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ALLOGENEIC RESPONSE

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https://www.readbyqxmd.com/read/29049232/case-report-central-nervous-system-involvement-of-human-graft-versus-host-disease-report-of-7-cases-and-a-review-of-literature
#1
Mathilde Ruggiu, Wendy Cuccuini, Karima Mokhtari, Véronique Meignin, Régis Peffault de Latour, Marie Robin, Flore Sicre de Fontbrune, Aliénor Xhaard, Gérard Socié, David Michonneau
RATIONALE: Central nervous system (CNS) involvement of graft versus host disease (GvHD) is a rare cause of CNS disorders after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Chronic CNS GvHD symptoms are heterogeneous and include cerebrovascular manifestations, demyelinating disease and immune-mediated encephalitis. CNS-Acute GvHD is not formally defined in literature. PATIENTS CONCERNS AND DIAGNOSES: We report 7 cases of CNS-GvHD among which two had histological-proven disease...
October 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/29048109/evaluation-of-a-disease-risk-index-for-adult-patients-undergoing-umbilical-cord-blood-transplantation-for-haematological-malignancies
#2
Annalisa Paviglianiti, Annalisa Ruggeri, Fernanda Volt, Guillermo Sanz, Noel Milpied, Sabine Furst, Albert Esquirol, William Arcese, Alessandra Picardi, Christelle Ferra, Norbert Ifrah, Jean H Bourhis, Kavita Raj, Peter A von dem Borne, Simona Sica, Anne-Lise Menard, Adrian Bloor, Chantal Kenzey, Eliane Gluckman, Vanderson Rocha
A disease risk index (DRI) has been defined for stratifying heterogeneous cohorts of patients undergoing allogeneic haematopoietic stem cell transplantation (HSCT). This index defines 4 distinct groups with different outcomes, dividing patients by disease type and status and considering cytogenetics for acute myeloid leukaemia and myelodysplastic syndromes (MDS). Recently, the DRI has been refined to include rare diseases and improve MDS stratification by blast percentage and response to prior therapy. Previous reports on DRI include only a small number of UCBT recipients...
October 19, 2017: British Journal of Haematology
https://www.readbyqxmd.com/read/29047158/hyper-cvad-plus-nelarabine-in-newly-diagnosed-adult-t-cell-acute-lymphoblastic-leukemia-and-t-lymphoblastic-lymphoma
#3
Yasmin Abaza, Hagop M Kantarjian, Stefan Faderl, Elias Jabbour, Nitin Jain, Deborah Thomas, Tapan Kadia, Gautam Borthakur, Joseph D Khoury, Jan Burger, William Wierda, Susan O'Brien, Marina Konopleva, Alessandra Ferrajoli, Partow Kebriaei, Bouthaina Dabaja, Steven Kornblau, Yesid Alvarado, Naval Daver, Naveen Pemmaraju, Prithviraj Bose, Philip Thompson, Hind Al Azzawi, Mary Kelly, Rebecca Garris, Preetesh Jain, Guillermo Garcia-Manero, Jorge Cortes, Farhad Ravandi
Nelarabine, a water soluble prodrug of 9-β-D-arabinofuranosylguanine (ara-G), is a T-cell specific purine nucleoside analogue. Given its activity in relapsed and refractory T acute lymphoblastic leukemia (T-ALL) and T lymphoblastic lymphoma (T-LBL), we sought to define its role in the frontline treatment of adult patients. Therefore, we conducted a single arm phase 2 study to determine the safety and efficacy of nelarabine in combination with hyper-CVAD in newly diagnosed patients. For induction/consolidation, patients received eight cycles of hyper-CVAD alternating with high-dose methotrexate and cytarabine plus two cycles of nelarabine given at a dose of 650 mg/m(2) intravenously daily for 5 days...
October 19, 2017: American Journal of Hematology
https://www.readbyqxmd.com/read/29046346/t-cell-derived-cd70-delivers-an-immune-checkpoint-function-in-inflammatory-t-cell-responses
#4
Rachel E O'Neill, Wei Du, Hemn Mohammadpour, Emad Alqassim, Jingxin Qiu, George Chen, Philip L McCarthy, Kelvin P Lee, Xuefang Cao
The CD27-CD70 pathway is known to provide a costimulatory signal, with CD70 expressed on APCs and CD27 functions on T cells. Although CD70 is also expressed on activated T cells, it remains unclear how T cell-derived CD70 affects T cell function. Therefore, we have assessed the role of T cell-derived CD70 using adoptive-transfer models, including autoimmune inflammatory bowel disease and allogeneic graft-versus-host disease. Surprisingly, compared with wild-type T cells, CD70(-/-) T cells caused more severe inflammatory bowel disease and graft-versus-host disease and produced higher levels of inflammatory cytokines...
October 18, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29045966/-immune-effects-of-specific-ctls-response-induced-by-dendritic-cells-pulsed-with-ny-eso-1-peptide
#5
J W Liu, X Lu, Z M Yang, L J Deng, L Yang
OBJECTIVE: To explore the potential of autologous dendritic cells (DCs) pulsed with caner/testis antigen NY-ESO-1 peptides in inducing specific cytotoxic T lymphocyte (CTLs) response and antineoplastic immune function of specific CTLs. METHODS: Fifteen patients with II to III stage positive HLA -A0201(+) and NY-ESO-1(+) were enrolled in the Cancer Hospital Chinese Academy of Medical Sciences on the basis of preclinical experiments from November 2014 to October 2015, and their peripheral blood mononuclear cells (PBMCs) and peripheral blood lymphocytes (PBLs) were isolated...
October 18, 2017: Beijing da Xue Xue Bao. Yi Xue Ban, Journal of Peking University. Health Sciences
https://www.readbyqxmd.com/read/29044495/urban-particulate-matter-stimulation-of-human-dendritic-cells-enhances-priming-of-na%C3%A3-ve-cd8-t-lymphocytes
#6
Paul E Pfeffer, Tzer R Ho, Elizabeth H Mann, Frank J Kelly, Maria Sehlstedt, Jamshid Pourazar, Rosamund E Dove, Thomas Sandstrom, Ian S Mudway, Catherine M Hawrylowicz
Epidemiological studies have consistently shown associations between elevated concentrations of urban particulate matter (UPM) air pollution and exacerbations of asthma and COPD, which are both associated with viral respiratory infections. The effects of urban PM on dendritic cell (DC) stimulated CD4 T lymphocytes have been investigated previously, however little work has focused on CD8 T lymphocyte responses despite their importance in anti-viral immunity. To address this, we examined the effects of UPM on DC-stimulated naïve CD8 T cell responses...
October 16, 2017: Immunology
https://www.readbyqxmd.com/read/29038036/overexpression-of-notch-ligand-delta-like-1-by-dendritic-cells-enhances-their-immunoregulatory-capacity-and-exerts-antiallergic-effects-on-th2-mediated-allergic-asthma-in-mice
#7
Chen-Chen Lee, Chu-Lun Lin, Sy-Jye Leu, Yueh-Lun Lee
Dendritic cells (DCs) are professional antigen-presenting cells, and Notch ligand Delta-like-1 (DLL1) on DCs was implicated in type 1T helper (Th1) differentiation. In this study, we produced genetically engineered bone marrow-derived DCs that expressed DLL1 (DLL1-DCs) by adenoviral transduction. DLL1-DCs exerted a fully mature phenotype, and had positive effects on expression levels of interleukin (IL)-12 and costimulatory molecules. Coculture of allogeneic T cells with ovalbumin (OVA)-pulsed DLL1-DCs enhanced T cell proliferative responses and promoted Th1 cell differentiation...
October 13, 2017: Clinical Immunology: the Official Journal of the Clinical Immunology Society
https://www.readbyqxmd.com/read/29035392/long-term-outcome-of-mixed-chimerism-after-stem-cell-transplantation-for-thalassemia-major-conditioned-with-busulfan-and-cyclophosphamide
#8
N A Fouzia, E S Edison, K M Lakshmi, A Korula, S R Velayudhan, P Balasubramanian, A Abraham, A Viswabandya, B George, V Mathews, A Srivastava
Mixed chimerism (MC) occurs frequently after allogeneic hematopoietic stem cell transplantation (HSCT) for thalassemia major (TM) and may be associated with rejection. We report the outcome of MC in 132 TM patients conditioned with Busulphan/Cyclophosphamide, who had successful engraftment and had ⩾1 year follow-up. Chimerism was first assessed at day +28, then every 3-9 months or more frequently if there was MC. If rejection was suspected, immunosuppression was stopped and donor-lymphocyte infusion (DLI) was given if there was no response...
October 16, 2017: Bone Marrow Transplantation
https://www.readbyqxmd.com/read/29032276/reversal-of-low-donor-chimerism-following-hematopoietic-cell-transplantation-using-pentostatin-and-donor-lymphocyte-infusion-a-prospective-phase-ii-multicenter-trial
#9
Merav Bar, Mary E D Flowers, Barry E Storer, Thomas R Chauncey, Michael A Pulsipher, Monica S Thakar, Wolfgang Bethge, Rainer Storb, David G Maloney, Brenda M Sandmaier
In a multicenter prospective Phase II study, we evaluated the safety and efficacy of pentostatin followed by donor lymphocyte infusion (DLI) in patients with low donor T-cell chimerism after allogeneic hematopoietic cell transplantation (HCT). Thirty-six patients with low donor blood CD3 chimerism were enrolled in this study. Thirty-five patients received a total of 41 DLIs following a dose of pentostatin, and one patient received pentostatin only. Median donor CD3 chimerism prompting the initiation of pentostatin/DLI was 28 (5 to 47)%...
October 12, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/29030092/a-phase-ii-study-of-clag-regimen-combined-with-imatinib-mesylate-for-relapsed-or-refractory-acute-myeloid-leukemia
#10
Abu-Sayeef Mirza, Jeffrey E Lancet, Kendra Sweet, Eric Padron, Javier Pinilla-Ibarz, Lisa Nardelli, Christopher Cubitt, Alan F List, Rami S Komrokji
INTRODUCTION: No standard salvage chemotherapy regimen is available for relapsed or refractory (RR) acute myeloid leukemia (AML). Preclinical data have suggested synergy in vitro between cytarabine and imatinib mesylate (IM) on AML cell growth inhibition. After demonstrating the safety and feasibility in a phase I study, we conducted a phase II clinical study of CLAG (cladribine, cytarabine, granulocyte colony-stimulating factor) regimen combined with IM for patients with RR-AML. PATIENTS AND METHODS: We performed a single-institution 2-stage phase II study...
September 19, 2017: Clinical Lymphoma, Myeloma & Leukemia
https://www.readbyqxmd.com/read/29025591/identification-of-a-novel-csf3r-sptan1-fusion-gene-in-an-atypical-chronic-myeloid-leukemia-patient-with-t-1-9-p34-q34-by-rna-seq
#11
Guangying Sheng, Jian Zhang, Zhao Zeng, Jinlan Pan, Qinrong Wang, Lijun Wen, Yang Xu, Depei Wu, Suning Chen
Membrane-proximal and truncated mutations of colony-stimulating factor 3 receptor (CSF3R) are frequently found in chronic neutrophilic leukemia (CNL) and atypical chronic myeloid leukemia (aCML). However, rearrangement involving CSF3R in hematological neoplasms has not been reported. Here, we report a case of a 21-year-old female diagnosed as aCML with t(1;9)(p34;q34) who presented a CSF3R rearrangement. First, RNA sequencing identified a novel fusion transcript involving exon 17 of CSF3R and exon 50 of non-erythrocytic-1-spectrin-alpha (SPTAN1)...
October 2017: Cancer Genetics
https://www.readbyqxmd.com/read/29024591/small-molecule-inhibitors-of-the-cd40-cd40l-costimulatory-protein-protein-interaction
#12
Jinshui Chen, Yun Song, Damir Bojadzic, Alejandro Tamayo-Garcia, Ana Marie Landin, Bonnie B Blomberg, Peter Buchwald
Costimulatory interactions are required for T cell activation and development of an effective immune response; hence, they are valuable therapeutic targets for immunomodulation. However, they, as all other protein-protein interactions, are difficult to target by small molecules. Here, we report the identification of novel small-molecule inhibitors of the CD40-CD40L interaction designed starting from the chemical space of organic dyes. For the most promising compounds such as DRI-C21045, activity (IC50) in the low micromolar range has been confirmed in cell assays including inhibition of CD40L-induced activation in NF-κB sensor cells, THP-1 myeloid cells, and primary human B cells as well as in murine allogeneic skin transplant and alloantigen-induced T cell expansion in draining lymph node experiments...
October 12, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29023857/preceding-haemorrhagic-shock-as-a-detrimental-risk-factor-for-respiratory-distress-after-excessive-allogeneic-blood-transfusion
#13
R Masuda, T Iijima, R Kondo, Y Itoda, M Matsuhashi, S Hashimoto, T Kohira, N Kobayashi, H Okazaki
BACKGROUND AND OBJECTIVES: Whether transfusion-associated circulatory overload arises as a simple result of over-transfusion or requires another trigger remains unclear. Here, we examined whether respiratory distress could be reproduced by massive transfusion alone in an animal model. MATERIALS AND METHODS: A total of 20 anaesthetized swine were equipped with monitors. Allogeneic blood was obtained from 10 donor swine. A 4-stage loading protocol with each stage equivalent to 25% of the blood volume (BV) in the recipient swine was then used to infuse crystalloid (CR), hydroxyethyl starch (HES) or allogeneic blood (TR) (n = 5 each)...
October 11, 2017: Vox Sanguinis
https://www.readbyqxmd.com/read/29023302/complete-resolution-of-lymphoid-interstitial-pneumonia-in-a-patient-with-juvenile-myelomonocytic-leukemia-treated-with-allogeneic-bone-marrow-transplant-killing-2-birds-with-1-stone
#14
Anant Vatsayan, Ravi Talati, Kristen Nagle, Linda Cabral, Sloane Cammock, Amy Dimarino, Rachel Egler, Shahrazad Saab, Jignesh Dalal
Lymphoid interstitial pneumonia (LIP) is a rare disease characterized by benign reactive polyclonal proliferation of bronchus-associated lymphoid tissue after exposure to inhaled or circulating antigen(s), leading to a disease symptomatology similar to idiopathic interstitial pneumonia. Its association with diseases that are caused due to immune dysregulation (autoimmune diseases, congenital/acquired immunodeficiency, and allogeneic bone marrow transplant) and response to immunomodulatory/suppressive medications suggests an immunologic pathophysiology...
October 11, 2017: Journal of Pediatric Hematology/oncology
https://www.readbyqxmd.com/read/29023267/enhanced-th17-responses-in-patients-with-il10-receptor-deficiency-and-infantile-onset-ibd
#15
Dror S Shouval, Liza Konnikova, Alexandra E Griffith, Sarah M Wall, Amlan Biswas, Lael Werner, Moran Nunberg, Jochen Kammermeier, Jeremy A Goettel, Rajsavi Anand, Hannah Chen, Batia Weiss, Jian Li, Anthony Loizides, Baruch Yerushalmi, Tadahiro Yanagi, Rita Beier, Laurie S Conklin, Christen L Ebens, Fernanda G M S Santos, Mary Sherlock, Jeffery D Goldsmith, Daniel Kotlarz, Sarah C Glover, Neil Shah, Athos Bousvaros, Holm H Uhlig, Aleixo M Muise, Christoph Klein, Scott B Snapper
BACKGROUND: IL10 receptor (IL10R) deficiency causes severe infantile-onset inflammatory bowel disease. Intact IL10R-dependent signals have been shown to be important for innate and adaptive immune cell functions in mice. We have previously reported a key role of IL10 in the generation and function of human anti-inflammatory macrophages. Independent of innate immune cell defects, the aim of the current study was to determine the role of IL10R signaling in regulating human CD4 T-cell function...
November 2017: Inflammatory Bowel Diseases
https://www.readbyqxmd.com/read/29019177/long-term-survival-after-complete-surgical-resection-and-adjuvant-immunotherapy-for-distant-melanoma-metastases
#16
Mark B Faries, Nicola Mozzillo, Mohammed Kashani-Sabet, John F Thompson, Mark C Kelley, Ronald C DeConti, Jeffrey E Lee, James F Huth, Jeffrey Wagner, Angus Dalgleish, Daniel Pertschuk, Christopher Nardo, Stacey Stern, Robert Elashoff, Guy Gammon, Donald L Morton
BACKGROUND: This phase III study was undertaken to evaluate the efficacy of an allogeneic whole-cell vaccine (Canvaxin™) plus bacillus Calmette-Guerin (BCG) after complete resection of stage IV melanoma. METHODS: After complete resection of ≤5 distant metastases, patients were randomly assigned to BCG+Canvaxin (BCG/Cv) or BCG+placebo (BCG/Pl). The primary endpoint was overall survival (OS); secondary endpoints were disease-free survival (DFS), and immune response measured by skin test (ClinicalTrials...
October 10, 2017: Annals of Surgical Oncology
https://www.readbyqxmd.com/read/29017084/disseminated-adenovirus-infection-after-allogeneic-stem-cell-transplant-and-the-potential-role-of-brincidofovir-case-series-and-10-year-experience-of-management-in-an-adult-transplant-cohort
#17
Isobel D Ramsay, Charlotte Attwood, Dianne Irish, Paul D Griffiths, Charalampia Kyriakou, David M Lowe
BACKGROUND: Adenovirus infection is a recognized complication following haematopoietic stem cell transplantation. We present a review of our experience of these infections in our transplant cohort over 10 years including 3 patients treated with the novel antiviral brincidofovir. OBJECTIVES: We aimed to describe the presentation, response to treatment and outcomes of adult stem cell transplant patients with disseminated adenovirus infection. STUDY DESIGN: All adult cases of disseminated adenovirus infection following haematopoietic stem cell transplant in our unit between 2005 and 2015 were identified...
October 3, 2017: Journal of Clinical Virology: the Official Publication of the Pan American Society for Clinical Virology
https://www.readbyqxmd.com/read/28990873/third-line-treatment-with-second-generation-tyrosine-kinase-inhibitors-dasatinib-or-nilotinib-in-patients-with-chronic-myeloid-leukemia-after-two-prior-tkis-real-life-data-on-a-single-center-experience-along-with-the-review-of-the-literature
#18
Seniz Ongoren, Ahmet Emre Eskazan, Veysel Suzan, Sercan Savci, Isil Erdogan Ozunal, Selin Berk, Fevzi Fırat Yalniz, Tugrul Elverdi, Ayse Salihoglu, Yucel Erbilgin, Sibel Aylin Iseri, Muhlis Cem Ar, Zafer Baslar, Yildiz Aydin, Nukhet Tuzuner, Ugur Ozbek, Teoman Soysal
OBJECTIVES: Newer tyrosine kinase inhibitors (TKIs) (bosutinib, ponatinib) and allogeneic hematopoietic stem cell transplantation (allo-HSCT) can be utilized as a salvage therapy in patients with chronic myeloid leukemia (CML) who failed two lines (imatinib → nilotinib or imatinib → dasatinib) of TKI therapy. However, these TKIs are not available in many countries and not all patients can undergo allo-HSCT. METHODS: In this study, CML patients who received dasatinib or nilotinib as a third-line treatment were retrospectively evaluated...
October 9, 2017: Hematology (Amsterdam, Netherlands)
https://www.readbyqxmd.com/read/28990426/gene-therapy-for-modulation-of-t-cell-mediated-immune-response-provoked-by-corneal-transplantation
#19
Marko Pastak, Veronika Kleff, Daniel Raphael Saban, Marta Czugala, Klaus-Peter Steuhl, Süleyman Ergün, Bernhard Singer, Thomas Armin Fuchsluger
Corneal transplantation (=keratoplasty) is the most common type of tissue replacement in the world. The increased rate of graft rejection after keratoplasty is a central problem for repeated transplantations and in inflamed host corneas. It has been shown that apoptosis of grafted epithelium has a role in corneal allograft rejection. Our study focused on the T cell response triggered in BALB/c mice after allogeneic corneal transplantation with and without anti-apoptotic p35-transduced epithelium. To restrict p35 expression to the epithelial cells we created modified allogeneic composite grafts...
October 7, 2017: Human Gene Therapy
https://www.readbyqxmd.com/read/28982299/multivariate-analysis-of-prognosis-for-patients-with-natural-killer-t-cell-lymphoma-associated-hemophagocytic-lymphohistiocytosis
#20
Zhili Jin, Yini Wang, Jingshi Wang, Lin Wu, Ruijun Pei, Wenyuan Lai, Zhao Wang
OBJECTIVE: A major cause of hemophagocytic lymphohistiocytosis (HLH) is malignant neoplasms of the blood system, among which NK/T cell lymphoma is one of the most common risk factors. Patients with NK/T cell lymphoma hemophagocytic lymphohistiocytosis (NK/T-LAHS) have a worse prognosis and higher mortality. We aimed to explore the factors that affect the prognosis of NK/T-LAHS. METHODS: Clinical data of 42 patients with NK/T-LAHS diagnosed by Beijing Friendship Hospital from June 2008 to June 2016 were analyzed retrospectively...
October 6, 2017: Hematology (Amsterdam, Netherlands)
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