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T-cells, hematopoietic cell transplant

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https://www.readbyqxmd.com/read/28527402/a-rare-e13a3-b2a3-bcr-abl1-fusion-transcript-with-normal-karyotype-in-chronic-myeloid-leukemia-the-challenges-in-diagnosis-and-monitoring-minimal-residual-disease-mrd
#1
M-H Duan, H Li, H Cai
Patients with chronic myeloid leukemia (CML) have a t (9;22)(q34;q11.2) or variant translocation that results in a BCR-ABL1 fusion gene. For many years, conventional karyotyping has been used as the standard diagnostic tool for t (9;22) (q34;q11.2). However, it has several limitations that may lead to failure for detecting BCR-ABL1 gene rearrangements in around 5% of all CML patients. Although reverse transcription polymerase chain reaction (RT-PCR) has evolved as a sensitive method for detecting BCR-ABL1 translocation, this method fail to detect certain BCR-ABL1 fusion transcript type, such as e13a3 (also known as b2a3), as a result of many commercially available and laboratory-developed primer sets...
May 12, 2017: Leukemia Research
https://www.readbyqxmd.com/read/28524832/measles-outbreak-in-pediatric-hematology-and-oncology-patients-in-shanghai-2015
#2
Yan-Ling Ge, Xiao-Wen Zhai, Yan-Feng Zhu, Xiang-Shi Wang, Ai-Mei Xia, Yue-Fang Li, Mei Zeng
BACKGROUND: Despite substantial progress toward measles control are making in China, measles outbreaks in immunocompromised population still pose a challenge to interrupt endemic transmission. This study aimed to investigate the features of measles in pediatric hematology and oncology patients and explore the reasons behind the outbreak. METHODS: We collected demographic, epidemiological, and clinical data of immunocompromised measles children. All suspected measles cases were laboratory-confirmed based on the presence of measles IgM and/or identification of measles RNA...
June 5, 2017: Chinese Medical Journal
https://www.readbyqxmd.com/read/28520587/complementary-roles-of-nod2-in-hematopoietic-and-nonhematopoietic-cells-in-preventing-gut-barrier-dysfunction-dependent-on-mlck-activity
#3
Ziad Al Nabhani, Nicolas Montcuquet, Maryline Roy, Monique Dussaillant, Jean-Pierre Hugot, Frédérick Barreau
BACKGROUND: Crohn's disease (CD) pathogenesis is multifactorial involving genetic and environmental factors. Loss of function mutations in the nucleotide oligomerization domain 2 (NOD2) gene are the main genetic risk factor for CD. Like patients with CD, Nod2 mice are characterized by an enhanced Th1 immune response and a defective mucosal barrier function evidenced by increased intestinal permeability. We previously showed that the latter is related to hematopoietic Nod2 deficiency. Our aim was to explore the mechanisms by which Nod2 expressed in the hematopoietic and in the nonhematopoietic compartments interplay to control epithelial paracellular permeability...
May 16, 2017: Inflammatory Bowel Diseases
https://www.readbyqxmd.com/read/28515365/ceramide-synthesis-regulates-t-cell-activity-and-gvhd-development
#4
M Hanief Sofi, Jessica Heinrichs, Mohammed Dany, Hung Nguyen, Min Dai, David Bastian, Steven Schutt, Yongxia Wu, Anusara Daenthanasanmak, Salih Gencer, Aleksandra Zivkovic, Zdzislaw Szulc, Holger Stark, Chen Liu, Ying-Jun Chang, Besim Ogretmen, Xue-Zhong Yu
Allogeneic hematopoietic cell transplantation (allo-HCT) is an effective immunotherapy for a variety of hematologic malignances, yet its efficacy is impeded by the development of graft-versus-host disease (GVHD). GVHD is characterized by activation, expansion, cytokine production, and migration of alloreactive donor T cells. Hence, strategies to limit GVHD are highly desirable. Ceramides are known to contribute to inflammation and autoimmunity. However, their involvement in T-cell responses to alloantigens is undefined...
May 18, 2017: JCI Insight
https://www.readbyqxmd.com/read/28515359/t-cell-progenitor-therapy-facilitated-thymopoiesis-depends-upon-thymic-input-and-continued-thymic-microenvironment-interaction
#5
Michelle J Smith, Dawn K Reichenbach, Sarah L Parker, Megan J Riddle, Jason Mitchell, Kevin C Osum, Mahmood Mohtashami, Heather E Stefanski, Brian T Fife, Avinash Bhandoola, Kristin A Hogquist, Georg A Holländer, Juan Carlos Zúñiga-Pflücker, Jakub Tolar, Bruce R Blazar
Infusion of in vitro-derived T cell progenitor (proT) therapy with hematopoietic stem cell transplant aids the recovery of the thymus damaged by total body irradiation. To understand the interaction between proTs and the thymic microenvironment, WT mice were lethally irradiated and given T cell-deficient (Rag1-/-) marrow with WT in vitro-generated proTs, limiting mature T cell development to infused proTs. ProTs within the host thymus led to a significant increase in thymic epithelial cells (TECs) by day 21 after transplant, increasing actively cycling TECs...
May 18, 2017: JCI Insight
https://www.readbyqxmd.com/read/28511686/intrathymic-injection-of-hematopoietic-progenitor-cells-establishes-functional-t-cell-development-in-a-mouse-model-of-severe-combined-immunodeficiency
#6
Andrea Z Tuckett, Raymond H Thornton, Richard J O'Reilly, Marcel R M van den Brink, Johannes L Zakrzewski
BACKGROUND: Even though hematopoietic stem cell transplantation can be curative in patients with severe combined immunodeficiency, there is a need for additional strategies boosting T cell immunity in individuals suffering from genetic disorders of lymphoid development. Here we show that image-guided intrathymic injection of hematopoietic stem and progenitor cells in NOD-scid IL2rγ(null) mice is feasible and facilitates the generation of functional T cells conferring protective immunity...
May 16, 2017: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/28510343/no-effect-of-hla-c-mismatch-after-allogeneic-hematopoietic-stem-cell-transplantation-with-unrelated-donors-and-t-cell-depletion-in-patients-with-hematological-malignancies
#7
I Magalhaes, M Uhlin, M Schaffer, M Sundin, D Hauzenberger, M Remberger, J Mattsson
HLA-C mismatch in unrelated donors hematopoeitic stem cell transplantation (HSCT) has been associated with poor patient outcome. However, the impact of HLA-C mismatch in the context of HSCT combined with in vivo T-cell depletion remains unclear. We therefore performed a single-center, retrospective analysis of the clinical outcome on patients with hematological malignancies treated with allo-HSCT, who underwent T-cell depletion. The majority of the patients (n=276) received a HLA-A, -B, -DRB1 matched graft that were either also HLA-C matched (n=260), or patients with the permissive HLA-C*03:03/03:04 mismatch (n=16), while the remaining patients (n=95) received a HLA-C mismatched graft (excluding HLA-C*03:03/03:04 mismatches)...
May 16, 2017: Clinical Transplantation
https://www.readbyqxmd.com/read/28507545/clinical-and-molecular-heterogeneity-of-rtel1-deficiency
#8
Carsten Speckmann, Sushree Sangita Sahoo, Marta Rizzi, Shinsuke Hirabayashi, Axel Karow, Nina Kathrin Serwas, Marc Hoemberg, Natalja Damatova, Detlev Schindler, Jean-Baptiste Vannier, Simon J Boulton, Ulrich Pannicke, Gudrun Göhring, Kathrin Thomay, J J Verdu-Amoros, Holger Hauch, Wilhelm Woessmann, Gabriele Escherich, Eckart Laack, Liliana Rindle, Maximilian Seidl, Anne Rensing-Ehl, Ekkehart Lausch, Christine Jandrasits, Brigitte Strahm, Klaus Schwarz, Stephan R Ehl, Charlotte Niemeyer, Kaan Boztug, Marcin W Wlodarski
Typical features of dyskeratosis congenita (DC) resulting from excessive telomere shortening include bone marrow failure (BMF), mucosal fragility, and pulmonary or liver fibrosis. In more severe cases, immune deficiency and recurring infections can add to disease severity. RTEL1 deficiency has recently been described as a major genetic etiology, but the molecular basis and clinical consequences of RTEL1-associated DC are incompletely characterized. We report our observations in a cohort of six patients: five with novel biallelic RTEL1 mutations p...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28506261/a-possible-role-of-low-regulatory-t-cells-in-anti-acetylcholine-receptor-antibody-positive-myasthenia-gravis-after-bone-marrow-transplantation
#9
Masahiko Fukatsu, Takenobu Murakami, Hiroshi Ohkawara, Shunichi Saito, Kazuhiko Ikeda, Suguru Kadowaki, Itaru Sasaki, Mari Segawa, Tomoko Soeda, Akihiko Hoshi, Hiroshi Takahashi, Akiko Shichishima-Nakamura, Kazuei Ogawa, Yoshihiro Sugiura, Hitoshi Ohto, Yasuchika Takeishi, Takayuki Ikezoe, Yoshikazu Ugawa
BACKGROUND: Chronic graft-versus-host disease (GVHD) appears several months following allogenic hematopoietic stem cell transplantation (HSCT) and is clinically analogous to autoimmune disorder. Polymyositis is a common neuromuscular disorder in chronic GVHD, but myasthenia gravis (MG) is extremely rare. Hence, its pathophysiology and treatment have not been elucidated. CASE PRESENTATION: A 63-year-old man with a history of chronic GVHD presented with ptosis, dropped head, and dyspnea on exertion, which had worsened over the previous several months...
May 15, 2017: BMC Neurology
https://www.readbyqxmd.com/read/28505028/cytomegalovirus-disease-in-hematopoietic-stem-cell-transplant-patients-current-and-future-therapeutic-options
#10
Shigeo Fuji, Hermann Einsele, Markus Kapp
PURPOSE OF REVIEW: Allogeneic hematopoietic stem cell transplantation (allo-HSCT) has become one of the standard treatment for hematological diseases. Although the clinical outcome has improved significantly during the last decades, the morbidity and mortality after allo-HSCT are still obstacles to cure. Out of major morbidities, opportunistic virus infections such as cytomegalovirus (CMV) infection are important complications, in particular in patients who received human leukocyte antigen-mismatched HSCT...
May 12, 2017: Current Opinion in Infectious Diseases
https://www.readbyqxmd.com/read/28498568/reconstitution-of-immune-cell-populations-in-multiple-sclerosis-patients-after-autologous-stem-cell-transplantation
#11
REVIEW
Fredrick G Karnell, Dongxia Lin, Samantha Motley, Thomas Duhen, Noha Lim, Daniel J Campbell, Laurence A Turka, Holden T Maecker, Kristina M Harris
Multiple sclerosis is an inflammatory T-cell-mediated autoimmune disease. In a phase II clinical trial, high-dose immunosuppressive therapy combined with autologous CD34(+) hematopoietic stem cell transplant resulted in 69.2% of subjects remaining disease-free without evidence of relapse, loss of neurological function or new MRI lesions through year 5 post-treatment. A combination of CyTOF mass cytometry and multi-parameter flow cytometry was used to explore the reconstitution kinetics of immune cell subsets in the periphery post HSCT and the impact of treatment on the phenotype of circulating T cells in this study population...
May 12, 2017: Clinical and Experimental Immunology
https://www.readbyqxmd.com/read/28497658/toxic-epidermal-necrolysis-in-a-child-6-months-post-hematopoietic-stem-cell-transplantation
#12
Utako Oba, Hiroshi Yamada, So-Ichi Suenobu, Yusuke Nakamura, Akiko Ito, Yutaka Hatano, Nobuyoshi Itonaga, Kouichi Ohshima, Yuhki Koga, Shouichi Ohga, Kenji Ihara
TEN is a rare and critical disease mostly caused by drugs. It is mediated by activated CD8+ T cells that cause keratinocyte apoptosis with the assistance of cytokines/chemokines. We herein report a pediatric case of TEN after allogeneic HSCT with precursor B-cell acute lymphoblastic leukemia (pre-B-ALL) in second complete remission. Although we did not evaluate the T-cell subpopulation in blood or skin lesion of the patient, an imbalanced immune reconstitution after HSCT might additively contribute to the development of TEN...
May 12, 2017: Pediatric Transplantation
https://www.readbyqxmd.com/read/28497366/evaluation-of-persistence-and-distribution-of-intra-dermally-administered-pkh26-labelled-goat-bone-marrow-derived-mesenchymal-stem-cells-in-cutaneous-wound-healing-model
#13
M D Pratheesh, Nitin E Gade, Amar Nath, Pawan K Dubey, T B Sivanarayanan, D N Madhu, T R Sreekumar, Amarpal, G Saikumar, G Taru Sharma
The current study was designed to study the persistence and distribution of caprine bone marrow derived mesenchymal stem cells (cBM-MSCs) when administered intra-dermally in experimentally induced cutaneous wounds in rabbits. MSC's from goat bone marrow were isolated and their differentiation potential towards adipogenic and osteogenic lineages were assayed in vitro. The isolated cells were phenotypically analysed using flow cytometry for the expression of MSC specific matrix receptors (CD73, CD105 and Stro-1) and absence of hematopoietic lineage markers...
May 11, 2017: Cytotechnology
https://www.readbyqxmd.com/read/28495643/humoral-immune-reconstitution-kinetics-following-allogeneic-hematopoietic-stem-cell-transplantation-in-children-a-maturation-block-of-igm-memory-b-cells-may-lead-to-impaired-antibody-immune-reconstitution
#14
Hisham Abdel-Azim, Amro Elshoury, Kris M Mahadeo, Robertson Parkman, Neena Kapoor
Although T cell immune reconstitution following allogeneic hematopoietic stem cell transplantation (allo-HSCT) has been well studied, long-term B cell immune reconstitution remains less characterized. We evaluated humoral immune reconstitution among 71-pediatric allo-HSCT recipients. While tetanus toxoid (TT) antibody levels were normal at 1-year post allo-HSCT, anti-polysaccharide carbohydrate (PRP) antibodies remained persistently low for up to 5-years. While naive B cell counts normalized by 6-months, IgM memory B cell deficiency persisted for up to 2-years (P=0...
May 8, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/28490811/high-efficacy-and-safety-of-low-dose-cd19-directed-car-t-cell-therapy-in-51-refractory-or-relapsed-b-acute-lymphoblastic-leukemia-patients
#15
J Pan, J Yang, B Deng, X Zhao, X Zhang, Y Lin, Y Wu, Z Deng, Y Zhang, S Liu, T Wu, P Lu, D Lu, A H Chang, C Tong
Refractory or relapsed B lymphoblastic leukemia (B-ALL) patients have a dismal outcome with current therapy. We treated 42 primary refractory/hematological relapsed (R/R) and 9 refractory minimal residual disease by flow cytometry (FCM-MRD(+)) B-ALL patients with optimized second generation CD19-directed CAR-T cells. The CAR-T cell infusion dosages were initially ranged from 0.05 to 14 × 10(5)/kg and were eventually settled at 1 × 10(5)/kg for the most recent 20 cases. 36/40 (90%) evaluated R/R patients achieved complete remission (CR) or CR with incomplete count recovery (CRi), and 9/9 (100%) FCM-MRD(+) patients achieved MRD(-)...
May 11, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28487696/natural-killer-cells-in-graft-versus-host-disease-after-allogeneic-hematopoietic-cell-transplantation
#16
REVIEW
Federico Simonetta, Maite Alvarez, Robert S Negrin
Allogeneic hematopoietic cell transplantation (HCT) is a well-established therapeutic modality effective for a variety of hematological malignancies but, unfortunately, is associated with significant morbidity and mortality related to cancer relapse as well as to transplant-related complications including graft-versus-host-disease (GvHD). Natural killer (NK) cells are the first donor-derived lymphocyte subset to recover after HCT, and their crucial role in protection against cancer relapse and infections is well established...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28484267/microrna-146a-reduces-mhc-ii-expression-via-targeting-jak-stat-signaling-in-dendritic-cells-after-stem-cell-transplantation
#17
N Stickel, K Hanke, D Marschner, G Prinz, M Köhler, W Melchinger, D Pfeifer, A Schmitt-Graeff, T Brummer, A Heine, P Brossart, D Wolf, N von Bubnoff, J Finke, J Duyster, J Ferrara, U Salzer, R Zeiser
Acute Graft-versus-host disease (GVHD) is a major immunological complication after allogeneic hematopoietic cell transplantation and a better understanding of the molecular regulation of the disease could help to develop novel targeted therapies. Here we found that a G/C polymorphism within the human microRNA-146a (miR-146a) gene of transplant-recipients, which causes reduced miR-146a levels, was strongly associated with the risk of developing severe acute GVHD (n=289). In mice, deficiency of miR-146a in the hematopoietic system or transfer of recipient-type miR-146a(-/-) dendritic cells (DCs) enhanced GVHD, while miR-146a mimic-transfected-DCs ameliorated disease...
May 9, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28482908/curative-or-pre-emptive-adenovirus-specific-t-cell-transfer-from-matched-unrelated-or-third-party-haploidentical-donors-after-hsct-including-ucb-transplantations-a-successful-phase-i-ii-multicenter-clinical-trial
#18
Chongsheng Qian, Arnaud Campidelli, Yingying Wang, Huili Cai, Véronique Venard, Hélène Jeulin, Jean Hugues Dalle, Cécile Pochon, Maud D'aveni, Benedicte Bruno, Catherine Paillard, Stéphane Vigouroux, Charlotte Jubert, Patrice Ceballos, Aude Marie-Cardine, Claire Galambrun, Clément Cholle, Isabelle Clerc Urmes, Nadine Petitpain, Marcelo De Carvalho Bittencourt, Véronique Decot, Loïc Reppel, Alexandra Salmon, Laurence Clement, Danièle Bensoussan
BACKGROUND: Allogeneic hematopoietic stem cell transplantation (HSCT), the most widely used potentially curable cellular immunotherapeutic approach in the treatment of hematological malignancies, is limited by life-threatening complications: graft versus host disease (GVHD) and infections especially viral infections refractory to antiviral drugs. Adoptive transfer of virus-specific T cells is becoming an alternative treatment for infections following HSCT. We report here the results of a phase I/II multicenter study which includes a series of adenovirus-specific T cell (ADV-VST) infusion either from the HSCT donor or from a third party haploidentical donor for patients transplanted with umbilical cord blood (UCB)...
May 8, 2017: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/28481353/b-cell-activating-factor-baff-plasma-level-at-the-time-of-chronic-gvhd-diagnosis-is-a-potential-predictor-of-non-relapse-mortality
#19
R M Saliba, S Sarantopoulos, C L Kitko, A Pawarode, S C Goldstein, J Magenau, A M Alousi, T Churay, H Justman, S Paczesny, P Reddy, D R Couriel
Biological markers for risk stratification of chronic GvHD (cGvHD) could improve the care of patients undergoing allogeneic hematopoietic stem cell transplantation. Increased plasma levels of B-cell activating factor (BAFF), chemokine (C-X-C motif) ligand 9 (CXCL9) and elafin have been associated with the diagnosis, but not with outcome in patients with cGvHD. We evaluated the association between levels of these soluble proteins, measured by ELISA at the time of cGvHD diagnosis and before the initiation of therapy, with non-relapse-mortality (NRM)...
May 8, 2017: Bone Marrow Transplantation
https://www.readbyqxmd.com/read/28480300/toward-a-rapid-production-of-multivirus-specific-t-cells-targeting-bkv-adenovirus-cmv-and-ebv-from-umbilical-cord-blood
#20
Hema Dave, Min Luo, J W Blaney, Shabnum Patel, Cecilia Barese, Conrad Russell Cruz, Elizabeth J Shpall, Catherine M Bollard, Patrick J Hanley
Umbilical cord blood (CB) has emerged as an effective alternative donor source for hematopoietic stem cell transplantation. Despite this success, the prolonged duration of immune suppression following CB transplantation and the naiveté of CB T cells leave patients susceptible to viral infections. Adoptive transfer of ex vivo-expanded virus-specific T cells from CB is both feasible and safe. However, the manufacturing process of these cells is complicated, lengthy, and labor-intensive. We have now developed a simplified method to manufacture a single culture of polyclonal multivirus-specific cytotoxic T cells in less than 30 days...
June 16, 2017: Molecular Therapy. Methods & Clinical Development
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