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Chronic graft versus host

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https://www.readbyqxmd.com/read/28941323/a-critical-role-for-donor-derived-il-22-in-cutaneous-chronic-gvhd
#1
Kate H Gartlan, Hemamalini Bommiasamy, Katelyn Paz, Andrew N Wilkinson, Mary Owen, Dawn K Reichenbach, Tatjana Banovic, Kimberly Wehner, Faith Buchanan, Antiopi Varelias, Rachel D Kuns, Karshing Chang, Yuri Fedoriw, Thomas Shea, James Coghill, Michael Zaiken, Maximilian W Plank, Paul S Foster, Andrew D Clouston, Bruce R Blazar, Jonathan S Serody, Geoffrey R Hill
Graft-versus-host disease (GVHD) is the major cause of non-relapse morbidity and mortality after allogeneic stem cell transplant (allo-SCT). Prevention and treatment of GVHD remains inadequate and commonly leads to end-organ dysfunction and opportunistic infection. The role of IL-17 and IL-22 in GVHD remains uncertain, due to an apparent lack of lineage fidelity and variable and contextually determined protective and pathogenic effects. We demonstrate that donor T-cell-derived IL-22 significantly exacerbates cutaneous chronic GVHD, and that IL-22 is produced by highly inflammatory donor CD4(+) T-cells post-transplant...
September 23, 2017: American Journal of Transplantation
https://www.readbyqxmd.com/read/28940837/a-case-of-the-nephrotic-syndrome-in-bone-marrow-transplantation-recipient-histologically-showing-overlapped-glomerular-lesions-of-thrombotic-microangiopathy-and-membranous-nephropathy
#2
Naoko Masuzawa, Ayako Nishimura, Takashi Kitani, Keiichi Tamagaki, Mio Sugitani, Hisao Nagoshi, Junya Kuroda, Eiichi Konishi
Nephrotic syndrome (NS) rarely occurs in post-hematopoietic stem cell transplantation (HSCT) recipients but represents the renal manifestation of graft-versus-host disease (GVHD). Membranous nephropathy (MN) accounts for almost two thirds of post-HSCT NS and is caused by immune complex deposition. Renal thrombotic microangiopathy (TMA) without fulfillment of clinical criteria for TMA has been underreported because of reduced opportunity for histological examination. However, renal TMA has recently been reported in association with GVHD and humoral immunological reactions...
September 20, 2017: Pathology International
https://www.readbyqxmd.com/read/28935847/cd56bright-nk-regulatory-cells-in-filgrastim-primed-donor-blood-or-marrow-products-regulate-chronic-gvhd-cbmtg-randomized-0601-study-results
#3
Amina Kariminia, Sabine Ivison, Bernard Ng, Jacob Rozmus, Susanna Sung, Avani Varshney, Mahmoud Aljurf, Silvy Lachance, Irwin Walker, Cindy Toze, Jeff Lipton, Stephanie J Lee, Jeff Szer, Richard Doocey, Ian Lewis, Clayton Smith, Naeen Chaudhri, Megan K Levings, Raewyn Broady, Gerald Devins, David Szwajcer, Ronan Foley, Sara Mostafavi, Steven Pavletic, Donna A Wall, Stephen Couban, Tony Panzarella, Kirk R Schultz
Randomized trials have conclusively shown higher rates of chronic graft-versus-host disease with filgrastim-stimulated apheresis peripheral blood as a donor source than unstimulated bone marrow. The Canadian Blood and Marrow Transplant Group conducted a phase 3 study of adults who received either filgrastim-stimulated apheresis peripheral blood or filgrastim-stimulated bone marrow from human leukocyte antigen-identical sibling donors. Because all donors received the identical filgrastim dosing schedule, this study allowed for a controlled evaluation of the impact of stem cell source on development of chronic graft-versus-host disease...
September 21, 2017: Haematologica
https://www.readbyqxmd.com/read/28934311/characteristics-and-risk-of-chronic-graft-versus-host-disease-of-liver-in-allogeneic-hematopoietic-stem-cell-transplant-recipients
#4
Chien-Ting Chen, Chun-Yu Liu, Yuan-Bin Yu, Chia-Jen Liu, Liang-Tsai Hsiao, Jyh-Pyng Gau, Tzeon-Jye Chiou, Jing-Hwang Liu, Yao-Chung Liu
Chronic graft-versus-host-disease (cGvHD) is a serious complication of allogeneic hematopoietic stem cell transplantation (allo-HSCT). Among various organ-specific cGvHD, the cGvHD of liver is less well-characterized. In this study, we applied the National Institutes of Health 2014 scoring criteria of cGvHD to analyze a retrospective cohort of 362 allo-HSCT recipients focusing on cGvHD of liver. The overall incidence of liver cGvHD with a score of 3 by 1.5 years post-transplant was 5.8% (21/362). Poor outcome, in terms of overall survival (OS), were observed in patients with scores of 3 liver cGvHD, comparing to those with scores less than 3 (hazard ratio [HR] 2...
2017: PloS One
https://www.readbyqxmd.com/read/28932763/a-co-culture-assay-to-determine-efficacy-of-tnf-%C3%AE-suppression-by-biomechanically-induced-human-bone-marrow-mesenchymal-stem-cells
#5
Miguel F Diaz, Siobahn M Evans, Scott D Olson, Charles S Cox, Pamela L Wenzel
The beneficial effects of mesenchymal stem cell (MSC)-based cellular therapies are believed to be mediated primarily by the ability odansf MSCs to suppress inflammation associated with chronic or acute injury, infection, autoimmunity, and graft-versus-host disease. To specifically address the effects of frictional force caused by blood flow, or wall shear stress (WSS), on human MSC immunomodulatory function, we have utilized microfluidics to model WSS at the luminal wall of arteries. Anti-inflammatory potency of MSCs was subsequently quantified via measurement of TNF-α production by activated murine splenocytes in co-culture assays...
August 20, 2017: Bio-protocol
https://www.readbyqxmd.com/read/28932558/results-of-quantitative-chest-ct-in-chronic-pulmonary-graft-vs-host-disease-cgvhd-3-years-after-allogeneic-stem-cell-transplantation
#6
Christopher Kloth, Wolfgang M Thaiss, Jürgen Hetzel, Georg Bier, Stefan Wirths, Konstantin Nikolaou, Marius Horger
BACKGROUND: To quantify lung parenchymal changes in symptomatic patients with chronic pulmonary graft-versus-host disease 3 years after allogeneic stem cell transplantation (allo-SCT) by means of CT-densitometry (CTD) and to compare results with those of established pulmonary function tests (PFT). METHODS: The study group consisted of 26 patients with pulmonary cGvHD (19 males, 7 females; mean age, 49.29±15.89; range, 19-72 years). The diagnosis was based on clinical symptoms, PFT and chest-CT findings...
August 2017: Journal of Thoracic Disease
https://www.readbyqxmd.com/read/28924018/ibrutinib-for-chronic-graft-versus-host-disease-after-failure-of-prior-therapy
#7
David Miklos, Corey S Cutler, Mukta Arora, Edmund K Waller, Madan Jagasia, Iskra Pusic, Mary E Flowers, Aaron C Logan, Ryotaro Nakamura, Bruce R Blazar, Yunfeng Li, Stephen Chang, Indu Lal, Jason Dubovsky, Danelle F James, Lori Styles, Samantha Jaglowski
Chronic graft-versus-host disease (cGVHD) is a serious complication of allogeneic stem cell transplantation with few effective options available after failure of corticosteroids. B and T cells play a role in the pathophysiology of cGVHD. Ibrutinib inhibits Bruton's tyrosine kinase in B cells and interleukin-2-inducible T-cell kinase in T cells. In preclinical models, ibrutinib reduced severity of cGVHD. This multicenter, open-label study evaluated the safety and efficacy of ibrutinib in patients with active cGVHD with inadequate response to corticosteroid-containing therapies...
September 18, 2017: Blood
https://www.readbyqxmd.com/read/28911060/reduced-intensity-versus-reduced-toxicity-myeloablative-fludarabine-busulfan-based-conditioning-regimens-for-allografted-non-hodgkin-lymphoma-adult-patients-a-retrospective-study-on-behalf-of-the-soci%C3%A3-t%C3%A3-francophone-de-greffe-de-moelle-et-de-th%C3%A3-rapie-cellulaire
#8
A Le Bourgeois, M Labopin, D Blaise, P Ceballos, S Vigouroux, R Peffault de Latour, A Marçais, C E Bulabois, J O Bay, S Chantepie, E Deconinck, E Daguindau, N Contentin, I Yakoub-Agha, J Cornillon, M Mercier, P Turlure, A Charbonnier, P S Rorhlich, S N'Guyen, N Maillard, T Marchand, M Mohty, P Chevallier
Background: Fludarabine/busulfan-based conditioning regimens are widely used to perform allogeneic stem-cell transplantation (allo-SCT) in high-risk non-Hodgkin lymphoma (NHL) patients. The impact of the dose intensity of busulfan on outcomes has not been reported yet. Patients and methods: This was a retrospective with the aim to compare the outcomes of NHL patients who received before allo-SCT a fludarabine/busulfan conditioning regimen, either of reduced intensity (FB2, 2 days of busulfan at 4 mg/kg/day oral or 3...
September 1, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/28899741/small-bowel-stenosis-a-manifestation-of-chronic-graft-versus-host-disease-in-children
#9
Mickael Tordjman, Marie Ouachee, Arnaud Bonnard, Bogdana Tilea, Karima Yakouben, Jerome Viala, Michel Peuchmaur, Dominique Berrebi
Digestive graft versus host disease (GVHD) is a frequent complication after bone marrow transplantation (BMT), but small bowel obstruction is an extremely rare event. We present herein the first pediatric series of 4 cases of small bowel obstruction after BMT with detailed gross, histological data and their genetic status of the NOD2 gene. All patients had a history of severe acute GVHD treated by immunosuppressive agents and/or infliximab (in 3 cases). Acute or progressively worsening abdominal pain accompanied by small bowel occlusion occurred 5-16months after graft and CT-scan revealed multiple small intestinal stenosis...
September 9, 2017: Human Pathology
https://www.readbyqxmd.com/read/28887808/comparison-of-reference-values-for-immune-recovery-between-event-free-patients-receiving-haploidentical-allografts-and-those-receiving-human-leukocyte-antigen-matched-sibling-donor-allografts
#10
Xuying Pei, Xiangyu Zhao, Yu Wang, Lanping Xu, Xiaohui Zhang, Kaiyan Liu, Yingjun Chang, Xiaojun Huang
To establish optimal reference values for recovered immune cell subsets, we prospectively investigated post-transplant immune reconstitution (IR) in 144 patients who received allogeneic stem cell transplantation (allo- SCT) and without showing any of the following events: poor graft function, grades II‒IV acute graft-versus-host disease (GVHD), serious chronic GVHD, serious bacterial infection, invasive fungal infection, or relapse or death in the first year after transplantation. IR was rapid in monocytes, intermediate in lymphocytes, CD3(+) Tcells, CD8(+) T cells, and CD19(+) B cells, and very slow in CD4(+) T cells in the entire patient cohort...
September 8, 2017: Frontiers of Medicine
https://www.readbyqxmd.com/read/28865973/recovery-of-pulmonary-function-after-allogeneic-hematopoietic-cell-transplantation-in-children-is-associated-with-improved-survival
#11
Ashok Srinivasan, Anusha Sunkara, William Mitchell, Sudeep Sunthankar, Guolian Kang, Dennis C Stokes, Saumini Srinivasan
Abnormal pulmonary function is prevalent in survivors of allogeneic hematopoietic cell transplantation. Post-transplant recovery of pulmonary function, and its effect on survival in children is not known. This is a retrospective cohort study of 308 children followed for 10 years after transplantation at a single institution. There were 2 groups of patients. Group 1 included 188 patients with 3 or more pulmonary function test (PFT) results, of which at least 1 was abnormal, group 2 included 120 patients with 3 or more PFTs, all of which were normal...
August 30, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/28864814/rituximab-based-first-line-treatment-for-chronic-gvhd-after-allogeneic-sct-results-of-a-phase-2-study
#12
Florent Malard, Myriam Labopin, Ibrahim Yakoub-Agha, Sylvain Chantepie, Thierry Guillaume, Didier Blaise, Reza Tabrizi, Leonardo Magro, Bernard Vanhove, Gilles Blancho, Philippe Moreau, Béatrice Gaugler, Patrice Chevallier, Mohamad Mohty
Chronic graft-versus-host disease (cGVHD) is the main cause of late non-relapse mortality and morbidity after allogeneic stem-cell transplantation (allo-SCT). In order to improve such patients' outcome, we conducted a phase 2, prospective, multicenter trial to test the efficacy of addition of rituximab to corticosteroid and cyclosporine A as first line therapy for newly diagnosed cGVHD after allo-SCT. Twenty-four patients (median age, 47 years) with mild (n=2), moderate (n=7) or severe (n=15) cGVHD were included...
September 1, 2017: Blood
https://www.readbyqxmd.com/read/28864139/optimizing-anti-thymocyte-globulin-dosing-for-unrelated-donor-allogeneic-hematopoietic-cell-transplant-based-on-recipient-absolute-lymphocyte-count
#13
Vanessa E Kennedy, Heidi Chen, Bipin N Savani, John Greer, Adetola A Kassim, Brian G Engelhardt, Stacey Goodman, Salyka Sengsayadeth, Wichai Chinratanalab, Madan Jagasia
Anti-thymocyte globulin (ATG) is used as prophylaxis against graft-versus-host-disease (GVHD). Current dosing regimens for ATG are empiric, weight-based, and do not account for patient-specific factors. Furthermore, the target of ATG, recipient T cells post-cytotoxic chemotherapy, is not a function of recipient weight. We hypothesized the recipient peripheral blood absolute lymphocyte count (ALC) on day of ATG administration would interact with the amount of ATG administered to predict transplant outcomes. We retrospectively analyzed 135 patients who received ATG for GVHD prophylaxis for unrelated allogeneic hematopoietic cell transplantation at three different doses: 10 mg/kg, 7...
August 29, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/28864138/comparison-of-different-rabbit-anti-thymocyte-globulin-formulations-in-allogeneic-stem-cell-transplantation-systematic-literature-review-and-network-meta-analysis
#14
Nico Gagelmann, Francis Ayuk, Christine Wolschke, Nicolaus Kröger
Since 2000, phase III randomized controlled trials (RCT) investigated the efficacy of rabbit anti-thymocyte globulins (ATG) in patients following allogeneic stem cell transplantation (allo-SCT). However, comparisons of different ATG formulations are lacking. Our aim was to synthesize all efficacy evidence, enabling a comparison of all available formulations of rabbit ATG in the allo-SCT setting. We performed a systematic literature review to identify all available phase III RCT evidence. We searched the Cochrane Library, MEDLINE, MEDLINE In-Process and the website www...
August 29, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/28859032/successful-reduced-intensity-conditioning-alternate-donor-stem-cell-transplant-for-wiskott-aldrich-syndrome
#15
Dhwanee Thakkar, Satyendra Katewa, Neha Rastogi, Shruti Kohli, Sagar Nivargi, Satya P Yadav
There are very few reports of reduced intensity conditioning (RIC) hematopoietic stem cell transplant (HSCT) with alternate donor for Wiskott-Aldrich syndrome (WAS) and there is no report of RIC with posttransplant cyclophosphamide (PTCy) in WAS. There is only 1 report of T cell receptor αβ and CD19-depleted haploidentical HSCT for WAS. Here we report successful outcome in 3 children with WAS who underwent successful RIC alternate donor HSCT of whom 2 (matched unrelated donor and T-cell replete haploidentical) received PTCy and 1 underwent T cell receptor αβ and CD19-depleted haploidentical HSCT...
August 30, 2017: Journal of Pediatric Hematology/oncology
https://www.readbyqxmd.com/read/28855905/mesenchymal-stem-cells-may-ameliorate-nephrotic-syndrome-post-allogeneic-hematopoietic-stem-cell-transplantation-case-report
#16
Xin Zhang, Yanwen Peng, Zhiping Fan, Ke Zhao, Xiaoyong Chen, Ren Lin, Jing Sun, Guobao Wang, AndyPeng Xiang, Qifa Liu
INTRODUCTION: Because of their immunomodulatory and anti-inflammatory effects, mesenchymal stem cells (MSCs) have been considered as potential therapeutic agents for treating immune-related or autoimmune diseases, such as graft-versus-host disease (GVHD). Nephrotic syndrome (NS) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) is an uncommon complication with unclear etiology and pathogenesis. It may be an immune disorder involving immune complex deposition, B cells, regulatory T cells (Tregs), and Th1 cytokines and be a manifestation of chronic GVHD...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28851699/an-aberrant-notch2-bcr-signaling-axis-in-b-cells-from-patients-with-chronic-gvhd
#17
Jonathan C Poe, Wei Jia, Hsuan Su, Sarah Anand, Jeremy J Rose, Prasanthi V Tata, Amy N Suthers, Corbin D Jones, Pei Fen Kuan, Benjamin G Vincent, Jonathan S Serody, Mitchell E Horwitz, Vincent T Ho, Steven Z Pavletic, Frances T Hakim, Kouros Owzar, Dadong Zhang, Bruce R Blazar, Christian W Siebel, Nelson J Chao, Ivan Maillard, Stefanie Sarantopoulos
B Cell Receptor (BCR)-activated B cells contribute to pathogenesis in chronic graft-versus-host disease (cGVHD), a condition manifested by both B cell autoreactivity and immune deficiency. We hypothesized that constitutive BCR activation precluded functional B cell maturation in cGVHD. To address this, we examined BCR-NOTCH2 synergy, since Notch has been shown to increase BCR responsiveness in normal mouse B cells. We conducted ex vivo activation and signaling assays of 30 primary samples from HCT patients with and without cGVHD...
August 29, 2017: Blood
https://www.readbyqxmd.com/read/28846465/post-transplantation-cyclophosphamide-based-haploidentical-transplantation-as-alternative-to-matched-sibling-or-unrelated-donor-transplantation-for-hodgkin-lymphoma-a-registry-study-of-the-lymphoma-working-party-of-the-european-society-for-blood-and-marrow
#18
Carmen Martínez, Jorge Gayoso, Carmen Canals, Hervé Finel, Karl Peggs, Alida Dominietto, Luca Castagna, Boris Afanasyev, Stephen Robinson, Didier Blaise, Paolo Corradini, Maija Itälä-Remes, Arancha Bermúdez, Edouard Forcade, Domenico Russo, Michael Potter, Grant McQuaker, Ibrahim Yakoub-Agha, Christof Scheid, Adrian Bloor, Silvia Montoto, Peter Dreger, Anna Sureda
Purpose To compare the outcome of patients with Hodgkin lymphoma who received post-transplantation cyclophosphamide-based haploidentical (HAPLO) allogeneic hematopoietic cell transplantation with the outcome of patients who received conventional HLA-matched sibling donor (SIB) and HLA-matched unrelated donor (MUD). Patients and Methods We retrospectively evaluated 709 adult patients with Hodgkin lymphoma who were registered in the European Society for Blood and Marrow Transplantation database who received HAPLO (n = 98), SIB (n = 338), or MUD (n = 273) transplantation...
August 28, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28846051/in-vivo-or-ex-vivo-t-cell-depletion-or-both-to-prevent-graft-versus-host-disease-after-hematopoietic-stem-cell-transplantation
#19
Alessandro Busca, Franco Aversa
Hematopoietic stem cell transplantation (HSCT) represents a widely accepted therapeutic strategy for the treatment of hematologic disorders which are otherwise considered incurable. Alloreactive T cells infused with the stem cell inoculum may generate graft-versus-host disease (GVHD) representing one the most relevant obstacles to the successful outcome of patients receiving allogeneic HSCT. Areas covered: In this review, the authors provide an overview of the most recent approaches of T-cell depletion (TCD) including ex-vivo αβ+ TCD and in-vivo TCD with anti-thymocyte globulin (ATG)...
August 28, 2017: Expert Opinion on Biological Therapy
https://www.readbyqxmd.com/read/28833039/minimally-manipulated-murine-regulatory-t-cells-purified-by-reversible-fab-multimers-are-potent-suppressors-for-adoptive-t-cell-therapy
#20
Fabian Mohr, Julius Clemens Fischer, Marc Nikolaus, Christian Stemberger, Stefan Dreher, Admar Verschoor, Tobias Haas, Hendrik Poeck, Dirk H Busch
The transfer of regulatory T cells, either freshly isolated, or modified, represents a promising therapeutic approach to dampen misdirected immune responses, like autoimmune diseases, chronic inflammatory syndromes and graft versus host disease. Clinical isolation of highly pure regulatory T cell (Treg) populations is still challenging and labeling reagents can influence their viability and functionality, potentially altering the potency of isolated Treg cell products. Here we show that reversible Fab multimer-based Treg purification can prevent conventional antibody label-induced interferences in vitro and in vivo...
August 17, 2017: European Journal of Immunology
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