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https://www.readbyqxmd.com/read/28542711/preventing-relapse-after-haematopoietic-stem-cell-transplantation-for-acute-leukaemia-the-role-of-post-transplantation-minimal-residual-disease-mrd-monitoring-and-mrd-directed-intervention
#1
REVIEW
Xiao-Dong Mo, Meng Lv, Xiao-Jun Huang
Relapse is the main cause of treatment failure after allogeneic haematopoietic stem cell transplantation (allo-HSCT) for acute leukaemia (AL). Post-transplantation minimal residual disease (MRD) monitoring enables risk stratification and identifies AL patients at higher risk of relapse. MRD assessment primarily involves the determination of leukaemia-associated immunophenotypic patterns using multiparameter flow cytometry, and the polymerase chain reaction (PCR)-based evaluation of expression levels of leukaemia-related genes (specific reciprocal gene rearrangements and other mutation types)...
May 23, 2017: British Journal of Haematology
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
#2
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/28521800/immunogenicity-and-immunomodulatory-effects-of-the-human-chondrocytes-hchonj
#3
Chae-Lyul Lim, Yeon-Ju Lee, Jong-Ho Cho, Heonsik Choi, Bumsup Lee, Myung Chul Lee, Sujeong Kim
BACKGROUND: Invossa™ (TissueGene-C) is a cell and gene therapy for osteoarthritis. It is composed of primary human chondrocytes (hChonJ cells) and irradiated human chondrocytes modified to express TGF-β1 (hChonJb#7 cells). The hChonJ cells were isolated from a polydactyly donor, and TGF-β1 cDNA was delivered to the cells, generating hChonJb#7 cells. Since the cells are allogeneic, the concern of immune response against cells has been raised. In this study, we investigated the immunogenicity of allogenic human chondrocyte, hChonJ cells...
May 18, 2017: BMC Musculoskeletal Disorders
https://www.readbyqxmd.com/read/28508465/proteomics-show-antigen-presentation-processes-in-human-immune-cells-after-as03-h5n1-vaccination
#4
Allison C Galassie, Johannes B Goll, Parimal Samir, Travis L Jensen, Kristen L Hoek, Leigh M Howard, Tara M Allos, Xinnan Niu, Laura E Gordy, C Buddy Creech, Heather Hill, Sebastian Joyce, Kathryn M Edwards, Andrew J Link
Adjuvants enhance immunity elicited by vaccines through mechanisms that are poorly understood. Using a systems biology approach, we investigated temporal protein expression changes in five primary human immune cell populations: neutrophils, monocytes, natural killer (NK) cells, T-cells, and B-cells after administration of either an Adjuvant System 03 (AS03)-adjuvanted or unadjuvanted split-virus H5N1 influenza vaccine. Monocytes demonstrated the strongest differential signal between vaccine groups. On day 3 post-vaccination, several antigen presentation-related pathways, including MHC class I-mediated antigen processing and presentation, were enriched in monocytes and neutrophils and expression of HLA Class I proteins was increased in the AS03 group...
May 15, 2017: Proteomics
https://www.readbyqxmd.com/read/28495643/humoral-immune-reconstitution-kinetics-following-allogeneic-hematopoietic-stem-cell-transplantation-in-children-a-maturation-block-of-igm-memory-b-cells-may-lead-to-impaired-antibody-immune-reconstitution
#5
Hisham Abdel-Azim, Amro Elshoury, Kris M Mahadeo, Robertson Parkman, Neena Kapoor
Although T cell immune reconstitution following allogeneic hematopoietic stem cell transplantation (allo-HSCT) has been well studied, long-term B cell immune reconstitution remains less characterized. We evaluated humoral immune reconstitution among 71-pediatric allo-HSCT recipients. While tetanus toxoid (TT) antibody levels were normal at 1-year post allo-HSCT, anti-polysaccharide carbohydrate (PRP) antibodies remained persistently low for up to 5-years. While naive B cell counts normalized by 6-months, IgM memory B cell deficiency persisted for up to 2-years (P=0...
May 8, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/28486431/mesenchymal-stem-cell-derived-extracellular-vesicles-a-role-in-hematopoietic-transplantation
#6
REVIEW
Luciana De Luca, Stefania Trino, Ilaria Laurenzana, Daniela Lamorte, Antonella Caivano, Luigi Del Vecchio, Pellegrino Musto
Mesenchymal stem cells (MSCs) are a heterogeneous cellular population containing different progenitors able to repair tissues, support hematopoiesis, and modulate immune and inflammatory responses. Several clinical trials have used MSCs in allogeneic hematopoietic stem cell transplantation (allo-HSCT) to prevent hematopoietic stem cell (HSC) engraftment failure, reduce aplasia post chemotherapy, and to control graft versus host disease (GvHD). The efficacy of MSCs is linked to their immune suppressive and anti-inflammatory properties primarily due to the release of soluble factors...
May 9, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28474504/mouse-nidovirus-ldv-infection-alleviates-graft-versus-host-disease-and-induces-type-i-ifn-dependent-inhibition-of-dendritic-cells-and-allo-responsive-t-cells
#7
Mélanie Gaignage, Reece G Marillier, Catherine Uyttenhove, Nicolas Dauguet, Anubha Saxena, Bernard Ryffel, Thomas Michiels, Jean-Paul Coutelier, Jacques Van Snick
INTRODUCTION: Viruses have developed multiple mechanisms to alter immune reactions. In 1969, it was reported that lactate dehydrogenase-elevating virus (LDV), a single stranded positive sense mouse nidovirus, delays skin allograft rejection and inhibits spleen alterations in graft versus host disease (GVHD). As the underlying mechanisms have remained unresolved and given the need for new therapies of this disease, we reassessed the effects of the virus on GVHD and tried to uncover its mode of action...
June 2017: Immunity, Inflammation and Disease
https://www.readbyqxmd.com/read/28457953/interferon-%C3%AE-is-effective-for-treatment-of-minimal-residual-disease-in-patients-with-acute-leukemia-after-allogeneic-hematopoietic-stem-cell-transplantation-results-of-a-registry-study
#8
Xiao-Dong Mo, Xiao-Hui Zhang, Lan-Ping Xu, Yu Wang, Chen-Hua Yan, Huan Chen, Yu-Hong Chen, Wei Han, Feng-Rong Wang, Jing-Zhi Wang, Kai-Yan Liu, Xiao-Jun Huang
The efficacy of minimal residual disease (MRD)-directed interferon-α (IFN-α) treatment was investigated in acute leukemia patients who were positive for MRD after allogeneic hematopoietic stem cell transplantation (allo-HSCT) (n=107). MRD-positive status was defined as positivity for leukemia-associated aberrant immune phenotypes or positivity for Wilms' tumor gene 1 in a single bone marrow sample. Recombinant human IFN-α-2b injections were administered subcutaneously 2-3 times per week for 6 months. The 2-year cumulative incidence of severe acute and chronic graft-versus-host disease after IFN-α treatment was 5...
April 27, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/28446226/xenotransplantation-of-interferon-gamma-pretreated-clumps-of-a-human-mesenchymal-stem-cell-extracellular-matrix-complex-induces-mouse-calvarial-bone-regeneration
#9
Kei Takeshita, Souta Motoike, Mikihito Kajiya, Nao Komatsu, Manabu Takewaki, Kazuhisa Ouhara, Tomoyuki Iwata, Katsuhiro Takeda, Noriyoshi Mizuno, Tsuyoshi Fujita, Hidemi Kurihara
BACKGROUND: Three-dimensional cultured clumps of a mesenchymal stem cell (MSC)/extracellular matrix (ECM) complex (C-MSC) consists of cells and self-produced ECM. C-MSC can regulate the cellular function in vitro and induce successful bone regeneration using ECM as a cell scaffold. Potentiating the immunomodulatory capacity of C-MSCs, which can ameliorate the allo-specific immune response, may be helpful in developing beneficial "off-the-shelf" cell therapy for tissue regeneration. It is well reported that interferon (IFN)-γ stimulates the immunosuppressive properties of MSC via upregulation of the immunomodulatory enzyme IDO...
April 26, 2017: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/28444181/allogeneic-human-mesenchymal-stem-cell-infusions-for-aging-frailty
#10
Samuel Golpanian, Darcy L DiFede, Aisha Khan, Ivonne Hernandez Schulman, Ana Marie Landin, Bryon A Tompkins, Alan W Heldman, Roberto Miki, Bradley J Goldstein, Muzammil Mushtaq, Silvina Levis-Dusseau, John J Byrnes, Maureen Lowery, Makoto Natsumeda, Cindy Delgado, Russell Saltzman, Mayra Vidro-Casiano, Marietsy V Pujol, Moisaniel Da Fonseca, Anthony A Oliva, Geoff Green, Courtney Premer, Audrey Medina, Krystalenia Valasaki, Victoria Florea, Erica Anderson, Jill El-Khorazaty, Adam Mendizabal, Pascal J Goldschmidt-Clermont, Joshua M Hare
Background: Impaired endogenous stem cell repair capacity is hypothesized to be a biologic basis of frailty. Therapies that restore regenerative capacity may therefore be beneficial. This Phase 1 study evaluated the safety and potential efficacy of intravenous, allogeneic, human mesenchymal stem cell (allo-hMSC)-based therapy in patients with aging frailty. Methods: In this nonrandomized, dose-escalation study, patients received a single intravenous infusion of allo-hMSCs: 20-million (n = 5), 100-million (n = 5), or 200-million cells (n = 5)...
April 21, 2017: Journals of Gerontology. Series A, Biological Sciences and Medical Sciences
https://www.readbyqxmd.com/read/28441942/rare-antibody-associated-hemolytic-transfusion-reaction-and-transfusion-related-acute-lung-injury-a-case-report
#11
Tim N Beck, Natalee G Young, Michelle L Erickson, Ignacio Prats
BACKGROUND: Hemolytic transfusion reactions and transfusion-related acute lung injury (TRALI) are life-threatening complications associated with the transfusion of blood products. Hemorrhage is one of the most common surgical complications and the risk of bleeding is particularly acute in patients with hematologic deficiencies. Management of surgical bleeding can be divided into two phases. The first phase centers on immediate control of acute bleeding and the second phase focuses on keeping the patient stable and on reducing the sequelae associated with blood transfusions and blood loss...
April 26, 2017: BMC Surgery
https://www.readbyqxmd.com/read/28424327/rig-i-mavs-and-sting-signaling-promote-gut-integrity-during-irradiation-and-immune-mediated-tissue-injury
#12
Julius C Fischer, Michael Bscheider, Gabriel Eisenkolb, Chia-Ching Lin, Alexander Wintges, Vera Otten, Caroline A Lindemans, Simon Heidegger, Martina Rudelius, Sébastien Monette, Kori A Porosnicu Rodriguez, Marco Calafiore, Sophie Liebermann, Chen Liu, Stefan Lienenklaus, Siegfried Weiss, Ulrich Kalinke, Jürgen Ruland, Christian Peschel, Yusuke Shono, Melissa Docampo, Enrico Velardi, Robert R Jenq, Alan M Hanash, Jarrod A Dudakov, Tobias Haas, Marcel R M van den Brink, Hendrik Poeck
The molecular pathways that regulate the tissue repair function of type I interferon (IFN-I) during acute tissue damage are poorly understood. We describe a protective role for IFN-I and the RIG-I/MAVS signaling pathway during acute tissue damage in mice. Mice lacking mitochondrial antiviral-signaling protein (MAVS) were more sensitive to total body irradiation- and chemotherapy-induced intestinal barrier damage. These mice developed worse graft-versus-host disease (GVHD) in a preclinical model of allogeneic hematopoietic stem cell transplantation (allo-HSCT) than did wild-type mice...
April 19, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28423227/a-national-survey-of-screening-and-management-of-hypogammaglobulinemia-in-canadian-transplantation-centers
#13
Samuel Bourassa-Blanchette, Greg Knoll, Jason Tay, Christopher Bredeson, Donald W Cameron, Juthaporn Cowan
BACKGROUND: Infection remains one of the most common transplant-related causes of death in patients undergoing transplantation. Secondary hypogammaglobulinemia (HGG) as a component of immune suppression and deficiency is associated with both solid organ transplantation (SOT) and hematopoietic cell transplantation (HCT). Available data and clinical experience for the supplementation of immunoglobulin (Ig) in these patients is conflicting, and differing clinical opinion accounts for non-uniform practice in the use of Ig treatment...
April 18, 2017: Transplant Infectious Disease: An Official Journal of the Transplantation Society
https://www.readbyqxmd.com/read/28412518/recipient-immune-modulation-with-atorvastatin-for-acute-graft-versus-host-disease-prophylaxis-after-allogeneic-transplantation
#14
Abraham S Kanate, Parameswaran N Hari, Marcelo C Pasquini, Alexis Visotcky, Kwang W Ahn, Jennifer Boyd, Guru Subramanian Guru Murthy, J Douglas Rizzo, Wael Saber, William Drobyski, Laura Michaelis, Ehab Atallah, Karen S Carlson, Anita D'Souza, Timothy S Fenske, Aaron Cumpston, Pamela Bunner, Michael Craig, Mary M Horowitz, Mehdi Hamadani
Atorvastatin administration to both the donors and recipients of matched related donor (MRD) allogeneic hematopoietic cell transplantation (allo-HCT) as acute graft-versus-host disease (GVHD) prophylaxis has been shown to be safe and effective. However, its efficacy as acute GVHD prophylaxis when given only to allo-HCT recipients is unknown. We conducted a phase II study to evaluate the safety and efficacy of atorvastatin-based acute GVHD prophylaxis given only to the recipients of MRD (n = 30) or matched unrelated donor (MUD) (n = 39) allo-HCT, enrolled in 2 separate cohorts...
April 12, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/28404894/induction-and-characterization-of-anti-tumor-endothelium-immunity-elicited-by-vallovax-therapeutic-cancer-vaccine
#15
Samuel C Wagner, Thomas E Ichim, Vladimir Bogin, Wei-Ping Min, Francisco Silva, Amit N Patel, Santosh Kesari
ValloVax is a placental endothelium derived vaccine which induces tissue-nonspecific antitumor immunity by blocking tumor angiogesis. To elucidate mechanisms of action, we showed that production of ValloVax, which involves treating placental endothelial cells with IFN-gamma, results in upregulation of HLA and costimulatory molecules. It was shown that in mixed lymphocyte reaction, ValloVax induces Type I cytokines and allo-proliferative responses. Plasma from ValloVax immunized mice was capable of killing in vitro tumor-like endothelium but not control endothelium...
April 25, 2017: Oncotarget
https://www.readbyqxmd.com/read/28344058/possible-impact-of-cytomegalovirus-specific-cd8-t-cells-on-immune-reconstitution-and-conversion-to-complete-donor-chimerism-after-allogeneic-stem-cell-transplantation
#16
Justyna Ogonek, Pavankumar Varanasi, Susanne Luther, Patrick Schweier, Wolfgang Kühnau, Gudrun Göhring, Elke Dammann, Michael Stadler, Arnold Ganser, Sylvia Borchers, Ulrike Koehl, Eva M Weissinger, Lothar Hambach
Complete donor chimerism is strongly associated with complete remission after allogeneic stem cell transplantation (allo-SCT) in patients with hematologic malignancies. Donor-derived allo-immune responses eliminate the residual host hematopoiesis and thereby mediate the conversion to complete donor chimerism. Recently, cytomegalovirus (CMV) reactivation was described to enhance overall T cell reconstitution, to increase graft-versus-host disease incidence, and to reduce the leukemia relapse risk. However, the link between CMV and allo-immune responses is still unclear...
March 23, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/28343935/blood-derived-products-in-pediatrics-new-laboratory-tools-for-optimizing-potency-assignment-and-reducing-side-effects
#17
REVIEW
Jean Amiral, Jerard Seghatchian
Neonates and children can develop rare bleeding disorders due to congenital/acquired coagulation Factor deficiencies, or allo-immune/autoimmune complications, or can undergo surgeries at high haemorrhagic risk. They then need specialized transfusion of blood components/products, or purified blood extracted products or recombinant proteins. Blood-derived therapies conventionally used for management of affected infants with genetic/acquired deficiencies, bleeding problems (coagulation Factor reduced or missing) or thrombotic disorders (reduced or missing anticoagulant proteins) pose some additional risks...
April 2017: Transfusion and Apheresis Science
https://www.readbyqxmd.com/read/28340805/association-between-hla-antibodies-and-different-sensitization-events-in-renal-transplant-candidates
#18
S U Akgul, H S Ciftci, S Temurhan, Y Caliskan, A Bayraktar, T Tefik, I A Kaya, I O Canitez, E Demir, H Yazici, H Bakkaloglu, A E Aydin, A Turkmen, I Nane, F Aydin, F S Oguz
BACKGROUND: Human leukocyte antigen (HLA) allo-immunization is caused by various events such as blood transfusions, pregnancies, or organ transplantations, which can lead to sensitization. In this retrospective study, we evaluated different sensitization models and their effects on panel-reactive antibody (PRA) profiles of renal transplantation candidates. METHODS: Anti-HLA class I/II antibody screening tests were performed in 906 renal transplantation candidates with the use of a microbead-based assay (Luminex)...
April 2017: Transplantation Proceedings
https://www.readbyqxmd.com/read/28298913/cathepsin-e-deficiency-ameliorates-graft-versus-host-disease-and-modifies-dendritic-cell-motility
#19
Jörg Mengwasser, Liane Babes, Steffen Cordes, Sarah Mertlitz, Katarina Riesner, Yu Shi, Aleixandria McGearey, Martina Kalupa, Thomas Reinheckel, Olaf Penack
Microbial products influence immunity after allogeneic hematopoietic stem cell transplantation (allo-SCT). In this context, the role of cathepsin E (Ctse), an aspartate protease known to cleave bacterial peptides for antigen presentation in dendritic cells (DCs), has not been studied. During experimental acute graft-versus-host disease (GVHD), we found infiltration by Ctse-positive immune cells leading to higher Ctse RNA- and protein levels in target organs. In Ctse-deficient allo-SCT recipients, we found ameliorated GVHD, improved survival, and lower numbers of tissue-infiltrating DCs...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28296584/intestinal-microbiota-and-relapse-after-hematopoietic-cell-transplantation
#20
Jonathan U Peled, Sean M Devlin, Anna Staffas, Melissa Lumish, Raya Khanin, Eric R Littmann, Lilan Ling, Satyajit Kosuri, Molly Maloy, John B Slingerland, Katya F Ahr, Kori A Porosnicu Rodriguez, Yusuke Shono, Ann E Slingerland, Melissa D Docampo, Anthony D Sung, Daniela Weber, Amin M Alousi, Boglarka Gyurkocza, Doris M Ponce, Juliet N Barker, Miguel-Angel Perales, Sergio A Giralt, Ying Taur, Eric G Pamer, Robert R Jenq, Marcel R M van den Brink
Purpose The major causes of mortality after allogeneic hematopoietic-cell transplantation (allo-HCT) are relapse, graft-versus-host disease (GVHD), and infection. We have reported previously that alterations in the intestinal flora are associated with GVHD, bacteremia, and reduced overall survival after allo-HCT. Because intestinal bacteria are potent modulators of systemic immune responses, including antitumor effects, we hypothesized that components of the intestinal flora could be associated with relapse after allo-HCT...
March 15, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
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