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Akimasa Sanagawa, Yuji Hotta, Tomoya Kataoka, Yasuhiro Maeda, Masahiro Kondo, Yoshihiro Kawade, Yoshihiro Ogawa, Ryohei Nishikawa, Masahiro Tohkin, Kazunori Kimura
We conducted data mining using the US Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) database on spontaneously reported adverse events to evaluate the association between anticancer drug therapy and hepatitis B infection. Reports of hepatitis B infection were retrieved from the FAERS database. The reporting odds ratio (ROR) was used to estimate the association between hepatitis B infection and various anticancer agents and drug combinations. We detected statistically significant risk signals of hepatitis B for 33 of 64 anticancer agents by ROR (26 cytotoxicity drugs and seven molecular-targeted drugs)...
April 16, 2018: Cancer Medicine
Sotirios G Papageorgiou, Diamantina Vasilatou, Christos K Kontos, Ioannis Kotsianidis, Argiris Symeonidis, Athanasios G Galanopoulos, Eleftheria Hatzimichael, Aekaterini Megalakaki, Elias Poulakidas, Panagiotis Diamantopoulos, Theodoros Vassilakopoulos, Panagiotis Zikos, Helen Papadaki, Despoina Mparmparousi, Eleni Bouronikou, Panayiotis Panayiotidis, Nora-Athina Viniou, Vassiliki Pappa
In this study, we investigated the incidence and prognostic impact of monosomal karyotype (MK) in 405 higher-risk MDS patients treated with 5-AZA. The MK was present in 66 out of 405 (16.3%) patients, most of whom had complex karyotype (CK). MK was strongly associated with CK and the cytogenetic risk defined according to IPSS-R, as well as with high-risk disease, according to IPSS (P=0.029), IPSS-R (P<0.001), and WPSS (P<0.001) classification systems. The overall response rate (ORR) was not different between MK+ and MK- patients (46...
April 16, 2018: American Journal of Hematology
Tomomi Takei, Kazuaki Yokoyama, Eigo Shimizu, Takaaki Konuma, Satoshi Takahashi, Rui Yamaguchi, Seiya Imoto, Satoru Miyano, Arinobu Tojo
No abstract text is available yet for this article.
April 12, 2018: Leukemia & Lymphoma
Kathryn T Maples, Roy T Sabo, John M McCarty, Amir A Toor, Kelly G Hawks
Allogeneic hematopoietic cell transplantation (HCT) is a curative option for patients with acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS), but carries a high risk of relapse. This retrospective review evaluates the effectiveness of maintenance azacitidine in high-risk AML and MDS patients to reduce the probability of relapse. Twenty-five patients who received maintenance azacitidine were matched to historical controls in a two-to-one ratio based on diagnosis, donor type, conditioning regimen intensity, and age...
April 4, 2018: Leukemia & Lymphoma
María Díez-Campelo, Jose I Lorenzo, Raphael Itzykson, Silvia M Rojas, Céline Berthon, Elisa Luño, Odile Beyne-Rauzy, Jaime Perez-Oteyza, Norbert Vey, Joan Bargay, Sophie Park, Teresa Cedena, Dominique Bordessoule, Juan A Muñoz, Emmanuel Gyan, Esperanza Such, Sorin Visanica, Félix López-Cadenas, Stéphane de Botton, Jesús M Hernández-Rivas, Shanti Ame, Aspasia Stamatoullas, Jacques Delaunay, Celia Salanoubat, Françoise Isnard, Romain Guieze, Joan Pérez Guallar, Llorenc Badiella, Guillermo Sanz, Consuelo Cañizo, Pierre Fenaux
Treatment with azacitidine (AZA) has been suggested to be of benefit for higher-risk myelodysplastic syndrome (HR-MDS) patients with chromosome 7 abnormalities (Abn 7). This retrospective study of 235 HR-MDS patients with Abn 7 treated with AZA (n = 115) versus best supportive care (BSC; n = 120), assessed AZA treatment as a time-varying variable in multivariable analysis. A Cox Regression model with time-interaction terms of overall survival (OS) at different time points confirmed that, while chromosome 7 cytogenetic categories (complex karyotype [CK] versus non-CK) and International Prognostic Scoring System risk (high versus intermediate-2) retained poor prognosis over time, AZA treatment had a favourable impact on OS during the first 3 years of treatment compared to BSC (Hazard ratio [HR] 0·5 P < 0·001 at 1 year, 0·7 P = 0·019 at 2 years; 0·73 P = 0·029 at 3 years)...
April 2, 2018: British Journal of Haematology
Amir T Fathi
No abstract text is available yet for this article.
March 29, 2018: Blood
Aleksandra Boba, Kamil Kostyn, Marta Preisner, Wioleta Wojtasik, Jan Szopa, Anna Kulma
Previously we described flax plants with expression of Arabidopsis lycopene β-cyclase (lcb) gene in which decreased expression of the endogenous lcb and increased resistance to fungal pathogen was observed. We suggested that co-suppression was responsible for the change. In this study we investigated the molecular basis of the observed effect in detail. We found that methylation changes in the Lulcb gene body might be responsible for repression of the gene. Treatment with azacitidine (DNA methylation inhibitor) confirmed the results...
March 21, 2018: Plant Physiology and Biochemistry: PPB
Bruno C Medeiros, Tiffany N Tanaka, Larisa Balaian, Asad Bashey, Amy Guzdar, Hongying Li, Karen Messer, Edward D Ball
INTRODUCTION: Treatment with hypomethylating agent therapy might enhance anti-CD33 monoclonal antibody-mediated cytotoxicity against acute myeloid leukemia (AML) blasts through epigenetic effects on Syk and SHP-1 expression. PATIENTS AND METHODS: In the present phase I/II study, we treated patients with relapsed or refractory AML with azacitidine, followed by 2 doses of gemtuzumab ozogamicin (GO) at 6 mg/m2 , the Food and Drug Administration-approved dose and schedule at study initiation...
March 2, 2018: Clinical Lymphoma, Myeloma & Leukemia
Jason X Cheng, Li Chen, Yuan Li, Adam Cloe, Ming Yue, Jiangbo Wei, Kenneth A Watanabe, Jamile M Shammo, John Anastasi, Qingxi J Shen, Richard A Larson, Chuan He, Michelle M Le Beau, James W Vardiman
The roles of RNA 5-methylcytosine (RNA:m5 C) and RNA:m5 C methyltransferases (RCMTs) in lineage-associated chromatin organization and drug response/resistance are unclear. Here we demonstrate that the RCMTs, namely NSUN3 and DNMT2, directly bind hnRNPK, a conserved RNA-binding protein. hnRNPK interacts with the lineage-determining transcription factors (TFs), GATA1 and SPI1/PU.1, and with CDK9/P-TEFb to recruit RNA-polymerase-II at nascent RNA, leading to formation of 5-Azacitidine (5-AZA)-sensitive chromatin structure...
March 21, 2018: Nature Communications
Ioannis Panagopoulos, Ludmila Gorunova, Hege Kilen Andersen, Astrid Bergrem, Anders Dahm, Kristin Andersen, Francesca Micci, Sverre Heim
Background: Acquired primary chromosomal changes in cancer are sometimes found as sole karyotypic abnormalities. They are specifically associated with particular types of neoplasia, essential in establishing the neoplasm, and they often lead to the generation of chimeric genes of pathogenetic, diagnostic, and prognostic importance. Thus, the report of new primary cancer-specific chromosomal aberrations is not only of scientific but also potentially of clinical interest, as is the detection of their gene-level consequences...
2018: Experimental Hematology & Oncology
Meagan A Jacoby, Eric J Duncavage, Gue Su Chang, Christopher A Miller, Jin Shao, Kevin Elliott, Joshua Robinson, Robert S Fulton, Catrina C Fronick, Michelle O'Laughlin, Sharon E Heath, Iskra Pusic, John S Welch, Daniel C Link, John F DiPersio, Peter Westervelt, Timothy J Ley, Timothy A Graubert, Matthew J Walter
Allogeneic hematopoietic cell transplantation (alloHCT) is a potentially curative treatment for myelodysplastic syndromes (MDS), but patients who relapse after transplant have poor outcomes. In order to understand the contribution of tumor clonal evolution to disease progression,we applied exome and error-corrected targeted sequencing coupled with copy number analysis to comprehensively define changes in the clonal architecture of MDS in response to therapy using 51 serially acquired tumor samples from 9 patients who progressed after an alloHCT...
March 8, 2018: JCI Insight
C Roy, J P Adam, F Morin, É Lemieux-Blanchard, S Doucet, D Friedmann, A Belisle, D Charpentier
Pyoderma gangrenosum (pg) is a rare neutrophilic dermatosis characterized by painful necrotic ulceration affecting preferentially the lower extremities. Diagnosis is challenging, and a thorough workup (including biopsy) is required. In this case report, we describe a 67-year-old patient with a diagnosis of myelodysplastic syndrome (mds) who developed fever and pg two days after the first cycle of subcutaneous azacitidine (Vidaza; Celgene Corporation, Summit, NJ, USA). On physical examination, the patient had four erythematous plaques at sites of subcutaneous injections of azacitidine on the arms, as well as three other plaques in proximity...
February 2018: Current Oncology
Naval Daver, Prajwal Boddu, Guillermo Garcia-Manero, Shalini Singh Yadav, Padmanee Sharma, James Allison, Hagop Kantarjian
Immune checkpoint inhibitors, as single-agent therapy, have shown modest clinical efficacy in the treatment of acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS). As has been successfully shown in other less immunogenic hematologic malignancies, rationally designed combination approaches may be more effective than single-agent checkpoint inhibitors, and may be the approach to pursue in AML/MDS. Hypomethylating agents (HMAs) such as azacitidine, while enhancing anti-tumor immune response, concurrently dampen immune response by upregulating inhibitory immune checkpoint molecule expression...
February 22, 2018: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
Riad El Fakih, Rami Komrokji, Marwan Shaheen, Fahad Almohareb, Walid Rasheed, Mona Hassanein
Azacitidine and decitabine are hypomethylating agents frequently used interchangeably to treat myeloid neoplasms in different settings. Azacitidine is metabolized intracellularly into decitabine. Hypomethylating agents work by inhibiting DNA methyltransferases, causing demethylation of aberrantly methylated promoter regions of genes involved in the pathogenesis of myeloid neoplasms. Azacitidine was the first agent approved by the US Food and Drug Administration for treatment of myelodysplastic syndrome in 2004, after which, the use of azacitidine in other myeloid neoplasms increased significantly...
February 8, 2018: Clinical Lymphoma, Myeloma & Leukemia
Jill A Bell, Aaron Galaznik, Rachel Huelin, Michael Stokes, Yelan Guo, Robert J Fram, Douglas V Faller
High-dose chemotherapy with allogeneic hematopoietic stem cell transplantation (allo-HSCT) can produce long-term remission in patients with higher-risk myelodysplastic syndromes (HR-MDS) and chronic myelomonocytic leukemia (CMML). However, this treatment regimen is not appropriate for elderly and/or comorbid patients; in these cases, azacitidine is a standard treatment. This systematic review was conducted to evaluate real-world evidence of treatment options for patients with HR-MDS/CMML. Medline and Embase (January 2006 to May 2016) were searched, in addition to conference proceedings and treatment guideline reviews...
February 8, 2018: Clinical Lymphoma, Myeloma & Leukemia
Rory M Shallis, Amer M Zeidan
Myelodysplastic syndromes (MDS) encompass a diverse group of hematologic disorders characterized by ineffective and malignant hematopoiesis, peripheral cytopenias and significantly increased risk of progression to acute myeloid leukemia (AML). The hypomethylating agents (HMA) azacitidine and decitabine induce meaningful clinical responses in a significant subset of patients with MDS. Though never compared directly with decitabine, only azacitidine has improved overall survival (OS) compared to conventional care in a randomized trial in patients with higher-risk MDS...
2018: BMC Hematology
Roman M Shapiro, Alejandro Lazo-Langner
Background: 5-Azacitidine administered as a 7-day dosing regimen (7-0-0) is approved in high risk IPSS myelodysplastic syndrome (MDS) patients. Alternative regimens such as a 5-day (5-0-0) or 7-day with a weekend break (5-2-2) are commonly used. No randomized controlled trial has been done directly comparing all three dosing regimens. The objective of this study was to compare the efficacies of the 5-0-0, 5-2-2, and 7-0-0 regimens in MDS and AML. Methods: A systematic review was conducted using MEDLINE, EMBASE and CENTRAL...
2018: BMC Hematology
Tobias Kratzsch, Susanne Antje Kuhn, Andreas Joedicke, Uwe Karsten Hanisch, Peter Vajkoczy, Jens Hoffmann, Iduna Fichtner
PURPOSE: Glioblastoma multiforme (GBM) is the most lethal primary brain tumor in adults. The epigenetically active ribonucleoside analog 5-azacitidine is a new therapy option that changes tumor cell chromatin, which is frequently modified by methylation and deacetylation in malignant gliomas. METHODS: In vitro, we analyzed cell viability, cell apoptosis, and migration of human GBM cells. In vivo, we established subcutaneous and intracerebral GBM mouse models originating from U87MG, U373MG, and primary GBM cells as well as one patient-derived xenograft...
February 9, 2018: Journal of Cancer Research and Clinical Oncology
Aurélie Berot, Claire Pluchart
No abstract text is available yet for this article.
January 31, 2018: Journal of Pediatric Hematology/oncology
Florian Huemer, Lukas Weiss, Viktoria Faber, Daniel Neureiter, Alexander Egle, Klaus Geissler, Daniela Voskova, Armin Zebisch, Sonja Burgstaller, Angelika Pichler, Reinhard Stauder, Wolfgang Sperr, Alois Lang, Michael Pfeilstöcker, Sigrid Machherndl-Spandl, Margarete Stampfl, Richard Greil, Lisa Pleyer
Chronic myelomonocytic leukaemia is a rare disease and data on the treatment are often extrapolated from myelodysplastic syndrome studies. Although several scores exist for the prognosis of overall survival in chronic myelomonocytic leukaemia, so far there is no designated score for the prediction of the time to first treatment. We tested clinical parameters and cytogenetic information for their ability to predict the time to first treatment in our single center cohort of 55 unselected consecutive chronic myelomonocytic leukaemia patients...
January 30, 2018: Wiener Klinische Wochenschrift
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