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https://www.readbyqxmd.com/read/29691600/a-proinflammatory-cd4-t-cell-phenotype-in-gestational-diabetes-mellitus
#1
Angela Sheu, Yixian Chan, Angela Ferguson, Mohammad B Bakhtyari, Wendy Hawke, Chris White, Yuk Fun Chan, Patrick J Bertolino, Heng G Woon, Umaimainthan Palendira, Frederic Sierro, Sue Mei Lau
AIMS/HYPOTHESIS: Numerous adaptations of the maternal immune system are necessary during pregnancy to maintain immunological tolerance to the semi-allogeneic fetus. Several complications of pregnancy have been associated with dysregulation of these adaptive mechanisms. While gestational diabetes mellitus (GDM) has been associated with upregulation of circulating inflammatory factors linked to innate immunity, polarisation of the adaptive immune system has not been extensively characterised in this condition...
April 24, 2018: Diabetologia
https://www.readbyqxmd.com/read/29691471/baricitinib-induced-blockade-of-interferon-gamma-receptor-and-interleukin-6-receptor-for-the-prevention-and-treatment-of-graft-versus-host-disease
#2
Jaebok Choi, Matthew L Cooper, Karl Staser, Kidist Ashami, Kiran R Vij, Bing Wang, Lynne Marsala, Jessica Niswonger, Julie Ritchey, Bader Alahmari, Samuel Achilefu, Ikuo Tsunoda, Mark A Schroeder, John F DiPersio
The therapeutic benefits of allogeneic hematopoietic stem cell transplantation (allo-HSCT) are derived from the graft-versus-leukemia (GvL) effects of the procedure. There is a strong association between the GvL effects and graft-versus-host disease (GvHD), a major life-threatening complication of allo-HSCT. The limiting of GvHD while maintaining the GvL effect remains the goal of allo-HSCT. Therefore, identifying optimal therapeutic targets to selectively suppress GvHD while maintaining the GvL effects represents a significant unmet medical need...
April 2, 2018: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/29691342/human-cytomegalovirus-encodes-a-novel-flt3-receptor-ligand-necessary-for-hematopoietic-cell-differentiation-and-viral-reactivation
#3
Lindsey B Crawford, Jung Heon Kim, Donna Collins-McMillen, Byeong-Jae Lee, Igor Landais, Christine Held, Jay A Nelson, Andrew D Yurochko, Patrizia Caposio
The ability of human cytomegalovirus (HCMV) to reactivate from latent infection of hematopoietic progenitor cells (HPCs) is intimately linked to cellular differentiation. HCMV encodes UL7 that our group has shown is secreted from infected cells and induces angiogenesis. In this study, we show that UL7 is a ligand for Fms-like tyrosine kinase 3 receptor (Flt-3R), a well-known critical factor in HPC differentiation. We observed that UL7 directly binds Flt-3R and induces downstream signaling cascades, including phosphatidylinositol 3-kinase (PI3K)/Akt and mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) pathways...
April 24, 2018: MBio
https://www.readbyqxmd.com/read/29691200/crispr-cas9-genome-editing-fueling-the-revolution-in-cancer-immunotherapy
#4
REVIEW
Xiaojun Liu, Yangbing Zhao
The development of genomic editing technologies expands the landscape of T cell engineering for adoptive cell therapy. Among the multiple tools that can be used, CRISPR/Cas9 has been shown to be relatively easy to use, simple to design and cost effective with highly efficient multiplex genome engineering capabilities. Allogeneic universal chimeric antigen receptor (CAR) T cells can be produced by disrupting T cell receptor (TCR) and beta-2-microglobulin (B2M) in CAR T cells or by directly knocking in a CAR at the disrupted TRAC locus...
April 21, 2018: Current Research in Translational Medicine
https://www.readbyqxmd.com/read/29690909/targeting-chemotherapy-resistant-leukemia-by-combining-dnt-cellular-therapy-with-conventional-chemotherapy
#5
Branson Chen, Jong Bok Lee, Hyeonjeong Kang, Mark D Minden, Li Zhang
BACKGROUND: While conventional chemotherapy is effective at eliminating the bulk of leukemic cells, chemotherapy resistance in acute myeloid leukemia (AML) is a prevalent problem that hinders conventional therapies and contributes to disease relapse, and ultimately patient death. We have recently shown that allogeneic double negative T cells (DNTs) are able to target the majority of primary AML blasts in vitro and in patient-derived xenograft models. However, some primary AML blast samples are resistant to DNT cell therapy...
April 24, 2018: Journal of Experimental & Clinical Cancer Research: CR
https://www.readbyqxmd.com/read/29688994/generation-of-immunodeficient-rats-with-rag1-and-il2rg-gene-deletions-and-human-tissue-grafting-models
#6
Séverine Ménoret, Laure-Hélène Ouisse, Laurent Tesson, Frédéric Delbos, Delphine Garnier, Séverine Remy, Claire Usal, Jean-Paul Concordet, Carine Giovannangeli, Vanessa Chenouard, Lucas Brusselle, Emmanuel Merieau, Véronique Nerrière-Daguin, Franck Duteille, Frédérique Bellier-Waast, Alexandre Fraichard, Tuan H Nguyen, Ignacio Anegon
BACKGROUND: Immunodeficient mice are invaluable tools to analyze the long-term effects of potentially immunogenic molecules in the absence of adaptive immune responses. Nevertheless, there are models and experimental situations that would beneficiate of larger immunodeficient recipients. Rats are ideally suited to perform experiments in which larger size is needed and are still a small animal model suitable for rodent facilities. Additionally, rats reproduce certain human diseases better than mice, such as ankylosing spondylitis and Duchenne disease and these disease models would greatly benefit of immunodeficient rats to test different immunogenic treatments...
April 23, 2018: Transplantation
https://www.readbyqxmd.com/read/29688266/anti-infective-vaccination-strategies-in-patients-with-hematologic-malignancies-or-solid-tumors-guideline-of-the-infectious-diseases-working-party-agiho-of-the-german-society-for-hematology-and-medical-oncology-dgho
#7
C T Rieger, B Liss, S Mellinghoff, D Buchheidt, O A Cornely, G Egerer, W J Heinz, M Hentrich, G Maschmeyer, K Mayer, M Sandherr, G Silling, A Ullmann, M J G T Vehreschild, M von Lilienfeld-Toal, H H Wolf, N Lehners
Infectious complications are a significant cause of morbidity and mortality in patients with malignancies specifically when receiving anticancer treatments. Prevention of infection through vaccines is an important aspect of clinical care of cancer patients. Immunocompromising effects of the underlying disease as well as of antineoplastic therapies need to be considered when devising vaccination strategies. This guideline provides clinical recommendations on vaccine use in cancer patients including autologous stem cell transplant recipients, while allogeneic stem cell transplantation is subject of a separate guideline...
April 24, 2018: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/29687881/relapse-in-teenage-and-young-adult-patients-treated-on-a-paediatric-minimal-residual-disease-stratified-all-treatment-protocol-is-associated-with-a-poor-outcome-results-from-ukall2003
#8
Rob S Sellar, Clare Rowntree, Ajay J Vora, Caroline L Furness, Nicholas Goulden, Chris Mitchell, Anthony V Moorman, Rachael Hough
Outcomes for teenage and young adult (TYA) patients with acute lymphoblastic leukaemia (ALL) who relapse on contemporary risk-adapted paediatric protocols are largely unknown and there is no consensus on optimal salvage strategies. We assessed the treatment and outcome of TYA patients (aged 16-24 years) recruited to the UKALL2003 trial, who relapsed following attainment of complete morphological remission. Forty-two of 223 patients (18·8%) relapsed, the majority (n = 26, 62%) on treatment. Thirty-eight (90%) patients received salvage treatment, with 22 (58%) achieving second remission (CR2) and 21 patients receiving an allogeneic haematopoietic cell transplant (alloHSCT)...
April 24, 2018: British Journal of Haematology
https://www.readbyqxmd.com/read/29687231/the-binding-of-an-anti-pd-1-antibody-to-fc%C3%AE-r%C3%AE-has-a-profound-impact-on-its-biological-functions
#9
Tong Zhang, Xiaomin Song, Lanlan Xu, Jie Ma, Yanjuan Zhang, Wenfeng Gong, Yilu Zhang, Xiaosui Zhou, Zuobai Wang, Yali Wang, Yingdi Shi, Huichen Bai, Ning Liu, Xiaolong Yang, Xinxin Cui, Yanping Cao, Qi Liu, Jing Song, Yucheng Li, Zhiyu Tang, Mingming Guo, Lai Wang, Kang Li
Antibodies targeting PD-1 have been demonstrated durable anti-cancer activity in certain cancer types. However, the anti-PD-1 antibodies are less or not efficacious in many situations, which might be attributed to co-expression of multiple inhibitory receptors or presence of immunosuppressive cells in the tumor microenvironment. Most of the anti-PD-1 antibodies used in clinical studies are of IgG4 isotype with the S228P mutation (IgG4S228P ). The functional impact by the interaction of anti-PD-1 IgG4S228P antibody with Fc gamma receptors (FcγRs) is poorly understood...
April 23, 2018: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/29687034/preclinical-efficacy-and-safety-evaluation-of-hematopoietic-stem-cell-gene-therapy-in-a-mouse-model-of-mngie
#10
Rana Yadak, Raquel Cabrera-Pérez, Javier Torres-Torronteras, Marianna Bugiani, Joost C Haeck, Marshall W Huston, Elly Bogaerts, Steffi Goffart, Edwin H Jacobs, Merel Stok, Lorena Leonardelli, Luca Biasco, Robert M Verdijk, Monique R Bernsen, George Ruijter, Ramon Martí, Gerard Wagemaker, Niek P van Til, Irenaeus F M de Coo
Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) is an autosomal recessive disorder caused by thymidine phosphorylase (TP) deficiency resulting in systemic accumulation of thymidine (d-Thd) and deoxyuridine (d-Urd) and characterized by early-onset neurological and gastrointestinal symptoms. Long-term effective and safe treatment is not available. Allogeneic bone marrow transplantation may improve clinical manifestations but carries disease and transplant-related risks. In this study, lentiviral vector-based hematopoietic stem cell gene therapy (HSCGT) was performed in Tymp -/- Upp1 -/- mice with the human phosphoglycerate kinase (PGK) promoter driving TYMP ...
March 16, 2018: Molecular Therapy. Methods & Clinical Development
https://www.readbyqxmd.com/read/29686677/mir-466a-targeting-of-tgf-%C3%AE-2-contributes-to-foxp3-regulatory-t-cell-differentiation-in-a-murine-model-of-allogeneic-transplantation
#11
William Becker, Mitzi Nagarkatti, Prakash S Nagarkatti
The promise of inducing immunological tolerance through regulatory T cell (Treg) control of effector T cell function is crucial for developing future therapeutic strategies to treat allograft rejection as well as inflammatory autoimmune diseases. In the current study, we used murine allograft rejection as a model to identify microRNA (miRNA) regulation of Treg differentiation from naïve CD4 cells. We performed miRNA expression array in CD4+ T cells in the draining lymph node (dLN) of mice which received syngeneic or allogeneic grafts to determine the molecular mechanisms that hinder the expansion of Tregs...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29685953/outcomes-of-medicare-age-eligible-nhl-patients-receiving-ric-allogeneic-transplantation-a-cibmtr-analysis
#12
Nirav N Shah, Kwang Woo Ahn, Carlos Litovich, Timothy S Fenske, Sairah Ahmed, Minoo Battiwalla, Nelli Bejanyan, Parastoo B Dahi, Javier Bolaños-Meade, Andy I Chen, Stefan O Ciurea, Veronika Bachanova, Zachariah DeFilipp, Narendranath Epperla, Nosha Farhadfar, Alex F Herrera, Bradley M Haverkos, Leona Holmberg, Nasheed M Hossain, Mohamed A Kharfan-Dabaja, Vaishalee P Kenkre, Hillard M Lazarus, Hemant S Murthy, Taiga Nishihori, Andrew R Rezvani, Anita D'Souza, Bipin N Savani, Matthew L Ulrickson, Edmund K Waller, Anna Sureda, Sonali M Smith, Mehdi Hamadani
The application of allogeneic hematopoietic cell transplantation (allo-HCT) in non-Hodgkin lymphoma (NHL) patients ≥65 years in the United States is limited by lack of Medicare coverage for this indication. Using the Center for International Blood and Marrow Transplant Research (CIBMTR) database, we report allo-HCT outcomes of NHL patients aged ≥65 years (older cohort; n = 446) compared with a cohort of younger NHL patients aged 55-64 years (n = 1183). We identified 1629 NHL patients undergoing a first reduced-intensity conditioning (RIC) or nonmyeloablative conditioning allo-HCT from 2008 to 2015 in the United States...
April 24, 2018: Blood Advances
https://www.readbyqxmd.com/read/29685874/impact-of-oral-side-effects-from-conditioning-therapy-before-hematopoietic-stem-cell-transplantation-protocol-for-a-multicenter-study
#13
Michael T Brennan, Bengt Hasséus, Allan J Hovan, Judith E Raber-Durlacher, Nicole Ma Blijlevens, Marie-Charlotte Huysmans, Karin Garming Legert, Jan-Erik Johansson, Charity G Moore, Inger von Bültzingslöwen
BACKGROUND: The oral cavity is a common site of complications related to the cytotoxic effect of high-dose chemotherapy and radiation therapy. Considering our limited understanding of the burden of illness in the oral cavity from various cytotoxic therapies, it is difficult to produce evidence-based, preventive and management protocols. A prospective multicenter study is necessary to collect data on the burden of illness from various cytotoxic regimens. OBJECTIVE: The objectives of this prospective international observational multicenter study in hematopoietic stem cell transplant (HSCT) patients are to establish the nature, incidence and temporal relationship of oral complications related to conditioning regimens (chemotherapy with or without total body irradiation), stem cell transplantation and the immunologic reactions (mainly graft-vs-host-disease) that may follow, and to determine what subjective and objective oral complications related to treatment can predict negative clinical and economic outcomes and reduced quality of life...
April 23, 2018: JMIR Research Protocols
https://www.readbyqxmd.com/read/29685460/adult-t-cell-leukemia-lymphoma-review-of-the-literature
#14
M J M Rodríguez-Zúñiga, F Cortez-Franco, E Qujiano-Gomero
Adult T-cell Leukemia/Lymphoma (ATLL) is an aggressive neoplasm of T lymphocytes associated with Human T-lymphotropic virus type1 (HTLV-1) infection. HTLV-1 is a public health problem because it is endemic in native groups in Latin America, and its infection leads to several chronic diseases as ATLL. We aimed to review current literature of ATLL in order to consider it as a differential diagnosis in front of patients with compatible symptoms. Prognosis is still poor in aggressive and indolent variants, with survival rates from months to few years...
April 20, 2018: Actas Dermo-sifiliográficas
https://www.readbyqxmd.com/read/29685455/62-year-old-man-with-encephalopathy-and-fatigue-after-allogeneic-bone-marrow-transplant
#15
Jack H Short, Ayan Sen
No abstract text is available yet for this article.
April 20, 2018: Mayo Clinic Proceedings
https://www.readbyqxmd.com/read/29685424/immunotherapy-for-the-treatment-of-hodgkin-lymphoma-an-evolving-paradigm
#16
REVIEW
Steven M Bair, Anthony Mato, Jakub Svoboda
Classical Hodgkin lymphoma (cHL) is one of the most common lymphomas in the Western world. Although most patients are cured with standard first-line therapy, up to 20% of patients will have relapsed or refractory disease. Although the conventional approach to treatment has consisted of chemotherapy, radiation, and for those who relapse, autologous or allogeneic transplantation, newer approaches have become available in recent years, including immunoconjugates and checkpoint inhibitors. These approaches have shown significant efficacy in clinical trials and might be associated with fewer long-term toxicities compared with conventional therapies...
March 31, 2018: Clinical Lymphoma, Myeloma & Leukemia
https://www.readbyqxmd.com/read/29684567/human-herpesvirus-6b-hhv-6b-reactivation-is-a-risk-factor-for-grade-2-4-acute-graft-versus-host-disease-agvhd-after-hematopoietic-stem-cell-transplantation-hct-a-systematic-review-and-meta-analysis
#17
REVIEW
Tuan L Phan, Kristen Carlin, Per Ljungman, Ioannis Politikos, Vicki Boussiotis, Michael Boeckh, Michele L Shaffer, Danielle M Zerr
BACKGROUND/OBJECTIVE: Graft-versus-host disease (GVHD) is an important cause of morbidity and mortality following allogeneic hematopoietic cell transplantation (HCT). Many studies have suggested that HHV-6B plays a role in acute GVHD (aGVHD) following HCT. Our objective was to systematically summarize and analyze evidence regarding HHV-6B reactivation and development of aGVHD. METHODS: PubMed and EMBASE databases were searched using terms for HHV-6, HCT, and aGVHD, yielding 865 unique results...
April 20, 2018: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/29684566/eltrombopag-for-the-treatment-of-of-refractory-pure-red-cell-aplasia-after-major-abo-incompatible-hematopoietic-stem-cell-transplantation
#18
Alessandro Busca, Chiara Dellacasa, Luisa Giaccone, Sara Manetta, Lucia Biale, Laura Godio, Semra Aydin, Moreno Festuccia, Lucia Brunello, Benedetto Bruno
Pure red cell aplasia (PRCS) is a well-recognized complication after allogeneic hematopoietic stem cell transplantation (HSCT). Many therapeutic options are available to treat this condition, including erythropoietin, rituximab, bortezomib, plasma exchange, immunoadsorption, donor lymphocyte infusion, mesenchymal stem cells, anti-thymocyte globulin and high-dose steroids; however treatment outcomes are often variable and can sometimes lead to disappointing results. In this brief article we report our experience with two patients with PRCA after major AB0-incompatible HSCT who were resistant to multiple therapeutic interventions and who eventually benefited from treatment with eltrombopag, a thrombopoietin mimetic approved by the Food and Drug Administration for the treatment of patients with immune thrombocytopenic purpura or severe aplastic anemia (SAA), refractory to immunosuppressive agents or not eligible to HSCT...
April 20, 2018: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/29684564/deep-npm1-sequencing-following-allogeneic-hematopoietic-cell-transplantation-improves-risk-assessment-in-adults-with-npm1-mutated-aml
#19
Yi Zhou, Megan Othus, Roland B Walter, Elihu H Estey, David Wu, Brent L Wood
Relapse is the major cause of death in patients with acute myeloid leukemia (AML) after allogeneic hematopoietic cell transplant (HCT). Measurable residual disease (MRD) detected by multiparameter flow cytometry (MFC) before and after HCT is a strong, independent risk factor for relapse. As next generation sequencing (NGS) is increasingly applied in AML MRD detection, it remains to be determined if NGS can improve prediction of post-HCT relapse. Herein, we investigated pre-HCT MRD detected by MFC and NGS in 59 adult patients with NPM1-mutated AML in morphologic remission; 45 of the 59 had post-HCT MRD determined by MFC and NGS around day 28...
April 20, 2018: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/29684563/long-term-results-of-prophylactic-donor-lymphocyte-infusions-for-patients-with-multiple-myeloma-after-allogeneic-stem-cell-transplantation
#20
Maximilian Gröger, Nico Gagelmann, Christine Wolschke, Ute-Marie von Pein, Evgeny Klyuchnikov, Max Christopeit, Axel Zander, Francis Ayuk, Nicolaus Kröger
OBJECTIVE: The major reason for treatment failure after allografting in multiple myeloma (MM) is relapse. Donor lymphocyte infusions are considered a valuable post-transplant strategy mainly for relapsed patients but using them to prevent relapse in MM has been reported rarely. In the present study we examined the efficacy of prophylactic donor lymphocyte infusions after allogeneic hematopoietic stem cell transplantation (allo-HSCT) in myeloma patients with a long-term follow-up of more than 5 years...
April 20, 2018: Biology of Blood and Marrow Transplantation
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