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T-cells, hematopoietic cell transplant

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https://www.readbyqxmd.com/read/28641094/emerging-concepts-in-cytomegalovirus-infection-following-hematopoietic-stem-cell-transplantation
#1
REVIEW
Jose F Camargo, Krishna V Komanduri
Despite the refinements in molecular methods for the detection of cytomegalovirus (CMV) and the advent of highly effective preemptive strategies, CMV remains a leading cause of morbidity and mortality in hematopoietic cell transplant (HCT) recipients. CMV can cause tissue-invasive disease including pneumonia, hepatitis, colitis, retinitis, and encephalitis. Mortality in HCT recipients with CMV disease can be as high as 60%. CMV infection has been associated with increased risk of secondary bacterial and fungal infections, increased risk of graft-versus-host disease, and high rates of nonrelapse mortality following HCT...
June 14, 2017: Hematology/oncology and Stem Cell Therapy
https://www.readbyqxmd.com/read/28636890/memory-t-cells-a-helpful-guard-for-allogeneic-hematopoietic-stem-cell-transplantation-without-causing-graft-versus-host-disease
#2
REVIEW
Wei Huang, Nelson J Chao
Graft-versus-host disease (GVHD) is a major complication of allogeneic hematopoietic stem cell transplantation (AHSCT) and the major cause of nonrelapse morbidity and mortality of AHSCT. In AHSCT, donor T cells facilitate hematopoietic stem cell (HSC) engraftment, contribute to anti-infection immunity, and mediate graft-versus-leukemia (GVL) responses. However, activated alloreactive T cells also attack recipient cells in vital organs, leading to GVHD. Different T-cell subsets, including naïve T (TN) cells, memory T (TM) cells, and regulatory T (Treg) cells mediate different forms of GVHD and GVL; TN cells mediate severe GVHD, whereas TM cells do not cause GVHD, but preserve T-cell function including GVL...
June 13, 2017: Hematology/oncology and Stem Cell Therapy
https://www.readbyqxmd.com/read/28632323/clinical-outcomes-of-hla-dpb1-mismatches-in-10-10-hla-matched-unrelated-donor-recipient-pairs-undergoing-allogeneic-stem-cell-transplant
#3
Ann M Moyer, Shahrukh K Hashmi, Cynthia M Kroning, Walter K Kremers, Steven R De Goey, Mrinal Patnaik, Mark Litzow, Dennis A Gastineau, William J Hogan, Eapen K Jacob, Justin D Kreuter, Laurie L Wakefield, Manish J Gandhi
OBJECTIVE: HLA-DPB1 matching may impact allogeneic hematopoietic stem cell transplantation (ASCT) outcomes; however, this locus is not in linkage disequilibrium with the remainder of the HLA genes. After classifying HLA-DPB1 mismatches based on T-cell epitope, avoiding non-permissive mismatches may impact survival. We tested this hypothesis at a single academic institution. METHODS: Retrospective HLA-DPB1 genotyping was performed on 153 adult patients who underwent ASCT and unrelated donors matched for HLA-A, B, C, DRB1 and DQB1 loci (10/10)...
June 20, 2017: European Journal of Haematology
https://www.readbyqxmd.com/read/28628089/elevated-bone-marrow-eosinophil-count-is-associated-with-high-incidence-of-severe-acute-gvhd-after-allogeneic-hematopoietic-stem-cell-transplantation
#4
Y Shimomura, M Hara, H Hashimoto, T Ishikawa
Predicting severe acute GvHD (aGvHD) after allogeneic hematopoietic stem cell transplantation (HSCT) is challenging but critical. Mild aGvHD may have a favorable impact on relapse, whereas severe aGvHD is associated with poor outcomes. The aim of this study was to evaluate whether elevated eosinophil count in the bone marrow (BM) at 1 month after HSCT is associated with a high incidence of new and severe aGvHD. We enrolled 101 consecutive patients; median age was 50 years, and 50.5% patients were male. The median eosinophil concentration in BM at 1 month after HSCT was 1...
June 19, 2017: Bone Marrow Transplantation
https://www.readbyqxmd.com/read/28628043/immunotherapy-for-transplantation-associated-viral-infections
#5
Claire Roddie, Karl S Peggs
Cytomegalovirus (CMV) and Epstein-Barr virus (EBV) infections following allogeneic hematopoietic stem cell transplantation (HSCT) are a major cause of morbidity and mortality. Early clinical trials demonstrate that adoptive transfer of donor-derived virus-specific T cells to restore virus-specific immunity is an effective strategy to control CMV and EBV infection after HSCT, conferring protection in 70%-90% of patients. The field has evolved rapidly to develop solutions to some of the manufacturing challenges identified in early clinical studies, such as prolonged in vitro culture, optimization of the purity of the virus-specific T cell product, the potential limitations of targeting a single viral antigen, and how to manage the patient with a virus-naive donor...
June 19, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28628037/alloimmune-t-cells-in-transplantation
#6
Susan DeWolf, Megan Sykes
Alloimmune T cells are central mediators of rejection and graft-versus-host disease in both solid organ and hematopoietic stem cell transplantation. Unique among immune responses in terms of its strength and diversity, the T cell alloresponse reflects extensive genetic polymorphisms between allogeneic donors and recipients, most prominently within the major histocompatibility complex (MHC), which encodes human leukocyte antigens (HLAs) in humans. The repertoire of alloreactive T cell clones is distinct for every donor-recipient pair and includes potentially thousands of unique HLA/peptide specificities...
June 19, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28627158/evaluation-of-serum-interleukin-21-and-hla-c1-polymorphism-in-pediatrician-hematopoietic-stem-cell-transplantation-for-early-diagnosis-of-acute-graft-versus-host-disease
#7
N Sehati, P Kokhaei, A Motevalizade Ardekani, R Tootoonchian, F Pak
Background: Allogenic hematopoietic stem cell transplantation (HSCT) is a strategy used for treatment of different malignant diseases. However, success of allo-HSCT can be hampered by graft-versus-host-disease (GVHD). Natural killer (NK) cells may play an important role in activating antigen presenting cells and subsequent activation of T cells. The main purpose of this study was the evaluation of IL-21, as a blood biomarker, for early detection of acute GVHD (aGVHD) in children after HSCT and also the study of human leukocytes antigen (HLA)-C1 polymorphism, as a targeting ligand for NK cells in these patients...
June 19, 2017: Iranian Biomedical Journal
https://www.readbyqxmd.com/read/28625828/precision-monitoring-of-immunotherapies-in-solid-organ-and-hematopoietic-stem-cell-transplantation
#8
Rose Diloreto, Kiran Khush, Iwijn De Vlaminck
Pharmacological immunotherapies are a key component of post-transplant therapy in solid-organ and hematopoietic stem cell transplantation. In current clinical practice, immunotherapies largely follow a one-size fits all approach, leaving a large portion of transplant recipients either over- or under-immunosuppressed, and consequently at risk of infections or immune-mediated complications. Our goal here is to review recent and rapid advances in precision and genomic medicine approaches to monitoring of post-transplant immunotherapies...
June 15, 2017: Advanced Drug Delivery Reviews
https://www.readbyqxmd.com/read/28624782/g-csf-inhibits-lfa-1-mediated-cd4-t-cell-functions-by-inhibiting-lck-and-zap-70
#9
Shasha Zhao, Zhenyang Gu, Li Wang, Lixun Guan, Feiyan Wang, Nan Yang, Lan Luo, Zhe Gao, Yingwei Song, Lili Wang, Daihong Liu, Chunji Gao
In this study, we showed that G-CSF mobilization increased the frequency of T cells, specifically CD3+CD4+ T cells. G-CSF mobilization decreased the secretion of inflammatory cytokines of CD4+ T cells through the LFA-1/ICAM-1 signaling pathway, whereas it did not alter the TH1/TH2 ratio. We found that G-CSF mobilization inhibited LFA-1-mediated CD4+ T cell polarization and motility. In vitro, G-CSF stimulation also attenuated the polarization and adhesiveness of CD4+ T cells through the LFA-1/ICAM-1 interaction...
May 25, 2017: Oncotarget
https://www.readbyqxmd.com/read/28621800/a-consensus-review-on-malignancy-associated-hemophagocytic-lymphohistiocytosis-in-adults
#10
REVIEW
Naval Daver, Kenneth McClain, Carl E Allen, Sameer A Parikh, Zaher Otrock, Cristhiam Rojas-Hernandez, Boris Blechacz, Sa Wang, Milen Minkov, Michael B Jordan, Paul La Rosée, Hagop M Kantarjian
Hemophagocytic lymphohistiocytosis (HLH) is a syndrome of severe immune activation and dysregulation resulting in extreme and often life-threatening inflammation. HLH has been well recognized in pediatric populations, and most current diagnostic and therapeutic guidelines are based on pediatric HLH. Recently there has been recognition of HLH in adults, especially secondary to immune deregulation by an underlying rheumatologic, infectious, or malignant condition. This review is focused on malignancy-associated HLH (M-HLH), in which possible mechanisms of pathogenesis include severe inflammation, persistent antigen stimulation by the tumor cells, and loss of immune homeostasis because of chemotherapy, hematopoietic stem cell transplantation, or infection...
June 16, 2017: Cancer
https://www.readbyqxmd.com/read/28620195/attenuation-of-cgvhd-by-c5a-c5ar-blockade-is-associated-with-increased-frequency-of-treg
#11
Yulian Wang, Peilong Lai, Xiaomei Chen, Chang He, Xin Huang, Suxia Geng, Chenwei Luo, Suijing Wu, Wei Ling, Liye Zhong, Zesheng Lu, Peng Li, Jianyu Weng, Xin Du
C5aR signaling plays an important role in the regulation of T cell activation and alloimmune responses in chronic graft-versus-host disease (cGVHD). However, direct evidence of this modulation and the efficacy of C5aR blockade in the treatment of cGVHD have not been demonstrated. We observed higher expression of C5aR on both monocytes and T cells of patients with cGVHD compared with healthy controls and non-GVHD patients after allogeneic hematopoietic stem cell transplantation. Our data also demonstrated a significant negative correlation between C5aR expression and regulatory T cells (Treg) frequency in cGVHD patients, indicating a potential role of C5aR in the generation and regulation of Treg...
June 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28618138/expansion-of-umbilical-cord-blood-aldehyde-dehydrogenase-expressing-cells-generates-myeloid-progenitor-cells-that-stimulate-limb-revascularization
#12
David M Putman, Tyler T Cooper, Stephen E Sherman, Ayesh K Seneviratne, Mark Hewitt, Gillian I Bell, David A Hess
Uncompromised by chronic disease-related comorbidities, human umbilical cord blood (UCB) progenitor cells with high aldehyde dehydrogenase activity (ALDH(hi) cells) stimulate blood vessel regeneration after intra-muscular transplantation. However, implementation of cellular therapies using UCB ALDH(hi) cells for critical limb ischemia, the most severe form of severe peripheral artery disease, is limited by the rarity (<0.5%) of these cells. Our goal was to generate a clinically-translatable, allogeneic cell population for vessel regenerative therapies, via ex vivo expansion of UCB ALDH(hi) cells without loss of pro-angiogenic potency...
June 15, 2017: Stem Cells Translational Medicine
https://www.readbyqxmd.com/read/28615219/zfp521-regulates-murine-hematopoietic-stem-cell-function-and-facilitates-mll-af9-leukemogenesis-in-mouse-and-human-cells
#13
Brian S Garrison, Adrian P Rybak, Isabel Beerman, Balthasar Heesters, Francois E Mercier, David T Scadden, David Bryder, Roland Baron, Derrick J Rossi
The concept that tumor-initiating cells can co-opt the self-renewal program of endogenous stem cells as a means of enforcing their unlimited proliferative potential is widely accepted, yet identification of specific factors that regulate self-renewal of normal and cancer stem cells remains limited. Using a comparative transcriptomic approach, we identify ZNF521/Zfp521 as a conserved hematopoietic stem cell (HSC)-enriched transcription factor in human and murine hematopoiesis, whose function in HSC biology remains elusive...
June 14, 2017: Blood
https://www.readbyqxmd.com/read/28615039/interleukin-21-promotes-thymopoiesis-recovery-following-hematopoietic-stem-cell-transplantation
#14
Aurélie Tormo, Fatemeh Khodayarian, Yun Cui, Edouard Al-Chami, Reem Kanjarawi, Beatriz Noé, Huijie Wang, Moutih Rafei
BACKGROUND: Impaired T cell reconstitution remains a major deterrent in the field of bone marrow (BM) transplantation (BMT) due to pre-conditioning-induced damages inflicted to the thymi of recipient hosts. Given the previously reported thymo-stimulatory property of interleukin (IL)-21, we reasoned that its use post-BMT could have a profound effect on de novo T cell development. METHODS: To evaluate the effect of IL-21 on de novo T cell development in vivo, BM derived from RAG2p-GFP mice was transplanted into LP/J mice...
June 14, 2017: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/28614804/in-vivo-kinetics-and-nonradioactive-imaging-of-rapidly-proliferating-cells-in-graft-versus-host-disease
#15
Nataliya P Buxbaum, Donald E Farthing, Natella Maglakelidze, Martin Lizak, Hellmut Merkle, Andrea C Carpenter, Brittany U Oliver, Veena Kapoor, Ehydel Castro, Gregory A Swan, Liliane M Dos Santos, Nicolas J Bouladoux, Catherine V Bare, Francis A Flomerfelt, Michael A Eckhaus, William G Telford, Yasmine Belkaid, Remy J Bosselut, Ronald E Gress
Hematopoietic stem cell transplantation (HSCT) offers a cure for cancers that are refractory to chemotherapy and radiation. Most HSCT recipients develop chronic graft-versus-host disease (cGVHD), a systemic alloimmune attack on host organs. Diagnosis is based on clinical signs and symptoms, as biopsies are risky. T cells are central to the biology of cGVHD. We found that a low Treg/CD4+ T effector memory (Tem) ratio in circulation, lymphoid, and target organs identified early and established mouse cGVHD. Using deuterated water labeling to measure multicompartment in vivo kinetics of these subsets, we show robust Tem and Treg proliferation in lymphoid and target organs, while Tregs undergo apoptosis in target organs...
June 15, 2017: JCI Insight
https://www.readbyqxmd.com/read/28613269/exploiting-cell-death-pathways-for-inducible-cell-elimination-to-modulate-graft-versus-host-disease
#16
REVIEW
Corey Falcon, Mustafa Al-Obaidi, Antonio Di Stasi
Hematopoietic stem cell transplantation is a potent form of immunotherapy, potentially life-saving for many malignant hematologic diseases. However, donor lymphocytes infused with the graft while exerting a graft versus malignancy effect can also cause potentially fatal graft versus host disease (GVHD). Our group has previously validated the inducible caspase-9 suicide gene in the haploidentical stem cell transplant setting, which proved successful in reversing signs and symptoms of GVHD within hours, using a non-therapeutic dimerizing agent...
June 14, 2017: Biomedicines
https://www.readbyqxmd.com/read/28607133/loss-of-thymic-innate-lymphoid-cells-leads-to-impaired-thymopoiesis-in-experimental-graft-vs-host-disease
#17
Jarrod A Dudakov, Anna M Mertelsmann, Margaret H O'Connor, Robert R Jenq, Enrico Velardi, Lauren F Young, Odette M Smith, Richard L Boyd, Marcel R M van den Brink, Alan M Hanash
Graft vs. host disease (GVHD) and post-transplant immunodeficiency are frequently related complications of allogeneic hematopoietic transplantation. Alloreactive donor T cells can damage thymic epithelium, thus limiting new T cell development. While the thymus has a remarkable capacity to regenerate after injury, endogenous thymic regeneration is impaired in GVHD. The mechanisms leading to this regenerative failure are largely unknown. Here we demonstrate in experimental mouse models that GVHD results in depletion of intrathymic group 3 innate lymphoid cells (ILC3s) necessary for thymic regeneration...
June 12, 2017: Blood
https://www.readbyqxmd.com/read/28605290/early-response-based-therapy-stratification-improves-survival-in-adult-early-thymic-precursor-acute-lymphoblastic-leukemia-a-group-for-research-on-adult-acute-lymphoblastic-leukemia-study
#18
Jonathan Bond, Carlos Graux, Ludovic Lhermitte, Diane Lara, Thomas Cluzeau, Thibaut Leguay, Agata Cieslak, Amélie Trinquand, Cedric Pastoret, Mohamed Belhocine, Salvatore Spicuglia, Véronique Lheritier, Stéphane Leprêtre, Xavier Thomas, Françoise Huguet, Norbert Ifrah, Hervé Dombret, Elizabeth Macintyre, Nicolas Boissel, Vahid Asnafi
Purpose Early thymic precursor (ETP) acute lymphoblastic leukemia (ALL) is an immunophenotypically defined subgroup of T-cell ALL (T-ALL) associated with high rates of intrinsic treatment resistance. Studies in children have shown that the negative prognostic impact of chemotherapy resistance is abrogated by the implementation of early response-based intensification strategies. Comparable data in adults are lacking. Patients and Methods We performed comprehensive clinicobiologic, genetic, and survival analyses of a large cohort of 213 adult patients with T-ALL, including 47 patients with ETP-ALL, treated in the GRAALL (Group for Research on Adult Acute Lymphoblastic Leukemia) -2003 and -2005 studies...
June 12, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28604557/antigen-presentation-by-individually-transferred-hla-class-i-genes-in-hla-a-hla-b-hla-c-null-human-cell-line-generated-using-the-multiplex-crispr-cas9-system
#19
Cheol-Hwa Hong, Hyun-Jung Sohn, Hyun-Joo Lee, Hyun-Il Cho, Tai-Gyu Kim
Human leukocyte antigens (HLAs) are essential immune molecules that affect transplantation and adoptive immunotherapy. When hematopoietic stem cells or organs are transplanted with HLA-mismatched recipients, graft-versus-host disease or graft rejection can be induced by allogeneic immune responses. The function of each HLA allele has been studied using HLA-deficient cells generated from mutant cell lines or by RNA interference, zinc finger nuclease, and the CRISPR/Cas9 system. To improve HLA gene editing, we attempted to generate an HLA class I null cell line using the multiplex CRISPR/Cas9 system by targeting exons 2 and 3 of HLA-A, HLA-B, and HLA-C genes simultaneously...
July 2017: Journal of Immunotherapy
https://www.readbyqxmd.com/read/28604385/differential-requirements-for-myeloid-leukemia-ifn-%C3%AE-conditioning-determine-graft-versus-leukemia-resistance-and-sensitivity
#20
Catherine Matte-Martone, Jinling Liu, Meng Zhou, Maria Chikina, Douglas R Green, John T Harty, Warren D Shlomchik
The graft-versus-leukemia (GVL) effect in allogeneic hematopoietic stem cell transplantation (alloSCT) is potent against chronic phase chronic myelogenous leukemia (CP-CML), but blast crisis CML (BC-CML) and acute myeloid leukemias (AML) are GVL resistant. To understand GVL resistance, we studied GVL against mouse models of CP-CML, BC-CML, and AML generated by the transduction of mouse BM with fusion cDNAs derived from human leukemias. Prior work has shown that CD4+ T cell-mediated GVL against CP-CML and BC-CML required intact leukemia MHCII; however, stem cells from both leukemias were MHCII negative...
June 12, 2017: Journal of Clinical Investigation
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