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haematopoietic stem cell transplant

Adam Gassas, Ponni Sivaprakasam, Michelle Cummins, Patricia Breslin, Katharine Patrick, Mary Slatter, Roderick Skinner, Geof Shenton, Brenda Gibson, Sarah Lawson, Toni Petterson, Michael Potter, Beki James, Rachael Hough, Prashant Hiwarkar, Ajay Vora, Paul Veys, Josu De La Fuente, Robert Wynn, Persis Amrolia
Paediatric therapy-related acute myeloid leukaemia (t-AML) is rare and the outcome is poor. While allogeneic haematopoietic stem cell transplantation (HSCT) is generally the accepted modality of treatment, data regarding salvage chemotherapy, remission induction, conditioning regimens, transplant-related mortality and outcome is scarce. Between 2000 and2016, 36 children with t-AML were treated in seven UK paediatric HSCT centres. The most common salvage protocol for remission induction was FLAG with or without idarubicin and 28 patients were in complete morphological remission prior to BMT...
March 15, 2018: Bone Marrow Transplantation
Gregory J Kato, Frédéric B Piel, Clarice D Reid, Marilyn H Gaston, Kwaku Ohene-Frempong, Lakshmanan Krishnamurti, Wally R Smith, Julie A Panepinto, David J Weatherall, Fernando F Costa, Elliott P Vichinsky
Sickle cell disease (SCD) is a group of inherited disorders caused by mutations in HBB, which encodes haemoglobin subunit β. The incidence is estimated to be between 300,000 and 400,000 neonates globally each year, the majority in sub-Saharan Africa. Haemoglobin molecules that include mutant sickle β-globin subunits can polymerize; erythrocytes that contain mostly haemoglobin polymers assume a sickled form and are prone to haemolysis. Other pathophysiological mechanisms that contribute to the SCD phenotype are vaso-occlusion and activation of the immune system...
March 15, 2018: Nature Reviews. Disease Primers
Paula Gutierrez-Martinez, Leah Hogdal, Manavi Nagai, Miriama Kruta, Rumani Singh, Kristopher Sarosiek, Andre Nussenzweig, Isabel Beerman, Anthony Letai, Derrick J Rossi
Ageing of haematopoietic stem cells (HSCs) contributes to deficits in the aged haematopoietic system. HSC decline is driven in part by DNA damage accumulation; yet, how ageing impacts the acute DNA damage response (DDR) of HSCs is poorly understood. We show that old HSCs exhibit diminished ATM activity and attenuated DDR, leading to elevated clonal survival in response to a range of genotoxins that was underwritten by diminished apoptotic priming. Distinct HSC subsets exhibited ageing-dependent and subtype-dependent differences in apoptotic priming and survival in response to DNA damage...
March 12, 2018: Nature Cell Biology
Starling A Sim, Vivian K Y Leung, David Ritchie, Monica A Slavin, Sheena G Sullivan, Benjamin W Teh
BACKGROUND: Viral respiratory tract infections (vRTI) are a significant cause of morbidity and mortality in patients undergoing allogeneic haematopoietic stem cell transplantation (alloHSCT). This study aimed to assess the epidemiological characteristics, risk factors, and outcomes of vRTI occurring from conditioning to 100 days after HSCT in the era of molecular testing. METHODS: This study was a retrospective record review of alloHSCT patients at Royal Melbourne Hospital from January 2010 to December 2015...
March 9, 2018: Biology of Blood and Marrow Transplantation
Carol Keen, Julie Skilbeck, Helen Ross, Lauren Smith, Karen Collins, Joanne Dixey, Stephen Walters, Diana M Greenfield, John A Snowden, Susan Mawson
INTRODUCTION: While myeloma is an incurable malignancy, developments in disease management have led to increased life expectancy in recent years. Treatment typically involves stem-cell transplantation. Increased survival rates equate to more patients living with the burden of both the disease and its treatment for increasing number of years, rendering myeloma a long-term condition.Evidence exists to demonstrate the benefits of exercise for patients recovering from stem-cell transplantation, and prehabilitation-exercise before treatment-has been shown to be effective in other disease areas...
March 9, 2018: BMJ Open
Mohamed Najib Mohamed Unni, Reem Elfeky, Kanchan Rao, Zohreh Nademi, Robert Chiesa, Persis Amrolia, Roderick Skinner, Olga Slater, Austen Worth, Terence Flood, Mario Abinun, Sophie Hambleton, Waseem Qasim, Hubert B Gaspar, Andrew J Cant, Andrew R Gennery, Paul Veys, Mary A Slatter
Secondary malignancy post haematopoietic stem cell transplantation (HSCT) for malignant disorders is well recognized. There are very few published reports on malignancy post HSCT for Primary Immunodeficiency (PID). We report 12 cases of 944 patients, who developed non-PTLD malignancy post-HSCT for PID.
March 7, 2018: Journal of Allergy and Clinical Immunology
Francesca Fioredda
The inherited form of Severe Chronic Neutropenia called Severe Congenital Neutropenia (SCN) is an intrinsic defect of neutrophils maturation. SCN affected patients are at risk to develop lethal in-fections and to transform into myelodisplasia (MDS) and/or acute laeukemia(AL). Use of Granulocyte-Colony-Stimulating Factor (G-CSF) has significantly improved the prognosis of affected patients, but the only definitive cure for the disease is Haematopoietic Stem Cell Trans-plantation (HSCT). Overall Survival of SCN patients has been assessed at around 85% after 3 years from transplantation ...
March 8, 2018: Current Drug Targets
Theo van den Broek, José A M Borghans, Femke van Wijk
Naive T cells have long been regarded as a developmentally synchronized and fairly homogeneous and quiescent cell population, the size of which depends on age, thymic output and prior infections. However, there is increasing evidence that naive T cells are heterogeneous in phenotype, function, dynamics and differentiation status. Current strategies to identify naive T cells should be adjusted to take this heterogeneity into account. Here, we provide an integrated, revised view of the naive T cell compartment and discuss its implications for healthy ageing, neonatal immunity and T cell reconstitution following haematopoietic stem cell transplantation...
March 8, 2018: Nature Reviews. Immunology
D Henrich, C Seebach, R Verboket, A Schaible, I Marzi, H Bonig
Bone marrow mononuclear cells (BMC) seeded on a scaffold of β-tricalcium phosphate (β-TCP) promote bone healing in a critical-size femur defect model. Being BMC a mixed population of predominantly mature haematopoietic cells, which cell type(s) is(are) instrumental for healing remains elusive. Although clinical therapies using BMC are often dubbed as stem cell therapies, whether stem cells are relevant for the therapeutic effects is unclear and, at least in the context of bone repair, seems dubious. Instead, in light of the critical contribution of monocytes and macrophages to tissue development, homeostasis and injury repair, in the current study it was hypothesised that BMC-mediated bone healing derived from the stem cell population...
March 6, 2018: European Cells & Materials
Jakob R Passweg, Helen Baldomero, Marc Ansari, Gabriela M Baerlocher, Mario Bargetzi, Yves Chalandon, Michel A Duchosal, Sabine Gerull, Tayfun Güngör, Jörg P Halter, Dominik Heim, Urs Hess, Kurt Leibundgut, Stavroula Masouridi-Levrat, Antonia Müller, Gayathri Nair, Thomas Pabst, Christoph Renner, Adrian Schmidt, Georg Stussi, Grazia Nicoloso de Faveri, Urs Schanz, For The Swiss Blood Stem Cell Transplantation Group Sbst
In 1997, the Swiss Blood Stem Cell Transplantation Group (SBST) initiated a mandatory national registry for all haematopoietic stem cell transplants (HCTs) in Switzerland. As of 2016, after 20 years, information was available for 7899 patients who had received an HCT (2781 allogeneic [35%] and 5118 autologous [65%]). As some patients had more than one transplant the total number of transplants was 3067 allogeneic and 6448 autologous. We compared patient characteristics and outcome of the first decade (1997-2006) and second decade (2007-2016) of the registry...
March 1, 2018: Swiss Medical Weekly
Chantal Lagresle-Peyrou, François Lefrère, Elisa Magrin, Jean-Antoine Ribeil, Oriana Romano, Leslie Weber, Alessandra Magnani, Hanem Sadek, Clémence Plantier, Aurélie Gabrion, Brigitte Ternaux, Tristan Félix, Chloé Couzin, Aurélie Stanislas, Jean-Marc Tréluyer, Lionel Lamhaut, Laure Joseph, Marianne Delville, Annarita Miccio, Isabelle André-Schmutz, Marina Cavazzana
Sickle cell disease is characterized by chronic anaemia and vaso-occlusive crises, which eventually lead to multi-organ damage and premature death. Haematopoietic stem cell transplantation is the only curative treatment but it is limited by toxicity and poor availability of HLA-compatible donors. A gene therapy approach based on the autologous transplantation of lentiviral-corrected haematopoietic stem and progenitor cells was shown to be efficacious in one patient. However, alterations of the bone marrow environment and the red blood cells' properties hamper the harvesting and immunoselection of patient stem cells from bone marrow...
February 22, 2018: Haematologica
Nina K Steckel, Christoph Groth, Jan-Henrik Mikesch, Rudolf Trenschel, Hellmut Ottinger, Lambros Kordelas, Carsten Mueller-Tidow, Christoph Schliemann, Christian Reicherts, Joern C Albring, Gerda Silling, Eva Schmidt, Wolfgang E Berdel, Georg Lenz, Markus Ditschkowski, Dietrich W Beelen, Matthias Stelljes
Considering the unsatisfactory results of salvage therapies for patients with relapsed/refractory acute myeloid leukaemia (R/R-AML), their value before allogeneic haematopoietic stem cell transplantation (HSCT) remains questionable. However, direct allogeneic HSCT following established conditioning regimens applied in patients with R/R-AML during active disease has been equally disappointing. In this retrospective observational study, high-dose melphalan, as part of a sequential preparative regimen, followed by a total body irradiation (4 × 2 Gy)-based or a treosulfan-based dose-adapted conditioning therapy for allogeneic HSCT was administered to 292 adult patients (median age 56 years, range 17-74) with primary refractory (144 patients), secondary refractory (97 patients) or relapsed AML (51 patients)...
February 21, 2018: British Journal of Haematology
Maria Domenica Cappellini, John B Porter, Vip Viprakasit, Ali T Taher
Beta-thalassaemia causes defective haemoglobin synthesis leading to ineffective erythropoiesis, chronic haemolytic anaemia, and subsequent clinical complications. Blood transfusion and iron chelation allow long-term disease control, and haematopoietic stem cell transplantation offers a potential cure for some patients. Nonetheless, there are still many challenges in the management of beta-thalassaemia. The main treatment option for most patients is supportive care; furthermore, the long-term efficacy and safety of current therapeutic strategies are limited and adherence is suboptimal...
February 12, 2018: Blood Reviews
Yusuke Shono, Marcel R M van den Brink
Allogeneic haematopoietic stem cell transplantation (allo-HSCT) is considered to be the strongest curative immunotherapy for various malignancies (primarily, but not limited to, haematologic malignancies). However, application of allo-HSCT is limited owing to its life-threatening major complications, such as graft-versus-host disease (GVHD), relapse and infections. Recent advances in large-scale DNA sequencing technology have facilitated rapid identification of the microorganisms that make up the microbiota and evaluation of their interactions with host immunity in various diseases, including cancer...
February 16, 2018: Nature Reviews. Cancer
G Kakourou, S Kahraman, G C Ekmekci, H A Tac, G Kourlaba, E Kourkouni, A Cervero Sanz, J Martin, H Malmgren, C Giménez, V Gold, F Carvalho, C Billi, J F C Chow, X Vendrell, G Kokkali, J Liss, J Steffann, J Traeger-Synodinos
STUDY QUESTION: Has PGD-HLA been successful relative to diagnostic and clinical efficacy? SUMMARY ANSWER: The diagnostic efficacy of PGD-HLA protocols was found lower in this study in comparison to published PGD-HLA protocols and to that reported for general PGD by ESHRE (78.5 vs 94.1% and vs 92.6%, respectively), while the clinical efficacy has proven very difficult to assess due to inadequate follow-up of both the ART/PGD and HSCT procedure outcomes. WHAT IS KNOWN ALREADY: The first clinical cases for PGD-HLA were reported in 2001...
February 8, 2018: Human Reproduction
Erden Atilla, Didem Sahin, Pinar Ataca Atilla, Istar Dolapci, Alper Tekeli, Sinem Civriz Bozdag, Meltem Kurt Yuksel, Selami Kocak Toprak, Osman Ilhan, Onder Arslan, Muhit Ozcan, Gunhan Gurman, Pervin Topcuoglu
BACKGROUND: Community respiratory viruses (CRVs) are associated with upper respiratory viral infections (URI), pneumonia or life-threatening respiratory disease in patients with allogeneic hematopoietic stem cell transplantation (allo-HSCT). Our aim is to demonstrate our URI experience related to CRVs after allo-HSCT. METHODS: From January 2013 to November 2015, 39 post allo-HSCT patients with acute URI symptoms were included to the study. We evaluated CRVs by multiplex PCR from nasopharyngeal wash and throat swabs...
February 9, 2018: Antiviral Therapy
Laurie Freire Boullosa, Payalben Savaliya, Stephanie Bonney, Laurence Orchard, Hannah Wickenden, Cindy Lee, Evelien Smits, Alison H Banham, Ken I Mills, Kim Orchard, Barbara-Ann Guinn
B-cell acute lymphoblastic leukemia (B-ALL) is a rare heterogeneous disease characterized by a block in lymphoid differentiation and a rapid clonal expansion of immature, non-functioning B cells. Adult B-ALL patients have a poor prognosis with less than 50% chance of survival after five years and a high relapse rate after allogeneic haematopoietic stem cell transplantation. Novel treatment approaches are required to improve the outcome for patients and the identification of B-ALL specific antigens are essential for the development of targeted immunotherapeutic treatments...
January 9, 2018: Oncotarget
Q Zhang, Y Zhou, J K Majaw, J Xu, Z Wei, Q Mai, C Zou, Y Zhang, Z Fan, F Huang, J Sun, Q Liu, Q Jiang
No abstract text is available yet for this article.
February 2018: Bone Marrow Transplantation
Suzanna M van Walraven, Torstein Egeland, Veronica Borrill, Grazia Nicoloso-de Faveri, Gabi Rall, Jeff Szer
No abstract text is available yet for this article.
February 2, 2018: Biology of Blood and Marrow Transplantation
María Bravo García-Morato, Francisco Javier Aracil Santos, Alejandro Contreras Briones, Alfonso Blázquez Moreno, Ángela Del Pozo Maté, Ángeles Domínguez-Soto, María José Beato Merino, Lucía Del Pino Molina, Juan Torres Canizales, Ana Victoria Marin, Elena Vallespín García, Marta Feito Rodríguez, Diego Plaza López Sabando, Anaïs Jiménez-Reinoso, Yasmina Mozo Del Castillo, Francisco José Sanz Santaeufemia, Raúl de Lucas-Laguna, Paula Cárdenas, Laura Casamayor Polo, María Coronel Díaz, Mar Valés-Gómez, Ernesto Roldán Santiago, Antonio Ferreira Cerdán, Julián Nevado Blanco, Ángel L Corbí, Hugh T Reyburn, José Ramón Regueiro, Eduardo López-Granados, Rebeca Rodríguez Pena
BACKGROUND: Interferon regulatory factor 4 (IRF4) is a fundamental transcription factor in adaptive and innate immunity, due to its key role in the differentiation and functional specialization of lymphoid and myeloid lineage cells. In mouse models, IRF4 participates in bone marrow central tolerance, naïve B cell activation, germinal centre formation, plasma cell differentiation, immunoglobulin secretion, T helper subset differentiation, macrophage polarization, and dendritic cell differentiation, among other processes...
February 2, 2018: Journal of Allergy and Clinical Immunology
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