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https://www.readbyqxmd.com/read/28636890/memory-t-cells-a-helpful-guard-for-allogeneic-hematopoietic-stem-cell-transplantation-without-causing-graft-versus-host-disease
#1
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/28636889/complications-of-hematopoietic-stem-transplantation-fungal-infections
#2
REVIEW
Ali S Omrani, Reem S Almaghrabi
Patients undergoing allogeneic hematopoietic stem cell transplantation (HSCT) are at increased risk of invasive fungal infections, especially during the early neutropenic phase and severe graft-versus-host disease. Mold-active prophylaxis should be limited to the highest risk groups. Empiric antifungal therapy for HSCT with persistent febrile neutropenia is associated with unacceptable response rates, unnecessary antifungal therapy, increased risk of toxicity, and inflated costs. Empiric therapy should not be a substitute for detailed work up to identify the cause of fever in such patients...
June 13, 2017: Hematology/oncology and Stem Cell Therapy
https://www.readbyqxmd.com/read/28635677/t-cell-manipulation-strategies-to-prevent-graft-versus-host-disease-in-haploidentical-stem-cell-transplantation
#3
REVIEW
Jayakumar Vadakekolathu, Sergio Rutella
Allogeneic haematopoietic stem cell transplantation (HSCT) from an human leukocyte antigen (HLA)-identical donor can be curative for eligible patients with non-malignant and malignant haematological disorders. HSCT from alternative donor sources, such as HLA-mismatched haploidentical donors, is increasingly considered as a viable therapeutic option for patients lacking HLA-matched donors. Initial attempts at haploidentical HSCT were associated with vigorous bidirectional alloreactivity, leading to unacceptably high rates of graft rejection and graft-versus-host disease (GVHD)...
June 21, 2017: Biomedicines
https://www.readbyqxmd.com/read/28630222/acute-pneumatosis-cystoides-intestinalis-with-atrophic-desmosis-of-the-colon-in-a-child
#4
Blanca Schuster, Johannes Mayr
Acute pneumatosis cystoides intestinalis (PCI) has been described after bone marrow transplantation (BMT). Several case series have demonstrated successful conservative treatment of PCI in children. We present a child with Fanconi anaemia, who developed severe graft versus host disease of the gastrointestinal tract, skin and liver after BMT and an acute, severe form of PCI. Our case report illustrates the complexity of diagnostic and therapeutic procedures in PCI in immunocompromised children.
June 19, 2017: BMJ Case Reports
https://www.readbyqxmd.com/read/28628037/alloimmune-t-cells-in-transplantation
#5
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/28627425/a-multicenter-retrospective-analysis-stressing-importance-of-long-term-follow-up-after-hematopoietic-cell-transplantation-for-%C3%AE-thalassemia
#6
S Chaudhury, M Ayas, C Rosen, M Ma, M Viqaruddin, S Parikh, S Kharbanda, K Y Chiang, A Haight, M Bhatia, Gmt Guilcher, A Thompson, S Shenoy
Allogeneic hematopoietic cell transplantation (HCT) is curative in patients with β-thalassemia major. However, the majority of reports on HCT outcomes lack long-term follow-up data with the exception of single center reports. An international multicenter retrospective data collection and analysis was conducted in 176 β-Thalassemia patients who were 1 year or beyond after first HCT to evaluate follow up methods and outcomes at 7 centers- Median age at HCT was 5.5 years (range, 0.6- 18.5) and median follow-up was 7 years (range, 1-20)...
June 13, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/28627413/modeling-esophagitis-using-human-three-dimensional-organotypic-culture-system
#7
Dorottya Laczkó, Fang Wang, F Bradley Johnson, Nirag Jhala, András Rosztóczy, Gregory G Ginsberg, Gary W Falk, Anil K Rustgi, John P Lynch
Esophagitis, whether caused by acid reflux, allergic responses, graft-versus-host disease, drugs, or infections, is a common condition of the gastrointestinal tract affecting nearly 20% of the US population. The instigating agent typically triggers an inflammatory response. The resulting inflammation is a risk factor for the development of esophageal strictures, Barrett esophagus, and esophageal adenocarcinoma. Research into the pathophysiology of these conditions has been limited by the availability of animal and human model systems...
June 13, 2017: American Journal of Pathology
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
#8
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/28626936/a-pilot-study-comparing-histological-and-immunophenotypic-patterns-in-stage-4-skin-graft-versus-host-disease-from-toxic-epidermal-necrolysis
#9
Haley Naik, Stephen Lockwood, Arturo Saavedra
Since the inception of bone marrow transplantation, clinicians have sought to distinguish stage 4 skin graft versus host disease (GVHD) from toxic epidermal necrolysis (TEN).(1-3) In certain contexts, it can be difficult to discern among these two entities, both clinically and histologically. However, the distinction is critical because both diseases can be life-threatening and their respective management and prognosis differ.
June 19, 2017: Journal of Cutaneous Pathology
https://www.readbyqxmd.com/read/28624782/g-csf-inhibits-lfa-1-mediated-cd4-t-cell-functions-by-inhibiting-lck-and-zap-70
#10
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/28623394/disease-specific-hematopoietic-stem-cell-transplantation-in-children-with-inherited-bone-marrow-failure-syndromes
#11
Qian Li, Changying Luo, Chengjuan Luo, Jianmin Wang, Benshang Li, Lixia Ding, Jing Chen
Hematopoietic stem cell transplantation (HSCT) using an optimized conditioning regimen is essential for the long-term survival of patients with inherited bone marrow failure syndromes (IBMFS). We report HSCT in 24 children with Fanconi anemia (FA, n = 12), Diamond-Blackfan anemia (DBA, n = 7), and dyskeratosis congenita (DC, n = 5) from a single HSCT center. The graft source was peripheral blood stem cells (n = 19) or cord blood stem cells (n = 5). FA and DC patients received reduced-intensity conditioning, while DBA patients had myeloablative conditioning...
June 16, 2017: Annals of Hematology
https://www.readbyqxmd.com/read/28623375/skin-immunity
#12
REVIEW
Agata Matejuk
Skin is the largest organ of the body with a complex network of multitude of cell types that perform plastic and dynamic cellular communication to maintain several vital processes such as inflammation, immune response including induction of tolerance and disease prevention, wound healing, and angiogenesis. Of paramount importance are immunological functions of the skin that protect from harmful exposure coming from external and internal environments. Awareness of skin immunity can provide a better comprehension of inflammation, autoimmunity, cancer, graft-versus-host disease, vaccination, and immunotherapy approaches...
June 16, 2017: Archivum Immunologiae et Therapiae Experimentalis
https://www.readbyqxmd.com/read/28620195/attenuation-of-cgvhd-by-c5a-c5ar-blockade-is-associated-with-increased-frequency-of-treg
#13
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/28617827/nog-hil-4-tg-a-new-humanized-mouse-model-for-producing-tumor-antigen-specific-igg-antibody-by-peptide-vaccination
#14
Yoshie Kametani, Ikumi Katano, Asuka Miyamoto, Yusuke Kikuchi, Ryoji Ito, Yukari Muguruma, Banri Tsuda, Sonoko Habu, Yutaka Tokuda, Kiyoshi Ando, Mamoru Ito
Immunodeficient mice transplanted with human peripheral blood mononuclear cells (PBMCs) are promising tools to evaluate human immune responses to vaccines. However, these mice usually develop severe graft-versus-host disease (GVHD), which makes estimation of antigen-specific IgG production after antigen immunization difficult. To evaluate antigen-specific IgG responses in PBMC-transplanted immunodeficient mice, we developed a novel NOD/Shi-scid-IL2rγnull (NOG) mouse strain that systemically expresses the human IL-4 gene (NOG-hIL-4-Tg)...
2017: PloS One
https://www.readbyqxmd.com/read/28616698/costs-of-hematopoietic-stem-cell-transplantation-in-a-developing-country
#15
Monica M Rivera-Franco, Eucario Leon-Rodriguez, Haydee L Castro-Saldaña
Costs of HSCT in the United States have been widely reported, but complete information on costs in developing countries is lacking. We performed an analysis designed to assess the real, detailed costs of HSCT in Mexico. Using the database of the Current Accounts Department at our Institution, we performed a micro-costing based analysis of patients from 2010 through 2015 to obtain the overall cost of HSCT during the in-patient procedure and 2-month follow-up. One hundred five transplantations (57% autologous) were performed...
June 14, 2017: International Journal of Hematology
https://www.readbyqxmd.com/read/28615039/interleukin-21-promotes-thymopoiesis-recovery-following-hematopoietic-stem-cell-transplantation
#16
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/28614903/thiotepa-based-conditioning-versus-total-body-irradiation-as-myeloablative-conditioning-prior-to-allogeneic-stem-cell-transplantation-for-acute-lymphoblastic-leukemia-a-matched-pair-analysis-from-the-acute-leukemia-working-party-of-the-european-society-for
#17
Sandra Eder, Jonathan Canaani, Eric Beohou, Myriam Labopin, Miguel A Sanz, William Arcese, Reuven Or, Juergen Finke, Agostino Cortelezzi, Dietrich Beelen, Jakob Passweg, Gerard Socié, Gunhan Gurman, Mahmoud Aljurf, Matthias Stelljes, Sebastian Giebel, Mohamad Mohty, Arnon Nagler
The optimal conditioning regimen to employ before hematopoieitic stem cell transplantation in acute lymphoblastic leukemia (ALL) is still undecided, and while Cy/TBI is the most commonly used myeloablative regimen, there are concerns regarding long term toxicity for patients conditioned with this regimen. Thiotepa based conditioning is an emerging radiation free regimen with recent publications indicative of comparable clinical outcomes to TBI based conditioning. In this analysis of the acute leukemia working party of the EBMT, we performed a retrospective matched-pair analysis, evaluating the outcome of adult patients with ALL who received thiotepa-based conditioning (n=180) with those receiving Cy/TBI conditioning (n=540)...
June 14, 2017: American Journal of Hematology
https://www.readbyqxmd.com/read/28614804/in-vivo-kinetics-and-nonradioactive-imaging-of-rapidly-proliferating-cells-in-graft-versus-host-disease
#18
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/28614794/an-activated-th17-prone-t-cell-subset-involved-in-chronic-graft-versus-host-disease-sensitive-to-pharmacological-inhibition
#19
Edouard Forcade, Katelyn Paz, Ryan Flynn, Brad Griesenauer, Tohti Amet, Wei Li, Liangyi Liu, Giorgos Bakoyannis, Di Jiang, Hong Wei Chu, Mercedes Lobera, Jianfei Yang, David S Wilkes, Jing Du, Kate Gartlan, Geoffrey R Hill, Kelli Pa MacDonald, Eduardo L Espada, Patrick Blanco, Jonathan S Serody, John Koreth, Corey S Cutler, Joseph H Antin, Robert J Soiffer, Jerome Ritz, Sophie Paczesny, Bruce R Blazar
Chronic graft-versus-host disease (cGvHD) remains a major complication of allogeneic stem cell transplantation requiring novel therapies. CD146 and CCR5 are expressed by activated T cells and associated with increased T cell migration capacity and Th17 polarization. We performed a multiparametric flow cytometry analysis in a cohort of 40 HSCT patients together with a cGvHD murine model to understand the role of CD146-expressing subsets. We observed an increased frequency of CD146+ CD4 T cells in the 20 patients with active cGvHD with enhanced RORγt expression...
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
#20
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
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