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https://www.readbyqxmd.com/read/28642760/interleukin-6-in-allogeneic-stem-cell-transplantation-its-possible-importance-for-immunoregulation-and-as-a-therapeutic-target
#1
REVIEW
Tor Henrik Anderson Tvedt, Elisabeth Ersvaer, Anders Aune Tveita, Øystein Bruserud
Allogeneic stem cell transplantation is associated with a high risk of treatment-related mortality mainly caused by infections and graft-versus-host disease (GVHD). GVHD is characterized by severe immune dysregulation and impaired regeneration of different tissues, i.e., epithelial barriers and the liver. The balance between pro- and anti-inflammatory cytokine influences the risk of GVHD. Interleukin-6 (IL-6) is a cytokine that previously has been associated with pro-inflammatory effects. However, more recent evidence from various autoimmune diseases (e...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28641651/-effect-of-infusion-of-recipient-spleen-cells-at-different-time-after-murine-haploidentical-hematopoietic-stem-cell-transplantation-on-graft-versus-host-disease
#2
Jun-Hui Wang, Lei Deng, Lu Wang, Chen Liang, Yi Wang, Tie-Qiang Liu, Shan Huang, Ya-Jing Huang, Bo Cai, Zheng Dong, Hong-Li Zuo, Qi-Yun Sun, Jian-Hui Qiao, Chang-Lin Yu, Kai-Xun Hu, Hui-Sheng Ai, Mei Guo
OBJECTIVE: To explore the effect of infusing G-CSF mobilized recipient spleen cells at different time after haploidentical stem cell transplantation(HSCT) on graft-versus-host disease (GVHD) in mice and its possible mechanism. METHODS: Forty mice after HSCT were randomly divided into 4 groups (n=10): GVHD positive control group (control group), 1st d recipient cell infusion group after transplantation (+1 d group), 4th d recipient cell infusion group after transplantation(+4 d group), 7th d recipient cell infusion group after transplantation(+7 d group)...
June 2017: Zhongguo Shi Yan Xue Ye Xue za Zhi
https://www.readbyqxmd.com/read/28641548/pediatric-cutaneous-graft-versus-host-disease-a-review
#3
Connie R Shi, Jennifer T Huang, Vinod E Nambudiri
BACKGROUND: Graft versus host disease (GVHD) is a significant complication following hematopoietic stem cell transplantation in the pediatric population. The most common clinical manifestation of GVHD is in the skin. This article will present a review of key concepts related to pediatric cutaneous GVHD, including pathophysiology, clinical epidemiology, diagnosis, and treatment options. GVHD is an immune-mediated process characterized by an inflammatory immune response in acute GVHD and mixed inflammatory and fibrotic states in chronic GVHD...
June 14, 2017: Current Pediatric Reviews
https://www.readbyqxmd.com/read/28638744/azacytidine-prevents-experimental-xenogeneic-graft-versus-host-disease-without-abrogating-graft-versus-leukemia-effects
#4
Grégory Ehx, Gilles Fransolet, Laurence de Leval, Stéphanie D'Hondt, Sophie Lucas, Muriel Hannon, Loïc Delens, Sophie Dubois, Pierre Drion, Yves Beguin, Stéphanie Humblet-Baron, Frédéric Baron
The demethylating agent 5-azacytidine (AZA) has proven its efficacy in the treatment of myelodysplastic syndrome and acute myeloid leukemia. In addition, AZA can demethylate FOXP3 intron 1 (FOXP3i1) leading to the generation of regulatory T cells (Treg). Here, we investigated the impact of AZA on xenogeneic graft-vs.-host disease (xGVHD) and graft-vs.-leukemia effects in a humanized murine model of transplantation (human PBMCs-infused NSG mice), and described the impact of the drug on human T cells in vivo...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28638739/ewing-sarcoma-partial-regression-without-gvhd-by-chondromodulin-i-hla-a-02-01-specific-allorestricted-t-cell-receptor-transgenic-t-cells
#5
Uwe Thiel, Sebastian J Schober, Ingo Einspieler, Andreas Kirschner, Melanie Thiede, David Schirmer, Katja Gall, Franziska Blaeschke, Oxana Schmidt, Susanne Jabar, Andreas Ranft, Rebeca Alba Rubío, Uta Dirksen, Thomas G P Grunewald, Poul H Sorensen, Günther H S Richter, Irene Teichert von Lüttichau, Dirk H Busch, Stefan E G Burdach
Background: Chondromodulin-I (CHM1) sustains malignancy in Ewing sarcoma (ES). Refractory ES carries a dismal prognosis and patients with bone marrow (BM) metastases do not survive irrespective of therapy. We assessed HLA-A*02:01/CHM1-specific allorestricted T cell receptor (TCR) wild-type and transgenic cytotoxic (CD8(+)) T cells against ES. Patients and Methods: Three refractory HLA-A2(+) ES patients were treated with HLA-A*02:01/peptide-specific allorepertoire-derived (i.e., allorestricted) CD8(+) T cells...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28637663/ny-eso-1-tcr-single-edited-central-memory-and-memory-stem-t-cells-to-treat-multiple-myeloma-without-inducing-gvhd
#6
Sara Mastaglio, Pietro Genovese, Zulma Magnani, Eliana Ruggiero, Elisa Landoni, Barbara Camisa, Giulia Schiroli, Elena Provasi, Angelo Lombardo, Andreas Reik, Nicoletta Cieri, Martina Rocchi, Giacomo Oliveira, Giulia Escobar, Monica Casucci, Bernhard Gentner, Antonello Spinelli, Anna Mondino, Attilio Bondanza, Luca Vago, Maurilio Ponzoni, Fabio Ciceri, Michael C Holmes, Luigi Naldini, Chiara Bonini
Transfer of T cell receptors (TCR) specific for tumor-associated antigens is a promising approach for cancer immunotherapy. We developed the TCR gene editing technology, that is based on the knockout of the endogenous TCR α and β genes, followed by the introduction of tumor-specific TCR genes, and that proved safer and more effective than conventional TCR gene transfer. While successful, complete editing requires extensive cell manipulation and four transduction procedures. Here we propose a novel and clinically feasible 'single TCR editing' (SE) approach, based on the disruption of the endogenous TCR α chain only, followed by the transfer of genes encoding for a tumor specific TCR...
June 21, 2017: Blood
https://www.readbyqxmd.com/read/28637512/single-or-double-unit-ucbt-following-ric-in-adults-with-al-a-report-from-eurocord-the-alwp-and-the-ctiwp-of-the-ebmt
#7
Frédéric Baron, Annalisa Ruggeri, Eric Beohou, Myriam Labopin, Mohamad Mohty, Didier Blaise, Jan J Cornelissen, Patrice Chevallier, Guillermo Sanz, Eefke Petersen, Bipin N Savani, Eliane Gluckman, Arnon Nagler
BACKGROUND: The feasibility of cord blood transplantation (CBT) in adults is limited by the relatively low number of hematopoietic stem/progenitor cells contained in one single CB unit. The infusion of two CB units from different partially HLA-matched donors (double CBT) is frequently performed in patients who lack a sufficiently rich single CB unit. METHODS: We compared CBT outcomes in patients given single or double CBT following reduced-intensity conditioning (RIC) in a retrospective multicenter registry-based study...
June 21, 2017: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/28636890/memory-t-cells-a-helpful-guard-for-allogeneic-hematopoietic-stem-cell-transplantation-without-causing-graft-versus-host-disease
#8
REVIEW
Wei Huang, Nelson J Chao
Graft-versus-host disease (GVHD) is a major complication of allogeneic hematopoietic stem cell transplantation (AHSCT) and the major cause of nonrelapse morbidity and mortality of AHSCT. In AHSCT, donor T cells facilitate hematopoietic stem cell (HSC) engraftment, contribute to anti-infection immunity, and mediate graft-versus-leukemia (GVL) responses. However, activated alloreactive T cells also attack recipient cells in vital organs, leading to GVHD. Different T-cell subsets, including naïve T (TN) cells, memory T (TM) cells, and regulatory T (Treg) cells mediate different forms of GVHD and GVL; TN cells mediate severe GVHD, whereas TM cells do not cause GVHD, but preserve T-cell function including GVL...
June 13, 2017: Hematology/oncology and Stem Cell Therapy
https://www.readbyqxmd.com/read/28635677/t-cell-manipulation-strategies-to-prevent-graft-versus-host-disease-in-haploidentical-stem-cell-transplantation
#9
REVIEW
Jayakumar Vadakekolathu, Sergio Rutella
Allogeneic haematopoietic stem cell transplantation (HSCT) from an human leukocyte antigen (HLA)-identical donor can be curative for eligible patients with non-malignant and malignant haematological disorders. HSCT from alternative donor sources, such as HLA-mismatched haploidentical donors, is increasingly considered as a viable therapeutic option for patients lacking HLA-matched donors. Initial attempts at haploidentical HSCT were associated with vigorous bidirectional alloreactivity, leading to unacceptably high rates of graft rejection and graft-versus-host disease (GVHD)...
June 21, 2017: Biomedicines
https://www.readbyqxmd.com/read/28632323/clinical-outcomes-of-hla-dpb1-mismatches-in-10-10-hla-matched-unrelated-donor-recipient-pairs-undergoing-allogeneic-stem-cell-transplant
#10
Ann M Moyer, Shahrukh K Hashmi, Cynthia M Kroning, Walter K Kremers, Steven R De Goey, Mrinal Patnaik, Mark Litzow, Dennis A Gastineau, William J Hogan, Eapen K Jacob, Justin D Kreuter, Laurie L Wakefield, Manish J Gandhi
OBJECTIVE: HLA-DPB1 matching may impact allogeneic hematopoietic stem cell transplantation (ASCT) outcomes; however, this locus is not in linkage disequilibrium with the remainder of the HLA genes. After classifying HLA-DPB1 mismatches based on T-cell epitope, avoiding non-permissive mismatches may impact survival. We tested this hypothesis at a single academic institution. METHODS: Retrospective HLA-DPB1 genotyping was performed on 153 adult patients who underwent ASCT and unrelated donors matched for HLA-A, B, C, DRB1 and DQB1 loci (10/10)...
June 20, 2017: European Journal of Haematology
https://www.readbyqxmd.com/read/28632322/reduced-intensity-conditioning-allogeneic-transplantation-after-salvage-treatment-with-dt-pace-in-myeloma-patients-relapsing-early-after-autologous-transplant
#11
K Randall, M Kaparou, E Xenou, S Paneesha, B Kishore, A Kanellopoulos, R Lovell, K Holder, J Suhr, L Baker, L Ryan, E Nikolousis
OBJECTIVE: In this retrospective single center study we have looked into the transplant outcomes(overall survival OS, progression free survival PFS,GvHD) and the role of chimerism, DLI and pre-transplant characteristics in patients who had a suboptimal response (<12 months)to an autologous stem cell transplant for myeloma and underwent an Alemtuzumab T-cell depleted reduced intensity allograft(RIC). METHODS: 24 patients were salvaged with 2 cycles of DT-PACE and received a RIC transplant with Fludarabine, Melphalan and Alemtuzumab...
June 20, 2017: European Journal of Haematology
https://www.readbyqxmd.com/read/28631269/missing-hla-c-group-1-ligand-in-patients-with-aml-and-mds-is-associated-with-reduced-risk-of-relapse-and-better-survival-after-allogeneic-stem-cell-transplantation-with-fludarabine-and-treosulfan-reduced-toxicity-conditioning
#12
Avichai Shimoni, Luca Vago, Massimo Bernardi, Ronit Yerushalmi, Jacopo Peccatori, Raffaella Greco, Noga Shem-Tov, Alessandro Lo Russo, Ivetta Danylesko, Arie Apel, Chiara Bonini, Maria Teresa Lupo Stanghellini, Arnon Nagler, Fabio Ciceri
Reduced-toxicity conditioning with fludarabine and treosulfan is a dose-intensive regimen with enhanced anti-leukemia effect and acceptable toxicity in AML/MDS. HLA-C regulates natural-killer (NK) cell function by inhibiting Killer immunoglobulin-like receptors (KIR) and is divided into C1 and C2 epitopes. The missing-ligand theory suggests that missing recipient KIR ligands drives NK-alloreactivity after SCT, in the absence of HLA-mismatch by activating unlicensed donor NK cells. We analyzed SCT outcomes in 203 patients with AML/MDS, median age 58 years, given SCT from matched-siblings (n=97) or matched-unrelated donors (n=106), using two treosulfan doses (total 36 or 42 gr/m2)...
June 19, 2017: American Journal of Hematology
https://www.readbyqxmd.com/read/28629761/cytokines-for-the-induction-of-antitumor-effectors-the-paradigm-of-cytokine-induced-killer-cik-cells
#13
Elisa Cappuzzello, Roberta Sommaggio, Paola Zanovello, Antonio Rosato
Cytokine-Induced killer (CIK) cells are raising growing interest in cellular antitumor therapy, as they can be easily expanded with a straightforward and inexpensive protocol, and are safe requiring only GMP-grade cytokines to obtain very high amounts of cytotoxic cells. CIK cells do not need antigen-specific stimuli to be activated and proliferate, as they recognize and destroy tumor cells in an HLA-independent fashion through the engagement of NKG2D. In several preclinical studies and clinical trials, CIK cells showed a reduced alloreactivity compared to conventional T cells, even when challenged across HLA-barriers; only in a few patients, a mild GVHD occurred after treatment with allogeneic CIK cells...
June 3, 2017: Cytokine & Growth Factor Reviews
https://www.readbyqxmd.com/read/28628276/acute-myeloid-leukaemia-relapsing-after-allogeneic-haematopoietic-stem-cell-transplantation-prognostic-factors-and-impact-of-initial-therapy-of-relapse
#14
Andrew B M Lim, Cameron Curley, Chun Yew Fong, Ian Bilmon, Ashanka Beligaswatte, Duncan Purtill, Bartlomiej Getta, Anne Maree Johnston, Tasman Armytage, Marnie Collins, Kate Mason, Katherine Fielding, Matthew Greenwood, John Gibson, Mark Hertzberg, Matthew Wright, Ian Lewis, John Moore, David Curtis, Jeff Szer, Glen Kennedy, David Ritchie
AIMS: We sought to determine factors associated with overall survival from relapse (OSR) of acute myeloid leukaemia (AML) after allogeneic haematopoietic stem cell transplantation (alloHSCT), and the effect of first salvage therapy and subsequent GVHD on OSR. METHODS: Data on 386 patients from nine Australian centres with relapsed AML post-alloHSCT were collected retrospectively. OSR was calculated using the Kaplan-Meier method. Univariate and multivariate analyses were conducted using the logrank test and proportional hazards modelling respectively, and a prognostic index for OSR was derived from multivariate modelling...
June 19, 2017: Internal Medicine Journal
https://www.readbyqxmd.com/read/28628090/against-the-odds-haplo-cord-grafts-protect-from-gvhd-and-relapse
#15
H K Choe, K van Besien
No abstract text is available yet for this article.
June 19, 2017: Bone Marrow Transplantation
https://www.readbyqxmd.com/read/28628089/elevated-bone-marrow-eosinophil-count-is-associated-with-high-incidence-of-severe-acute-gvhd-after-allogeneic-hematopoietic-stem-cell-transplantation
#16
Y Shimomura, M Hara, H Hashimoto, T Ishikawa
Predicting severe acute GvHD (aGvHD) after allogeneic hematopoietic stem cell transplantation (HSCT) is challenging but critical. Mild aGvHD may have a favorable impact on relapse, whereas severe aGvHD is associated with poor outcomes. The aim of this study was to evaluate whether elevated eosinophil count in the bone marrow (BM) at 1 month after HSCT is associated with a high incidence of new and severe aGvHD. We enrolled 101 consecutive patients; median age was 50 years, and 50.5% patients were male. The median eosinophil concentration in BM at 1 month after HSCT was 1...
June 19, 2017: Bone Marrow Transplantation
https://www.readbyqxmd.com/read/28627425/a-multicenter-retrospective-analysis-stressing-importance-of-long-term-follow-up-after-hematopoietic-cell-transplantation-for-%C3%AE-thalassemia
#17
S Chaudhury, M Ayas, C Rosen, M Ma, M Viqaruddin, S Parikh, S Kharbanda, K Y Chiang, A Haight, M Bhatia, Gmt Guilcher, A Thompson, S Shenoy
Allogeneic hematopoietic cell transplantation (HCT) is curative in patients with β-thalassemia major. However, the majority of reports on HCT outcomes lack long-term follow-up data with the exception of single center reports. An international multicenter retrospective data collection and analysis was conducted in 176 β-Thalassemia patients who were 1 year or beyond after first HCT to evaluate follow up methods and outcomes at 7 centers- Median age at HCT was 5.5 years (range, 0.6- 18.5) and median follow-up was 7 years (range, 1-20)...
June 13, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/28627158/evaluation-of-serum-interleukin-21-and-hla-c1-polymorphism-in-pediatrician-hematopoietic-stem-cell-transplantation-for-early-diagnosis-of-acute-graft-versus-host-disease
#18
N Sehati, P Kokhaei, A Motevalizade Ardekani, R Tootoonchian, F Pak
Background: Allogenic hematopoietic stem cell transplantation (HSCT) is a strategy used for treatment of different malignant diseases. However, success of allo-HSCT can be hampered by graft-versus-host-disease (GVHD). Natural killer (NK) cells may play an important role in activating antigen presenting cells and subsequent activation of T cells. The main purpose of this study was the evaluation of IL-21, as a blood biomarker, for early detection of acute GVHD (aGVHD) in children after HSCT and also the study of human leukocytes antigen (HLA)-C1 polymorphism, as a targeting ligand for NK cells in these patients...
June 19, 2017: Iranian Biomedical Journal
https://www.readbyqxmd.com/read/28626936/a-pilot-study-comparing-histological-and-immunophenotypic-patterns-in-stage-4-skin-graft-versus-host-disease-from-toxic-epidermal-necrolysis
#19
Haley Naik, Stephen Lockwood, Arturo Saavedra
Since the inception of bone marrow transplantation, clinicians have sought to distinguish stage 4 skin graft versus host disease (GVHD) from toxic epidermal necrolysis (TEN).(1-3) In certain contexts, it can be difficult to discern among these two entities, both clinically and histologically. However, the distinction is critical because both diseases can be life-threatening and their respective management and prognosis differ.
June 19, 2017: Journal of Cutaneous Pathology
https://www.readbyqxmd.com/read/28624476/measuring-immune-response-to-commonly-used-vaccinations-in-adult-recipients-of-allogeneic-hematopoietic-cell-transplantation
#20
REVIEW
Lucy Boyce Kennedy, Zhuoyan Li, Bipin N Savani, Per Ljungman
Recipients of hematopoietic cell transplantation are at risk for potentially preventable infectious complications due to defects in humoral and cell-mediated immunity. Studies of vaccine immunogenicity in HCT recipients have shown that antibody response rates depend on age, the type of vaccine, and presence or absence of GVHD. However, there are few large-scale studies assessing the immune response to vaccination in HCT recipients. Additionally, HCT recipients have much higher rates of potentially preventable infections compared to the general population even after vaccination...
June 14, 2017: Biology of Blood and Marrow Transplantation
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