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Myelodysplastic syndrom

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https://www.readbyqxmd.com/read/29332326/carcinogenic-potential-of-antitumor-therapies-is-the-risk-predictable
#1
Ivanka Nenova, Janet Grudeva-Popova
The growing number of successfully cured cancer patients has created a new field in oncogenesis. The life expectancy of such patients has increased, however this favorable event may create enough time for epigenetic events to occur which can cause a new carcinognic event, i.e. a secondary malignancy. The terms in use are second primary malignancies as well as therapy-related neoplasms in case the treatment of the first neoplasm is a direct cause. Second primary malignancies can be hematological neoplasms or solid tumors, with solid tumors having higher frequency...
November 2017: Journal of B.U.ON.: Official Journal of the Balkan Union of Oncology
https://www.readbyqxmd.com/read/29331736/dysfunctional-telomeres-and-hematological-disorders
#2
REVIEW
Elena Fiorini, Andrea Santoni, Simona Colla
Telomere biology disorders, which are characterized by telomerase activity haploinsufficiency and accelerated telomere shortening, most commonly manifest as degenerative diseases. Tissues with high rates of cell turnover, such as those in the hematopoietic system, are particularly vulnerable to defects in telomere maintenance genes that eventually culminate in bone marrow (BM) failure syndromes, in which the BM cannot produce sufficient new blood cells. Here, we review how telomere defects induce degenerative phenotypes across multiple organs, with particular focus on how they impact the hematopoietic stem and progenitor compartment and affect hematopoietic stem cell (HSC) self-renewal and differentiation...
January 4, 2018: Differentiation; Research in Biological Diversity
https://www.readbyqxmd.com/read/29331635/sotatercept-with-long-term-extension-for-the-treatment-of-anaemia-in-patients-with-lower-risk-myelodysplastic-syndromes-a-phase-2-dose-ranging-trial
#3
Rami Komrokji, Guillermo Garcia-Manero, Lionel Ades, Thomas Prebet, David P Steensma, Joseph G Jurcic, Mikkael A Sekeres, Jesus Berdeja, Michael R Savona, Odile Beyne-Rauzy, Aspasia Stamatoullas, Amy E DeZern, Jacques Delaunay, Gautam Borthakur, Robert Rifkin, Thomas E Boyd, Abderrhamane Laadem, Bond Vo, Jennie Zhang, Marie Puccio-Pick, Kenneth M Attie, Pierre Fenaux, Alan F List
BACKGROUND: Myelodysplastic syndromes are characterised by ineffective erythropoiesis leading to anaemia. Sotatercept (ACE-011) is a novel activin receptor type IIA fusion protein that acts as a ligand trap to neutralise negative regulators of late-stage erythropoiesis. The aim of the study was to establish a safe and effective dose of sotatercept for the treatment of anaemia in patients with lower-risk myelodysplastic syndromes. METHODS: This open-label, multicentre, dose-ranging, phase 2 trial took place at 11 treatment centres in the USA and France...
January 10, 2018: Lancet Haematology
https://www.readbyqxmd.com/read/29330757/-myelodysplastic-syndrome-acute-leukemia-and-stem-cell-transplantation
#4
REVIEW
M Schmalzing, M Aringer, M Bornhäuser, J Atta
Myelodysplastic syndromes (MDS) represent a heterogeneous group of clonal hematopoietic stem cell disorders. They are characterized by inefficient hematopoiesis leading to peripheral cytopenia of one or more lineages and a variable risk of transformation into acute myeloid leukemia. They may either arise de novo as well as following exposition to environmental toxins, previous radiotherapy or chemotherapy or in the context of autoinflammatory diseases and related therapy. Characteristic cytogenetic abnormalities, along with the numbers of hematopoietic lineages affected and bone marrow blasts, enable an assessment of the risk of leukemic transformation...
October 2017: Zeitschrift Für Rheumatologie
https://www.readbyqxmd.com/read/29326122/growth-factor-independence-1b-a-key-player-in-the-genesis-and-maintenance-of-acute-myeloid-leukaemia-and-myelodysplastic-syndrome
#5
Aniththa Thivakaran, Lacramiora Botezatu, Judith M Hönes, Judith Schütte, Lothar Vassen, Yahya S Al-Matary, Pradeep Patnana, Amos Zeller, Michael Heuser, Felicitas Thol, Razif Gabdoulline, Nadine Olberding, Daria Frank, Marina Suslo, Renata Köster, Klaus Lennartz, Andre Görgens, Bernd Giebel, Bertram Opalka, Ulrich Dührsen, Cyrus Khandanpour
Differentiation of haematopoietic stem cells is regulated by a concert of different transcription factors. Disturbed transcription factors function can be the basis of (pre)malignancies such as myelodysplastic syndrome or acute myeloid leukaemia. Growth factor independence 1b is a repressing transcription factor regulating quiescence of hematopoietic stem cellss and differentiation of erythrocytes and platelets. Here, we show that low expression of Growth factor independence 1b in blast cells is associated with an inferior prognosis of myelodysplastic syndrome and acute myeloid leukaemia patients...
January 11, 2018: Haematologica
https://www.readbyqxmd.com/read/29325829/allogeneic-stem-cell-transplantation-for-advanced-myelodysplastic-syndrome-comparison-of-outcomes-between-cd34-selected-or-unmodified-hematopoietic-stem-cells-transplants
#6
Roni Tamari, Betul Oran, Patrick Hilden, Molly Maloy, Piyanuch Kongtim, Esperanza B Papadopoulos, Gabriela Rondon, Ann A Jakubowski, Borje S Andersson, Sean M Devlin, Sairah Ahmed, Uday R Popat, Doris Ponce, Julianne Chen, Craig Sauter, James W Young, Marcos de Lima, Miguel-Angel Perales, Richard J O'Reilly, Sergio A Giralt, Richard E Champlin, Hugo Castro-Malaspina
PURPOSE: To compare transplant outcomes in patients with advanced myelodysplastic syndrome (MDS) after CD34+ selected or unmodified allografts. PATIENTS AND METHODS: This analysis included initially 181 patients; 60 underwent CD34+ selected transplant and 121 had an unmodified transplant. Due to significant differences in disease characteristics, the analysis was limited to patients who had <10% blasts prior to transplant (N=145). Two groups were defined: (1) low risk: good and intermediate risk cytogenetics (CD34+, N=39; unmodified, N=46), and (2) high risk: poor and very poor risk cytogenetic (CD34+, N=19; unmodified, N=41)...
January 8, 2018: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/29322849/safety-profile-of-lenalidomide-in-patients-with-lower-risk-myelodysplastic-syndromes-without-del-5q-results-of-a-phase-3-trial
#7
Antonio Almeida, Pierre Fenaux, Guillermo Garcia-Manero, Stuart L Goldberg, Stefanie Gröpper, Anna Jonasova, Norbert Vey, Carmen Castaneda, Jianhua Zhong, C L Beach, Valeria Santini
The safety profile of lenalidomide use in lower-risk myelodysplastic syndromes (MDS) patients with del(5q) is well-established, but less is known in non-del(5q) patients. We provide safety data from a randomized, phase 3 trial evaluating lenalidomide in 239 patients with lower-risk non-del(5q) MDS ineligible/refractory to erythropoiesis-stimulating agents (ESAs). Compared with placebo, lenalidomide was associated with a higher incidence of grade 3-4 treatment-emergent adverse events (TEAEs; 86% vs. 44%), but not risk of infection (p = ...
January 11, 2018: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/29311715/the-bone-marrow-niche-in-mds-and-mgus-implications-for-aml-and-mm
#8
REVIEW
Irene M Ghobrial, Alexandre Detappe, Kenneth C Anderson, David P Steensma
Several haematological malignancies, including multiple myeloma (MM) and acute myeloid leukaemia (AML), have well-defined precursor states that precede the development of overt cancer. MM is almost always preceded by monoclonal gammopathy of undetermined significance (MGUS), and at least a quarter of all patients with myelodysplastic syndromes (MDS) have disease that evolves into AML. In turn, MDS are frequently anteceded by clonal haematopoiesis of indeterminate potential (CHIP). The acquisition of additional genetic and epigenetic alterations over time clearly influences the increasingly unstable and aggressive behaviour of neoplastic haematopoietic clones; however, perturbations in the bone-marrow microenvironment are increasingly recognized to have key roles in initiating and supporting oncogenesis...
January 9, 2018: Nature Reviews. Clinical Oncology
https://www.readbyqxmd.com/read/29296959/somatic-mutations-in-children-with-gata2-associated-myelodysplastic-syndrome-who-lack-other-features-of-gata2-deficiency
#9
Kevin E Fisher, Amy P Hsu, Christopher L Williams, Hadi Sayeed, Brian Y Merritt, M Tarek Elghetany, Steven M Holland, Alison A Bertuch, Maria Monica Gramatges
Approximately 10% of children with primary myelodysplastic syndrome (MDS) have germ line GATA2 mutations, leading to the proposal that all children with primary MDS and certain cytogenetic findings, including monosomy 7, be tested for germ line GATA2 mutations regardless of family history or other clinical features associated with GATA2 deficiency. In adults with familial GATA2-MDS, those with somatic mutations in ASXL1 experience rapid disease progression to acute myeloid leukemia (AML) and poor prognosis after stem cell transplantation; however, the prevalence of somatic mutations in primary pediatric GATA2-MDS is unclear...
February 28, 2017: Blood Advances
https://www.readbyqxmd.com/read/29296910/aging-hematopoiesis-and-the-myelodysplastic-syndromes
#10
REVIEW
Stephen S Chung, Christopher Y Park
The aging hematopoietic system undergoes numerous changes, including reduced production of red blood cells and lymphocytes as well as a relative increase in the production of myeloid cells. Emerging evidence indicates that many of these changes are due to selection pressures from cell-intrinsic and cell-extrinsic factors that result in clonal shifts in the hematopoietic stem cell (HSC) pool, resulting in predominant HSC clones that exhibit the functional characteristics associated with HSC aging. Given the recent descriptions of clonal hematopoiesis in aged populations, the increased risk of developing hematologic malignancies in individuals with clonal hematopoiesis, and the many similarities in hematopoietic aging and acquired bone marrow failure (BMF) syndromes, such as myelodysplastic syndromes (MDS), this raises significant questions regarding the relationship between aging hematopoiesis and MDS, including the factors that regulate HSC aging, whether clonal hematopoiesis is required for the development of MDS, and even whether BMF is an inevitable consequence of aging...
December 12, 2017: Blood Advances
https://www.readbyqxmd.com/read/29296875/vaccination-with-autologous-myeloblasts-admixed-with-gm-k562-cells-in-patients-with-advanced-mds-or-aml-after-allogeneic-hsct
#11
Vincent T Ho, Haesook T Kim, Natalie Bavli, Martin Mihm, Olga Pozdnyakova, Matthias Piesche, Heather Daley, Carol Reynolds, Nicholas C Souders, Corey Cutler, John Koreth, Edwin P Alyea, Joseph H Antin, Jerome Ritz, Glenn Dranoff, Robert J Soiffer
We report a clinical trial testing vaccination of autologous myeloblasts admixed with granulocyte-macrophage colony-stimulating factor secreting K562 cells after allogeneic hematopoietic stem cell transplantation (HSCT). Patients with myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML) with ≥5% marrow blasts underwent myeloblast collection before HSCT. At approximately day +30, 6 vaccines composed of irradiated autologous myeloblasts mixed with GM-K562 were administered. Tacrolimus-based graft-versus-host disease (GVHD) prophylaxis was not tapered until vaccine completion (∼day 100)...
November 14, 2017: Blood Advances
https://www.readbyqxmd.com/read/29296849/risk-and-timing-of-cardiovascular-death-among-patients-with-myelodysplastic-syndromes
#12
Andrew M Brunner, Traci M Blonquist, Gabriela S Hobbs, Philip C Amrein, Donna S Neuberg, David P Steensma, Gregory A Abel, Amir T Fathi
Myelodysplastic syndromes (MDS) are clonal hematopoietic stem cell disorders associated with progression to leukemia and poor survival. Clonal hematopoiesis in people without an MDS diagnosis carries an increased risk of cardiovascular death. Many clonally restricted mutations are shared between patients with MDS and those with non-MDS clonal hematopoiesis; therefore, we evaluated the risk of cardiovascular death among patients with MDS. We evaluated adults with MDS in the Surveillance, Epidemiology, and End Results database of the National Cancer Institute and compared them with the general population living in the same states...
October 24, 2017: Blood Advances
https://www.readbyqxmd.com/read/29296834/haploidentical-transplant-in-patients-with-myelodysplastic-syndrome
#13
Marie Robin, Raphael Porcher, Fabio Ciceri, Maria Teresa van Lint, Stella Santarone, Gerhard Ehninger, Didier Blaise, Zafer Güllbas, Soledad Gonzáles Muñiz, Mauricette Michallet, Andrea Velardi, Linda Koster, Johan Maertens, Jorge Sierra, Dominik Selleslag, Aleksandar Radujkovic, José L Díez-Martin, Lothar Kanz, Concepcion Herrera Arroyo, Dietger Niederwieser, He Huang, Andrew McDonald, Theo de Witte, Yener Koc, Nicolaus Kröger
The only curative treatment in patients with intermediate or high-risk myelodysplastic syndrome (MDS) is allogeneic hematopoietic stem cell transplantation (HSCT), which usually results in a long-term, disease-free survival rate of between 30% and 50%, depending on the disease risk and the type of donor. In patients without an HLA-matched sibling donor, a family haploidentical donor is an alternative option. The present study reports the European Group for Blood and Marrow Transplantation activity for haploidentical transplantation in MDS patients...
October 10, 2017: Blood Advances
https://www.readbyqxmd.com/read/29296812/loss-of-mdia1-causes-neutropenia-via-attenuated-cd11b-endocytosis-and-increased-neutrophil-adhesion-to-the-endothelium
#14
Yang Mei, Gong Feng, Nina Rahimi, Baobing Zhao, Jingxin Zhang, Lan Cao, Jing Yang, Juehua Gao, Yihua Chen, Ronen Sumagin, William A Muller, Ling Zhang, Peng Ji
Formin protein mDia1 is involved in actin polymerization and plays important roles in the migration and adhesion of hematopoietic cells. The mDia1 encoding gene is located on chromosome 5q, which is commonly deleted in patients with del(5q) myelodysplastic syndromes (MDSs). We previously reported that mice with mDia1 deficiency developed neutropenia that closely mimics MDS. However, the mechanism of neutropenia in these mice and patients with del(5q) MDS remains incompletely defined. Here, we reveal that mDia1 knockout mice show cell-autonomously increased CD11b expression on neutrophils in the peripheral blood and bone marrow...
September 12, 2017: Blood Advances
https://www.readbyqxmd.com/read/29296797/patient-derived-antibody-recognizes-a-unique-cd43-epitope-expressed-on-all-aml-and-has-antileukemia-activity-in-mice
#15
Marijn A Gillissen, Greta de Jong, Martijn Kedde, Etsuko Yasuda, Sophie E Levie, Gemma Moiset, Paul J Hensbergen, Arjen Q Bakker, Koen Wagner, Jullien Villaudy, Pauline M van Helden, Hergen Spits, Mette D Hazenberg
Immunotherapy has proven beneficial in many hematologic and nonhematologic malignancies, but immunotherapy for acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) is hampered by the lack of tumor-specific targets. We took advantage of the tumor-immunotherapeutic effect of allogeneic hematopoietic stem cell transplantation and searched the B-cell repertoire of a patient with a lasting and potent graft-versus-AML response for the presence of AML-specific antibodies. We identified an antibody, AT1413, that was of donor origin and that specifically recognizes a novel sialylated epitope on CD43 (CD43s)...
August 22, 2017: Blood Advances
https://www.readbyqxmd.com/read/29296795/erythropoiesis-stimulating-agents-in-elderly-patients-with-anemia-response-and-cardiovascular-outcomes
#16
Zachary Gowanlock, Swetha Sriram, Alison Martin, Anargyros Xenocostas, Alejandro Lazo-Langner
A specific cause of anemia cannot be identified in many elderly patients. Erythropoiesis-stimulating agents (ESAs) may play a role in treating these patients with anemia of unknown etiology (AUE). This study examines hemoglobin and cardiovascular outcomes among elderly anemic patients treated with ESAs. We conducted a retrospective cohort study that included all anemic patients older than age 60 years who had erythropoietin (EPO) measured between 2005 and 2013 at a single center. Three independent reviewers used defined criteria to assign each patient's anemia to 1 of 4 groups: chronic kidney disease (CKD), myelodysplastic syndrome, AUE, or other etiology...
August 22, 2017: Blood Advances
https://www.readbyqxmd.com/read/29296792/a-4-lncrna-scoring-system-for-prognostication-of-adult-myelodysplastic-syndromes
#17
Chi-Yuan Yao, Ching-Hsuan Chen, Huai-Hsuan Huang, Hsin-An Hou, Chien-Chin Lin, Mei-Hsuan Tseng, Chein-Jun Kao, Tzu-Pin Lu, Wen-Chien Chou, Hwei-Fang Tien
Long noncoding RNAs (lncRNAs) not only participate in normal hematopoiesis but also contribute to the pathogenesis of acute leukemia. However, their clinical and prognostic relevance in myelodysplastic syndromes (MDSs) remains unclear to date. In this study, we profiled lncRNA expressions in 176 adult patients with primary MDS, and identified 4 lncRNAs whose expression levels were significantly associated with overall survival (OS). We then constructed a risk-scoring system with the weighted sum of these 4 lncRNAs...
August 22, 2017: Blood Advances
https://www.readbyqxmd.com/read/29296763/a-case-of-lenalidomide-dependent-myelodysplastic-syndrome
#18
Ira J Miller, Wei-Tong Hsu, James Weisberger, Parameswaran Venugopal
A man with cytopenias, dysplasia, excess blasts, P53 and RUNX1 mutations, and ring chromosome 7 recovered after stopping lenalidomide.
July 11, 2017: Blood Advances
https://www.readbyqxmd.com/read/29295649/is-bone-marrow-examination-always-necessary-to-establish-the-diagnosis-of-myelodysplastic-syndromes-a-proposed-non-invasive-diagnostic-model
#19
Howard S Oster, Gal Carmi, Alex Kolomansky, Erel Joffe, Irit Kaye, Ilya Kirgner, Uri Greenbaum, Doron Comaneshter, Moshe Mittelman
A non-invasive myelodysplastic syndromes (MDS) diagnostic model would allow for care while avoiding invasive bone marrow examinations (BME). BME-established MDS patients were compared to non-MDS (BME-excluded) patients. Variables (gender, age, hemoglobin (Hb), mean red blood cell corpuscular volume (MCV), platelet (PLT), and white blood cell (WBC)) were combined with multivariate logistic regression; a probability score (Y) was calculated. MDS (n = 48) and non-MDS (n = 63) patients were used to establish the model...
January 2, 2018: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/29291002/mutations-in-the-dna-methylation-pathway-and-number-of-driver-mutations-predict-response-to-azacitidine-in-myelodysplastic-syndromes
#20
M Teresa Cedena, Inmaculada Rapado, Alejandro Santos-Lozano, Rosa Ayala, Esther Onecha, María Abaigar, Esperanza Such, Fernando Ramos, José Cervera, María Díez-Campelo, Guillermo Sanz, Jesús Hernández Rivas, Alejandro Lucía, Joaquin Martínez-López
We evaluated the association of mutations in 34 candidate genes and response to azacitidine in 84 patients with myelodysplastic syndrome (MDS), with 217 somatic mutations identified by next-generation sequencing. Most patients (93%) had ≥1 mutation (mean=2.6/patient). The overall response rate to azacitidine was 42%. No clinical characteristic was associated with response to azacitidine. However, total number of mutations/patient was negatively associated with overall drug response (odds ratio [OR]: 0.56, 95% confidence interval [CI]: 0...
December 5, 2017: Oncotarget
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