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Allogenic transplant

A Antar, Z K Otrock, J El-Cheikh, M A Kharfan-Dabaja, G Battipaglia, R Mahfouz, M Mohty, A Bazarbachi
FMS-like tyrosine kinase 3 (FLT3) is one of the most commonly mutated genes in AML. FLT3 is mutated in ~30% of patients with AML, either by internal tandem duplications (FLT3-ITD) of the juxta-membrane domain or by a point mutation, usually involving the tyrosine kinase domain. Several FLT3 tyrosine kinase inhibitors are being evaluated in multiple studies aiming at improving outcomes. The most widely used is sorafenib, a potent multikinase inhibitor approved for hepatocellular carcinoma and renal cell carcinoma...
October 24, 2016: Bone Marrow Transplantation
Prithviraj Bose, Srdan Verstovsek
INTRODUCTION: Primary myelofibrosis (PMF) is the least common but the most aggressive of the classic Philadelphia chromosome-negative myeloproliferative neoplasms. Survival is much shorter in PMF than in polycythemia vera (PV) or essential thrombocythemia (ET). Post-PV/ET myelofibrosis (MF) is clinically indistinguishable from PMF and approached similarly. AREAS COVERED: Current pharmacologic therapy of MF revolves around the Janus kinase 1/2 (JAK1/2) inhibitor ruxolitinib, which dramatically improves constitutional symptoms and splenomegaly in the majority of patients, and improves overall survival (OS)...
October 22, 2016: Expert Opinion on Pharmacotherapy
A S Vidane, A O Pinheiro, J B Casals, D Passarelli, McFns Hage, R S Bueno, D S Martins, C E Ambrósio
Chronic kidney disease (CKD) is a common clinical condition in domestic cats, characterized by tubulointerstitial, vascular and glomerular inflammation and severe fibrosis. Studies in rodent model of induced CKD have shown a decrease and stabilization of the clinical condition. In this study was evaluated the safety and effect of intrarenal and intravenous infusion of allogeneic mesenchymal stem cells (AMSCs) derived from feline amniotic membrane in cats with naturally occurring CKD. Cat AMSCs were harvested after mechanical and enzymatic digestion of amnion...
October 23, 2016: Reproduction in Domestic Animals, Zuchthygiene
Anke Theil, Carmen Wilhelm, Matthias Kuhn, Andreas Petzold, Sebastian Tuve, Uta Oelschlägel, Andreas Dahl, Martin Bornhäuser, Ezio Bonifacio, Anne Eugster
T regulatory cell (Treg) therapy has been exploited in autoimmune disease, solid organ transplantation and in efforts to prevent or treat graft-versus-host disease (GvHD). However, our knowledge on in vivo persistence of transfused Treg is limited. Whether Treg transfusion leads to notable changes in the overall Treg repertoire and or whether longevity of Treg in the periphery is restricted to certain clones is unknown. Here we use T cell receptor alpha chain sequencing (TCRα-NGS) to monitor changes in the repertoire of Treg upon polyclonal expansion and after subsequent adoptive transfer...
October 24, 2016: Clinical and Experimental Immunology
John S Thompson, Debra L Hardin, Judy F Glass, Joshua Dziba, Jeffrey Campion, Stephen A Brown
We have previously reported that GR-1 neutrophil/monocytes rose dramatically in the spleen, peaked by day 7 and declined through day 14. This period corresponded to the peak of acute Graft-Versus-Host Disease (aGVHD) in BALB/c mice transplanted with allogeneic donor cells. We now asked: what cytokines did these splenic neutrophil/monocytes express on day 7 and 14 post transplant? BALB/c mice were transplanted with allogeneic B6 or syngeneic BALB/c donor cells. Long term survival was recorded through day 31...
2016: SOJ Immunology
Wei Du, Nicholas D Leigh, Guanglin Bian, Emad Alqassim, Rachel E O'Neill, Lin Mei, Jingxin Qiu, Hong Liu, Philip L McCarthy, Xuefang Cao
Granzyme B (GzmB) is a key cytotoxic molecule utilized by T cells to kill pathogen-infected cells or transformed tumor cells. Previous studies using allogeneic hematopoietic cell transplantation (allo-HCT) murine models showed that GzmB is required for CD8(+) T cells to cause graft-versus-host disease (GVHD). However, our recent study demonstrated that GzmB-mediated damage of CD8(+) T cells diminished their graft-versus-tumor (GVT) activity. In this study, we examined the role of GzmB in GVT effect mediated by conventional CD4(+)CD25(-) T cells (CD4(+) Tcon)...
2016: J Immunol Res Ther
Adewumi Adediran, Modu Baba Kagu, Tamunomieibi Wakama, Aliyu Ahmadu Babadoko, Dapus Obadiah Damulak, Sunday Ocheni, Marcus Inyama Asuquo
Background. Sickle cell anaemia (SCA) is an inherited condition whose clinical manifestations arise from the tendency of haemoglobin to polymerize and deform red blood cells into characteristic sickle shape. Allogeneic bone marrow transplantation offers a cure. The aim of this study was to determine the level of awareness, knowledge, and acceptance of this beneficial procedure in Nigeria. Materials and Methods. This multicentre cross-sectional study was conducted in 7 tertiary hospitals in Nigeria in 2015. Approval was obtained from each institution's research and ethics committee...
2016: Bone Marrow Research
Hyun-Je Kim, Nari Byun, Ohsang Kwon, Chung-Gyu Park
The number of patients in need of organ transplantation is continuously on the rise. However, because of organ donor shortage, xenotransplantation has been highlighted as an alternative. Among the various porcine organs and tissues, porcine islets are considered to be the best-matching implantable candidates for clinical application based on recent progress in nonhuman primate pre-clinical studies. Nevertheless, before initiation of clinical trials, it should be confirmed whether the requisite xeno-antigen sensitization would have a deleterious effect on subsequent allo-transplantation or vice versa...
October 20, 2016: Biochemical and Biophysical Research Communications
Katsuto Tamai, Jouni Uitto
Epidermolysis bullosa is a group of heritable skin fragility disorders with considerable morbidity and mortality. It is known to be caused by mutations in as many as 18 distinct genes, but there is no specific or effective treatment. Preclinical developments of gene correction, protein replacement, and cell-based approaches for treatment have suggested new therapeutic avenues, and some of them, including bone marrow transplantation and mesenchymal stem cell therapy, have entered into early clinical trials. Hammersen et al...
November 2016: Journal of Investigative Dermatology
Worawut Choeyprasert, Suradej Hongeng, Usanarat Anurathapan, Samart Pakakasama
Bacteremia during neutropenic episodes is a cause of morbidity and mortality in patients undergoing hematopoietic stem cell transplantation (HSCT). We have used oral ciprofloxacin and penicillin V, from the start of the conditioning regimen until engraftment, for the prophylaxis of bacterial infection. The objective of this study was to retrospectively analyze the prevalence of and risk factors for breakthrough bacteremia during neutropenic episodes in autologous and allogeneic HSCT patients. There were 215 patients enrolled, with a median age of 8...
October 22, 2016: International Journal of Hematology
Monica Cabrero, Alejandro Martin, Javier Briones, Jorge Gayoso, Isidro Jarque, Javier López, Carlos Grande, Inmaculada Heras, Reyes Arranz, Teresa Bernal, Estefania Perez-Lopez, Oriana López-Godino, Eulogio Conde, Dolores Caballero
We designed a phase-II clinical trial including Y-90-ibritumomab-tiuxetan as part of a reduced-intensity conditioning (RIC) allogeneic stem cell transplant (AlloSCT) in high-risk NHL (Clinical Trials Identifier: NCT00644371). Eligible patients were high-risk relapsed/refractory aggressive lymphoma. Conditioning regimen consisted of rituximab 250 mg (days -21 and -14), Y-90 ibritumomab IV (0.4 mCi/kg, day -14), fludarabine 30 mg/m(2) IV (days -3 and -2) plus melphalan 70 mg/m(2) IV (days -3 and -2) or one dose of melphalan and thiotepa 5 mg/kg (day -8)...
October 19, 2016: Biology of Blood and Marrow Transplantation
Samah Nassereddine, Taiga Nishihori, Eric Padron, Rami Mahfouz, Ali Bazarbachi, Rami S Komrokji, Mohamed A Kharfan-Dabaja
Myelodysplastic syndrome (MDS) is a heterogeneous group of clonal hematopoietic neoplastic disorders most commonly occurring in the elderly population; MDS has a tendency to progress to acute leukemia. Although epigenetic therapies have improved the outcomes of MDS patients, allogeneic hematopoietic cell transplantation remains the only curative option. Molecular characterization of MDS using next-generation sequencing has expanded not only the knowledge on MDS but also the depth of understanding of evolution and contribution of recurrent somatic mutations in precursor conditions...
September 16, 2016: Clinical Lymphoma, Myeloma & Leukemia
Xiaodan Luo, Lihua Xu, Yangqiu Li, Huo Tan
Graft-versus-host disease (GVHD) induced by host antigen-presenting cells (APCs) and donor-derived T cells remains the major limitation of allogeneic bone marrow transplantation (allo-BMT). Notch signaling pathway is a highly conserved cell-cell communication that is important in T cell development. Recently, Notch signaling pathway is reported to be involved in regulating GVHD. To investigate the role of Notch inhibition in modulating GVHD, we established MHC-mismatched murine allo-BMT model. We found that inhibition of Notch signaling pathway by γ-secretase inhibitor in vivo could reduce aGVHD, which was shown by the onset time of aGVHD, body weight, clinical aGVHD scores, pathology aGVHD scores, and survival...
October 21, 2016: Cell Biology and Toxicology
Sofia Morfopoulou, Edward T Mee, Sarah M Connaughton, Julianne R Brown, Kimberly Gilmour, W K 'Kling' Chong, W Paul Duprex, Deborah Ferguson, Mike Hubank, Ciaran Hutchinson, Marios Kaliakatsos, Stephen McQuaid, Simon Paine, Vincent Plagnol, Christopher Ruis, Alex Virasami, Hong Zhan, Thomas S Jacques, Silke Schepelmann, Waseem Qasim, Judith Breuer
Routine childhood vaccination against measles, mumps and rubella has virtually abolished virus-related morbidity and mortality. Notwithstanding this, we describe here devastating neurological complications associated with the detection of live-attenuated mumps virus Jeryl Lynn (MuV(JL5)) in the brain of a child who had undergone successful allogeneic transplantation for severe combined immunodeficiency (SCID). This is the first confirmed report of MuV(JL5) associated with chronic encephalitis and highlights the need to exclude immunodeficient individuals from immunisation with live-attenuated vaccines...
October 21, 2016: Acta Neuropathologica
Min-Min Shi, Yuan Kong, Yang Song, Yu-Qian Sun, Yu Wang, Xiao-Hui Zhang, Lan-Ping Xu, Kai-Yan Liu, Xiao-Jun Huang
Poor graft function (PGF) is a serious complication after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Murine studies suggest that endothelial progenitor cells (EPCs) are preferential supporting cells for hematopoietic stem cells (HSCs) in the bone marrow (BM) microenvironment. Our previous work found that a reduced number of BM EPCs was an independent risk factor for the occurrence of PGF after allo-HSCT. However, little is known about the functional role of BM EPCs and how to improve impaired BM EPCs in PGF...
October 21, 2016: Blood
Serdar Sivgin, Sinan Nazlim, Gokmen Zararsiz, Osman Baspinar, Leylagul Kaynar, Kemal Deniz, Mustafa Cetin, Ali Unal, Bulent Eser
BACKGROUND: Iron overload is one of the most significant problems as a leading cause of death in patients with leukemia and those who underwent allogeneic hematopoietic stem cell transplantation (alloHSCT). METHODS: In the current study, we retrospectively evaluated the bone marrow iron scores (BMIS) in patients who underwent alloHSCT (n = 125). The first available bone marrow biopsy specimens prior to the alloHSCT procedure or date of hospitalization (control group) were assessed in a blinded fashion using a standardized scoring system...
October 2016: Clinical Lymphoma, Myeloma & Leukemia
S J Lang, D Böhringer, G Geerling, T Reinhard
AimThe objective of the study was to evaluate the long-term results of allogenic penetrating limbo-keratoplasy. This method allows simultaneous transplantation of a corneal graft and limbal stem cells of the donor by means of eccentric trephination of the donor button.MethodThe data of 192 consecutive cases of allogenic penetrating limbo-keratoplasty from 1995 to 2015 were reviewed. These had been performed exclusively in eyes with complete failure of the limbal stem cells, in combination with deep corneal scarring...
October 21, 2016: Eye
Emmanuelle Ginoux, Diane Kottler, Bruno Anglaret, Brigitte Balme, Claude-Eric Bulabois, François Skowron
No abstract text is available yet for this article.
September 2016: JAAD Case Reports
Janet Ayello, Jessica Hochberg, Allyson Flower, Yaya Chu, Laxmi V Baxi, William Quish, Carmella van de Ven, Mitchell S Cairo
NK cells play a significant role in reducing relapse in patients with hematological malignancies following allogeneic stem cell transplantation but NK cell number and naturally occurring inhibitory signals limit their capability. IL-15 and 4-1BBL are important modulators of NK expansion and functional activation. With an aim to overcome these limitations, cord blood (CB) mononuclear cells (MNC) were ex-vivo expanded (EvE) for 7 days with genetically modified K562-mbIL15-41BBL (MODK562) or wildtype K562 (WTK562)...
October 17, 2016: Experimental Hematology
Mª Carmen Herrero-Sánchez, Concepción Rodríguez-Serrano, Julia Almeida, Laura San Segundo, Susana Inogés, Ángel Santos-Briz, Jesús García-Briñón, Luis Antonio Corchete, Jesús F San Miguel, Consuelo Del Cañizo, Belén Blanco
BACKGROUND: Graft-versus-host disease (GvHD) remains the major obstacle to successful allogeneic hematopoietic stem cell transplantation, despite of the immunosuppressive regimens administered to control T cell alloreactivity. PI3K/AKT/mTOR pathway is crucial in T cell activation and function and, therefore, represents an attractive therapeutic target to prevent GvHD development. Recently, numerous PI3K inhibitors have been developed for cancer therapy. However, few studies have explored their immunosuppressive effect...
October 20, 2016: Journal of Hematology & Oncology
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