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Azacitidine

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https://www.readbyqxmd.com/read/27914067/5q-syndrome-like-features-as-the-first-manifestation-of-myelodysplastic-syndrome-in-a-patient-with-an-unbalanced-whole-arm-translocation-der-5-19-p10-q10
#1
Hiroshi Ureshino, Haruna Kizuka, Kana Kusaba, Haruhiko Sano, Atsujiro Nishioka, Takero Shindo, Yasushi Kubota, Toshihiko Ando, Kensuke Kojima, Shinya Kimura
Derivative (5;19)(p10;q10) [der(5;19)(p10;q10)] is a rare chromosomal abnormality in myelodysplastic syndrome (MDS), and is genetically similar to deletion 5q [del(5q)]. However, MDS with der(5;19)(p10;q10) and 5q- syndrome are generally characterized as distinct subtypes. Here, we report a case of a patient with 5q- syndrome-like features as the first manifestation of MDS with der(5; 19)(p10;q10). A 59-year-old woman was admitted to our hospital for anemia without leukopenia and thrombocytopenia. She had received chemotherapy comprising carboplatin and docetaxel for endometrial cancer eight years before...
December 2, 2016: International Journal of Hematology
https://www.readbyqxmd.com/read/27911276/the-mtor-inhibitor-everolimus-in-combination-with-azacitidine-in-patients-with-relapsed-refractory-acute-myeloid-leukemia-a-phase-ib-ii-study
#2
Peter Tan, Ing Soo Tiong, Shaun Fleming, Giovanna Pomilio, Nik Cummings, Mark Droogleever, Julie McManus, Anthony Schwarer, John Catalano, Sushrut Patil, Sharon Avery, Andrew Spencer, Andrew Wei
Therapeutic options are limited in relapsed/refractory acute myeloid leukemia (AML). We evaluated the maximum tolerated dose (MTD) and preliminary efficacy of mammalian target of rapamycin (mTOR) inhibitor, everolimus (days 5-21) in combination with azacitidine 75 mg/m2 subcutaneously (days 1-5 and 8-9 every 28 days) in 40 patients with relapsed (n = 27), primary refractory (n = 11) or elderly patients unfit for intensive chemotherapy (n = 2). MTD was not reached following everolimus dose escalation (2.5, 5 or 10 mg; n = 19) to the 10 mg dose level which was expanded (n = 21)...
November 29, 2016: Oncotarget
https://www.readbyqxmd.com/read/27905102/elevated-fetal-haemoglobin-is-a-predictor-of-better-outcome-in%C3%A2-mds-aml-patients-receiving-5-aza-2-deoxycytidine-decitabine
#3
Michael Lübbert, Gabriele Ihorst, Philipp N Sander, Ljudmila Bogatyreva, Heiko Becker, Pierre W Wijermans, Stefan Suciu, Emmanuel Bissé, Rainer Claus
Although azanucleoside DNA-hypomethylating agents (HMAs) are routinely used for the treatment of myelodysplastic syndrome/acute myeloid leukaemia (MDS/AML), very few outcome predictors have been established. Expression of the β-like globin gene locus is tightly regulated by DNA methylation, is HMA-sensitive in vitro, and fetal haemoglobin (HbF) expression is under study as a potential biomarker for response of MDS patients to azacitidine. We determined HbF expression in 16 MDS and 36 AML patients receiving decitabine (DAC)...
December 1, 2016: British Journal of Haematology
https://www.readbyqxmd.com/read/27893163/sorafenib-and-azacitidine-as-salvage-therapy-for-relapse-of-flt3-itd-mutated-aml-after-allo-sct
#4
Christina Rautenberg, Kathrin Nachtkamp, Ariane Dienst, Pia Verena Schmidt, Claudia Heyn, Mustafa Kondakci, Ulrich Germing, Rainer Haas, Guido Kobbe, Thomas Schroeder
OBJECTIVE: Patients with acute myeloid leukemia (AML) carrying FLT3-ITD mutations (FLT3-ITD+) who relapse after allogeneic 3transplantation (allo-SCT) have a very dismal prognosis with the currently available treatment options. METHODS: We treated 8 patients with FLT3-ITD+ AML who had relapsed in median 91 days (range, 28 - 249) following allo-SCT with a combination of the multikinase inhibitor Sorafenib and the DNA methyltransferase inhibitor Azacitidine (Aza)...
November 28, 2016: European Journal of Haematology
https://www.readbyqxmd.com/read/27883945/recent-advances-in-the-treatment-of-lower-risk-non-del-5q-myelodysplastic-syndromes-mds
#5
REVIEW
Antonio Almeida, Pierre Fenaux, Alan F List, Azra Raza, Uwe Platzbecker, Valeria Santini
Patients with lower-risk myelodysplastic syndromes (MDS) are affected primarily by symptoms of chronic anemia and fatigue rather than progression to acute myeloid leukemia. Severe thrombocytopenia, although less common in lower-risk MDS, is associated with increased risk of bleeding. For anemic patients, the principal aim of treatment is to improve anemia and decrease red blood cell transfusions. For transfusion-dependent patients with lower-risk MDS without chromosome 5q deletion [non-del(5q) MDS], there are limited effective treatments...
November 13, 2016: Leukemia Research
https://www.readbyqxmd.com/read/27881579/a-mirnas-dnmt1-axis-is-involved-in-azacitidine-resistance-and-predicts-survival-in-higher-risk-myelodysplastic-syndrome-and-low-blast-count-acute-myeloid-leukemia
#6
Françoise Solly, Catherine Koering, Aminetou Mint-Mohamed, Delphinne Maucort-Boulch, Guillaume Robert, Patrick Auberger, Pascale Flandrin-Gresta, Lionel Ades, Pierre Fenaux, Olivier Kosmider, Emmanuelle Tavernier-Tardy, Jerome Cornillon, Denis Guyotat, Lydia Lydia Campos, Franck Mortreux, Eric Wattel
PURPOSE: Azacitidine (AZA) inhibits DNA methyltransferases, including DNMT1, and is currently the standard of care for patients with higher risk myelodysplastic syndrome (HRMDS) or low blast count AML (AML). EXPERIMENTAL DESIGN: The expression of 754 microRNAs (miRNAs) was compared in AZA-resistant and AZA-sensitive MDS cells. We investigated the role of differentially expressed miRNAs on DNMT1 expression and AZA-resistance in vitro. We next evaluated anti-DNMT1 miRNAs expression in pretreatment bone marrow samples deriving from 75 patients treated with AZA for HRMDS or AML...
November 23, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/27862100/role-of-epigenetic-modification-and-immunomodulation-in-a-murine-prostate-cancer-model
#7
Jay E Sulek, Samuel P Robinson, Albert A Petrossian, Shaoqing Zhou, Ekaterine Goliadze, Masoud H Manjili, Amir Toor, Georgi Guruli
INTRODUCTION: Decreased expression of highly immunogenic cancer-testis antigens (CTA) might help tumor to achieve low immunogenicity, escape immune surveillance and grow unimpeded. Our aim was to evaluate CTA expression in tumor and normal tissues and to investigate possible means of improving the immune response in a murine prostate cancer (CaP) model by using the combination of epigenetic modifier 5-azacitidine (5-AzaC) and immunomodulator lenalidomide. No study to date has examined the effect of this combination on the prostate cancer or its impact on antigen-presenting cells (APC)...
November 8, 2016: Prostate
https://www.readbyqxmd.com/read/27849645/current-management-of-patients-with-chronic-myelomonocytic-leukemia
#8
Ana Alfonso, Guillermo Montalban-Bravo, Guillermo Garcia-Manero
PURPOSE OF REVIEW: The present review will focus on the current management of patients with chronic myelomonocytic leukemia (CMML) as well as in future therapeutic perspectives. RECENT FINDINGS: CMML is a clonal hematopoietic stem cell disorder characterized by peripheral blood monocytosis and myelodysplastic and myeloproliferative alterations in the bone marrow. Clinical behavior of the disease can be heterogeneous, with some patients having an indolent form of the disease, whereas others experience an aggressive course with decreased survival and eventual transformation to leukemia...
January 2017: Current Opinion in Oncology
https://www.readbyqxmd.com/read/27836862/phase-i-study-of-epigenetic-priming-with-azacitidine-prior-to-standard-neoadjuvant-chemotherapy-for-patients-with-resectable-gastric-and-esophageal-adenocarcinoma
#9
Bryan J Schneider, Manish A Shah, Kelsey Klute, Allyson Ocean, Elizabeta Popa, Nasser K Altorki, Michael D Lieberman, Andrew Schreiner, Rhonda K Yantiss, Paul J Christos, Romae Palmer, Agnes Viale, Daoqi You, Pouneh Kermani, Joseph M Scandura
PURPOSE: Epigenetic silencing of tumor suppressor genes (TSGs) is an acquired abnormality observed in cancer and is prototypically linked to DNA methylation. We postulated that pre-treatment (priming) with 5-azacitidine would increase the efficacy of chemotherapy by reactivating TSGs. This study was conducted to identify a tolerable dose of 5-azacitidine prior to EOX (epirubicin, oxaliplatin, capecitabine) neoadjuvant chemotherapy in patients with locally-advanced esophageal/gastric adenocarcinoma (EGC)...
November 10, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/27829292/efficacy-of-azacitidine-in-the-treatment-of-adult-patients-aged-65-years-or-older-with-aml
#10
Elena Tenti, Cristina Papayannidis, Giovanni Marconi, Sarah Parisi, Giorgia Simonetti, Stefania Paolini, Chiara Sartor, Emanuela Ottaviani, Nicoletta Testoni, Giovanni Martinelli
Therapy for acute myeloid leukemia (AML) in elderly populations (>65 years) is still a challenge for scientists and hematologists worldwide, and represents an urgent medical need. Notably, the identification and the recognition of molecular and epigenetic mechanisms involved in the pathogenesis of such a heterogeneous disease, are providing new tools for a more successful and 'targeted' approach. Azacitidine is a hypomethylating agent (HMA) with relevant activity in patients affected by myelodysplastic syndrome (MDS) and AML with low blast cells percentage (>30%), in terms of reduction of transfusion dependence, and improvement of quality of life...
December 2016: Expert Opinion on Pharmacotherapy
https://www.readbyqxmd.com/read/27815858/a-retrospective-study-of-azacitidine-treatment-in-patients-with-intermediate-2-or-high-risk-myelodysplastic-syndromes-in-a-real-world-clinical-setting-in-greece
#11
Vasiliki Pappa, Achilles Anagnostopoulos, Eleni Bouronikou, Evangelos Briasoulis, Ioannis Kotsianidis, Maria Pagoni, Panagiotis Zikos, Konstantinos Tsionos, Nora Viniou, John Meletis, Helen Papadaki, Anna Kioumi, Athanasios Galanopoulos, Elisavet-Christine Vervessou, Elias Poulakidas, Panagiotis Karmas, Kiki Karvounis, Argiris Symeonidis
For patients with intermediate-2 or high risk [according to the International Prognostic Scoring System (IPSS)] myelodysplastic syndromes (MDS), azacitidine treatment offers hematologic improvement (HI) but also has the potential to modify the natural disease course. 'RETRO-AZA-MDS-001', a retrospective chart review study was conducted from February to November 2012 across 17 hematology hospital sites of Greece, aiming to evaluate the clinical efficacy and safety profile of azacitidine in IPSS intermediate-2/high risk adult MDS patients in routine care...
November 4, 2016: International Journal of Hematology
https://www.readbyqxmd.com/read/27795561/a-clinical-trial-for-patients-with-acute-myeloid-leukemia-or-myelodysplastic-syndromes-not-eligible-for-standard-clinical-trials
#12
G Montalban-Bravo, X Huang, E Jabbour, G Borthakur, C D DiNardo, N Pemmaraju, J Cortes, S Verstovsek, T Kadia, N Daver, W Wierda, Y Alvarado, M Konopleva, F Ravandi, Z Estrov, N Jain, A Alfonso, M Brandt, T Sneed, H-C Chen, H Yang, C Bueso-Ramos, S Pierce, E Estey, Z Bohannan, H M Kantarjian, G Garcia-Manero
Most clinical trials exclude patients with poor performance or comorbidities. To study whether patients with these characteristics can be treated within a clinical trial, we conducted a study for patients with acute myeloid leukemia (AML) or myelodysplastic syndromes (MDS) with poor performance, organ dysfunction or comorbidities. Primary endpoint was 60-day survival. Study included stopping rules for survival and response. Treatment consisted on a combination of azacitidine and vorinostat. Thirty patients (16 with MDS, 14 with AML) were enrolled...
October 31, 2016: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/27795554/monitoring-therapy-responses-at-the-leukemic-subclone-level-by-ultra-deep-amplicon-resequencing-in-acute-myeloid-leukemia
#13
P N Ojamies, M Kontro, H Edgren, P Ellonen, S Lagström, H Almusa, T Miettinen, S Eldfors, D Tamborero, K Wennerberg, C Heckman, K Porkka, M Wolf, O Kallioniemi
In our individualized systems medicine program, personalized treatment options are identified and administered to chemorefractory AML patients based on exome sequencing and ex-vivo drug sensitivity and resistance testing data. Here, we analyzed how clonal heterogeneity impacts on the responses of 13 AML patients to chemotherapy or targeted treatments using ultra-deep (average 68 000x coverage) amplicon resequencing. Using amplicon resequencing, we identified 16 variants from four patients (frequency 0,54-2%) that were not detected previously by exome sequencing...
October 31, 2016: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/27789363/factors-determining-responses-to-azacitidine-in-patients-with-myelodysplastic-syndromes-and-acute-myeloid-leukemia-with-early-post-transplantation-relapse-a-prospective-trial
#14
Janghee Woo, H Joachim Deeg, Barry Storer, Cecilia Yeung, Min Fang, Marco Mielcarek, Bart L Scott
Retrospective analyses suggest a benefit of therapy with hypomethylating agents in patients with myelodysplastic syndromes (MDS) or acute myeloid leukemia (AML) who relapse after allogeneic hematopoietic cell transplantation (HCT). We conducted a prospective trial in 39 patients with MDS or AML who relapsed within 100 days of HCT. Relapse was documented by morphology, flow cytometry, or cytogenetics. Treatment consisted of 5-azacitidine, 75 mg/m(2)/day for 7 days, administered every 28 days. Patients were followed by sequential marrow examinations, and responses were assessed at 6 months...
October 24, 2016: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/27774847/differential-response-to-hypomethylating-agents-based-on-sex-a-report-on-behalf-of-the-mds-clinical-research-consortium-mds-crc
#15
Amy E DeZern, Amer M Zeidan, John Barnard, Wesley Hand, Najla Al Ali, Francis Brown, Cassie Zimmerman, Gail J Roboz, Guillermo Garcia-Manero, David P Steensma, Rami S Komrokji, Mikkael A Sekeres
First-line therapy for higher-risk myelodysplastic syndromes (MDS) includes decitabine (DAC) or azacitidine (AZA). Variables have not identified differential response rates between these. We assessed the influence of patient sex on outcomes including overall survival (OS) in 642 patients with higher-risk MDS treated with AZA or DAC. DAC-treated patients (35% of females, 31% of males) had marginally better OS than AZA-treated patients (p = .043), (median OS of 18.7 months versus 16.4 months), but the difference varied strongly by sex...
October 24, 2016: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/27752999/azacitidine-for-treating-acute-myeloid-leukaemia-with-more-than-30%C3%A2-bone-marrow-blasts-an-evidence-review-group-perspective-of-a-national-institute-for-health-and-care-excellence-single-technology-appraisal
#16
Irina A Tikhonova, Martin W Hoyle, Tristan M Snowsill, Chris Cooper, Joanna L Varley-Campbell, Claudius E Rudin, Ruben E Mujica Mota
The National Institute for Health and Care Excellence (NICE) invited the manufacturer of azacitidine (Celgene) to submit evidence for the clinical and cost effectiveness of this drug for the treatment of acute myeloid leukaemia with more than 30 % bone marrow blasts in adults who are not eligible for haematopoietic stem cell transplantation, as part of the NICE's Single Technology Appraisal process. The Peninsula Technology Assessment Group was commissioned to act as the Evidence Review Group (ERG). The ERG produced a critical review of the evidence contained within the company's submission to NICE...
October 17, 2016: PharmacoEconomics
https://www.readbyqxmd.com/read/27745715/selecting-initial-treatment-of-acute-myeloid-leukaemia-in-older-adults
#17
Nikolai A Podoltsev, Maximilian Stahl, Amer M Zeidan, Steven D Gore
More than half of the patients with acute myeloid leukaemia (AML) are older than 60years. The treatment outcomes in this group remain poor with a median overall survival of <1year. Selecting initial treatment for these patients involves an assessment of 'fitness' for induction chemotherapy. This is done based on patient and disease-related characteristics which help to estimate treatment-related mortality and chance of complete remission with induction chemotherapy. If the risk of treatment-related mortality is high and/or the likelihood of a patient achieving a complete remission is low, lower-intensity treatment (low-dose cytarabine, decitabine and azacitidine) should be discussed...
October 8, 2016: Blood Reviews
https://www.readbyqxmd.com/read/27739920/incidence-rates-of-treatment-emergent-adverse-events-and-related-hospitalization-are-reduced-with-azacitidine-compared-with-conventional-care-regimens-in-older-patients-with-acute-myeloid-leukemia
#18
John F Seymour, Hartmut Döhner, Mark D Minden, Richard Stone, Dominique Gambini, Donna Dougherty, C L Beach, Jerry Weaver, Hervé Dombret
Relative risks of treatment-emergent adverse events (TEAEs) and related hospitalization is most accurate when accounting for treatment exposure. AZA-AML-001 showed azacitidine (AZA) prolonged overall survival versus conventional care regimens (CCR) in older patients (≥65 years) with acute myeloid leukemia (AML) by 3.9 months. Preselection of CCR before study randomization allows evaluation of AZA safety in patient subgroups with similar clinical features. Within preselection groups, AZA exposure was greater than each CCR...
October 14, 2016: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/27738797/impact-of-antibacterial-prophylaxis-during-reinduction-chemotherapy-for-relapse-refractory-acute-myeloid-leukemia
#19
Beejal R Ganti, Bernard L Marini, Jerod Nagel, Dale Bixby, Anthony J Perissinotti
PURPOSE: This study evaluated the impact of antibacterial prophylaxis with levofloxacin in relapsed/refractory acute myeloid leukemia (AML) patients. METHODS: This was a retrospective, single-center, cohort study. Adult patients with relapsed/refractory AML admitted for reinduction chemotherapy between November 1, 2006 and June 15, 2015 were screened for inclusion. A protocol initiating levofloxacin prophylaxis was implemented on December 1, 2013. Patients receiving hypomethylating agents (decitabine/azacitidine) were not administered antibacterial prophylaxis and thus not included in this analysis...
October 14, 2016: Supportive Care in Cancer: Official Journal of the Multinational Association of Supportive Care in Cancer
https://www.readbyqxmd.com/read/27714772/mammalian-target-of-rapamycin-inhibition-with-temsirolimus-in-myelodysplastic-syndromes-mds-patients-is-associated-with-considerable-toxicity-results-of-the-temsirolimus-pilot-trial-by-the-german-mds-study-group-d-mds
#20
Martin Wermke, Claudia Schuster, Florian Nolte, Haifa-Kathrin Al-Ali, Philipp Kiewe, Claudia Schönefeldt, Christiane Jakob, Malte von Bonin, Leopold Hentschel, Ina-Maria Klut, Gerhard Ehninger, Martin Bornhäuser, Gustavo Baretton, Ulrich Germing, Regina Herbst, Detelef Haase, Wolf K Hofmann, Uwe Platzbecker
The mammalian-target of rapamycin (also termed mechanistic target of rapamycin, mTOR) pathway integrates various pro-proliferative and anti-apoptotic stimuli and is involved in regulatory T-cell (TREG) development. As these processes contribute to the pathogenesis of myelodysplastic syndromes (MDS), we hypothesized that mTOR modulation with temsirolimus (TEM) might show activity in MDS. This prospective multicentre trial enrolled lower and higher risk MDS patients, provided that they were transfusion-dependent/neutropenic or relapsed/refractory to 5-azacitidine, respectively...
October 7, 2016: British Journal of Haematology
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