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ALLOGENEIC RESPONSE

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https://www.readbyqxmd.com/read/28338506/a-preliminary-report-radical-surgery-and-stem-cell-transplantation-for-the-treatment-of-patients-with-pancreatic-cancer
#1
Brigitta Omazic, Burcu Ayoglu, Matthias Löhr, Ralf Segersvärd, Caroline Verbeke, Isabelle Magalhaes, Zuzana Potacova, Jonas Mattsson, Alexei Terman, Sam Ghazi, Nils Albiin, Nikolaos Kartalis, Peter Nilsson, Thomas Poiret, Liu Zhenjiang, Rainer Heuchel, Jochen M Schwenk, Johan Permert, Markus J Maeurer, Olle Ringden
We examined the immunologic effects of allogeneic hematopoietic stem cell transplantation (HSCT) in the treatment of pancreatic ductal adenocarcinoma, a deadly disease with a median survival of 24 months for resected tumors and a 5-year survival rate of 6%. After adjuvant chemotherapy, 2 patients with resected pancreatic ductal adenocarcinoma underwent HSCT with HLA-identical sibling donors. Comparable patients who underwent radical surgery, but did not have a donor, served as controls (n=6). Both patients developed humoral and cellular (ie, HLA-A*01:01-restricted) immune responses directed against 2 novel tumor-associated antigens (TAAs), INO80E and UCLH3 after HSCT...
March 23, 2017: Journal of Immunotherapy
https://www.readbyqxmd.com/read/28335642/voriconazole-for-prophylaxis-of-invasive-fungal-infections-after-allogeneic-hematopoietic-stem-cell-transplantation
#2
David I Marks, Qifa Liu, Monica Slavin
Invasive fungal infections (IFIs) following allogeneic hematopoietic stem cell transplantation (alloHSCT) are associated with a high mortality, and accordingly most alloHSCT recipients receive prophylaxis with antifungal agents. Despite some improvement in outcomes of IFIs over time, they continue to represent substantial clinical risk, mortality, and financial burden. Areas covered: We review the main pathogens responsible for IFIs in recipients of alloHSCT, current treatment recommendations, and discuss clinical and economic considerations associated with voriconazole prophylaxis of IFIs in these patients...
March 24, 2017: Expert Review of Anti-infective Therapy
https://www.readbyqxmd.com/read/28334641/humanized-mouse-model-for-assessing-the-human-immune-response-to-xenogeneic-and-allogeneic-decellularized-biomaterials
#3
Raymond M Wang, Todd D Johnson, Jingjin He, Zhili Rong, Michelle Wong, Vishal Nigam, Atta Behfar, Yang Xu, Karen L Christman
Current assessment of biomaterial biocompatibility is typically implemented in wild type rodent models. Unfortunately, different characteristics of the immune systems in rodents versus humans limit the capability of these models to mimic the human immune response to naturally derived biomaterials. Here we investigated the utility of humanized mice as an improved model for testing naturally derived biomaterials. Two injectable hydrogels derived from decellularized porcine or human cadaveric myocardium were compared...
March 11, 2017: Biomaterials
https://www.readbyqxmd.com/read/28332214/serum-eye-drops-a-survey-of-international-production-methods
#4
D C Marks, P F van der Meer
BACKGROUND: Serum eye drops (SEDs) are used to treat dry eye syndrome and non-healing corneal lesions when other treatments fail. Despite many clinical studies demonstrating the efficacy of both autologous and allogeneic SEDs, there is no internationally harmonized method for producing SEDs. MATERIALS AND METHODS: A 40-question survey requesting information regarding donor selection, blood collection and processing, infectious disease screening, shelf life and regulatory requirements for the production of autologous and allogeneic SEDs was developed by the Biomedical Excellence for Safer Transfusion Collaborative...
March 23, 2017: Vox Sanguinis
https://www.readbyqxmd.com/read/28323004/fresh-or-cryopreserved-cd34-selected-mobilized-peripheral-blood-stem-and-progenitor-cells-for-the-treatment-of-poor-graft-function-following-allogeneic-hematopoietic-cell-transplantation
#5
Armin Ghobadi, Mark A Fiala, Giridharan Ramsingh, Feng Gao, Camille N Abboud, Keith Stockerl-Goldstein, Geoffrey L Uy, Brenda J Grossman, Peter Westervelt, John F DiPersio
CD34(+)-selected stem cell boost (SCB) without conditioning have recently been utilized for poor graft function (PGF) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) with promising results. Unfortunately, many patients have been unable to receive the boost infusion as their donors were unwilling or unable to undergo an additional stem cell collection. Therefore, we conducted this study utilizing either fresh or cryopreserved peripheral blood stem cell products to create CD34(+)-selected boost infusions for the treatment of PGF...
March 17, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/28321641/transformed-follicular-lymphoma-tfl-consolidation-therapy-may-improve-survival
#6
E Elhassadi, R Flavin, P Browne, E Conneally, P Hayden, F Quinn, E Higgins, E Vandenberghe
PURPOSE: Retrospective study to evaluate the outcome of patients with transformed follicular lymphoma (tFL) treated with rituximab-containing chemotherapy and consolidation. PATIENTS AND METHODS: Patients diagnosed with tFL from 2003 to 2013 treated with consolidation therapy with last follow-up in December 2015 were identified from the institutional lymphoma database and included in this study. Data collected included age, gender, stage, interval to tFL diagnosis, R-IPI score, histological diagnosis and therapy...
March 21, 2017: Irish Journal of Medical Science
https://www.readbyqxmd.com/read/28320826/biologic-scaffolds
#7
Alessandra Costa, Juan Diego Naranjo, Ricardo Londono, Stephen F Badylak
Biologic scaffold materials composed of allogeneic or xenogeneic extracellular matrix are commonly used for the repair and functional reconstruction of injured and missing tissues. These naturally occurring bioscaffolds are manufactured by the removal of the cellular content from source tissues while preserving the structural and functional molecular units of the remaining extracellular matrix (ECM). The mechanisms by which these bioscaffolds facilitate constructive remodeling and favorable clinical outcomes include release or creation of effector molecules that recruit endogenous stem/progenitor cells to the site of scaffold placement and modulation of the innate immune response, specifically the activation of an anti-inflammatory macrophage phenotype...
March 20, 2017: Cold Spring Harbor Perspectives in Medicine
https://www.readbyqxmd.com/read/28320635/safety-and-efficacy-of-multipotent-adult-progenitor-cells-in-acute-ischaemic-stroke-masters-a-randomised-double-blind-placebo-controlled-phase-2-trial
#8
David C Hess, Lawrence R Wechsler, Wayne M Clark, Sean I Savitz, Gary A Ford, David Chiu, Dileep R Yavagal, Ken Uchino, David S Liebeskind, Alexander P Auchus, Souvik Sen, Cathy A Sila, Jeffrey D Vest, Robert W Mays
BACKGROUND: Multipotent adult progenitor cells are a bone marrow-derived, allogeneic, cell therapy product that modulates the immune system, and represents a promising therapy for acute stroke. We aimed to identify the highest, well-tolerated, and safest single dose of multipotent adult progenitor cells, and if they were efficacious as a treatment for stroke recovery. METHODS: We did a phase 2, randomised, double-blind, placebo-controlled, dose-escalation trial of intravenous multipotent adult progenitor cells in 33 centres in the UK and the USA...
March 17, 2017: Lancet Neurology
https://www.readbyqxmd.com/read/28319080/adverse-impact-of-high-donor-cd3-cell-dose-on-outcome-following-tandem-auto-nma-allogeneic-transplantation-for-high-risk-myeloma
#9
A P Nair, P Walker, A Kalff, K Bergin, J Hocking, S Avery, D J Curtis, S Patil, T Das, D Klarica, S Morgan, J Muirhead, M Gorniak, J Reynolds, A Spencer
High-risk (HR) multiple myeloma (MM) has poor outcomes with conventional therapy. Tandem autologous-non-myeloablative (NMA) allogeneic stem cell transplantation (autologous stem cell transplantation (ASCT)-NMA allogeneic SCT) is potentially curative secondary to graft-versus-myeloma effect. We retrospectively analysed ASCT-NMA allogeneic SCT outcomes of 59 HR and relapsed MM patients. At a median follow-up of 35.8 months, the outcomes for HR-MM upfront tandem ASCT-NMA allogeneic SCT and standard-risk (SR) MM upfront ASCT alone were comparable (median PFS 1166 days versus 1465 days, P=0...
March 20, 2017: Bone Marrow Transplantation
https://www.readbyqxmd.com/read/28319046/t-cells-take-directions-from-supporting-cast-in-graft-versus-host-disease
#10
Derk Amsen
Allogeneic hematopoietic stem cell transplantation (HSCT) remains the only treatment option for several severe hematological malignancies. The development of graft-versus-host disease (GVHD) is a common complication of the procedure and results when donor T cells become activated against recipient-specific antigens. The factors that drive the alloreactive T cell response are not completely understood. In this issue of the JCI, Chung and colleagues present evidence that stromal cells within lymphoid tissue express the Notch ligands Delta-like 1/4 (DLL1 and DLL4), which in turn directly activate T cells...
March 20, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28319044/fibroblastic-niches-prime-t-cell-alloimmunity-through-delta-like-notch-ligands
#11
Jooho Chung, Christen L Ebens, Eric Perkey, Vedran Radojcic, Ute Koch, Leonardo Scarpellino, Alexander Tong, Frederick Allen, Sherri Wood, Jiane Feng, Ann Friedman, David Granadier, Ivy T Tran, Qian Chai, Lucas Onder, Minhong Yan, Pavan Reddy, Bruce R Blazar, Alex Y Huang, Todd V Brennan, D Keith Bishop, Burkhard Ludewig, Christian W Siebel, Freddy Radtke, Sanjiv A Luther, Ivan Maillard
Alloimmune T cell responses induce graft-versus-host disease (GVHD), a serious complication of allogeneic bone marrow transplantation (allo-BMT). Although Notch signaling mediated by Delta-like 1/4 (DLL1/4) Notch ligands has emerged as a major regulator of GVHD pathogenesis, little is known about the timing of essential Notch signals and the cellular source of Notch ligands after allo-BMT. Here, we have shown that critical DLL1/4-mediated Notch signals are delivered to donor T cells during a short 48-hour window after transplantation in a mouse allo-BMT model...
March 20, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28300028/comparison-of-allogeneic-and-syngeneic-rat-glioma-models-by-using-mri-and-histopathologic-evaluation
#12
Elena Biasibetti Alberto Valazza Maria T Capucchio Laura Annovazzi Luigi Battaglia Daniela Chirio Marina Gallarate Marta Mellai Elisabetta Muntoni Elena Peira Chiara Riganti Davide Schiffer Pierpaolo Panciani And Michele Lanotte
Research in neurooncology traditionally requires appropriate in vivo animal models, on which therapeutic strategies aretestedbefore human trials are designed and proceed. Several reproducible animal experimental models, in which human physiologic conditions can be mimicked, are available for studying glioblastoma multiforme. In an ideal rat model, the tumor is of glial origin,grows in predictable and reproducible patterns, closely resembles human gliomas histopathologically, and is weakly or nonimmunogenic...
March 15, 2017: Comparative Medicine
https://www.readbyqxmd.com/read/28297581/systemic-delivery-of-bone-marrow-mesenchymal-stem-cells-for-in-situ-intervertebral-disc-regeneration
#13
Carla Cunha, Catarina R Almeida, Maria Inês Almeida, Andreia M Silva, Maria Molinos, Sofia Lamas, Catarina L Pereira, Graciosa Q Teixeira, António T Monteiro, Susana G Santos, Raquel M Gonçalves, Mário A Barbosa
Cell therapies for intervertebral disc (IVD) regeneration presently rely on transplantation of IVD cells or stem cells directly to the lesion site. Still, the harsh IVD environment, with low irrigation and high mechanical stress, challenges cell administration and survival. In this study, we addressed systemic transplantation of allogeneic bone marrow mesenchymal stem cells (MSCs) intravenously into a rat IVD lesion model, exploring tissue regeneration via cell signaling to the lesion site. MSC transplantation was performed 24 hours after injury, in parallel with dermal fibroblasts as a control; 2 weeks after transplantation, animals were killed...
March 2017: Stem Cells Translational Medicine
https://www.readbyqxmd.com/read/28296584/intestinal-microbiota-and-relapse-after-hematopoietic-cell-transplantation
#14
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
https://www.readbyqxmd.com/read/28295914/development-of-a-gastric-carcinoid-tumor-following-allogeneic-hematopoietic-stem-cell-transplantation-for-early-t-cell-precursor-acute-lymphoblastic-leukemia
#15
Tsung-Yen Chang, Jin-Yao Lai, Chao-Jan Wang, Shih-Yen Chen, Tang-Her Jaing, Chuen Hsueh, Lee-Yung Shih, Shih-Hsiang Chen
Gastric carcinoid tumor is rarely diagnosed in children. We report a case of gastric carcinoid tumor that occurred after allogeneic HSCT. A 13-year-old girl with ETP acute lymphoblastic leukemia underwent allogeneic HSCT from a 7/8 HLA-matched unrelated donor. She presented with rashes, abdominal pain, and diarrhea, which were suggestive of GVHD, 7 months after HSCT. Immunosuppressive agents failed to resolve these symptoms well. After a series of evaluations, carcinoid syndrome caused by a gastric carcinoid tumor was diagnosed...
March 11, 2017: Pediatric Transplantation
https://www.readbyqxmd.com/read/28295181/long-term-follow-up-of-patients-receiving-allogeneic-stem-cell-transplant-for-chronic-lymphocytic-leukaemia-mixed-t-cell-chimerism-is-associated-with-high-relapse-risk-and-inferior-survival
#16
Philip A Thompson, Francesco Stingo, Michael J Keating, William G Wierda, Susan M O'Brien, Zeev Estrov, Celina Ledesma, Katayoun Rezvani, Muzaffar Qazilbash, Nina Shah, Simrit Parmar, Uday Popat, Paolo Anderlini, Nieto Yago, Stefan O Ciurea, Partow Kebriaei, Richard Champlin, Elizabeth J Shpall, Chitra M Hosing
There is limited information regarding the immunological predictors of post-allogeneic stem cell transplant (alloSCT) outcome in chronic lymphocytic leukaemia (CLL), such as mixed T-cell chimerism. We analysed 143 consecutive patients with relapsed/refractory CLL, transplanted between 2000 and 2012, to determine the prognostic relevance of mixed chimerism post-alloSCT and the ability of post-transplant immunomodulation to treat relapse. Mixed T-cell chimerism occurred in 50% of patients at 3 months and 43% at 6 months post-alloSCT; upon 3- and 6-month landmark analysis, this was associated with inferior progression-free survival (PFS) [Hazard ratio (HR) 1·93, P = 0·003 and HR 2·58, P < 0·001] and survival (HR 1·66, P = 0·05 and HR 2·17, P < 0·001), independent of baseline patient characteristics, and a lower rate of grade II-IV acute graft-versus-host disease (GHVD) (16% vs...
March 14, 2017: British Journal of Haematology
https://www.readbyqxmd.com/read/28292332/aberrant-t-cell-responses-in-the-bone-marrow-microenvironment-of-patients-with-poor-graft-function-after-allogeneic-hematopoietic-stem-cell-transplantation
#17
Yuan Kong, Yu-Tong Wang, Xie-Na Cao, Yang Song, Yu-Hong Chen, Yu-Qian Sun, Yu Wang, Xiao-Hui Zhang, Lan-Ping Xu, Xiao-Jun Huang
BACKGROUND: Poor graft function (PGF) is a life-threatening complication after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Nevertheless, whether abnormalities of T cell subsets in the bone marrow (BM) immune microenvironment, including Th17, Tc17, Th1, Tc1, Th2, Tc2 cells and regulatory T cells (Tregs), are involved in the pathogenesis of PGF remains unclear. METHODS: This prospective nested case-control study enrolled 20 patients with PGF, 40 matched patients with good graft function (GGF) after allo-HSCT, and 20 healthy donors (HD)...
March 14, 2017: Journal of Translational Medicine
https://www.readbyqxmd.com/read/28289860/the-pd-l1-pd-1-pathway-promotes-dysfunction-but-not-exhaustion-in-tumor-responding-t-cells-from-pleural-effusions-in-lung-cancer-patients
#18
Heriberto Prado-Garcia, Susana Romero-Garcia, Alejandra Puerto-Aquino, Uriel Rumbo-Nava
Malignant pleural effusions are frequent in patients with advanced stages of lung cancer and are commonly infiltrated by lymphocytes and tumor cells. CD8+ T cells from these effusions have reduced effector functions. The programmed death receptor 1(PD-1)/programmed death ligand 1 (PD-L1) pathway is involved in T-cell exhaustion, and it might be responsible for T-cell dysfunction in lung cancer patients. Here, we show that PD-L1 is expressed on tumor cell samples from malignant effusions, on lung cancer cell lines, and, interestingly, on MRC-5 lung fibroblasts...
March 13, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/28287510/adsc-sheet-transplantation-to-prevent-stricture-after-extended-esophageal-endoscopic-submucosal-dissection
#19
Guillaume Perrod, Laetitia Pidial, Sophie Camilleri, Alexandre Bellucci, Amaury Casanova, Thomas Viel, Bertrand Tavitian, Chirstophe Cellier, Olivier Clément, Gabriel Rahmi
In past years, the cell-sheet construct has spurred wide interest in regenerative medicine, especially for reconstructive surgery procedures. The development of diversified technologies combining adipose tissue-derived stromal cells (ADSCs) with various biomaterials has led to the construction of numerous types of tissue-engineered substitutes, such as bone, cartilage, and adipose tissues from rodent, porcine, or human ADSCs. Extended esophageal endoscopic submucosal dissection (ESD) is responsible for esophageal stricture formation...
February 10, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/28286924/treatment-of-relapsed-refractory-acute-myeloid-leukemia
#20
REVIEW
Prithviraj Bose, Pankit Vachhani, Jorge E Cortes
Approximately 40-45% of younger and 10-20% of older adults with acute myeloid leukemia (AML) will be cured with current standard chemotherapy. The outlook is particularly gloomy for patients with relapsed and/or refractory disease (cure rates no higher than 10%). Allogeneic hematopoietic stem cell transplantation (HSCT), the only realistic hope of cure for these patients, is an option for only a minority. In recent years, much has been learned about the genomic and epigenomic landscapes of AML, and the clonal architecture of both de novo and secondary AML has begun to be unraveled...
March 2017: Current Treatment Options in Oncology
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