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https://www.readbyqxmd.com/read/28728493/treating-breast-cancer-with-cell-based-approaches-an-overview
#1
Susanna Gallo, Dario Sangiolo, Fabrizio Carnevale Schianca, Massimo Aglietta, Filippo Montemurro
Breast cancer is the most common malignancy in women. Despite there being considerable progress in the treatment of this disease, metastatic dissemination is still considered an incurable condition at the present time, causing 500,000 deaths worldwide every year. Although most of the research efforts have been focused on pharmacological approaches, over the last three decades, the use of bone marrow and peripheral blood-derived cell therapy approaches have been attempted and developed. Areas covered: This review will briefly address cell therapy for breast cancer, including autologous stem cell transplantations for overcoming the myelosuppressive effects of high-dose chemotherapy, allogeneic stem cell transplants and adoptive immunotherapy using bone-marrow derived T-cells...
July 20, 2017: Expert Opinion on Biological Therapy
https://www.readbyqxmd.com/read/28727801/proponent-or-collaborative-physician-perspectives-and-approaches-to-disease-modifying-therapies-in-sickle-cell-disease
#2
Nitya Bakshi, Cynthia B Sinha, Diana Ross, Kirshma Khemani, George Loewenstein, Lakshmanan Krishnamurti
Sickle cell disease (SCD) is an inherited blood disorder that primarily affects African-American and other ethnic minority populations. There are three available disease-modifying therapies for sickle cell disease: hydroxyurea (HU), bone marrow transplantation (BMT), and chronic blood transfusion (CBT). Since these treatments vary in their therapeutic intent, efficacy in preventing progression of the disease, short and long-term adverse effects, costs and patient burden, the decision-making process regarding these therapies is complicated for both the patient and healthcare provider...
2017: PloS One
https://www.readbyqxmd.com/read/28725968/microglial-mediated-pdgf-cc-activation-increases-cerebrovascular-permeability-during-ischemic-stroke
#3
Enming Joseph Su, Chunzhang Cao, Linda Fredriksson, Ingrid Nilsson, Christina Stefanitsch, Tamara K Stevenson, Juanjuan Zhao, Margret Ragsdale, Yu-Yo Sun, Manuel Yepes, Chia-Yi Kuan, Ulf Eriksson, Dudley K Strickland, Daniel A Lawrence, Li Zhang
Treatment of acute ischemic stroke with the thrombolytic tissue plasminogen activator (tPA) can significantly improve neurological outcomes; however, thrombolytic therapy is associated with an increased risk of intra-cerebral hemorrhage (ICH). Previously, we demonstrated that during stroke tPA acting on the parenchymal side of the neurovascular unit (NVU) can increase blood-brain barrier (BBB) permeability and ICH through activation of latent platelet-derived growth factor-CC (PDGF-CC) and signaling by the PDGF receptor-α (PDGFRα)...
July 19, 2017: Acta Neuropathologica
https://www.readbyqxmd.com/read/28721499/treg-protected-donor-lymphocyte-infusions-a-new-tool-to-address-the-graft-versus-leukemia-effect-in-the-absence-of-graft-versus-host-disease-in-patients-relapsed-after-hsct
#4
Mauro Di Ianni, Paola Olioso, Raffaella Giancola, Stella Santarone, Annalisa Natale, Gabriele Papalinetti, Ida Villanova, Stefano Baldoni, Ambra Di Tommaso, Tiziana Bonfini, Patrizia Accorsi, Paolo Di Bartolomeo
In high-risk acute leukemia patients undergoing haploidentical hematopoietic stem cell transplantation (HSCT), adoptive immunotherapy with T regulatory cells (Tregs) and T conventional cells (Tcons) prevented acute and chronic graft-versus-host disease (GvHD), favored post-transplant immunological reconstitution and was associated with a powerful graft-versus-leukemia (GvL) effect. With a particularly innovative approach, we developed a treatment with a Treg-protected donor lymphocyte infusion (DLI) for patients with early relapse after HSCT and we report here the results obtained in the first patient with APL (M3v) relapsed after a second matched allogeneic HSCT (15% blasts and 75% of donor cells in bone marrow)...
July 18, 2017: International Journal of Hematology
https://www.readbyqxmd.com/read/28719653/isolation-of-a-monoclonal-antibody-from-a-phage-display-library-binding-the-rhesus-macaque-mhc-class-i-allomorph-mamu-a1-001
#5
Nathan Holman, Jason T Weinfurter, Trevor R Harsla, Roger W Wiseman, Aaron J Belli, Anthony J Michaels, Keith A Reimann, Robert I DeMars, Matthew R Reynolds
Monoclonal antibodies that bind to human leukocyte antigen (HLA) are useful tools for HLA-typing, tracking donor-recipient chimerisms after bone marrow transplants, and characterizing specific major histocompatibility complexes (MHC) on cell surfaces. Unfortunately, equivalent reagents are not available for rhesus macaques, which are commonly used animal as models in organ transplant and infectious disease research. To address this deficiency, we isolated an antibody that recognizes the common Indian rhesus macaque MHC class I molecule, Mamu-A1*001...
2017: PloS One
https://www.readbyqxmd.com/read/28719147/human-immunology-studies-using-organ-donors-impact-of-clinical-variations-on-immune-parameters-in-tissues-and-circulation
#6
D J Carpenter, T Granot, N Matsuoka, T Senda, B V Kumar, J J C Thome, C L Gordon, M Miron, J Weiner, T Connors, H Lerner, A Friedman, T Kato, A D Griesemer, D L Farber
Organ donors are sources of physiologically healthy organs and tissues for life-saving transplantation, and have been recently used for human immunology studies which are typically confined to the sampling of peripheral blood. Donors comprise a diverse population with different causes of death and clinical outcomes during hospitalization, and the effects of such variations on immune parameters in blood and tissues are not known. We present here coordinate analyses of innate and adaptive immune components in blood, lymphoid (bone marrow, spleen, lymph nodes), and mucosal (lungs, intestines) sites from a population of brain-dead organ donors (3-months-93-years; n=291) across eight clinical parameters...
July 18, 2017: American Journal of Transplantation
https://www.readbyqxmd.com/read/28719093/bone-marrow-harvest-from-unrelated-donors-up-to-date-methodology
#7
Katarzyna Pruszczyk, Kamila Skwierawska, Małgorzata Król, Albert Moskowicz, Dariusz Jabłoński, Tigran Torosian, Iwona Piotrowska, Elżbieta Urbanowska, Wiesław Wiktor-Jędrzejczak, Emilian Snarski
OBJECTIVES: Bone marrow harvesting is one of the essential sources of stem cells for hematopoietic stem cell transplantation. We describe here the current "up to date" standard of the bone marrow harvest in unrelated stem cell donors. METHODS: We analyzed medical data of 187 unrelated hematopoietic stem cell donors who underwent bone marrow harvest without previous peripheral blood stem collection at the center between 2011 and 2015. The methodology of marrow collection includes multiple cells aimed at safety of the procedure e...
July 18, 2017: European Journal of Haematology
https://www.readbyqxmd.com/read/28718265/haemoglobinuria-and-portal-venous-thrombosis-in-a-young-male
#8
Zain Ul Abideen, Munnam Sohail Jafar, Nasir Hameed, Ahmad Malik
Paroxysmal nocturnal haemoglobinuria is a non-malignant stem cell disorder due to acquired somatic mutations in cell surface anchored proteins CD55 and CD59. Both have a compliment inhibitory role and their deficiency leads to intravascular haemolysis. This paper reports a challenging case of a 25 years old male who presented with generalized weakness, exertional dyspnoea and episodic early morning haematuria. Recently, he started developing progressive abdominal distention and dull generalized abdominal pain...
April 2017: Journal of Ayub Medical College, Abbottabad: JAMC
https://www.readbyqxmd.com/read/28718264/malignant-infantile-osteopetrosis
#9
Saima Gillani, Zaheer Abbas
Two main forms of osteopetrosis are recognized, a severe autosomal recessive form (MIM 259700) with an incidence of approximately 1 in 250,000 births and a mild autosomal dominant form (MIM166600) with an incidence of 1 in 20,000 births. Intrinsic disturbances of osteoclastic function due to mutations in genes encoding osteoclast-specific subunits of the vacuolar proton pump (TCIRG1, CLCN7) are found in most patients with recessive form. Mutations of CLCN7 are observed in dominant form of osteopetrosis .The recessive form of ostreopetrosis, i...
April 2017: Journal of Ayub Medical College, Abbottabad: JAMC
https://www.readbyqxmd.com/read/28714945/impact-of-molecular-residual-disease-post-allografting-in-myelofibrosis-patients
#10
C Wolschke, A Badbaran, T Zabelina, M Christopeit, F Ayuk, I Triviai, A Zander, H Alchalby, U Bacher, B Fehse, N Kröger
We screened 136 patients with myelofibrosis and a median age of 58 years who underwent allogeneic stem cell transplantation (AHSCT) for molecular residual disease for JAKV617F (n=101), thrombopoietin receptor gene (MPL) (n=4) or calreticulin (CALR) (n=31) mutation in peripheral blood on day +100 and +180 after AHSCT. After a median follow-up of 78 months, the 5-year estimated overall survival was 60% (95% confidence interval (CI): 50-70%) and the cumulative incidence of relapse at 5 years was 26% (95% CI: 18-34%) for the entire study population...
July 17, 2017: Bone Marrow Transplantation
https://www.readbyqxmd.com/read/28713380/targeting-the-human-t-cell-inducible-costimulator-molecule-with-a-monoclonal-antibody-prevents-graft-vs-host-disease-and-preserves-graft-vs-leukemia-in-a-xenograft-murine-model
#11
Aude Burlion, Simon Brunel, Nicolas Y Petit, Daniel Olive, Gilles Marodon
BACKGROUND: Graft-vs-host disease (GVHD) is a major complication of allogenic bone marrow transplantation (BMT). Targeting costimulatory molecules with antagonist antibodies could dampen the excessive immune response that occurs, while preserving the beneficial graft vs leukemia (GVL) of the allogeneic response. Previous studies using a mouse model of GVHD have shown that targeting the T-cell Inducible COStimulator (ICOS, CD278) molecule is beneficial, but it is unclear whether the same applies to human cells...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28711728/allogeneic-blood-or-marrow-transplantation-with-post-transplantation-cyclophosphamide-as-graft-versus-host-disease-prophylaxis-in-multiple-myeloma
#12
Nilanjan Ghosh, Xiaobu Ye, Hua-Ling Tsai, Javier Bolaños-Meade, Ephraim J Fuchs, Leo Luznik, Lode J Swinnen, Douglas E Gladstone, Richard F Ambinder, Ravi Varadhan, Satish Shanbhag, Robert A Brodsky, Ivan M Borrello, Richard J Jones, William Matsui, Carol Ann Huff
Allogeneic blood or marrow transplantation (alloBMT) may lead to long-term disease control in patients with multiple myeloma (MM). However, historically, the use of alloBMT in MM has been limited by its high non-relapse mortality (NRM) rates primarily from graft versus host disease (GVHD). We previously demonstrated that post-transplantation cyclophosphamide (PTCy) decreases the toxicities of both acute and chronic GVHD rates following alloBMT. Here we examine the impact of PTCy in MM patients undergoing alloBMT at Johns Hopkins Hospital...
July 12, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/28711727/a-chemotherapy-only-regimen-of-busulfan-melphalan-and-fludarabine-and-rabbit-atg-followed-by-allogeneic-t-cell-depleted-hematopoietic-stem-cell-transplants-for-the-treatment-of-myeloid-malignancies
#13
Barbara Spitzer, Ann A Jakubowski, Esperanza B Papadopoulos, Kirsten Fuller, Patrick D Hilden, James W Young, Juliet Barker, Guenther Koehne, Miguel-Angel Perales, Katharine C Hsu, Marcel R M van den Brink, Nancy A Kernan, Susan E Prockop, Andromachi Scaradavou, Hugo Castro-Malaspina, Richard J O'Reilly, Farid Boulad
We sought to develop a myeloablative chemotherapeutic regimen to secure consistent engraftment of T-cell depleted (TCD) hematopoietic stem cell transplants (HSCT) without the need for total body irradiation, thereby reducing toxicity, while maintaining low rates of GvHD and without increasing relapse. We investigated the myeloablative combination of busulfan and melphalan, with the immunosuppressive agents fludarabine and rabbit anti-thymocyte gloubin (r-ATG) as cytoreduction prior to a T-cell depleted HSCT...
July 12, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/28711452/hematopoietic-stem-cell-transplantation-in-algeria
#14
REVIEW
M A Bekadja, M Brahimi, S Osmani, N Yafour, A Krim, F Serradj, S Talhi, K Amani, R Bouhass
Algeria is a country of 40.4 million inhabitants half of whom are younger than 30years. In Algeria, healthcare insurance covers 90% of the population. Healthcare is free and it is supported by the Ministry of Health. Sixteen university hospitals exist in Algeria and only two (Algiers and Oran) practice bone marrow transplant. Hematologic malignancies in adults account for 10% (∼4000 new cases/y) of the malignancy affecting in most cases young patients under 65years of age. In 2016, 270 transplants were performed (Algiers and Oran), including 149 allografts (related donor transplants: 99%) and 121 autografts...
July 11, 2017: Hematology/oncology and Stem Cell Therapy
https://www.readbyqxmd.com/read/28707754/non-sibling-hematopoietic-stem-cell-transplantation-using-myeloablative-conditioning-regimen-in-children-with-maroteaux-lamy-syndrome-a-brief-report
#15
Maryam Behfar, S Sharareh Dehghani, Tahereh Rostami, Ardeshir Ghavamzadeh, Amir Ali Hamidieh
Maroteaux-Lamy syndrome is a rare inherited lysosomal storage disorder with a progressive course. HSCT is a curable option for treatment in these patients. The following report describes our experience in HSCT for three patients with Maroteaux-Lamy syndrome using non-sibling donors. All of the patients received the same myeloablative regimen consisting of intravenous busulfan, cyclophosphamide, and rabbit antithymocyte globulin. Patients underwent HSCT from haploidentical other-related (n=1), full-matched other-related (n=1), and one-locus-mismatched unrelated donor...
August 2017: Pediatric Transplantation
https://www.readbyqxmd.com/read/28705454/efficacy-of-two-different-doses-of-rabbit-anti-t-lymphocyte-globulin-to-prevent-graft-versus-host-disease-in-children-with-haematological-malignancies-transplanted-from-an-unrelated-donor-a-multicentre-randomised-open-label-phase-3-trial
#16
Franco Locatelli, Maria Ester Bernardo, Alice Bertaina, Carla Rognoni, Patrizia Comoli, Attilio Rovelli, Andrea Pession, Franca Fagioli, Claudio Favre, Edoardo Lanino, Giovanna Giorgiani, Pietro Merli, Daria Pagliara, Arcangelo Prete, Marco Zecca
BACKGROUND: Although rabbit anti-T-lymphocyte globulin (ATLG) is largely used for the prevention of immune-mediated complications in patients given allogeneic haemopoietic stem-cell transplantation (HSCT) from an unrelated donor, the optimum dose of this drug in children is still undefined. We aimed to test whether a higher dose of ATLG was superior to a lower dose for prevention of grade II-IV acute graft-versus-host disease (GVHD). METHODS: We conducted a multicentre, randomised, open-label, phase 3 trial in seven Italian centres comparing two different doses of ATLG (30 mg/kg vs 15 mg/kg, given intravenously over 3 days, from day -4 to -2) in children (aged 0-18 years) with haematological malignancies transplanted from an unrelated donor, selected using high-resolution typing for HLA-class I/II loci...
July 10, 2017: Lancet Oncology
https://www.readbyqxmd.com/read/28699667/mantle-cell-lymphoma-2017-update-on-diagnosis-risk-stratification-and-clinical-management
#17
Julie M Vose
DISEASE OVERVIEW: Mantle cell lymphoma (MCL) is a non-Hodgkin lymphoma characterized by involvement of the lymph nodes, spleen, blood and bone marrow with a short remission duration to standard therapies and a median overall survival (OS) of 4-5 years. DIAGNOSIS: Diagnosis is based on lymph node, bone marrow, or tissue morphology of centrocytic lymphocytes, small cell type, or blastoid variant cells. A chromosomal translocation t (11:14) is the molecular hallmark of MCL, resulting in the overexpression of cyclin D1...
August 2017: American Journal of Hematology
https://www.readbyqxmd.com/read/28698779/bacterial-blood-stream-infections-negatively-impact-on-outcome-of-patients-treated-with-allogeneic-stem-cell-transplantation-6-years-single-centre-experience
#18
Michele Malagola, Bendetta Rambaldi, Giuseppe Ravizzola, Chiara Cattaneo, Erika Borlenghi, Nicola Polverelli, Alessandro Turra, Enrico Morello, Cristina Skert, Valeria Cancelli, Federica Cattina, Giorgio Giannetta, Simona Bernardi, Simone Perucca, Camillo Almici, Aldo Roccaro, Liana Signorini, Roberto Stellini, Francesco Castelli, Arnaldo Caruso, Domenico Russo
BACKGROUND: Blood stream infections (BSIs) represent a major complication of allo-SCT and are a major cause of morbidity and mortality during and after bone marrow aplasia. OBJECTIVES: The objective of this study was to describe the incidence and outcome of BSIs in a cohort of patients submitted to allo-SCT, in order to track changes of the epidemiology and bacteria resistance. METHODS: We retrospectively analyzed the microbiological data of 162 patients allotransplanted in Brescia University Hospital, over a period of 6 years...
2017: Mediterranean Journal of Hematology and Infectious Diseases
https://www.readbyqxmd.com/read/28697759/the-distinct-biological-implications-of-asxl1-mutation-and-its-roles-in-leukemogenesis-revealed-by-a-knock-in-mouse-model
#19
Yueh-Chwen Hsu, Yu-Chiao Chiu, Chien-Chin Lin, Yuan-Yeh Kuo, Hsin-An Hou, Yi-Shiuan Tzeng, Chein-Jun Kao, Po-Han Chuang, Mei-Hsuan Tseng, Tzu-Hung Hsiao, Wen-Chien Chou, Hwei-Fang Tien
BACKGROUND: Additional sex combs-like 1 (ASXL1) is frequently mutated in myeloid malignancies. Recent studies showed that hematopoietic-specific deletion of Asxl1 or overexpression of mutant ASXL1 resulted in myelodysplasia-like disease in mice. However, actual effects of a "physiological" dose of mutant ASXL1 remain unexplored. METHODS: We established a knock-in mouse model bearing the most frequent Asxl1 mutation and studied its pathophysiological effects on mouse hematopoietic system...
July 11, 2017: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/28694008/-reduced-intensity-conditioning-haematopoietic-stem-cell-transplantation-in-genetic-diseases-experience-of-the-spanish-working-group-for-bone-marrow-transplantation-in-children
#20
Lucía López-Granados, Montserrat Torrent, Ana Sastre, Marta Gonzalez-Vicent, Cristina Díaz de Heredia, Bienvenida Argilés, Antonia Pascual, José M Pérez-Hurtado, Luisa Sisinni, Miguel Ángel Diaz, Izaskun Elorza, M Angeles Dasí, Isabel Badell
INTRODUCTION: Haematopoietic stem cell transplantation (HSCT) involves implanting cellular elements capable of generating a new and healthy haematopoietic system. Reduced intensity conditioning (RIC) consists of an immunosuppressive treatment to facilitate a progressive implant with lower morbidity. This type of conditioning can also lead to myelosuppression, which is potentially reversible over time. Reduced intensity conditioning enables HSCT to be performed on patients with genetic diseases for whom added comorbidity is undesirable due to the high doses of chemotherapy that accompanies conventional myeloablative regimens...
July 7, 2017: Anales de Pediatría: Publicación Oficial de la Asociación Española de Pediatría (A.E.P.)
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