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https://www.readbyqxmd.com/read/28550198/host-derived-cd70-suppresses-murine-graft-versus-host-disease-by-limiting-donor-t-cell-expansion-and-effector-function
#1
Nicholas D Leigh, Rachel E O'Neill, Wei Du, Chuan Chen, Jingxin Qiu, Jonathan D Ashwell, Philip L McCarthy, George L Chen, Xuefang Cao
Allogeneic hematopoietic cell transplantation (allo-HCT) is a potentially curative treatment for hematologic and immunologic diseases. However, graft-versus-host disease (GVHD) may develop when donor-derived T cells recognize and damage genetically distinct normal host tissues. In addition to TCR signaling, costimulatory pathways are involved in T cell activation. CD27 is a TNFR family member expressed on T cells, and its ligand, CD70, is expressed on APCs. The CD27/CD70 costimulatory pathway was shown to be critical for T cell function and survival in viral infection models...
May 26, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28550042/t-cell-expression-of-ahr-inhibits-the-maintenance-of-ptreg-cells-in-the-gi-tract-in-acute-gvhd
#2
Trisha A Dant, Kaifeng L Lin, Danny W Bruce, Stephanie A Montgomery, Oleg V Kolupaev, Hemamalini Bommiasamy, Lisa M Bixby, John T Woosley, Karen P McKinnon, Frank J Gonzalez, Bruce R Blazar, Benjamin G Vincent, James M Coghill, Jonathan S Serody
The Aryl-hydrocarbon-receptor (AhR) is a ligand-activated transcription factor that affects the function and development of immune cells. Here, we show that recipient mice receiving AhR(-/-) T cells have improved survival and decreased acute graft versus host disease (aGvHD) in two different murine allogeneic bone marrow transplant models (BMT). We also show that CD4(+) T cells lacking AhR demonstrate reduced accumulation in secondary lymphoid tissue due to low levels of proliferation 4 days after BMT. Additionally, we found a significant increase in the quantity of peripherally induced regulatory donor T cells (pTregs) in the colon of recipients transplanted with AhR(-/-) T cells 14 days after transplant...
May 26, 2017: Blood
https://www.readbyqxmd.com/read/28549771/calcineurin-and-mtor-inhibitor-free-post-transplantation-cyclophosphamide-and-bortezomib-combination-for-graft-versus-host-disease-prevention-after-peripheral-blood-allogeneic-hematopoietic-stem-cell-transplantation-a-phase-i-ii-study
#3
A Samer Al-Homsi, Kelli Cole, Marlee Muilenburg, Austin Goodyke, Muneer Abidi, Ulrich Duffner, Stephanie Williams, Jessica Parker, Aly Abdel-Mageed
Graft-versus-host disease (GvHD) hampers the utility of allogeneic hematopoietic stem cell transplantation (AHSCT). The purpose of this study was to determine the feasibility, safety, and efficacy of a novel combination of post-transplantation cyclophosphamide (PTC) and bortezomib for the prevention of GvHD. Patients undergoing peripheral blood AHSCT for hematological malignancies following reduced-intensity conditioning with grafts from human leukocyte antigen (HLA)-matched related or unrelated donors were enrolled in a phase I-II clinical trial...
May 23, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/28549770/inversion-3-cytogenetic-abnormality-in-an-allogeneic-hematopoietic-cell-transplant-recipient-representative-of-a-donor-derived-constitutional-abnormality
#4
Ajoy Dias, Aref Al-Kali, Daniel Van Dyke, Dietger Niederwieser, Vladan Vucinic, Johannes Lemke, Christel Muller, Sebastian Schwind, Anne-Christin Teichmann, Ruth Bakken, Linda J Burns, Mark Litzow
Allogeneic hematopoietic cell transplantation (HCT) is an important treatment for many severe hematological disorders. However HCT can be associated with significant complications including organ toxicity, graft -versus-host disease and relapse. One other serious but rare complication is the transmission of hematologic and non- hematologic diseases from the donor to the recipient. With older donors, the risk of an abnormality in the donor may be higher. Here we describe the transmission of an inversion 3 constitutional cytogenetic abnormality from an unrelated donor to a recipient and review the clinical implications of the discovery of donor-derived constitutional cytogenetic abnormalities...
May 23, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/28549768/myasthenia-gravis-after-allogeneic-bone-marrow-transplantation-a-case-report-and-literature-review
#5
Yutaka Tsutsumi, Takashi Kamiishi, Ryo Kikuchi, Shinichi Ito, Satomi Matsuoka, Takanori Teshima
A 52-year-old man with acute myeloid leukemia underwent allogeneic hematopoietic stem cell transplantation and developed extensive chronic graft-versus-host disease and myasthenia gravis (MG), which became involved with oculobulbar and proximal upper and lower limb weakness in 677days. In the literature, we identified 24 cases where MG developed after allo-SCT. Graft-versus-host disease development and male recipients of female donors might be prone to the development of posttransplant MG (odds ratio, 3.75)...
May 18, 2017: Hematology/oncology and Stem Cell Therapy
https://www.readbyqxmd.com/read/28549237/haploidentical-allogeneic-hematopoietic-stem-cell-transplantation-compared-to-matched-unrelated-transplantation-for-philadelphia-chromosome-positive-acute-lymphoblastic-leukemia
#6
Bin Gu, Xiaojin Wu, Guanghua Chen, Xiao Ma, Zhengming Jin, Xiaowen Tang, Yue Han, Chengcheng Fu, Huiying Qiu, Aining Sun, Depei Wu
To investigate the effect of haploidentical allogeneic hematopoietic stem cell transplantation (Haplo-HCT) in Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL), the outcome of 58 patients with Ph+ ALL who received Haplo-HCT (n=42) or matched unrelated donor transplantation (MUD-HCT) (n=16) during the same period were analyzed retrospectively. All patients received a tyrosine kinase inhibitor (TKI)-based regimen before transplantation, and TKI was resumed primarily after transplantation...
May 16, 2017: Leukemia Research
https://www.readbyqxmd.com/read/28549148/risk-factors-for-invasive-fungal-disease-in-pediatric-cancer-and-hematopoietic-stem-cell-transplantation-a-systematic-review
#7
Brian T Fisher, Paula D Robinson, Thomas Lehrnbecher, William J Steinbach, Theoklis E Zaoutis, Bob Phillips, Lillian Sung
Background.: Although a number of risk factors have been associated with invasive fungal disease (IFD), a systematic review of the literature to document pediatric-specific factors has not been performed. Methods.: We used the Ovid SP platform to search Medline, Medline In-Process, and Embase for studies that identified risk factors for IFD in children with cancer or those who undergo hematopoietic stem cell transplantation (HSCT). We included studies if they consisted of children or adolescents (<25 years) who were receiving treatment for cancer or undergoing HSCT and if the study evaluated risk factors among patients with and those without IFD...
May 26, 2017: Journal of the Pediatric Infectious Diseases Society
https://www.readbyqxmd.com/read/28547857/confocal-endomicroscopy-in-diagnosis-of-intestinal-chronic-graft-versus-host-disease
#8
Kathrin Rieger, Ute Günther, Ulrike Erben, Anja Kühl, Christoph Loddenkemper, Antonio Pezzutto, Britta Siegmund, Christian Bojarski
Graft-versus-host disease (GvHD) is a major complication of allogeneic stem cell transplantation. High-resolution in vivo histology of the intestine by confocal endomicroscopy (CEM) detects acute GvHD (aGvHD) with high sensitivity. This pilot study aims to evaluate the diagnostic value of CEM for intestinal chronic GvHD (cGvHD). The study included 20 patients with gastrointestinal symptoms and confirmed cGvHD in other organs as well as 20 patients with clinically suspected acute GvHD for control. Confocal endomicroscopy was performed as gastroscopy followed by sigmoidoscopy after intravenous injection of fluorescein (10%) and topical application of acriflavine (0...
May 25, 2017: Hematological Oncology
https://www.readbyqxmd.com/read/28546779/emerging-treatment-options-for-the-management-of-hodgkin-s-lymphoma-clinical-utility-of-nivolumab
#9
REVIEW
David A Bond, Lapo Alinari
Classical Hodgkin's lymphoma (cHL) is a B-cell malignancy comprised of pathologic Reed Sternberg cells with a surrounding immune-tolerant inflammatory milieu. RS cells evade immune recognition in part through programmed death ligand 1 (PD-L1) overexpression, which is genetically programmed through copy number alterations, polysomy, and amplification of the 9p24.1 locus encoding PD-L1. By engaging with PD-1+ T-cells, PD-L1 delivers a potent immune suppressive signal promoting immunologic escape of the tumor cell...
2017: Journal of Blood Medicine
https://www.readbyqxmd.com/read/28542105/national-trends-and-in-hospital-outcomes-of-patients-with-solid-organ-transplant-undergoing-spinal-fusion
#10
Hiroyuki Yoshihara, Daisuke Yoneoka, Carl Paulino, Sanjeev Agarwal, Jose R Reyna, Kazuhiro Hasegawa
STUDY DESIGN: A retrospective analysis of population-based national hospital discharge data collected for the Nationwide Inpatient Sample (NIS) OBJECTIVES.: To examine the demographics and in-hospital outcomes of patients with solid organ transplant (SOT) undergoing spinal fusion on a national level SUMMARY OF BACKGROUND DATA.: Solid organ transplantation has become more common in recent years and some of these patients undergo spinal fusion surgery. However, there is little information regarding the trends and outcomes in such patients...
May 25, 2017: Spine
https://www.readbyqxmd.com/read/28537251/antigen-specific-cd8-t-cell-feedback-activates-nlrp3-inflammasome-in-antigen-presenting-cells-through-perforin
#11
Yikun Yao, Siyuan Chen, Mengtao Cao, Xing Fan, Tao Yang, Yin Huang, Xinyang Song, Yongqin Li, Lilin Ye, Nan Shen, Yufang Shi, Xiaoxia Li, Feng Wang, Youcun Qian
The connection between innate and adaptive immunity is best exemplified by antigen presentation. Although antigen-presenting cells (APCs) are required for antigen receptor-mediated T-cell activation, how T-cells feedback to APCs to sustain an antigen-specific immune response is not completely clear. Here we show that CD8(+) T-cell (also called cytotoxic T lymphocytes, CTL) feedback activates the NLRP3 inflammasome in APCs in an antigen-dependent manner to promote IL-1β maturation. Perforin from antigen-specific CTLs is required for NLRP3 inflammasome activation in APCs...
May 24, 2017: Nature Communications
https://www.readbyqxmd.com/read/28536906/current-status-of-bruton-s-tyrosine-kinase-inhibitor-development-and-use-in-b-cell-malignancies
#12
REVIEW
Andrew Aw, Jennifer R Brown
The B-cell receptor (BCR) pathway plays an important role in the survival, proliferation and trafficking of cancer cells in a variety of B-cell malignancies. Recently, a number of agents have been developed to target various components of the BCR pathway. One such target is Bruton's tyrosine kinase (BTK), a Tec family kinase member found near the cell membrane that is involved in upstream BCR signaling. The biological function of BTK in several B-cell lymphoid malignancies has led to the development of the oral BTK inhibitor ibrutinib...
May 23, 2017: Drugs & Aging
https://www.readbyqxmd.com/read/28536356/hla-c-kir-ligands-determine-the-impact-of-anti-thymocyte-globulin-atg-on-graft-versus-host-and-graft-versus-leukemia-effects-following-hematopoietic-stem-cell-transplantation
#13
Johannes Clausen, Alexandra Böhm, Irene Straßl, Olga Stiefel, Veronika Buxhofer-Ausch, Sigrid Machherndl-Spandl, Josef König, Stefan Schmidt, Hansjörg Steitzer, Martin Danzer, Hedwig Kasparu, Ansgar Weltermann, David Nachbaur
Rabbit anti-thymocyte globulins (ATGs) are widely used for the prevention of acute and chronic graft versus host disease (aGVHD, cGVHD) following allogeneic hematopoietic stem cell transplantation (HSCT). However, most prospective and retrospective studies did not reveal an overall survival (OS) benefit associated with ATG. Homozygosity for human leukocyte antigen (HLA)-C group 1 killer-cell immunoglobulin-like receptor ligands (KIR-L), i.e. C1/1 KIR-L status, was recently shown to be a risk factor for severe aGVHD...
March 28, 2017: Biomedicines
https://www.readbyqxmd.com/read/28536321/-disruption-of-gut-immune-system-caused-by-damage-of-intestinal-stem-cells-and-their-niche-in-graft-versus-host-disease-after-allogeneic-hematopoietic-stem-cell-transplantation
#14
Eiko Hayase, Takanori Teshima
Allogeneic hematopoietic stem cell transplantation(allo-SCT)is curative therapy for various hematological diseases. Graft-versus-host disease(GVHD)and infection remain the main problems in allo-SCT. Gastrointestinal tract is targeted by GVHD. In intestinal GVHD, intestinal stem cells and Paneth cells reside at the base of crypts are damaged by donor T cells. These damage leads to disruption of intestinal mucosal barrier and intestinal dysbiosis, resulting in more exaggerated GVHD. Recently, we and others have reported that R-Spondin1 and interleukin-22 as factors regenerated intestinal tissue homeostasis in murine model of bone marrow transplantation...
2017: Clinical Calcium
https://www.readbyqxmd.com/read/28533059/graft-versus-host-disease-of-the-gut-a-histologic-activity-grading-system-and-validation
#15
David Myerson, Gideon Steinbach, Ted A Gooley, Howard M Shulman
The pathologic interpretation of gut biopsies in hematopoietic cell transplant recipients to assess graft-versus-disease (GVHD) is well accepted and supplements clinical and endoscopic findings. However, the histologic activity grading of GVHD is controversial, with attempts to predict prognosis or response to treatment largely unsuccessful. GVHD is being diagnosed earlier in its course, raising the possibility that the pathologic grading system can be profitably modified. We have developed a histologic activity grading system designed to replace the commonly used modified-Lerner grading systems...
May 19, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/28532344/pre-transplantation-thymic-function-is-associated-with-the-risk-of-acute-graft-versus-host-disease-and-cytomegalovirus-viremia-after-allogeneic-hematopoietic-stem-cell-transplantation
#16
Xin Yang, Yuanxin Sun, Sudong Zhang, Hui Yang, Jialin Wei, Yi He, Donglin Yang, Erlie Jiang, Mingzhe Han, Xuemei Qin, Sizhou Feng
OBJECTIVES: To analyze the kinetics of T-cell subsets and thymic function reconstitution after allogeneic hematopoietic stem cell transplantation (AHSCT); to determine whether sjTREC (signal joint TCR rearrangement excision circle) and CD31-positive recent thymic emigrant (CD31 + RTE) are correlated with acute graft versus host disease (aGVHD) or CMV (cytomegalovirus) viremia after AHSCT. METHODS: Forty-nine patients who underwent AHSCT in our institution were prospectively enrolled...
May 22, 2017: Hematology (Amsterdam, Netherlands)
https://www.readbyqxmd.com/read/28531813/immunomodulatory-function-of-whole-human-umbilical-cord-derived-mesenchymal-stem-cells
#17
Hao Zhang, Yanling Tao, Haihui Liu, Saisai Ren, Bin Zhang, Hu Chen
Bone marrow derived mesenchymal stem cells (MSCs) play a critical role in immune modulation. However, immunomodulatory function of whole human umbilical cord derived mesenchymal stem cells (UC-MSCs) remains unclear. In this study, UC-MSCs were separated from whole umbilical cord using a single enzyme digestion. UC-MSCs (CD73(+), CD90(+), CD105(+), and CD34(-), CD45(-), HLA-DR(-)) were differentiated into adipocytes, osteocytes and chondrocytes in vitro under specific stimulatory environments. UC-MSCs suppressed umbilical cord blood lymphocyte proliferation stimulated by mitogen, and ELISA showed that the secretion of INF-γ was downregulated, and the secretion of IL-4 was upregulated, with CD8(+) T cells markedly decreased and CD4(+) T cells changed lightly...
May 19, 2017: Molecular Immunology
https://www.readbyqxmd.com/read/28529840/adoptive-cell-therapy-with-tregs-to-improve-transplant-outcomes-the-promise-and-the-stumbling-blocks
#18
Mohamed B Ezzelarab, Angus W Thomson
The contribution of regulatory T cells (Treg) to the induction and maintenance of tolerance is well-recognized in rodents and may contribute to long-term human organ allograft survival. The therapeutic efficacy of adoptively-transferred Treg in promoting tolerance to organ allografts is well-recognized in mouse models. Early phase 1/2 clinical studies of Treg therapy have been conducted in patients with type-1 (autoimmune) diabetes and refractory Crohn's disease, and for inhibition of graft-versus-host disease following bone marrow transplantation with proven safety...
December 2016: Current Transplantation Reports
https://www.readbyqxmd.com/read/28529723/role-of-major-histocompatibility-complex-variation-in-graft-versus-host-disease-after-hematopoietic-cell-transplantation
#19
REVIEW
Effie W Petersdorf
Graft-versus-host disease (GVHD) remains a significant potentially life-threatening complication of allogeneic hematopoietic cell transplantation (HCT). Since the discovery of the human leukocyte antigen (HLA) system over 50 years ago, significant advances have clarified the nature of HLA variation between transplant recipients and donors as a chief etiology of GVHD. New information on coding and non-coding gene variation and GVHD risk provides clinicians with options to consider selected mismatched donors when matched donors are not available...
2017: F1000Research
https://www.readbyqxmd.com/read/28527984/personalized-prognostic-risk-score-for-long-term-survival-for-children-with-acute-leukemia-after-allogeneic-transplant
#20
Menachem Bitan, Kwang Woo Ahn, Heather R Millard, Michael A Pulsipher, Hisham Abdel-Azim, Jeffery J Auletta, Valerie Brown, Ka Wah Chan, Miguel Angel Diaz, Andrew Dietz, Marta González Vincent, Gregory Guilcher, Gregory A Hale, Robert J Hayashi, Amy Keating, Parinda Mehta, Kasiani Myers, Kristin Page, Tim Prestidge, Nirali N Shah, Angela R Smith, Ann Woolfrey, Elizabeth Thiel, Stella M Davies, Mary Eapen
We studied leukemia-free (LFS) and overall survival (OS) in children with acute myeloid (AML; n=790) and acute lymphoblastic leukemia (ALL; n=1096), transplanted between 2000 and 2010, who survived for at least 1 year in remission after related or unrelated donor transplantation. Analysis of patient-, disease- and transplantation characteristics and acute and chronic graft versus host disease (GVHD) were performed to identify factors with adverse effects on LFS and OS. These data were used to develop risk scores for survival...
May 17, 2017: Biology of Blood and Marrow Transplantation
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