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ALLOGENEIC RESPONSE

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https://www.readbyqxmd.com/read/28821525/point-of-care-washing-of-allogeneic-red-blood-cells-for-the-prevention-of-transfusion-related-respiratory-complications-war-prc-a-protocol-for-a-multicenter-randomised-clinical-trial-in-patients-undergoing-cardiac-surgery
#1
Matthew A Warner, Ian J Welsby, Phillip J Norris, Christopher C Silliman, Sarah Armour, Erica D Wittwer, Paula J Santrach, Laurie A Meade, Lavonne M Liedl, Chelsea M Nieuwenkamp, Brian Douthit, Camille M van Buskirk, Phillip J Schulte, Rickey E Carter, Daryl J Kor
INTRODUCTION: The transfusion-related respiratory complications, transfusion-related acute lung injury (TRALI) and transfusion-associated circulatory overload (TACO), are leading causes of transfusion-related morbidity and mortality. At present, there are no effective preventive strategies with red blood cell (RBC) transfusion. Although mechanisms remain incompletely defined, soluble biological response modifiers (BRMs) within the RBC storage solution may play an important role. Point-of-care (POC) washing of allogeneic RBCs may remove these BRMs, thereby mitigating their impact on post-transfusion respiratory complications...
August 18, 2017: BMJ Open
https://www.readbyqxmd.com/read/28819574/sequential-kinase-inhibition-idelalisib-ibrutinib-induces-clinical-remission-in-b-cell-prolymphocytic-leukemia-harboring-a-17p-deletion
#2
H Coelho, M Badior, T Melo
B-cell prolymphocytic leukemia (B-PLL) is a rare lymphoid neoplasm with an aggressive clinical course. Treatment strategies for B-PLL remain to be established, and, until recently, alemtuzumab was the only effective therapeutic option in patients harboring 17p deletions. Herein, we describe, for the first time, a case of B-cell prolymphocytic leukemia harboring a 17p deletion in a 48-year-old man that was successfully treated sequentially with idelalisib-rituximab/ibrutinib followed by allogeneic hematopoietic stem cell transplant (allo-HSCT)...
2017: Case Reports in Hematology
https://www.readbyqxmd.com/read/28817727/pilot-study-of-lithium-to-restore-intestinal-barrier-function-in-severe-graft-versus-host-disease
#3
Gideon Steinbach, David M Hockenbery, Gerwin Huls, Terry Furlong, David Myerson, Keith R Loeb, Jesse R Fann, Christina Castilla-Llorente, George B McDonald, Paul J Martin
Severe intestinal graft-vs-host disease (GVHD) after allogeneic hematopoietic cell transplantation (HCT) causes mucosal ulceration and induces innate and adaptive immune responses that amplify and perpetuate GVHD and the associated barrier dysfunction. Pharmacological agents to target mucosal barrier dysfunction in GVHD are needed. We hypothesized that induction of Wnt signaling by lithium, an inhibitor of glycogen synthase kinase (GSK3), would potentiate intestinal crypt proliferation and mucosal repair and that inhibition of GSK3 in inflammatory cells would attenuate the deregulated inflammatory response to mucosal injury...
2017: PloS One
https://www.readbyqxmd.com/read/28817182/centralized-patient-reported-outcome-data-collection-in-transplantation-is-feasible-and-clinically-meaningful
#4
Bronwen E Shaw, Ruta Brazauskas, Heather R Millard, Rachel Fonstad, Kathryn E Flynn, Amy Abernethy, Jenny Vogel, Charney Petroske, Deborah Mattila, Rebecca Drexler, Stephanie J Lee, Mary M Horowitz, J Douglas Rizzo
BACKGROUND: Allogeneic hematopoietic cell transplantation (HCT) cures many patients, but often with the risk of late effects and impaired quality of life. The value of quantifying patient-reported outcomes (PROs) is increasingly being recognized, but the routine collection of PROs is uncommon. This study evaluated the feasibility of prospective PRO collection by an outcome registry at multiple time points from unselected HCT patients undergoing transplantation at centers contributing clinical data to the Center for International Blood and Marrow Transplant Research (CIBMTR), and then it correlated the PRO data with clinical and demographic data...
August 17, 2017: Cancer
https://www.readbyqxmd.com/read/28816104/the-immune-response-to-allogeneic-differentiated-mesenchymal-stem-cells-in-the-context-of-bone-tissue-engineering
#5
Caoimhe H Kiernan, Eppo B Wolvius, Pieter A J Brama, Eric Farrell
The use of allogeneic differentiated mesenchymal stem cells (MSCs) to mediate bone formation may be a potential alternative to the current gold standards of bone repair. While it is known that undifferentiated MSCs are immunomodulatory and weakly immunogenic, the host immune reaction to differentiated MSCs is less known. Implantation of allogeneic osteogenic or chondrogenically differentiated MSC pellets may be promising routes to induce bone repair via the processes of intramembranous and endochondral ossification...
August 17, 2017: Tissue Engineering. Part B, Reviews
https://www.readbyqxmd.com/read/28810255/ponatinib-induced-graft-versus-host-disease-graft-versus-leukemia-effect-in-a-patient-with-philadelphia-positive-acute-lymphoblastic-leukemia-without-the-t315i-mutation-relapsing-after-allogeneic-transplant
#6
Annamaria Petrungaro, Massimo Gentile, Carla Mazzone, Rosa Greco, Giuseppina Uccello, Anna Grazia Recchia, Laura De Stefano, Sabrina Bossio, Angela Palummo, Rosellina Morelli, Caterina Musolino, Fortunato Morabito, Ernesto Vigna
We describe the case of a patient with Philadelphia-positive acute lymphoblastic leukemia treated with dasatinib plus steroids as first-line therapy, who achieved a major molecular response (MMR) before undergoing matched, unrelated donor allogeneic stem cell transplant. Eleven months after the transplant, she experienced molecular relapse. Mutational screening showed negativity for the T315I mutation, The patient underwent a salvage chemotherapy regimen with clofarabine + cyclophosphamide + steroids and ponatinib (clofarabine 70 mg i...
August 16, 2017: Chemotherapy
https://www.readbyqxmd.com/read/28809824/creation-and-transplantation-of-an-adipose-derived-stem-cell-asc-sheet-in-a-diabetic-wound-healing-model
#7
Yuka Kato, Takanori Iwata, Kaoru Washio, Toshiyuki Yoshida, Hozue Kuroda, Shunichi Morikawa, Mariko Hamada, Kazuki Ikura, Nobuyuki Kaibuchi, Masayuki Yamato, Teruo Okano, Yasuko Uchigata
Artificial skin has achieved considerable therapeutic results in clinical practice. However, artificial skin treatments for wounds in diabetic patients with impeded blood flow or with large wounds might be prolonged. Cell-based therapies have appeared as a new technique for the treatment of diabetic ulcers, and cell-sheet engineering has improved the efficacy of cell transplantation. A number of reports have suggested that adipose-derived stem cells (ASCs), a type of mesenchymal stromal cell (MSC), exhibit therapeutic potential due to their relative abundance in adipose tissue and their accessibility for collection when compared to MSCs from other tissues...
August 4, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/28807569/il-10-engineered-human-cd4-tr1-cells-eliminate-myeloid-leukemia-in-an-hla-class-i-dependent-mechanism
#8
Grazia Locafaro, Grazia Andolfi, Fabio Russo, Luca Cesana, Antonello Spinelli, Barbara Camisa, Fabio Ciceri, Angelo Lombardo, Attilio Bondanza, Maria Grazia Roncarolo, Silvia Gregori
T regulatory cells (Tregs) play a key role in modulating T cell responses. Clinical trials showed that Tregs modulate graft-versus-host disease (GvHD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT). However, their ability to mediate anti-leukemic activity (graft-versus-leukemia [GvL]) is largely unknown. Enforced interleukin-10 (IL-10) expression converts human CD4(+) T cells into T regulatory type 1 (Tr1)-like (CD4(IL-10)) cells that suppress effector T cells in vitro and xenoGvHD in humanized mouse models...
July 5, 2017: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/28805723/hitting-the-holy-grail-of-hematopoietic-cell-transplantation-with-naive-t-cell-depleted-allografts-graft-engineered-hematopoietic-stem-cell-transplant
#9
Riad El Fakih, Shahrukh K Hashmi
Hematopoietic cell transplant is a potentially curative procedure for many benign and malignant conditions. The efficacy of allogeneic transplant relies in part on the cytotoxicity of the conditioning regimen and the graft versus tumor effect mediated by alloreactive donor T cells; the same cells are also implicated in the development of graft versus host disease (GVHD). Selective identification and depletion of the T cells implicated in GVHD, while preserving the T cells responsible for graft versus tumor effect has been the focus of many research groups in the recent years...
August 14, 2017: Biomedicines
https://www.readbyqxmd.com/read/28790849/immunotargeting-relapsed-or-refractory-precursor-b-cell-acute-lymphoblastic-leukemia-role-of-blinatumomab
#10
REVIEW
Manon Queudeville, Rupert Handgretinger, Martin Ebinger
Patients with refractory or relapsed (R/R) acute lymphoblastic leukemia (ALL) have a dismal prognosis of around 5% long-term survival when treated with cytotoxic chemotherapy and allogenic stem cell transplantation. T-cell immunobased strategies open up new therapeutic perspectives. Blinatumomab is the first of a new class of antibody constructs that was labeled bispecific T-cell engager (BiTE): it consists of two single chain variable fragment connected with a flexible linker, one side binding CD3, the other CD19...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28783664/donor-sirp%C3%AE-polymorphism-modulates-the-innate-immune-response-to-allogeneic-grafts
#11
Hehua Dai, Andrew J Friday, Khodor I Abou-Daya, Amanda L Williams, Steven Mortin-Toth, Matthew L Nicotra, David M Rothstein, Warren D Shlomchik, Takashi Matozaki, Jeffrey S Isenberg, Martin H Oberbarnscheidt, Jayne S Danska, Fadi G Lakkis
Mice devoid of T, B, and natural killer (NK) cells distinguish between self and allogeneic nonself despite the absence of an adaptive immune system. When challenged with an allograft, they mount an innate response characterized by accumulation of mature, monocyte-derived dendritic cells (DCs) that produce interleukin-12 and present antigen to T cells. However, the molecular mechanisms by which the innate immune system detects allogeneic nonself to generate these DCs are not known. To address this question, we studied the innate response of Rag2(-/-) γc(-/-) mice, which lack T, B, and NK cells, to grafts from allogeneic donors...
June 23, 2017: Science Immunology
https://www.readbyqxmd.com/read/28783452/off-the-shelf-virus-specific-t-cells-to-treat-bk-virus-human-herpesvirus-6-cytomegalovirus-epstein-barr-virus-and-adenovirus-infections-after-allogeneic-hematopoietic-stem-cell-transplantation
#12
Ifigeneia Tzannou, Anastasia Papadopoulou, Swati Naik, Kathryn Leung, Caridad A Martinez, Carlos A Ramos, George Carrum, Ghadir Sasa, Premal Lulla, Ayumi Watanabe, Manik Kuvalekar, Adrian P Gee, Meng-Fen Wu, Hao Liu, Bambi J Grilley, Robert A Krance, Stephen Gottschalk, Malcolm K Brenner, Cliona M Rooney, Helen E Heslop, Ann M Leen, Bilal Omer
Purpose Improvement of cure rates for patients treated with allogeneic hematopoietic stem-cell transplantation (HSCT) will require efforts to decrease treatment-related mortality from severe viral infections. Adoptively transferred virus-specific T cells (VSTs) generated from eligible, third-party donors could provide broad antiviral protection to recipients of HSCT as an immediately available off-the-shelf product. Patient and Methods We generated a bank of VSTs that recognized five common viral pathogens: Epstein-Barr virus (EBV), adenovirus (AdV), cytomegalovirus (CMV), BK virus (BKV), and human herpesvirus 6 (HHV-6)...
August 7, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28783148/clinical-characteristics-and-outcome-of-human-herpesvirus-6-encephalitis-after-allogeneic-hematopoietic-stem-cell-transplantation
#13
M Ogata, K Oshima, T Ikebe, K Takano, H Kanamori, T Kondo, Y Ueda, T Mori, H Hashimoto, H Ogawa, T Eto, T Ueki, T Miyamoto, T Ichinohe, Y Atsuta, T Fukuda
In this retrospective analysis using the Transplant Registry Unified Management Program, we identified 145 patients with human herpesvirus (HHV)-6 encephalitis among 6593 recipients. The cumulative incidences of HHV-6 encephalitis at 100 days after transplantation in all patients, recipients of bone marrow or PBSCs and recipients of cord blood were 2.3%, 1.6% and 5.0%, respectively. Risk factors identified in multivariate analysis were male sex, type of transplanted cells (relative risk in cord blood transplantation, 11...
August 7, 2017: Bone Marrow Transplantation
https://www.readbyqxmd.com/read/28775323/ex-vivo-pretreatment-of-human-vessels-with-sirna-nanoparticles-provides-protein-silencing-in-endothelial-cells
#14
Jiajia Cui, Lingfeng Qin, Junwei Zhang, Parwiz Abrahimi, Hong Li, Guangxin Li, Gregory T Tietjen, George Tellides, Jordan S Pober, W Mark Saltzman
Human endothelial cells are initiators and targets of the rejection response. Pre-operative modification of endothelial cells by small interfering RNA transfection could shape the nature of the host response post-transplantation. Ablation of endothelial cell class II major histocompatibility complex molecules by small interfering RNA targeting of class II transactivator can reduce the capacity of human endothelial cells to recruit and activate alloreactive T cells. Here, we report the development of small interfering RNA-releasing poly(amine-co-ester) nanoparticles, distinguished by their high content of a hydrophobic lactone...
August 4, 2017: Nature Communications
https://www.readbyqxmd.com/read/28768873/human-herpesvirus-8-infects-and-replicates-in-langerhans-cells-and-interstitial-dermal-dendritic-cells-and-impairs-their-function
#15
Giovanna Rappocciolo, Mariel Jais, Paolo A Piazza, Diana C DeLucia, Frank J Jenkins, Charles R Rinaldo
The predominant types of dendritic cells (DC) in the skin and mucosa are Langerhans cells (LC) and interstitial dermal DC (iDDC). LC and iDDC process cutaneous antigens and migrate out of the skin and mucosa to the draining lymph nodes to present antigens to T and B cells. Because of the strategic location of LC and iDDC and the ability of these cells to capture and process pathogens, we hypothesized that they could be infected with human herpesvirus 8 (HHV-8; Kaposi's sarcoma-associated herpesvirus) and have an important role in the development of Kaposi's sarcoma (KS)...
August 2, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28768528/safety-tolerability-clinical-and-joint-structural-outcomes-of-a-single-intra-articular-injection-of-allogeneic-mesenchymal-precursor-cells-in-patients-following-anterior-cruciate-ligament-reconstruction-a-controlled-double-blind-randomised-trial
#16
Yuanyuan Wang, Andrew Shimmin, Peter Ghosh, Paul Marks, James Linklater, David Connell, Stephen Hall, Donna Skerrett, Silviu Itescu, Flavia M Cicuttini
BACKGROUND: Few clinical trials have investigated the safety and efficacy of mesenchymal stem cells for the management of post-traumatic osteoarthritis. The objectives of this pilot study were to determine the safety and tolerability and to explore the efficacy of a single intra-articular injection of allogeneic human mesenchymal precursor cells (MPCs) to improve clinical symptoms and retard joint structural deterioration over 24 months in patients following anterior cruciate ligament (ACL) reconstruction...
August 2, 2017: Arthritis Research & Therapy
https://www.readbyqxmd.com/read/28766541/-use-of-crizotinib-for-refractory-alk-positive-lymphomas
#17
L N Shelikhova, V V Fominykh, D S Abramov, N V Myakova, M A Maschan, A A Maschan
AIM: To evaluate the safety and efficacy of crizotinib used in pediatric patients with relapsed or refractory ALK-positive anaplastic large-cell lymphoma (ALCL). SUBJECTS AND METHODS: The paper describes the experience with crizotinib used in 8 patients with refractory ALK-ALCL before and after allogeneic hematopoietic stem cell transplantation (HSCT). RESULTS: All the 8 (100%) patients treated with crizotinib were recorded to have complete responses, including complete metabolic ones (tumor disappearance as evidenced by positron emission tomography (PET)/computed tomography...
2017: Terapevticheskiĭ Arkhiv
https://www.readbyqxmd.com/read/28763099/autologous-tolerogenic-dendritic-cells-derived-from-monocytes-of-systemic-lupus-erythematosus-patients-and-healthy-donors-show-a-stable-and-immunosuppressive-phenotype
#18
Javiera Obreque, Fabián Vega, Andy Torres, Loreto Cuitino, Juan P Mackern-Oberti, Paola Viviani, Alexis Kalergis, Carolina Llanos
Systemic Lupus Erythematosus (SLE) is an autoimmune disease with unrestrained T-cell and B cell activity towards self-antigens. Evidence shows that apoptotic cells (ApoCells) trigger an autoreactive response against nuclear antigens in susceptible individuals. In this study, we focus on generating and characterizing tolerogenic dendritic cells (tolDCs) to restore tolerance to ApoCells. Monocyte-derived dendritic cells (DCs) from healthy controls (HC) and SLE patients were treated with dexamethasone (DEXA) and rosiglitazone (RGZ) to induce tolDCs...
August 1, 2017: Immunology
https://www.readbyqxmd.com/read/28760298/minimal-residual-disease-assessment-and-risk-based-therapy-in-acute-lymphoblastic-leukemia
#19
REVIEW
Renato Bassan, Tamara Intermesoli, Annamaria Scattolin, Piera Viero, Elena Maino, Rosaria Sancetta, Francesca Carobolante, Francesca Gianni, Paola Stefanoni, Manuela Tosi, Orietta Spinelli, Alessandro Rambaldi
The study of minimal residual disease (MRD) in adult patients with acute lymphoblastic leukemia (ALL) allows a greater refinement of the individual risk classification and is the best support for risk-specific therapy with or without allogeneic hematopoietic cell transplantation (HCT). Using case-specific sensitive molecular probes or multiparametric flow cytometry on marrow samples obtained from the end of induction until midconsolidation, MRD assays can detect up to 1 leukemic cell of 10,000 total mononuclear cells (sensitivity, 0...
July 2017: Clinical Lymphoma, Myeloma & Leukemia
https://www.readbyqxmd.com/read/28758974/immunotherapeutic-concepts-to-target-acute-myeloid-leukemia-focusing-on-the-role-of-monoclonal-antibodies-hypomethylating-agents-and-the-leukemic-microenvironment
#20
REVIEW
Olumide Babajide Gbolahan, Amer M Zeidan, Maximilian Stahl, Mohammad Abu Zaid, Sherif Farag, Sophie Paczesny, Heiko Konig
Intensive chemotherapeutic protocols and allogeneic stem cell transplantation continue to represent the mainstay of acute myeloid leukemia (AML) treatment. Although this approach leads to remissions in the majority of patients, long-term disease control remains unsatisfactory as mirrored by overall survival rates of approximately 30%. The reason for this poor outcome is, in part, due to various toxicities associated with traditional AML therapy and the limited ability of most patients to tolerate such treatment...
July 31, 2017: International Journal of Molecular Sciences
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