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Acute graft versus host disease

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https://www.readbyqxmd.com/read/28428057/natural-killer-cells-differentiated-in-vitro-from-cord-blood-cd34-cells-are-more-advantageous-for-use-as-an-immunotherapy-than-peripheral-blood-and-cord-blood-natural-killer-cells
#1
Anna Domogala, Michael Blundell, Adrian Thrasher, Mark W Lowdell, J Alejandro Madrigal, Aurore Saudemont
BACKGROUND AIMS: Natural killer (NK) cells have the potential to become a successful immunotherapy as they can target malignant cells without being direct effectors of graft-versus-host disease. Our group has previously shown that large numbers of functional NK cells can be differentiated in vitro from umbilical cord blood (CB) CD34(+) cells. To produce a clinically relevant and effective immunotherapy, we hypothesized that it is essential that the NK cells are able to proliferate and persist in vivo while maintaining an optimal activation status and killing capacity...
April 17, 2017: Cytotherapy
https://www.readbyqxmd.com/read/28427167/dynamic-changes-in-serum-cytokine-levels-and-their-clinical-significance-in-predicting-acute-gvhd
#2
Chunyan Zhang, Wenrong Huang, Pengjun Zhang, Qingyi Zhang, Guanghong Guo, Feng Gu, Hua Yang, Yurong Wang, Xueliang Huang, Qian Jia, Yaping Tian
To explore the clinical significance of cytokines and biochemical tests in acute graft-versus-host disease (aGVHD), we detected the concentrations of 8 cytokines and 19 conventional biochemical markers in the sera of aGVHD and non-GVHD patients throughout the process of allogeneic hematopoietic stem cell transplantation and the onset of aGVHD. Predictive models were then established using the 27 indices, and models were verified by a prospective trial. The 27 indices showed significant differences between aGVHD patients and non-GVHD control subjects (two-tailed p<0...
February 25, 2017: Oncotarget
https://www.readbyqxmd.com/read/28424327/rig-i-mavs-and-sting-signaling-promote-gut-integrity-during-irradiation-and-immune-mediated-tissue-injury
#3
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/28423578/endothelial-microparticles-delivering-microrna-155-into-t-lymphocytes-are-involved-in-the-initiation-of-acute-graft-versus-host-disease-following-allogeneic-hematopoietic-stem-cell-transplantation
#4
Ran Zhang, Xiaoxiao Wang, Mei Hong, Ting Luo, Miaomiao Zhao, Haorui Shen, Jun Fang, Xiaojie Li, Sibin Zang, Ping Chen, Dimin Nie, Peng Zheng, Qiuling Wu, Linghui Xia
Endothelial microparticles (EMPs) upregulation has been observed in acute graft-versus-host disease (aGVHD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT). However, the role of EMPs remains unclear. We found that EMPs derived from TNF-α-stimulated human umbilical vein endothelial cells (EA.hy926) concentrated more microRNA-155 (miR-155) compared with maternal cells. The miR-155 levels in MPs from peripheral blood of aGVHD patients and mice were remarkably elevated and significantly higher than the levels in plasma...
April 4, 2017: Oncotarget
https://www.readbyqxmd.com/read/28419210/dasatinib-use-and-risk-of-cytomegalovirus-reactivation-after-allogeneic-hematopoietic-cell-transplantation
#5
Daniel P Prestes, Esther Arbona, Alexandra Nevett-Fernandez, Ann E Woolley, Vincent T Ho, Sophia Koo, Lindsey R Baden, John Koreth, Sarah P Hammond, Nicolas C Issa, Francisco M Marty
Viral infections have been reported with dasatinib use, but its cytomegalovirus risk after hematopoietic-cell transplantation (HCT) is not known. We found that post-HCT dasatinib use increased the risk of cytomegalovirus reactivation (adjusted hazard ratio 7.65; 95% CI, 1.84-31.7), controlling for acute graft-versus-host disease, in 109 patients with Philadelphia-chromosome-positive malignancies.
April 13, 2017: Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
https://www.readbyqxmd.com/read/28413062/assessment-of-mucosal-integrity-by-quantifying-neutrophil-granulocyte-influx-in-murine-models-of-acute-intestinal-injury
#6
Julius Clemens Fischer, Alexander Wintges, Tobias Haas, Hendrik Poeck
Intact epithelial body surfaces represent physical barriers which protect the organism from invading pathogens and loss of nutrients. Barrier malfunction is closely linked to disorders such as inflammatory bowel disease and graft-versus-host disease. In fact, several pharmacological or radiobiological therapeutic strategies have side effects that affect epithelial surfaces. In this context, assays that accurately assess epithelial barrier integrity in patients and animal models are crucial to create a better understanding of the mechanisms leading to disease or limiting therapeutic approaches due to barrier disruption...
April 11, 2017: Cellular Immunology
https://www.readbyqxmd.com/read/28412518/recipient-immune-modulation-with-atorvastatin-for-acute-graft-versus-host-disease-prophylaxis-following-allogeneic-transplantation
#7
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 two separate cohorts...
April 12, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/28405514/regulatory-b-cells-promote-graft-versus-host-disease-prevention-and-maintain-graft-versus-leukemia-activity-following-allogeneic-bone-marrow-transplantation
#8
Yue Hu, Gan-Lin He, Xiang-Yu Zhao, Xiao-Su Zhao, Yu Wang, Lan-Ping Xu, Xiao-Hui Zhang, Xue-Zhong Yu, Kai-Yan Liu, Ying-Jun Chang, Xiao-Jun Huang
Regulatory B cells (Bregs) are involved in the pathogenesis of graft-versus-host disease (GVHD). However, whether Bregs can alleviate acute GVHD without compromising graft-versus-leukemia (GVL) effects remains unclear. Here, we evaluated the role of Bregs in acute GVHD and GVL activity in both a mouse model and a clinical cohort study. In the acute GVHD mouse model, co-transplantation of Bregs prevents onset through inhibiting Th1 and Th17 differentiation and expanding regulatory T cells. In the GVL mouse model, Bregs contributed to the suppression of acute GVHD but had no adverse effect on GVL activity...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28405499/combining-therapeutic-antibodies-using-basiliximab-and-etanercept-for-severe-steroid-refractory-acute-graft-versus-host-disease-a-multi-center-prospective-study
#9
Yamin Tan, Haowen Xiao, Depei Wu, Yi Luo, Jianping Lan, Qifa Liu, Kang Yu, Jimin Shi, Jingsong He, Weiyan Zheng, Xiaoyu Lai, Yuanyuan Zhu, Kaili Du, Yishan Ye, Yanmin Zhao, Gaofeng Zheng, Yongxian Hu, Xiaoyan Han, Yanlong Zheng, Guoqing Wei, Zhen Cai, He Huang
Acute graft versus host disease (aGVHD) remains a major problem after allogeneic hematopoietic stem cell transplantation. Standard frontline therapy for aGVHD involves corticosteroids. However, fewer than half of patients have a lasting complete response. The long-term mortality rate of steroid-refractory aGVHD (SR-aGVHD) remains around 70%. To date, no consensus has been reached regarding the optimal salvage treatment for SR-aGVHD. We performed the first prospective, multi-center clinical trial to assess the efficacy and safety of a novel approach to treat severe (grades III-IV) SR-aGVHD with the combination of basiliximab and etanercept...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28401745/hypocellular-acute-myeloid-leukemia-treated-with-bone-marrow-transplantation
#10
Dai Keino, Kensuke Kondoh, Ryo Ohyama, Mizuho Morimoto, Tetsuya Mori, Masafumi Ito, Akitoshi Kinoshita
Hypocellular acute myeloid leukemia (AML) mainly occurs in elderly patients, and is extremely rare in childhood. There is still no established treatment for hypocellular AML. We report the case of an 11-year-old boy with hypocellular AML who was treated successfully with allogenic bone marrow transplantation (allo-BMT). He presented with fever, pallor and pancytopenia. Bone marrow aspiration and biopsy confirmed a diagnosis of hypocellular AML. Although low-dose cytarabine induced reduction of blasts, it did not lead to complete remission...
April 2017: Pediatrics International: Official Journal of the Japan Pediatric Society
https://www.readbyqxmd.com/read/28399164/sequential-monitoring-of-lymphocyte-subsets-and-of-t-and-b-cell-neogenesis-indexes-to-identify-time-varying-immunologic-profiles-in-relation-to-graft-versus-host-disease-and-relapse-after-allogeneic-stem-cell-transplantation
#11
Cristina Skert, Simone Perucca, Marco Chiarini, Viviana Giustini, Alessandra Sottini, Claudia Ghidini, Stefano Martellos, Federica Cattina, Benedetta Rambaldi, Valeria Cancelli, Michele Malagola, Alessandro Turra, Nicola Polverelli, Simona Bernardi, Luisa Imberti, Domenico Russo
T and B lymphocyte subsets have been not univocally associated to Graft-versus-host disease (GVHD) and relapse of hematological malignancies after stem cell transplantation (SCT). Their sequential assessment together with B and T cell neogenesis indexes has been not thoroughly analysed in relation to these changing and interrelated immunologic/clinic events yet. Lymphocyte subsets in peripheral blood (PB) and B and T cell neogenesis indexes were analysed together at different time points in a prospective study of 50 patients...
2017: PloS One
https://www.readbyqxmd.com/read/28396159/a-time-to-event-model-for-acute-kidney-injury-after-reduced-intensity-conditioning-stem-cell-transplantation-using-a-tacrolimus-and-sirolimus-based-graft-versus-host-disease-prophylaxis
#12
Jose Luis Piñana, Alejandro Perez-Pitarch, Irene Garcia-Cadenas, Pere Barba, Juan Carlos Hernandez-Boluda, Albert Esquirol, María Laura Fox, María José Terol, Josep M Queraltó, Jaume Vima, David Valcarcel, Rafael Ferriols-Lisart, Jorge Sierra, Carlos Solano, Rodrigo Martino
There is a paucity of data evaluating acute kidney injury (AKI) incidence and its relationship with the tacrolimus-sirolimus (Tac-Sir) concentrations in the setting of reduced intensity conditioning after allogeneic stem cell transplantation (RIC-allo-HSCT). This multicenter retrospective study evaluated risk factors of AKI defined by two classification systems (KDIGO score and "Grade 0-3 staging") in 186 consecutive RIC-allo-HSCT recipients with Tac-Sir as graft-versus-host disease prophylaxis. Conditioning regimens consisted of fludarabine and busulfan (n=53), or melphalan (n=83), or a combination of thiotepa, fludarabine and busulfan (n=50)...
April 7, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/28395942/ex-vivo-t-cell-depleted-allogeneic-stem-cell-transplantation-for-hematologic-malignancies-the-search-for-an-optimum-transplant-t-cell-dose-and-t-cell-add-back-strategy
#13
Prathima Anandi, Xin Tian, Sawa Ito, Pawel Muranski, Puja D Chokshi, Noelle Watters, Upneet Chawla, Nancy Hensel, David F Stroncek, Minoo Battiwalla, A John Barrett
BACKGROUND: T-cell depletion (TCD) of allogeneic stem cell transplants (SCT) can reduce graft-versus-host disease but may negatively affect transplant outcome by delaying immune recovery. To optimize TCD in HLA-matched siblings with hematologic malignancies, we explored varying the transplant CD3+ T-cell dose between 2 and 50 × 10(4)/kg (corresponding to 3-4 log depletion) and studied the impact of 0-6 × 10(7)/kg CD3+ donor lymphocyte infusion (DLI) "add-back" on immune recovery post-SCT...
April 7, 2017: Cytotherapy
https://www.readbyqxmd.com/read/28395546/post-transplant-cyclophosphamide-a-promising-anti-graft-versus-host-disease-prophylaxis-where-do-we-stand
#14
Alberto Mussetti, Raffaella Greco, Jacopo Peccatori, Paolo Corradini
Post transplant cyclophosphamide (PT/Cy) in association to other immunosuppressive agents or alone has emerged as a promising pharmacological strategy in the setting of allogeneic hematopoietic cell transplant (allo-HCT). Its safety profile and effectiveness in reducing GvHD (acute GvHD incidence comprised between 15 and 30%, chronic GvHD 20-30% in the haploidentical setting) contributed to the spreading of this technique all over the world. Areas covered: This review summarizes the use of PT/Cy in the setting of allo-HCT, both for oncological and non-malignant hematological diseases...
April 11, 2017: Expert Review of Hematology
https://www.readbyqxmd.com/read/28395445/-clinical-efficacy-of-recombinant-activated-factor-%C3%A2-a-for-16-hematonosis-with-moderate-or-severe-bleeding
#15
F Yang, L J Kong, J W Hu, N Liu, Y F Su, Y H Li, J L Chen, Z Y Yu, Z Q Qiao, Q H Wang, M Jiang
Objective: To analyze the efficacy of recombinant activated factor Ⅶ a (rF Ⅶ a) on hematonosis with moderate or severe bleeding signs. Methods: Of total 16 cases with rF Ⅶ a treatment from May 2013 to May 2016, 8 cases received allogeneic hematopoietic stem cells transplantation (allo-HSCT) and the other were non-transplantation patients. In two groups, there was no significant difference on rF Ⅶ a usage and dosage. 15 patients with acute graft-versus-host disease (aGVHD) after allo-HSCT were control group (without rF Ⅶ a) ...
March 14, 2017: Zhonghua Xue Ye Xue za Zhi, Zhonghua Xueyexue Zazhi
https://www.readbyqxmd.com/read/28392786/expression-of-serum-micrornas-is-altered-during-acute-graft-versus-host-disease
#16
Rachel E Crossland, Jean Norden, Mateja Kralj Juric, Kile Green, Kim F Pearce, Clare Lendrem, Hildegard T Greinix, Anne M Dickinson
Acute graft-versus-host disease (aGvHD) is the most frequent and serious complication following hematopoietic stem cell transplantation (HSCT), with a high mortality rate. A clearer understanding of the molecular pathogenesis may allow for improved therapeutic options or guide personalized prophylactic protocols. Circulating microRNAs are expressed in body fluids and have recently been associated with the etiology of aGvHD, but global expression profiling in a HSCT setting is lacking. This study profiled expression of n = 799 mature microRNAs in patient serum, using the NanoString platform, to identify microRNAs that showed altered expression at aGvHD diagnosis...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28390986/pericardial-effusion-following-hematopoietic-cell-transplantation-in-children-is-associated-with-increased-risk-of-mortality
#17
Kelly Cox, Rajesh Punn, Elizabeth Schnorr, Benjamin A Pinsky, Sandhya Kharbanda
Hematopoietic cell transplantation (HCT) is curative for many pediatric malignant and non-malignant disorders, but is associated with significant morbidity and mortality, including development of pericardial effusion (PEF). We report the results of a retrospective chart review performed to assess the incidence, risk factors and prognostic effect of PEF in the pediatric HCT patients at Lucile Packard Children's Hospital (LPCH), Stanford University. One hundred and nineteen patients receiving HCT between January of 2010 through December of 2013 were selected through the LPCH Pediatric Stem Cell Transplant Program database...
April 5, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/28389255/relative-telomere-length-prior-to-hematopoietic-cell-transplantation-hct-and-outcome-after-unrelated-donor-hct-for-acute-leukemia
#18
Youjin Wang, Tao Wang, Casey Dagnall, Michael Haagenson, Stephen R Spellman, Belynda Hicks, Kristine Jones, Stephanie J Lee, Sharon A Savage, Shahinaz M Gadalla
Telomeres are tandem nucleotide repeats and a protein complex located at the end of the chromosomes maintaining genomic stability. Their potential as a predictive biomarker for outcomes after allogeneic hematopoietic cell transplant (HCT) in hematologic malignancies is still unclear. From the Center for International Blood and Marrow Transplant Research (CIBMTR), we randomly selected 536 acute leukemia (AL) patients from those who underwent myeloablative 8/8 HLA-matched unrelated donor HCT between 2005 and 2012, and who had an available pre-HCT blood sample in the repository...
April 4, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/28387928/efficacy-and-feasibility-of-sorafenib-as-a-maintenance-agent-after-allogeneic-hematopoietic-stem-cell-transplantation-for-fms-like-tyrosine-kinase-3-mutated-acute-myeloid-leukemia
#19
Giorgia Battipaglia, Annalisa Ruggeri, Radwan Massoud, Jean El Cheikh, Matthieu Jestin, Ahmad Antar, Syed Osman Ahmed, Walid Rasheed, Marwan Shaheen, Ramdane Belhocine, Eolia Brissot, Remy Dulery, Sandra Eder, Federica Giannotti, Francoise Isnard, Simona Lapusan, Marie-Therese Rubio, Anne Vekhoff, Mahmoud Aljurf, Ollivier Legrand, Mohamad Mohty, Ali Bazarbachi
BACKGROUND: Sorafenib has shown encouraging results in patients with Fms-like tyrosine kinase 3 (FLT3)-positive acute myeloid leukemia. Its role after allogeneic stem cell transplantation (HSCT) has been reported in a few cases with encouraging results. METHODS: The authors describe the use of sorafenib as a maintenance agent after HSCT in 27 patients with FLT3-positive acute myeloid leukemia. RESULTS: The median age of the patients was 46 years (range, 15-57 years)...
April 7, 2017: Cancer
https://www.readbyqxmd.com/read/28384840/causal-inference-in-survival-analysis-using-pseudo-observations
#20
Per K Andersen, Elisavet Syriopoulou, Erik T Parner
Causal inference for non-censored response variables, such as binary or quantitative outcomes, is often based on either (1) direct standardization ('G-formula') or (2) inverse probability of treatment assignment weights ('propensity score'). To do causal inference in survival analysis, one needs to address right-censoring, and often, special techniques are required for that purpose. We will show how censoring can be dealt with 'once and for all' by means of so-called pseudo-observations when doing causal inference in survival analysis...
April 6, 2017: Statistics in Medicine
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