin, Tae Kim, Joshua J Wilhelm, Sarah Jane Schwarzenberg, Srinath Chinnakotla
In patients undergoing total pancreatectomy for chronic pancreatitis, isolation and infusion of autologous islets must comply with Good Manufacturing Practices standards established by the Food and Drug Administration (FDA) but does not standardly require an Investigational New Drug status. We report a case of a 4 year old child with severe hereditary pancreatitis who developed clinical sepsis during total pancreatectomy (TP) surgery; subsequent pancreas, islet, and blood cultures were positive for enterococcus...
August 16, 2019: American Journal of Transplantation
Hera E Schlagintweit, Marie-Josée Lynch, Christian S Hendershot
Alcohol-related liver disease (ALD) is a common indication for liver transplantation. Reflecting growing consensus that early transplant (i.e., prior to sustained abstinence) can be a viable option for acute alcoholic hepatitis, access to liver transplantation for ALD patients has increased. Prevention of alcohol relapse is critical to pre-transplant stabilization and post-transplant survival. Behavioral interventions are a fundamental component of alcohol use disorder treatment, but have rarely been studied in the transplant context...
August 16, 2019: American Journal of Transplantation
Jennifer Husson, Emmanuel F Mongodin, Jonathan S Bromberg
Despite advances in immunosuppressive management in lung transplantation, acute and chronic rejection remain challenging. One under-studied area of research is the role of the microbiota and its effects on alloimmunity and allograft rejection. Prior work has shown that the microbiota modulates innate and adaptive immunity through pathways such as the induction of suppressive Foxp3+ CD4+ regulatory T cells (Treg). Guo et al in this issue of the AJT demonstrate vendor-specific differences in lung allograft rejection in a minor histocompatibility mismatch murine model, and these differences are ameliorated by antibiotics...
August 13, 2019: American Journal of Transplantation
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