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https://www.readbyqxmd.com/read/27917176/graft-immune-cell-composition-associates-with-clinical-outcome-of-allogeneic-hematopoietic-stem-cell-transplantation-in-patients-with-aml
#1
Ulla Impola, Antti Larjo, Urpu Salmenniemi, Mervi Putkonen, Maija Itälä-Remes, Jukka Partanen
Complications of allogeneic hematopoietic stem cell transplantation (HSCT) have been attributed to immune cells transferred into the patient with the graft. However, a detailed immune cell composition of the graft is usually not evaluated. In the present study, we determined the level of variation in the composition of immune cells between clinical HSCT grafts and whether this variation is associated with clinical outcome. Sizes of major immune cell populations in 50 clinical grafts from a single HSCT Centre were analyzed using flow cytometry...
2016: Frontiers in Immunology
https://www.readbyqxmd.com/read/27916512/impact-of-conditioning-regimen-on-outcomes-for-children-with-acute-myeloid-leukemia-transplanted-in-first-complete-remission-an-analysis-on-behalf-of-the-pediatric-disease-working-party-of-the-ebmt
#2
G Lucchini, M Labopin, E Beohou, A Dalissier, J H Dalle, J Cornish, M Zecca, S Samarasinghe, B Gibson, F Locatelli, Y Bertrand, F Abdel-Rahman, G Socie', M Sundin, A Lankester, P Sedlacek, R M Hamladji, C Heilmann, B Afanasyev, R Hough, C Peters, P Bader, P Veys
HSCT represents the cornerstone of treatment in pediatric high risk and relapsed AML. The aim of the present study was to compare outcomes of pediatric AML patients undergoing HSCT using three different conditioning regimens: TBI and cyclophosphamide (TBI-Cy), Busulfan and Cyclophosphamide (BuCy) or Busulfan, Cyclophosphamide and Melphalan (BuCyMel). In this retrospective study, registry data for pts>2 and <18 yrs age undergoing matched allogeneic HSCT for AML in CR1 in 204 EBMT Centres between 2000 and 2010 were analyzed...
December 1, 2016: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/27916046/-a-comparative-study-of-unrelated-donor-and-matched-sibling-donor-allogeneic-hematopoietic-stem-cell-transplantation-in-children-and-adolescents-with-acquired-severe-aplastic-anemia
#3
J Zhou, Y W Fu, L J Liang, Q Wang, L J Han, Y L Zu, Yanli Zhang, X H Zhu, F K Yu, B J Fang, X D Wei, Y P Song
Objective: To evaluate the efficacy of unrelated donor allogeneic hematopoietic stem cell transplantation(URD allo-HSCT) for children and adolescents with severe aplastic anemia (SAA). Methods: Clinical data of 34 SAA children and adolescents undergoing allo-HSCT were retrospectively analyzed from October 2001 to October 2015. According to the source of donor, the patients were divided into matched sibling donor allo-HSCT group (MSD group) and unrelated donor group (URD group). The clinical outcome of SAA children and adolescents receiving URD allo-HSCT was assessed, and patients in MSD allo-HSCT group were enrolled as control at the same period...
December 1, 2016: Zhonghua Nei Ke za Zhi [Chinese Journal of Internal Medicine]
https://www.readbyqxmd.com/read/27914967/survival-advantage-and-comparable-toxicity-in-reduced-toxicity-treosulfan-based-vs-reduced-intensity-busulfan-based-conditioning-regimen-in-mds-and-aml-patients-post-allogeneic-hematopoietic-cell-transplantation
#4
Ioanna Sakellari, Despina Mallouri, Eleni Gavriilaki, Ioannis Batsis, Maria Kaliou, Varnavas Constantinou, Apostolia Papalexandri, Chrysavgi Lalayanni, Chrysanthi Vadikolia, Anastasia Athanasiadou, Evangelia Yannaki, Damianos Sotiropoulos, Christos Smias, Achilles Anagnostopoulos
Treosulfan has been incorporated in conditioning regimens for sustained remissions without substantial toxicity and treatment related mortality (TRM). We aimed to analyze the safety and efficacy of FluTreo conditioning regimen (fludarabine 150mg/m(2), treosulfan 42g/m(2)) in medically infirm patients. Patients' outcome was compared with a similar historical group treated with FluBuATG (fludarabine 150-180mg/m(2), busulfex 6.4mg/Kg, thymoglobulin-ATG 5-7.5mg/kg). Thirty one consecutive patients suffering from AML (21), MDS (6) or treatment-related AML (4) received FluTreo conditioning...
November 30, 2016: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/27913470/role-of-the-intestinal-mucosa-in-acute-gastrointestinal-gvhd
#5
Jonathan U Peled, Alan M Hanash, Robert R Jenq
Intestinal graft-versus-host disease (GVHD) remains a significant obstacle to the success of allogeneic hematopoietic cell transplantation. The intestinal mucosa comprises the inner lining of the intestinal tract and maintains close proximity with commensal microbes that reside within the intestinal lumen. Recent advances have significantly improved our understanding of the interactions between the intestinal mucosa and the enteric microbiota. Changes in host mucosal tissue and commensals posttransplant have been actively investigated, and provocative insights into mucosal immunity and the enteric microbiota are now being translated into clinical trials of novel approaches for preventing and treating acute GVHD...
December 2, 2016: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/27913467/transplantation-for-bone-marrow-failure-current-issues
#6
Régis Peffault de Latour
The preferred treatment of idiopathic aplastic anemia (AA) is allogeneic hematopoietic stem cell transplantation (HSCT) from a human leukocyte antigen (HLA)-identical sibling donor. Transplantation from a well-matched unrelated donor (MUD) may be considered for patients without a sibling donor after failure of immunosuppressive therapy, as may alternative transplantation (mismatched, cord blood or haplo-identical HSCT) for patients without a MUD. HSCT may also be contemplated for congenital disorders in cases of pancytopenia or severe isolated cytopenia...
December 2, 2016: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/27905258/hla-mismatched-haploidentical-transplantation-using-low-dose-anti-thymocyte-globulin-atg-thymoglobulin
#7
Shinichi Kako, Yu Akahoshi, Naonori Harada, Hirofumi Nakano, Kazuaki Kameda, Tomotaka Ugai, Ryoko Yamasaki, Hidenori Wada, Yuko Ishihara, Koji Kawamura, Kana Sakamoto, Miki Sato, Masahiro Ashizawa, Kiriko Terasako-Saito, Shun-Ichi Kimura, Misato Kikuchi, Hideki Nakasone, Rie Yamazaki, Junya Kanda, Yoshinobu Kanda
Objectives To clarify optimal strategies for human leukocyte antigen (HLA)-mismatched haploidentical hematopoietic stem cell transplantation (HSCT). Methods Twelve patients who underwent HSCT from a haploidentical related donor using low-dose thymoglobulin were analyzed retrospectively. Thymoglobulin was added to conditioning regimens at 2.5 mg/kg/day for 2 days (days -4 and -3). Prophylaxis against graft-versus-host disease (GVHD) was performed with cyclosporine and methotrexate. Results The median age of the patients was 33 years...
December 1, 2016: Hematology (Amsterdam, Netherlands)
https://www.readbyqxmd.com/read/27903524/graft-versus-host-disease-targets-ovary-and-causes-female-infertility-in-mice
#8
Sonoko Shimoji, Daigo Hashimoto, Hidetsugu Tsujigiwa, Kohta Miyawaki, Koji Kato, Shuichiro Takahashi, Reiki Ogasawara, Takashi Jiromaru, Hiromi Iwasaki, Toshihiro Miyamoto, Koichi Akashi, Takanori Teshima
Infertility associated with ovarian failure is a serious late complication for female survivors of allogeneic hematopoietic stem cell transplantation (SCT). While the role of pretransplant conditioning regimen has been well appreciated, increasing application of reduced-intensity conditioning facilitated us to revisit the other factors possibly affecting ovarian function after allogeneic SCT. We have addressed whether donor T-cell mediated graft-versus-host disease (GVHD) could be causally related to female infertility in mice...
November 30, 2016: Blood
https://www.readbyqxmd.com/read/27899803/novel-targets-in-the-treatment-of-chronic-graft-versus-host-disease
#9
REVIEW
A Im, F T Hakim, S Z Pavletic
Despite advances that have improved survival after allogeneic hematopoietic stem cell transplantation (HCT), chronic graft-versus-host disease (GVHD) remains a leading cause of late morbidity and mortality after transplant. Current treatment options show limited efficacy in steroid-refractory disease, and there exists a paucity of robust data to guide management decisions. Lack of United States Food and Drug Administration (FDA) or European Medicines Agency (EMA) approved agents in GVHD underscore the importance of developing novel therapies...
November 30, 2016: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/27899357/a-phase-iii-randomized-trial-comparing-inolimomab-vs-usual-care-in-steroid-resistant-acute-gvhd
#10
Gérard Socié, Stéphane Vigouroux, Ibrahim Yakoub-Agha, Jacques-Olivier Bay, Sabine Fürst, Karin Bilger, Felipe Suarez, Mauricette Michallet, Dominique Bron, Philippe Gard, Zakaria Medeghri, Philippe Lehert, Chinglin Lai, Tim Corn, Jean-Paul Vernant
Treatment of steroid resistant (SR) aGVHD remains an unmet clinical need. Inolimomab, a monoclonal antibody to CD25, has shown encouraging results in phase II trials. This phase III randomized, open-label, multicenter compared Inolimomab vs. usual care in adult patients with steroid-refractory aGvHD. Patients were randomized to treatment with Inolimomab or usual care [control group were all treated with Anti Thymocyte Globulin (ATG)]. The primary objective was to evaluate overall survival at 1 year without changing baseline allocated therapy...
November 29, 2016: Blood
https://www.readbyqxmd.com/read/27895644/recent-developments-in-cellular-immunotherapy-for-hsct-associated-complications
#11
REVIEW
Monica Reis, Justyna Ogonek, Marsela Qesari, Nuno M Borges, Lindsay Nicholson, Liane Preußner, Anne Mary Dickinson, Xiao-Nong Wang, Eva M Weissinger, Anne Richter
Allogeneic hematopoietic stem cell transplantation is associated with serious complications, and improvement of the overall clinical outcome of patients with hematological malignancies is necessary. During the last decades, posttransplant donor-derived adoptive cellular immunotherapeutic strategies have been progressively developed for the treatment of graft-versus-host disease (GvHD), infectious complications, and tumor relapses. To date, the common challenge of all these cell-based approaches is their implementation for clinical application...
2016: Frontiers in Immunology
https://www.readbyqxmd.com/read/27893415/pentraxin-3-plasma-levels-at-graft-versus-host-disease-onset-predict-disease-severity-and-response-to-therapy-in-children-given-haematopoietic-stem-cell-transplantation
#12
Erica Dander, Paola De Lorenzo, Barbara Bottazzi, Paola Quarello, Paola Vinci, Adriana Balduzzi, Francesca Masciocchi, Sonia Bonanomi, Claudia Cappuzzello, Giulia Prunotto, Fabio Pavan, Fabio Pasqualini, Marina Sironi, Ivan Cuccovillo, Roberto Leone, Giovanni Salvatori, Matteo Parma, Elisabetta Terruzzi, Fabio Pagni, Franco Locatelli, Alberto Mantovani, Franca Fagioli, Andrea Biondi, Cecilia Garlanda, Maria Grazia Valsecchi, Attilio Rovelli, Giovanna D'Amico
Acute Graft-versus-Host Disease (GvHD) remains a major complication of allogeneic haematopoietic stem cell transplantation, with a significant proportion of patients failing to respond to first-line systemic corticosteroids. Reliable biomarkers predicting disease severity and response to treatment are warranted to improve its management. Thus, we sought to determine whether pentraxin 3 (PTX3), an acute-phase protein produced locally at the site of inflammation, could represent a novel acute GvHD biomarker. Using a murine model of the disease, we found increased PTX3 plasma levels after irradiation and at GvHD onset...
November 21, 2016: Oncotarget
https://www.readbyqxmd.com/read/27892949/the-ebmt-eln-working-group-recommendations-on-the-prophylaxis-and-treatment-of-gvhd-a-change-control-analysis
#13
T Ruutu, A Gratwohl, D Niederwieser, T de Witte, S van der Werf, A van Biezen, M Mohty, N Kröger, A Rambaldi, E McGrath, A Sureda, G Basak, H Greinix, R F Duarte
In 2013, recommendations for a standardized practice in the prophylaxis and treatment of GvHD were adopted and published by the European Society for Blood and Marrow Transplantation and the European LeukemiaNet. One year later, all 341 European Society for Blood and Marrow Transplantation centres performing allogeneic haematopoietic stem cell transplantation were contacted for a change-control analysis and asked to fill in a questionnaire; 111 centres (33%) responded. Of these, 83% had been aware of the recommendations...
November 28, 2016: Bone Marrow Transplantation
https://www.readbyqxmd.com/read/27891662/acute-mechanical-hemolysis-as-a-complication-of-extracorporeal-photopheresis-in-a-low-weight-child
#14
Robert A DeSimone, Sandeep N Wontakal, Alexander K Lyashchenko, Joseph Schwartz
Graft-versus-host disease (GVHD) is a complication of allogeneic hematopoietic stem cell transplantation with high morbidity and mortality. Extracorporeal photopheresis (ECP) is an effective therapy for treating medication-refractory GVHD, however, there is scant evidence of whether ECP can be safely performed in patients weighing less than 15 kg. Here, we report the implementation of a successful protocol to perform ECP in a 21-month-old, 10.6 kg female with medication-refractory GVHD. Our initial ECP treatment resulted in significant hemolysis that was most likely mechanical...
November 28, 2016: Journal of Clinical Apheresis
https://www.readbyqxmd.com/read/27890428/vancomycin-resistant-enterococcus-colonization-and-bacteremia-and-hematopoietic-stem-cell-transplantation-outcomes
#15
Clyde D Ford, Michaela A Gazdik, Bert K Lopansri, Brandon Webb, Birgitta Mitchell, Jana Coombs, Daanish Hoda, Finn Bo Petersen
The association between pre-hematopoietic stem cell transplantation (HSCT) vancomycin-resistant Enterococcus (VRE) colonization, HSCT associated VRE bacteremia, and HSCT mortality is disputed. We studied 161 consecutive patients with acute leukemia who underwent HSCT at our hospital between 2006 and 2014, of whom 109 also received leukemia induction/consolidation on our unit. All inpatients had weekly VRE stool surveillance. Pre-HSCT colonization was not associated with increases in HSCT mortality but did identify a subgroup of HSCT recipients with a higher risk for VRE bacteremia and possibly bacteremia from other organisms...
November 23, 2016: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/27890259/how-important-is-nk-alloreactivity-and-kir-in-allogeneic-transplantation
#16
REVIEW
Brian C Shaffer, Katharine C Hsu
Relapse of acute myelogenous leukemia (AML) after allogeneic hematopoietic cell transplantation (allo HCT) is a major cause of death in transplant recipients. Efforts to control relapse by promoting donor T-cell alloreactivity, such as withdrawal of immune suppression or donor lymphocyte infusions, are limited by the propensity to induce graft versus host disease (GVHD) and by inadequate efficacy. Therefore, options for AML patients who have relapsed AML after allo HCT are few and outcomes are poor. Similar to T-cells, natural killer (NK) cells have potent anti-leukemia effector capacity, and yet unlike T-cells, NK cells do not mediate GVHD...
December 2016: Best Practice & Research. Clinical Haematology
https://www.readbyqxmd.com/read/27890255/chimeric-antigen-receptor-t-cell-therapy-in-aml-how-close-are-we
#17
REVIEW
Saar Gill
The majority of patients presenting with acute myeloid leukemia (AML) initially respond to chemotherapy but post-remission therapy is required to consolidate this response and achieve long-term disease-free survival. The most effective form of post-remission therapy relies on T cell immunotherapy in the form of allogeneic hematopoietic cell transplantation (HCT). However, patients with active disease cannot usually expect to be cured with HCT. This inherent dichotomy implies that traditional T cell-based immunotherapy in the form of allogeneic HCT stops being efficacious somewhere between the measurable residual disease (MRD) and the morphologically obvious range...
December 2016: Best Practice & Research. Clinical Haematology
https://www.readbyqxmd.com/read/27888016/post-transplantation-cyclophosphamide-and-ixazomib-combination-rescues-mice-subjected-to-experimental-gvhd-and-is-superior-to-either-agent-alone
#18
A Samer Al-Homsi, Austin Goodyke, Michael McLane, Sarah Abdel-Mageed, Kelli Cole, Marlee Muilenburg, Yuxin Feng
Lapses in the prevention of graft-versus-host disease (GvHD) following allogeneic hematopoietic stem cell transplantation (HSCT) warrants novel approaches. Such approaches include, among others, the use of post-transplantation cyclophosphamide (PTC) and proteasome inhibitors. Although PTC alone consistently produces low rates of chronic GvHD, the incidence of acute GvHD remains significant. Inversely, prolonged post-transplantation administration of proteasome inhibitors carries a risk of paradoxical aggravation of GvHD...
November 22, 2016: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/27888014/nonmyeloablative-haploidentical-bone-marrow-transplantation-with-post-transplant-cyclophosphamide-for-pediatric-and-young-adult-patients-with-high-risk-hematologic-malignancies
#19
Orly R Klein, Jessica Buddenbaum, Noah Tucker, Allen R Chen, Christopher J Gamper, David Loeb, Elias Zambidis, Nicolas J Llosa, Jeffrey S Huo, Nancy Robey, Mary Jo Holuba, Yvette L Kasamon, Shannon R McCurdy, Richard Ambinder, Javier Bolaños-Meade, Leo Luznik, Ephraim J Fuchs, Richard J Jones, Kenneth R Cooke, Heather J Symons
Lower intensity conditioning regimens for haploidentical blood or marrow transplantation (BMT) are safe and efficacious for adult patients with hematologic malignancies. We report data for pediatric/young adult patients with high-risk hematologic malignancies (n=40) treated with nonmyeloablative haploidentical BMT with post-transplantation cyclophosphamide (PT/Cy) from 2003-2015. Patients received a preparative regimen of fludarabine, cyclophosphamide, and total body irradiation. Post-transplant immunosuppression consisted of cyclophosphamide, mycophenolate mofetil, and tacrolimus...
November 22, 2016: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/27887864/optimization-of-cgmp-purification-and-expansion-of-umbilical-cord-blood-derived-t-regulatory-cells-in-support-of-first-in-human-clinical-trials
#20
David H McKenna, Darin Sumstad, Diane M Kadidlo, Bjorn Batdorf, Colin J Lord, Sarah C Merkel, Christine M Koellner, Julie M Curtsinger, Carl H June, James L Riley, Bruce L Levine, Jeffrey S Miller, Claudio G Brunstein, John E Wagner, Bruce R Blazar, Keli L Hippen
BACKGROUND AIMS: Thymic-derived regulatory T cells (tTreg) are critical regulators of the immune system. Adoptive tTreg transfer is a curative therapy for murine models of autoimmunity, graft rejection, and graft-versus-host disease (GVHD). We previously completed a "first-in-human" clinical trial using in vitro expanded umbilical cord blood (UCB)-derived tTreg to prevent GVHD in patients undergoing UCB hematopoietic stem cell transplantation (HSCT). tTreg were safe and demonstrated clinical efficacy, but low yield prevented further dose escalation...
November 22, 2016: Cytotherapy
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