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https://www.readbyqxmd.com/read/28723562/integrative-genomics-identifies-the-molecular-basis-of-resistance-to-azacitidine-therapy-in-myelodysplastic-syndromes
#1
Ashwin Unnikrishnan, Elli Papaemmanuil, Dominik Beck, Nandan P Deshpande, Arjun Verma, Ashu Kumari, Petter S Woll, Laura A Richards, Kathy Knezevic, Vashe Chandrakanthan, Julie A I Thoms, Melinda L Tursky, Yizhou Huang, Zara Ali, Jake Olivier, Sally Galbraith, Austin G Kulasekararaj, Magnus Tobiasson, Mohsen Karimi, Andrea Pellagatti, Susan R Wilson, Robert Lindeman, Boris Young, Raj Ramakrishna, Christopher Arthur, Richard Stark, Philip Crispin, Jennifer Curnow, Pauline Warburton, Fernando Roncolato, Jacqueline Boultwood, Kevin Lynch, Sten Eirik W Jacobsen, Ghulam J Mufti, Eva Hellstrom-Lindberg, Marc R Wilkins, Karen L MacKenzie, Jason W H Wong, Peter J Campbell, John E Pimanda
Myelodysplastic syndromes and chronic myelomonocytic leukemia are blood disorders characterized by ineffective hematopoiesis and progressive marrow failure that can transform into acute leukemia. The DNA methyltransferase inhibitor 5-azacytidine (AZA) is the most effective pharmacological option, but only ∼50% of patients respond. A response only manifests after many months of treatment and is transient. The reasons underlying AZA resistance are unknown, and few alternatives exist for non-responders. Here, we show that AZA responders have more hematopoietic progenitor cells (HPCs) in the cell cycle...
July 18, 2017: Cell Reports
https://www.readbyqxmd.com/read/28698788/treatment-of-low-blast-count-aml-using-hypomethylating-agents
#2
REVIEW
Eleonora De Bellis, Luana Fianchi, Francesco Buccisano, Marianna Criscuolo, Luca Maurillo, Laura Cicconi, Mattia Brescini, Maria Ilaria Del Principe, Ambra Di Veroli, Adriano Venditti, Sergio Amadori, William Arcese, Francesco Lo-Coco, Maria Teresa Voso
In 2002, the WHO classification reduced the proportion of blasts in the bone marrow (BM) necessary for the diagnosis of acute myeloid leukemia (AML) from 30% to 20%, eliminating the RAEB-t subtype of myelodysplastic syndromes (MDS). However, this AML subtype, defined as low-blast count AML (LBC-AML, with 20-30% BM-blasts) is characterized by peculiar features, as increased frequency in elderly individuals and after cytotoxic treatment for a different primary disease (therapy-related), poor-risk cytogenetics, lower white blood cell counts, and less frequent mutations of NPM1 and FLT3 genes...
2017: Mediterranean Journal of Hematology and Infectious Diseases
https://www.readbyqxmd.com/read/28693797/azacitidine-in-adult-patients-with-acute-myeloid-leukemia
#3
REVIEW
Andre C Schuh, Hartmut Döhner, Lisa Pleyer, John F Seymour, Pierre Fenaux, Hervé Dombret
Azacitidine is recommended front-line treatment for older patients with acute myeloid leukemia (AML) who are not candidates for intensive treatment regimens, and was recently granted approval in the European Union for treatment of adult AML. Reviewed here is azacitidine experience in AML, including: mechanistic and pharmacokinetic data; safety and efficacy in controlled trials; treatment effects in AML subpopulations defined by disease characteristics; experience in unselected patients treated in the community setting; clinical outcomes relative to other approved AML therapies; and experience with azacitidine-based combination treatment regimens...
August 2017: Critical Reviews in Oncology/hematology
https://www.readbyqxmd.com/read/28693140/acute-myeloid-leukemia-with-t-3-21-q26-2-q22-developing-following-low-dose-methotrexate-therapy-for-rheumatoid-arthritis-and-expressing-two-aml1-mds1-evi1-fusion-proteins-a-case-report
#4
Keisuke Tanaka, Gaku Oshikawa, Hiroki Akiyama, Shinya Ishida, Toshikage Nagao, Masahide Yamamoto, Osamu Miura
The t(3;21)(q26.2;q22) translocation is a rare chromosomal abnormality exhibited almost exclusively in therapy-related myelodysplastic syndrome/acute myeloid leukemia (t-MDS/AML) or in the blastic crisis phase of chronic myelogenous leukemia, which results in the fusion of the runt related transcription factor 1 (RUNX1, also called AML1) gene at 21q22 to the myelodysplasia syndrome 1 (MDS1)-ecotropic virus integration site 1 (EVI1) complex locus (MECOM) at 3q26.2, generating various fusion transcripts, including AML1/MDS1/EVI1 (AME)...
July 2017: Oncology Letters
https://www.readbyqxmd.com/read/28687222/tp53-and-idh2-somatic-mutations-are-associated-with-inferior-overall-survival-after-allogeneic-hematopoietic-cell-transplantation-for-myelodysplastic-syndrome
#5
Mohamed A Kharfan-Dabaja, Rami S Komrokji, Qing Zhang, Ambuj Kumar, Athanasios Tsalatsanis, Janelle Perkins, Taiga Nishihori, Teresa Field, Najla Al Ali, Asmita Mishra, David Sallman, Karma Z Salem, Ling Zhang, Lynn Moscinski, Hugo F Fernandez, Jeffrey Lancet, Alan List, Claudio Anasetti, Eric Padron
BACKGROUND: Next-generation sequencing has identified somatic mutations that are prognostic of cancer. PATIENTS AND METHODS: We evaluated the incidence and prognostic significance of somatic mutations in 89 myelodysplastic syndrome (MDS) patients who received an allogeneic hematopoietic cell transplantation. Next-generation sequencing was performed on paraffin embedded bone marrow, which was obtained at a median of 31 days before initiating the preparative regimen...
June 16, 2017: Clinical Lymphoma, Myeloma & Leukemia
https://www.readbyqxmd.com/read/28685821/pd-1-pd-l1-inhibitors-in-haematological-malignancies-update-2017
#6
REVIEW
Tomas Jelinek, Jana Mihalyova, Michal Kascak, Juraj Duras, Roman Hajek
The introduction of PD-1/PD-L1 pathway inhibitors is an important landmark in solid oncology with unprecedented practice-changing activity in various types of solid tumours. Amongst haematological malignancies, PD-1/PD-L1 inhibitors have been successful, so far, only in the treatment of classical Hodgkin lymphoma, which typically exhibits an over-expression of PD-1 ligands (PD-L1, PD-L2) due to alterations in chromosome 9p24.1. Such positive outcomes led to the FDA approval of nivolumab use in relapsed Hodgkin lymphoma in 2016 as the first haematological indication...
July 6, 2017: Immunology
https://www.readbyqxmd.com/read/28679990/myelodysplastic-syndrome-with-neutrophilic-dermatosis-successfully-treated-with-azacitidine
#7
Daisuke Kudo, Misayo Shimizu, Akihiro Kuroda, Takuya Suyama, Atsushi Shinagawa, Syusaku Ito
A 66-year-old male underwent prednisolone (PSL) therapy of 13 mg/day for rheumatoid arthritis (RA). Antiphospholipid antibody syndrome, neutrophilic dermatosis (ND), and myelodysplastic syndrome (MDS) developed. Treatment of MDS required red cell concentrate transfusion, and second courses of azacitidine therapy (75 mg/m(2) daily, intravenous injection for 7 consecutive days) led to hematologic remission. Furthermore, ND improved early after the start of azacitidine therapy, making it possible to decrease the dose of PSL...
2017: [Rinshō Ketsueki] the Japanese Journal of Clinical Hematology
https://www.readbyqxmd.com/read/28679989/myelodysplastic-syndrome-with-myelofibrosis-in-which-azacitidine-therapy-was-effective-and-cord-blood-transplantation-was-carried-out
#8
Rie Ohba, Noriko Usui, Yuta Ito, Hirofumi Yamauchi, Tomohito Machishima, Hiroto Ishii, Ryoko Fukushima, Hiroki Yokoyama, Yuko Shiota, Yuichi Yahagi, Shingo Yano, Nobuaki Dobashi, Keisuke Aiba
Myelodysplastic syndrome with myelofibrosis (MDS-F) is a disease with a poor prognosis, and patients with this condition are at an increased risk of engraftment failures after allogeneic hematopoietic stem cell transplantation (SCT). Azacitidine (AZA) is effective in high-risk MDS patients. However, the effects of AZA on MDS-F have not been elucidated. AZA was administered to a 62-year-old male with MDS-F for 7 days at a dose of 75 mg/m(2). Hematological improvements were observed after only 1 course of treatment...
2017: [Rinshō Ketsueki] the Japanese Journal of Clinical Hematology
https://www.readbyqxmd.com/read/28679300/the-emerging-role-of-immune-checkpoint-based-approaches-in-aml-and-mds
#9
Prajwal Boddu, Hagop Kantarjian, Guillermo Garcia-Manero, James Allison, Padmanee Sharma, Naval Daver
The development of immune checkpoint inhibitors represents a major breakthrough in the field of cancer therapeutics. Pursuant to their success in melanoma and numerous solid tumor malignancies, these agents are being investigated in hematological malignancies including acute myelogenous leukemia (AML) and myelodysplastic syndromes (MDS). Although AML/MDS have traditionally been considered to be less immunogenic than solid tumor malignancies, recent pre-clinical models suggest a therapeutic role for immune checkpoint inhibition in these diseases...
July 6, 2017: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/28675638/azacitidine-successfully-maintained-the-second-remission-in-an-infant-with-kmt2a-rearranged-acute-lymphoblastic-leukemia-who-relapsed-after-unrelated-cord-blood-transplantation
#10
Ikue Chijimatsu, Yusuke Imanaka, Daisuke Tomizawa, Mariko Eguchi, Shiho Nishimura, Shuhei Karakawa, Mizuka Miki, Kazuko Hamamoto, Naoto Fujita
The outcome for infants with KMT2A (MLL)-rearranged acute lymphoblastic leukemia (MLL-r ALL) is dismal despite intensive therapy, including hematopoietic stem cell transplantation (HSCT). Epigenetic dysregulation is considered a key driver of MLL-r leukemogenesis, which theoretically supports the use of epigenetic modifiers as a treatment option. We report an infant MLL-r ALL case with post-HSCT relapse. After achieving a second remission, which was maintained for 10 months using only the DNA methyltransferase inhibitor, azacitidine, the patient successfully received the second HSCT...
July 4, 2017: Pediatric Blood & Cancer
https://www.readbyqxmd.com/read/28674363/ebv-positive-diffuse-large-b-cell-lymphoma-as-a-secondary-malignancy-arising-in-a-myelodysplastic-syndrome-patient-who-was-treated-with-azacitidine
#11
Naruko Suzuki, Junji Hiraga, Hiroki Kato, Yusuke Takagi, Nobuko Ujihira, Michihiko Narita, Yoshitoyo Kagami
We report a case of secondary diffuse large B-cell lymphoma (DLBCL) after azacitidine (AZA) treatment in a 63-years-old man with myelodysplastic syndrome. The patient suffered from febrile neutropenia after 10 cycles of AZA treatment. Despite the performance of a whole-body CT scan, which showed a multifocal low-density area in the liver and a multifocal nodular shadow in the lung, no malignant neoplasms could be detected. An autopsy was performed 6 months later, and a histopathological examination of the lesions of the liver and lung revealed the infiltration of large round-shaped tumor cells with necrotizing lesions...
2017: Internal Medicine
https://www.readbyqxmd.com/read/28670436/bridging-to-transplant-with-azacitidine-for-myelodysplastic-syndrome-and-acute-myeloid-leukemia-reduces-the-incidence-of-acute-graft-versus-host-disease
#12
Koichi Murakami, Hironori Ueno, Takashi Okabe, Toshiya Kagoo, Saigen Boku, Takahiro Yano, Akihiro Yokoyama
Allogeneic stem cell transplantation (allo-SCT) is the only curative option for myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). Azacitidine (AZA) has a good toxicity profile compared with intensive chemotherapy and can be considered a pre-transplant regimen in elderly patients and in patients with comorbidities. To investigate the impact of pre-transplant AZA on patient outcome after allo-SCT, we conducted a retrospective analysis of AZA pre-treatment followed by allo-SCT in patients with high-risk MDS and AML...
June 1, 2017: Hematology Reports
https://www.readbyqxmd.com/read/28652781/combination-of-azacitidine-and-trichostatin-a-decreased-the-tumorigenic-potential-of-lung-cancer-cells
#13
Yang Yang, Wei Yin, Fengying Wu, Jiang Fan
PURPOSE: This study aims to investigate the possibility of using epigenetic inhibitors against lung cancer. METHODS: The changes in the proliferation of human lung cancer cells, NCI-H1975 and NCI-H1299 cells, treated with various doses of inhibitors of DNA methyltransferase (azacitidine [5-AZA]) or histone deacetylase inhibitors (trichostatin A [TSA]) were determined by cell counting. The cell viability of NCI-H1975 and NCI-H1299 cells treated with 5-AZA and/or TSA was measured by the MTT assay...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28644756/immunological-effects-of-hypomethylating-agents
#14
Katherine E Lindblad, Meghali Goswami, Christopher S Hourigan, Karolyn A Oetjen
Epigenetic changes resulting from aberrant methylation patterns are a recurrent observation in hematologic malignancies. Hypomethylating agents have a well-established role in the management of patients with high-risk myelodysplastic syndrome or acute myeloid leukemia. In addition to the direct effects of hypomethylating agents on cancer cells, there are several lines of evidence indicating a role for immune-mediated anti-tumor benefits from hypomethylating therapy. Areas Covered: We reviewed the clinical and basic science literature for the effects of hypomethylating agents, including the most commonly utilized therapeutics azacitidine and decitabine, on immune cell subsets...
June 23, 2017: Expert Review of Hematology
https://www.readbyqxmd.com/read/28628013/modulation-of-antitumor-immune-response-in-mouse-prostate-cancer-model
#15
N Mitskevich, T Tsertsvadze, K Mchedlishvili, K Matchavariani, G Guruli
Aim of study - prostate cancer is second most common cancer in men worldwide, and fifth leading cause of death from cancer in men (6.6% of the total men deaths). Unfortunately, once cancer spreads outside of prostate, it becomes incurable. Androgen deprivation can provide some relief, but resistance will develop eventually, and at that time no effective treatment options are left to the patient. Therefore, the search of alternative treatment modalities is paramount. In this article we evaluated the role of epigenetic modifier 5-azacitidine (5-AzaC) and immunomodulator - Lenalidomide and their possible impact on the immune response in the murine prostate cancer model...
May 2017: Georgian Medical News
https://www.readbyqxmd.com/read/28621841/hypomethylating-agent-therapy-use-and-survival-in-older-patients-with-chronic-myelomonocytic-leukemia-in-the-united-states-a-large-population-based-study
#16
Amer M Zeidan, Xin Hu, Jessica B Long, Rong Wang, Xiaomei Ma, Nikolai A Podoltsev, Scott F Huntington, Steven D Gore, Amy J Davidoff
BACKGROUND: Despite the approval of azacitidine in 2004 and the approval of decitabine in 2006 in the United States for chronic myelomonocytic leukemia (CMML), the overall survival (OS) benefit with hypomethylating agent (HMA) therapy is unclear. METHODS: Older adults (age ≥ 66 years) who had been diagnosed with CMML from 2001 to 2011 were selected from the Surveillance, Epidemiology, and End Results-Medicare database, and propensity score matching was used to match patients who had been diagnosed after HMA approval (2007-2011) and had received HMA treatment with patients diagnosed before HMA approval (2001-2003)...
June 16, 2017: Cancer
https://www.readbyqxmd.com/read/28618329/therapy-of-older-persons-with-acute-myeloid-leukaemia
#17
REVIEW
Utz Krug, Robert Peter Gale, Wolfgang E Berdel, Carsten Müller-Tidow, Matthias Stelljes, Klaus Metzeler, M Cristina Sauerland, Wolfgang Hiddemann, Thomas Büchner
Most persons age≥60 y with acute myeloid leukaemia (AML) die from their disease. When interpreting clinical trials data from these persons one must be aware of substantial selection biases. Randomized trials of post-remission treatments can be performed upfront or after achieving defined landmarks. Both strategies have important limitations. Selection of the appropriate treatment is critical. Age, performance score, co-morbidities and frailty provide useful data to treatment selection. If an intensive remission induction therapy is appropriate, therapy with cytarabine and an anthracycline is the most common regimen...
June 1, 2017: Leukemia Research
https://www.readbyqxmd.com/read/28610766/feasibility-and-cost-effectiveness-of-at-home-azacitidine-administration
#18
Antonia Sampol, Elena Delgado, Bernardo López
No abstract text is available yet for this article.
June 10, 2017: Medicina Clínica
https://www.readbyqxmd.com/read/28574488/maintenance-therapy-with-alternating-azacitidine-and-lenalidomide-in-elderly-fit-patients-with-poor-prognosis-acute-myeloid-leukemia-a-phase-ii-multicentre-filo-trial
#19
M Hunault-Berger, N Maillard, C Himberlin, C Recher, A Schmidt-Tanguy, B Choufi, C Bonmati, M Carré, M-A Couturier, E Daguindau, J-P Marolleau, F Orsini-Piocelle, J Delaunay, E Tavernier, S Lissandre, M Ojeda-Uribe, L Sanhes, L Sutton, A Banos, L M Fornecker, M Bernard, D Bouscary, A Saad, M Puyade, V Rouillé, I Luquet, M C Béné, J-F Hamel, F Dreyfus, N Ifrah, A Pigneux
No abstract text is available yet for this article.
June 2, 2017: Blood Cancer Journal
https://www.readbyqxmd.com/read/28546581/a-phase-1b-2b-multicenter-study-of-oral-panobinostat-plus-azacitidine-in-adults-with-mds-cmml-or-aml-with-%C3%A2-30-blasts
#20
G Garcia-Manero, M A Sekeres, M Egyed, M Breccia, C Graux, J D Cavenagh, H Salman, A Illes, P Fenaux, D J DeAngelo, R Stauder, K Yee, N Zhu, J-H Lee, D Valcarcel, A MacWhannell, Z Borbenyi, L Gazi, S Acharyya, S Ide, M Marker, O G Ottmann
Treatment with azacitidine (AZA), a demethylating agent, prolonged overall survival (OS) vs conventional care in patients with higher-risk myelodysplastic syndromes (MDS). As median survival with monotherapy is <2 years, novel agents are needed to improve outcomes. This phase 1b/2b trial (n=113) was designed to determine the maximum tolerated dose (MTD) or recommended phase 2 dose (RP2D) of panobinostat (PAN)+AZA (phase 1b) and evaluate the early efficacy and safety of PAN+AZA vs AZA monotherapy (phase 2b) in patients with higher-risk MDS, chronic myelomonocytic leukemia or oligoblastic acute myeloid leukemia with <30% blasts...
May 26, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
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