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Myelodysplastic syndromes

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https://www.readbyqxmd.com/read/29777631/effect-of-deferasirox-erythropoietin-vs-erythropoietin-on-erythroid-response-in-low-int-1-risk-mds-patients-results-of-the-phase-ii-kallisto-trial
#1
Norbert Gattermann, Rosa Coll, Lutz Jacobasch, Allameddine Allameddine, Amin Azmon, Laurie DeBonnett, Andreas Bruederle, Jie Jin
OBJECTIVES: Erythropoiesis-stimulating agents (ESAs) remain first-choice to treat symptomatic anemia and delay transfusion dependence in most patients with lower-risk myelodysplastic syndromes (MDS) without del(5q). Deferasirox increased erythroid responses in some lower-risk MDS patients in clinical trials, and adding low-dose deferasirox to ESA treatment may further improve erythroid response. METHODS: KALLISTO (NCT01868477) was a randomized, open-label, multicenter, phase II study...
May 19, 2018: European Journal of Haematology
https://www.readbyqxmd.com/read/29776423/minimally-invasive-mitral-valve-repair-via-right-mini-thoracotomy-in-patient-with-myelodysplastic-syndrome
#2
Takura Taguchi, Hiroyuki Nishi, Kimihiro Kurose, Kohei Horikawa, Go Kanazawa, Toshiki Takahashi
BACKGROUND: Cardiac surgery for myelodysplastic syndrome (MDS) patients is challenging because anemia and neutropenia develop as a result of the syndrome, leading to infection and bleeding tendency during surgery. We report the case of minimally invasive mitral valve repair via a right mini-thoracotomy and perioperative use of granulocyte colony-stimulating factor (G-CSF) in a patient with MDS. CASE PRESENTATION: A 77-year-old man with myelodysplastic syndrome (MDS) was referred for surgical treatment for mitral valve regurgitation and underwent a minimally invasive mitral valve repair via a right mini-thoracotomy (MICS mitral procedure)...
May 18, 2018: Journal of Cardiothoracic Surgery
https://www.readbyqxmd.com/read/29774987/an-increased-percentage-of-myeloid-cd34-bone-marrow-cells-stratifies-intermediate-ipss-r-myelodysplastic-syndrome-patients-into-prognostically-significant-groups
#3
T-H Chen-Liang, A M Casado-Prieto, V Campos-Rodríguez, A M Hurtado, M L Amigo, M D García-Malo, V Vicente, F J Ortuño, A Jerez
INTRODUCTION: The Revised International Prognostic Scoring System (IPSS-R) for myelodysplastic syndromes (MDS) has established an intermediate category where a disease-modifying intervention is a matter of debate. Flow cytometry allows us to determine a fraction of immature myeloid cells in a semiautomated procedure. The aim of this study, mirroring IPSS-R study inclusion criteria, was to test whether bone marrow (BM) CD34+My percentage has independent prognostic value in the MDS setting...
May 18, 2018: International Journal of Laboratory Hematology
https://www.readbyqxmd.com/read/29774075/plectin-targeted-liposomes-enhance-the-therapeutic-efficacy-of-a-parp-inhibitor-in-the-treatment-of-ovarian-cancer
#4
Siva Sai Krishna Dasa, Galina Diakova, Ryo Suzuki, Anne M Mills, Michael F Gutknecht, Alexander L Klibanov, Jill K Slack-Davis, Kimberly A Kelly
Advances in genomics and proteomics drive precision medicine by providing actionable genetic alterations and molecularly targeted therapies, respectively. While genomic analysis and medicinal chemistry have advanced patient stratification with treatments tailored to the genetic profile of a patient's tumor, proteomic targeting has the potential to enhance the therapeutic index of drugs like poly(ADP-ribose) polymerase (PARP) inhibitors. PARP inhibitors in breast and ovarian cancer patients with BRCA1/2 mutations have shown promise...
2018: Theranostics
https://www.readbyqxmd.com/read/29773600/the-interleukin-3-receptor-cd123-targeted-sl-401-mediates-potent-cytotoxic-activity-against-cd34-cd123-cells-from-acute-myeloid-leukemia-myelodysplastic-syndrome-patients-and-healthy-donors
#5
Rajeswaran Mani, Swagata Goswami, Bhavani Gopalakrishnan, Rahul Ramaswamy, Ronni Wasmuth, Minh Tranh, Xiaokui Mo, Amber Gordon, Donna Bucci, David M Lucas, Alice Mims, Christopher Brooks, Adrienne Dorrance, Alison Walker, William Blum, John C Byrd, Gerard Lozanski, Sumithira Vasu, Natarajan Muthusamy
Diseases with clonal hematopoiesis such as myelodysplastic syndrome and acute myeloid leukemia have high rates of relapse. Only a small subset of acute myeloid leukemia patients are cured with chemotherapy alone. Relapse in these diseases occurs at least in part due to the failure to eradicate leukemic stem cells or hematopoietic stem cells in myelodysplastic syndrome. CD123, the alpha chain of the interleukin-3 receptor heterodimer, is expressed on the majority of leukemic stem cells and myelodysplastic syndrome hematopoietic stem cells and in 80% of acute myeloid leukemia...
May 17, 2018: Haematologica
https://www.readbyqxmd.com/read/29773599/tgf%C3%AE-1-mediated-functional-inhibition-of-mesenchymal-stromal-cells-in-myelodysplastic-syndromes-and-acute-myeloid-leukemia
#6
Stefanie Geyh, Manuel Rodríguez-Paredes, Paul Jäger, Annemarie Koch, Felix Bormann, Julian Gutekunst, Christoph Zilkens, Ulrich Germing, Guido Kobbe, Frank Lyko, Rainer Haas, Thomas Schroeder
Mesenchymal stromal cells are involved in the pathogenesis of myelodysplastic syndromes and acute myeloid leukemia, but the underlying mechanisms are incompletely understood. To further characterize the pathological phenotype we performed RNA sequencing of mesenchymal stromal cells from patients with myelodysplastic syndromes and acute myeloid leukemia revealing a specific molecular signature of genes commonly deregulated in myelodysplastic syndromes and acute myeloid leukemia. Pathway analysis showed a strong enrichment of genes related to osteogenesis, senescence, inflammation and inhibitory cytokines thereby reflecting the structural and functional deficits of mesenchymal stromal cells in myelodysplastic syndromes and acute myeloid leukemia on a molecular level...
May 17, 2018: Haematologica
https://www.readbyqxmd.com/read/29773061/development-of-novel-therapeutics-targeting-isocitrate-dehydrogenase-mutations-in-cancer
#7
Horrick Sharma
Isocitrate dehydrogenases 1 and 2 (IDH1 and IDH2) are key metabolic enzymes that catalyze the conversion of isocitrate to α-ketoglutarate (αKG). IDH 1 and IDH2 regulate several cellular processes, including oxidative respiration, glutamine metabolism, lipogenesis, and cellular defense against oxidative damage. Mutations in IDH1 and IDH2 have recently been observed in multiple tumor types, including gliomas, acute myeloid leukemia, myelodysplastic syndromes, and chondrosarcoma. IDH1 and IDH2 mutations involve a gain in neomorphic activity that catalyze αKG conversion to (R)-2-hydroxyglutarate ((R)-2HG)...
May 17, 2018: Current Topics in Medicinal Chemistry
https://www.readbyqxmd.com/read/29767474/mesenchymal-stromal-cells-from-shwachman-diamond-syndrome-patients-fail-to-recreate-a-bone-marrow-niche-in-vivo-and-exhibit-impaired-angiogenesis
#8
Donatella Bardelli, Erica Dander, Cristina Bugarin, Claudia Cappuzzello, Alice Pievani, Grazia Fazio, Paolo Pierani, Paola Corti, Piero Farruggia, Carlo Dufour, Simone Cesaro, Marco Cipolli, Andrea Biondi, Giovanna D'Amico
Shwachman-Diamond syndrome (SDS) is a rare multi-organ recessive disease mainly characterised by pancreatic insufficiency, skeletal defects, short stature and bone marrow failure (BMF). As in many other BMF syndromes, SDS patients are predisposed to develop a number of haematopoietic malignancies, particularly myelodysplastic syndrome and acute myeloid leukaemia. However, the mechanism of cancer predisposition in SDS patients is only partially understood. In light of the emerging role of mesenchymal stromal cells (MSCs) in the regulation of bone marrow homeostasis, we assessed the ability of MSCs derived from SDS patients (SDS-MSCs) to recreate a functional bone marrow niche, taking advantage of a murine heterotopic MSC transplant model...
May 16, 2018: British Journal of Haematology
https://www.readbyqxmd.com/read/29767427/azacitidine-in-the-real-world-an-evaluation-of-1101-higher-risk-myelodysplastic-syndrome-low-blast-count-acute-myeloid-leukaemia-patients-in-ontario-canada
#9
Lee Mozessohn, Matthew C Cheung, Saber Fallahpour, Tripat Gill, Asmaa Maloul, Liying Zhang, Olivia Lau, Rena Buckstein
The outcome of myelodysplastic syndrome (MDS) patients with uniformly higher-risk disease treated with azacitidine (AZA) in the 'real-world' remains largely unknown. We evaluated 1101 consecutive higher-risk MDS patients (International Prognostic Scoring System intermediate-2/high) and low-blast count acute myeloid leukaemia (AML; 21-30% blasts) patients treated in Ontario, Canada. By dosing schedule, 24·7% received AZA for seven consecutive days, 12·4% for six consecutive days and 62·9% by 5-2-2. Overall, median number of cycles was 6 (range 1-67) and 8 (range 6-14) when restricted to the 692 (63%) patients who received at least 4 cycles...
May 16, 2018: British Journal of Haematology
https://www.readbyqxmd.com/read/29764573/-clinical-and-laboratory-characteristics-of-juvenile-myelomonocytic-leukemia
#10
Yuan-Yuan Wu, Sheng-Yang Cai, Wei Huang, Si-Si Li, Wei Li, Ao Dong
OBJECTIVE: To study the clinical and laboratory characteristics of juvenile myelomonocytic leukemia (JMML). METHODS: The clinical characteristics and laboratory results were retrospectively analyzed in 10 children with newly diagnosed JMML. They were compared with those of 28 children with myelodysplastic syndrome (MDS) and 44 children with chronic myeloid leukemia (CML). RESULTS: Compared with the children with CML or MDS, the children with JMML had significantly higher rates of skin rashes, ecchymosis, and lymphadenectasis, a significantly lower serum cholinesterase (ChE) level, and a significantly higher fetal hemoglobin level (P<0...
May 2018: Zhongguo Dang Dai Er Ke za Zhi, Chinese Journal of Contemporary Pediatrics
https://www.readbyqxmd.com/read/29761371/tolerability-and-efficacy-of-deferasirox-in-patients-with-transfusional-iron-overload-results-from-a-german-2-year-non-interventional-study
#11
Florian Nolte, Holger Nückel, Burkhard Schmidt, Thomas Geer, Oleg Rubanov, Holger Hebart, Andrea Jarisch, Stefan Albrecht, Christiane Johr, Christiane Schumann, Wolf-Karsten Hofmann
BACKGROUND: Iron overload (IOL) due to repetitive transfusions of packed red blood cells (pRBC) has a major impact on morbidity and mortality in patients with inherited bone marrow failure syndromes and hemoglobinopathies such as thalassemia and sickle cell disease. However, whether IOL influences the outcome of elderly patients with myeloid malignancies is not yet clear. Moreover, clinical trials have reported high drop-out rates during treatment with the oral iron chelator deferasirox (DFX)...
May 14, 2018: Journal of Cancer Research and Clinical Oncology
https://www.readbyqxmd.com/read/29761072/sezary-syndrome-manifesting-as-posttransplant-lymphoproliferative-disorder
#12
Thanh-Phuong Afiat, Xiaohui Zhang, Hailing Zhang, Ernesto Ayala, Ling Zhang, Lubomir Sokol
Posttransplant lymphoproliferative disorders (PTLDs) of T-cell orgin are rare biologically heterogeneous diseases of mature lymphoid cells manifesting in immunosuppressed patients. Only a few cases of mycosis fungoides diagnosed post allogeneic hematopoietic cell transplant (alloHSCT) have been described so far. We present a patient with myelodysplastic syndrome (MDS) post matched unrelated donor alloHSCT who was on long-term immunosuppressive therapy due to graft versus host disease. Three years after an alloHSCT, she developed generalized erythroderma and peripheral blood lymphocytosis...
2018: Leukemia Research Reports
https://www.readbyqxmd.com/read/29758592/comparison-of-a-therapeutic-only-versus-prophylactic-platelet-transfusion-policy-for-people-with-congenital-or-acquired-bone-marrow-failure-disorders
#13
REVIEW
Reem Malouf, Asma Ashraf, Andreas V Hadjinicolaou, Carolyn Doree, Sally Hopewell, Lise J Estcourt
BACKGROUND: Bone marrow disorders encompass a group of diseases characterised by reduced production of red cells, white cells, and platelets, or defects in their function, or both. The most common bone marrow disorder is myelodysplastic syndrome. Thrombocytopenia, a low platelet count, commonly occurs in people with bone marrow failure. Platetet transfusions are routinely used in people with thrombocytopenia secondary to bone marrow failure disorders to treat or prevent bleeding. Myelodysplastic syndrome is currently the most common reason for receiving a platelet transfusion in some Western countries...
May 14, 2018: Cochrane Database of Systematic Reviews
https://www.readbyqxmd.com/read/29758108/comparison-of-transplant-specific-prognostic-scoring-systems-in-haploidentical-transplantation-for-myelodysplastic-syndrome
#14
Seung-Hwan Shin, Young-Woo Jeon, Jae-Ho Yoon, Seung-Ah Yahng, Sung-Eun Lee, Byung-Sik Cho, Ki-Seong Eom, Seok Lee, Hee-Je Kim, Chang-Ki Min, Seok-Goo Cho, Dong-Wook Kim, Jong-Wook Lee, Woo-Sung Min, Yoo-Jin Kim
OBJECTIVES: We intended to identify the predictive abilities of recently published transplant-specific prognostic scoring systems in myelodysplastic syndrome (MDS) patients receiving haploidentical transplantation. METHODS: The outcomes of 73 MDS patients receiving haploidentical transplantation were analyzed, according to the MTPSS, the TRI, and the CIBMTR scoring systems. RESULTS: The median age of patients at transplantation was 50 (range, 19-69) years...
May 14, 2018: European Journal of Haematology
https://www.readbyqxmd.com/read/29757120/prognostic-significance-of-srsf2-mutations-in-myelodysplastic-syndromes-and-chronic-myelomonocytic-leukemia-a-meta-analysis
#15
Pourya Arbab Jafari, Hossein Ayatollahi, Ramin Sadeghi, Maryam Sheikhi, Amir Asghari
OBJECTIVE: Serine/arginine-rich splicing factor 2 (SRSF2) mutations were detected frequently in myelodysplastic syndrome (MDS) and chronic myelomonocytic leukemia (CMML) patients. However, its prognostic value has not yet been fully clarified. METHODS: In this meta-analysis, Hazard Ratio (HR) and 95% confidence interval (CI) for overall-survival (OS) were chosen to evaluate the prognostic impact of SRSF2 mutations and to compare SRSF2 mutations to those with wild-type...
May 14, 2018: Hematology (Amsterdam, Netherlands)
https://www.readbyqxmd.com/read/29754984/donor-lymphocyte-infusion-in-myeloid-disorders
#16
REVIEW
Selami Koçak Toprak
A number of modalities including both pharmaceutical and cell-based treatments have long been tested and developed to prevent and treat relapses after allogeneic stem cell transplantation (allo-HSCT). The ability of donor T cells to recognize antigenic structures on leukemic cell surfaces and destroy them is a well-known fact. Based on this fact, the idea of using donor T cells to contribute to the development of adoptive immunotherapy has emerged. Donor lymphocytes are easy to obtain and donor lymphocyte infusions (DLI) have a simple rational while this treatment modality is an effective example of cellular therapy...
April 18, 2018: Transfusion and Apheresis Science
https://www.readbyqxmd.com/read/29753917/assessment-of-intrafamilial-clinical-variability-of-poikiloderma-with-neutropenia-by-a-10-year-follow-up-of-three-affected-siblings
#17
Daniela Concolino, Simona Sestito, Francesca Falvo, Giusy Romano, Miriam Ceravolo, Elisa Anastasio, Licia Pensabene, Elisa A Colombo, Lidia Larizza
Clericuzio-type poikiloderma with neutropenia is a well-defined nosological entity, but despite a remarkable number of clinical reports, no long term follow-up data has been presented to date regarding patients with this rare condition. Here we describe the results of clinical follow-up of three siblings, one male (Patient 1) and two females (Patients 2 and 3), subsequent to their first clinical and then molecular diagnosis of Clericuzio-type poikiloderma with neutropenia syndrome due to mutation of USB1gene...
May 10, 2018: European Journal of Medical Genetics
https://www.readbyqxmd.com/read/29753838/wilms-tumor-1-wt1-expression-using-a-standardized-european-leukemia-net-certified-assay-compared-to-other-methods-for-detection-of-minimal-residual-disease-in-mds-and-aml-patients-after-allogeneic-blood-stem-cell-transplantation
#18
Christina Rautenberg, Sabrina Pechtel, Barbara Hildebrandt, Beate Betz, Ariane Dienst, Kathrin Nachtkamp, Mustafa Kondakci, Stefanie Geyh, Dagmar Wieczorek, Rainer Haas, Ulrich Germing, Guido Kobbe, Thomas Schroeder
Overexpressed Wilms' Tumor 1 (WT1) gene is informative in many patients with acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS) and is measurable in peripheral blood (PB). Despite these advantages WT1 has not broadly been established as marker for minimal residual disease (MRD) monitoring after allogeneic transplantation (allo-HSCT) due to limited patient numbers, differing sample sources and non-standardized in-house methods. To estimate its value as MRD marker we serially quantified PB WT1 expression using a standardized European Leukemia Net-certified assay in 59 patients with AML and MDS after allo-HSCT...
May 10, 2018: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/29753157/treosulfan-fludarabine-and-low-dose-total-body-irradiation-for-children-and-young-adults-with-acute-myeloid-leukemia-or-myelodysplastic-syndrome-undergoing-allogeneic-hematopoietic-cell-transplantation-a-prospective-phase-ii-trial-of-the-pediatric-blood-and
#19
Eneida R Nemecek, Ralf A Hilger, Alexia Adams, Bronwen E Shaw, Deidre Kiefer, Jennifer Le-Rademacher, John E Levine, Gregory Yanik, Wing Leung, Julie-An Talano, Paul Haut, David Delgado, Neena Kapoor, Aleksandra Petrovic, Roberta Adams, Rabi Hanna, Hemalatha Rangarajan, Jignesh Dalal, Joseph Chewning, Michael R Verneris, Stacy Epstein, Lauri Burroughs, Evelio D Perez-Albuerne, Michael A Pulsipher, Colleen Delaney
This multicenter study evaluated a treosulfan-based regimen in children and young adults with acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) undergoing allogeneic hematopoietic cell transplant (HCT). Forty patients with median age 11 years (1-19) underwent allogeneic HCT for AML in first (n=18), second (n=11), third or greater remission (n=3); or MDS (n=8) using bone marrow (n=25), peripheral blood stem cells (n=5) or cord blood (n=9). The regimen consisted of body surface area (BSA)-based treosulfan 10 g/m2 /day (BSA ≤ 0...
May 9, 2018: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/29752743/therapy-related-acute-myeloid-leukemia-and-myelodysplastic-syndrome-among-refractory-germ-cell-tumor-patients
#20
Yuta Inoue, Terukazu Nakamura, Hiroyuki Nakanishi, Masakatsu Oishi, Fumiya Hongo, Koji Okihara, Shinsuke Mizutani, Junya Kuroda, Osamu Ukimura
OBJECTIVES: To analyze cases of therapy-related acute myeloid leukemia and myelodysplastic syndrome diagnosed after chemotherapy for refractory testicular and extragonadal germ cell tumor in our experience. METHODS: A total of 171 consecutive patients who were diagnosed and treated as refractory germ cell tumor and had records of detailed chemotherapy doses between April 1998 and December 2015 were retrospectively reviewed. RESULTS: Four testicular tumor patients (4/171, 2...
May 11, 2018: International Journal of Urology: Official Journal of the Japanese Urological Association
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