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Acute promyelocytic leukemia high risk

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https://www.readbyqxmd.com/read/29892554/incident-adverse-events-following-therapy-for-acute-promyelocytic-leukemia
#1
Peter Geon Kim, Kelly Bridgham, Evan C Chen, Mahesh K Vidula, Olga Pozdnyakova, Andrew M Brunner, Amir T Fathi
The use of all-trans retinoic acid (ATRA) combined with arsenic trioxide (ATO) with or without cytotoxic chemotherapy is highly effective in acute promyelocytic leukemia (APL) but incident chronic adverse events (AEs) after initiation of therapy are not well understood. We retrospectively analyzed adult patients with newly diagnosed APL from 2004 through 2014 to identify incident AEs following treatment and contributing risk factors. Cardiac and neurologic AEs were more common and characterized in detail. Cardiac AEs such as the development of coronary artery disease (CAD), arrhythmias, and heart failure had a cumulative incidence of 6...
2018: Leukemia Research Reports
https://www.readbyqxmd.com/read/29876014/multi-omics-profiling-reveals-a-distinctive-epigenome-signature-for-high-risk-acute-promyelocytic-leukemia
#2
Abhishek A Singh, Francesca Petraglia, Angela Nebbioso, Guoqiang Yi, Mariarosaria Conte, Sergio Valente, Amit Mandoli, Lucia Scisciola, Rik Lindeboom, Hinri Kerstens, Eva M Janssen-Megens, Farzin Pourfarzad, Ehsan Habibi, Kim Berentsen, Bowon Kim, Colin Logie, Simon Heath, Albertus T J Wierenga, Laura Clarke, Paul Flicek, Joop H Jansen, Taco Kuijpers, Marie Laure Yaspo, Veronique Della Valle, Olivier Bernard, Ivo Gut, Edo Vellenga, Hendrik G Stunnenberg, Antonello Mai, Lucia Altucci, Joost H A Martens
Epigenomic alterations have been associated with both pathogenesis and progression of cancer. Here, we analyzed the epigenome of two high-risk APL (hrAPL) patients and compared it to non-high-risk APL cases. Despite the lack of common genetic signatures, we found that human hrAPL blasts from patients with extremely poor prognosis display specific patterns of histone H3 acetylation, specifically hyperacetylation at a common set of enhancer regions. In addition, unique profiles of the repressive marks H3K27me3 and DNA methylation were exposed in high-risk APLs...
May 22, 2018: Oncotarget
https://www.readbyqxmd.com/read/29862538/improved-long-term-survival-in-all-sanz-risk-patients-of-newly-diagnosed-acute-promyelocytic-leukemia-treated-with-a-combination-of-retinoic-acid-and-arsenic-trioxide-based-front-line-therapy
#3
Yinjun Lou, Ying Lu, Zhijuan Zhu, Yafang Ma, Shanshan Suo, Yungui Wang, Dong Chen, Hongyan Tong, Wenbin Qian, Haitao Meng, Wenyuan Mai, Wenjun Yu, Weilai Xu, Lei Wang, Liping Mao, Renzhi Pei, Jie Jin
Limited data was available for long-term follow-up in newly diagnosed acute promyelocytic leukemia (APL) patients treated with all-trans-retinoic acid (ATRA) plus intravenously arsenic trioxide (ATO)-based front-line therapy. The aim of this work was to retrospectively analyze the long-term survival rate and frequency of therapy-related myeloid neoplasia (t-MN) occurring in a large cohort of APL patients. A total of 760 newly diagnosed patients with APL between January 1999 and May 2016 were evaluated. The early death rate was 9...
June 3, 2018: Hematological Oncology
https://www.readbyqxmd.com/read/29789356/risk-adapted-treatment-of-acute-promyelocytic-leukemia-results-from-international-consortium-for-childhood-apl
#4
Anna Maria Testi, Andrea Pession, Daniela Diverio, David Grimwade, Brenda Gibson, Amilcar Cardoso de Azevedo, Lorena Moran, Guy Leverger, Sarah Elitzur, Henrik Hasle, Jutte van der Werff Ten Bosch, Owen Smith, Marisa De Rosa, Alfonso Piciocchi, Francesco Lo Coco, Robin Foà, Franco Locatelli, Gertjan J L Kaspers
Pediatric acute promyelocytic leukemia (APL), a rare childhood neoplasm, can be cured with all-trans retinoic acid (ATRA) and anthracycline. However, most published trials to date have employed high cumulative doses of anthracyclines. Here, we report the outcome of patients with newly diagnosed APL enrolled into the International Consortium for Childhood APL (ICC-APL-01) trial, which reduced anthracycline exposure but extended that of ATRA. The study recruited 258 children/adolescents with molecularly/cytogenetically-proven APL...
May 22, 2018: Blood
https://www.readbyqxmd.com/read/29771870/hyperfibrinolysis-is-an-important-cause-of-early-hemorrhage-in-patients-with-acute-promyelocytic-leukemia
#5
Yu-Hua Song, Chun Qiao, Li-Chan Xiao, Run Zhang, Hua - Lu
BACKGROUND The objective of the current study was to guide the early clinical treatment strategies by assessing the recovery of abnormal coagulation in acute promyelocytic leukemia (APL) patients during induction therapy. MATERIAL AND METHODS Retrospective analysis was performed in 112 newly-diagnosed patients with APL during induction treatment. RESULTS The early death (ED) rate in our study was 5.36% and the main cause was fetal hemorrhage. The presence of bleeding symptoms was significantly correlated with low platelet and fibrinogen levels...
May 17, 2018: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/29743722/management-of-patients-with-acute-promyelocytic-leukemia
#6
REVIEW
Sabine Kayser, Richard F Schlenk, Uwe Platzbecker
With the introduction of all-trans retinoic acid (ATRA) and arsenic trioxide (ATO) acute promyelocytic leukemia (APL) has become from a detrimental to one of the most curable malignant diseases in humans. In particular, the chemotherapy-free regimen with ATO/ATRA has been proven to be highly effective in de novo APL and has become standard first-line therapy in younger adult, non-high-risk patients. Nevertheless, early death is still a major issue in APL, particularly in older patients, emphasizing the need of rapid diagnostics and supportive care together with immediate access to ATRA-based therapy...
June 2018: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/29728404/oral-arsenic-and-all-trans-retinoic-acid-for-high-risk-acute-promyelocytic-leukemia
#7
Hong-Hu Zhu, Yan-Rong Liu
No abstract text is available yet for this article.
May 4, 2018: Blood
https://www.readbyqxmd.com/read/29703489/mechanisms-and-management-of-coagulopathy-in-acute-promyelocytic-leukemia
#8
Sachin David, Vikram Mathews
Acute promyelocytic leukemia (APL) is a subtype of leukemia which is associated with unique and distinctive coagulopathy. In the absence of treatment it is rapidly fatal and even after initiation of therapy the major cause of early mortality is related to hemorrhagic complications. The coagulopathy can be exacerbated with the start of treatment. In the absence of early hemorrhage related deaths the probability of cure exceeds 90% in low and intermediate risk patients and 80% even in high risk patients, highlighting the importance of understanding the pathophysiology of this complication and instituting prompt and appropriate management strategies...
April 2018: Thrombosis Research
https://www.readbyqxmd.com/read/29572500/basophil-lineage-commitment-in-acute-promyelocytic-leukemia-predicts-for-severe-bleeding-after-starting-therapy
#9
Sergio Matarraz, Pilar Leoz, Carlos Fernández, Enrique Colado, María Carmen Chillón, María Belén Vidriales, Marcos González, Daniel Rivera, Carlos Salvador Osuna, Teresa Caballero-Velázquez, Vincent Van Der Velden, Mojca Jongen-Lavrencic, Oliver Gutiérrez, Ana Yeguas Bermejo, Luis García Alonso, Monique Bourgeois García, Cristina De Ramón Sánchez, Gloria García-Donas, Aránzazu García Mateo, Isabel Recio, Javier Sánchez-Real, Andrea Mayado, María Laura Gutiérrez, Paloma Bárcena, Susana Barrena, Antonio López, Jacques Van Dongen, Alberto Orfao
Severe hemorrhagic events occur in a significant fraction of acute promyelocytic leukemia patients, either at presentation and/or early after starting therapy, leading to treatment failure and early deaths. However, identification of independent predictors for high-risk of severe bleeding at diagnosis, remains a challenge. Here, we investigated the immunophenotype of bone marrow leukemic cells from 109 newly diagnosed acute promyelocytic leukemia patients, particularly focusing on the identification of basophil-related features, and their potential association with severe bleeding episodes and patient overall survival...
March 23, 2018: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
https://www.readbyqxmd.com/read/29566848/corrigendum-to-comparison-of-induction-therapy-in-non-high-risk-acute-promyelocytic-leukemia-with-arsenic-trioxide-or-in-combination-with-atra-leukemia-research-66-2018-85-88
#10
Ardeshir Ghavamzadeh, Mahdi Jalili, Sharbanoo Rostami, Marjan Yaghmaie, Leyla Sharifi Aliabadi, Seyed Asadollah Mousavi, Mohammad Vaezi, Hossein Kamranzadeh Fumani, Mohammad Jahani, Kamran Alimoghaddam
No abstract text is available yet for this article.
April 2018: Leukemia Research
https://www.readbyqxmd.com/read/29554366/zyh005-a-novel-dna-intercalator-overcomes-all-trans-retinoic-acid-resistance-in-acute-promyelocytic-leukemia
#11
Qingyi Tong, Huijuan You, Xintao Chen, Kongchao Wang, Weiguang Sun, Yufeng Pei, Xiaodan Zhao, Ming Yuan, Hucheng Zhu, Zengwei Luo, Yonghui Zhang
Despite All-trans retinoic acid (ATRA) has transformed acute promyelocytic leukemia (APL) from the most fatal to the most curable hematological cancer, there remains a clinical challenge that many high-risk APL patients who fail to achieve a complete molecular remission or relapse and become resistant to ATRA. Herein, we report that 5-(4-methoxyphenethyl)-[1, 3] dioxolo [4, 5-j] phenanthridin-6(5H)-one (ZYH005) exhibits specific anticancer effects on APL and ATRA-resistant APL in vitro and vivo, while shows negligible cytotoxic effect on non-cancerous cell lines and peripheral blood mononuclear cells from healthy donors...
March 15, 2018: Nucleic Acids Research
https://www.readbyqxmd.com/read/29541170/early-mortality-in-acute-promyelocytic-leukemia-potential-predictors
#12
Can Chen, Xilian Huang, Kaile Wang, Kuang Chen, Danquan Gao, Shenxian Qian
Acute promyelocytic leukemia (APL) is a rare leukemia characterized by the balanced reciprocal translocation between the promyelocytic leukemia gene on chromosome 15 and the retinoic acid receptor α (RARα) gene on chromosome 17, and accounts for 10-15% of newly diagnosed acute myeloid leukemia each year. The combined use of all-trans retinoic acid and arsenic trioxide (ATO) as primary therapy has markedly improved the survival rate of patients with APL. Mortality in the first 30 days following therapy remains a major contribution to treatment failure...
April 2018: Oncology Letters
https://www.readbyqxmd.com/read/29409083/-acute-promyelocytic-leukemia-a-rare-life-threatening-disease-with-high-healing-chance
#13
Florian Nolte, Eva Lengfelder, Wolf-Karsten Hofmann
The acute promyelocytic leukemia (APL) is a rare disease. However, if diagnosed early and treated immediately high cure rates can be achieved. Signs of hematopoietic insufficiency such as cytopenias or leucocytosis can be present at first presentation of the patients. Moreover, hemorrhagic diatheses due to coagulpathy are present in approximately 80 % of cases and contribute substatially to the high early death rate in APL patients, which has been reported as high as 30 % in population based studies. In case of initial suspicion of APL treatment with all-trans retinoic acid (ATRA) should be initated immediately to reduce the risk of fatal bleeding events and confirmation or exclusion of the PML-RARA transcript should not be awaited before start of ATRA treatment...
February 2018: Deutsche Medizinische Wochenschrift
https://www.readbyqxmd.com/read/29407588/comparison-of-induction-therapy-in-non-high-risk-acute-promyelocytic-leukemia-with-arsenic-trioxide-or-in-combination-with-atra
#14
Ardeshir Ghavamzadeh, Mahdi Jalili, Sharbanoo Rostami, Marjan Yaghmaie, Leyla Sharifi Aliabadi, Seyed Asadollah Mousavi, Mohammad Vaezi, Hossein Kamranzadeh Fumani, Mohammad Jahani, Kamran Alimoghaddam
BACKGROUND: Acute promyelocytic leukemia (APL) is a curable form of acute myeloid leukemia; in recent years, the use of new treatment strategies, such as combination therapy, have led to improved APL outcomes. Here, outcomes of patients treated with a combination of arsenic trioxide (ATO) and all-trans-retinoic acid (ATRA) are compared against patients treated with single ATO therapy. PATIENTS AND METHODS: In total, 67 patients with non-high-risk APL were evaluated...
March 2018: Leukemia Research
https://www.readbyqxmd.com/read/29390508/analysis-of-early-death-in-newly-diagnosed-acute-promyelocytic-leukemia-patients
#15
Fang Xu, Chunli Wang, Changxin Yin, Xuejie Jiang, Ling Jiang, Zhixiang Wang, Fanyi Meng
The aim of this study was to identify risk factors for early death (ED) in acute promyelocitic leukemia (APL) patients.Clinical records of 49 APL patients who suffered ED were divided into 4 groups: death before treatment or within the first 3 days (immediate death; iED group), death during treatment at least 3 days after commencement (ED after treatment), low/intermediate risk, and high-risk groups.White blood cell (WBC) count, high-risk cases, prothrombin time (PT) prolongation, international society on thrombosis and hemostasis (ISTH) scores (P < ...
December 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/29296827/clinical-impact-of-baalc-expression-in-high-risk-acute-promyelocytic-leukemia
#16
Antonio R Lucena-Araujo, Diego A Pereira-Martins, Luisa C Koury, Pedro L Franca-Neto, Juan L Coelho-Silva, Virginia M de Deus Wagatsuma, Raul A M Melo, Rosane Bittencourt, Katia Pagnano, Ricardo Pasquini, Carlos S Chiattone, Evandro M Fagundes, Maria de Lourdes Chauffaille, Stanley L Schrier, Martin S Tallman, Raul C Ribeiro, David Grimwade, Arnold Ganser, Bob Löwenberg, Francesco Lo-Coco, Miguel A Sanz, Nancy Berliner, Eduardo M Rego
Although overexpression of the brain and acute leukemia, cytoplasmic ( BAALC ) gene is associated with primary resistant disease and shorter relapse-free, disease-free, and overall survival in different subsets of acute myeloid leukemia (AML), little is known about its clinical impact in acute promyelocytic leukemia (APL). Using real-time reverse transcriptase polymerase chain reaction, we showed that BAALC expression is significantly lower in APL compared with other subsets of AML ( P < .001). We also demonstrated that BAALC overexpression was associated with shorter disease-free survival (DFS) (hazard ratio [HR], 4...
September 26, 2017: Blood Advances
https://www.readbyqxmd.com/read/29212418/clinical-characteristics-and-outcome-of-childhood-acute-promyelocitic-leukemia-apl-in-saudi-arabia-a-multicenter-saphos-leukemia-group-study
#17
Wasil Jastaniah, Abdulrahman Alsultan, Saad Al Daama, Walid Ballourah, Mohamed Bayoumy, Faisal Al-Anzi, Omar Al Shareef, Mohammed Burhan Abrar, Reem Al Sudairy, Ibrahim Al Ghemlas
BACKGROUND: Acute promyelocytic leukemia (APL) is a rare form of acute myelogenous leukemia (AML). Survival rates exceed 80% in developed countries. Successful treatments rely on all-trans retinoic acid with anthracycline-based chemotherapy. Availability of modern care and public knowledge play important roles in pediatric APL survival. METHOD: A cytogenetic diagnosis of APL was confirmed in 30 (14.5%) out of 207 children consecutively diagnosed with de novo AML between January 2005 and December 2012 at nine cancer care centers in Saudi Arabia...
December 7, 2017: Hematology (Amsterdam, Netherlands)
https://www.readbyqxmd.com/read/29114972/frontline-therapy-of-acute-promyelocytic-leukemia-randomized-comparison-of-atra-and-intensified-chemotherapy-versus-atra-and-anthracyclines
#18
Eva Lengfelder, Dennis Görlich, Daniel Nowak, Karsten Spiekermann, Claudia Haferlach, Utz Krug, Karl-Anton Kreuzer, Jan Braess, Christoph Schliemann, Hans-Walter Lindemann, Heinz A Horst, Xaver Schiel, Michael Flasshove, Anna Hecht, Susanne Schnittger, Stephanie Schneider, Bernhard Wörmann, Wolf-Karsten Hofmann, Wolfgang E Berdel, Eike Bormann, Cristina Sauerland, Thomas Büchner, Wolfgang Hiddemann
OBJECTIVES: Randomized comparison of two treatment strategies in frontline therapy of acute promyelocytic leukemia (APL): all-trans retinoic acid (ATRA) and double induction intensified by high-dose cytosine arabinoside (HD ara-C) (German AMLCG) and therapy with ATRA and anthracyclines (Spanish PETHEMA, LPA99). PATIENTS AND RESULTS: Eighty of 87 adult patients with genetically confirmed APL of all risk groups were eligible. The outcome of both arms was similar: AMLCG vs PETHEMA: hematological complete remission 87% vs 83%, early death 13% vs 17% (P = ...
February 2018: European Journal of Haematology
https://www.readbyqxmd.com/read/29113277/sequence-variations-of-mitochondrial-dna-d-loop-region-in-patients-with-acute-myeloid-leukemia
#19
Juan Zhou, Haimei Gou, Yuanxin Ye, Yi Zhou, Xiaojun Lu, Binwu Ying
The aim of the present study was to explore variations of the displacement (D)-loop region in patients with acute myeloid leukemia (AML) and their possible associations with AML pathogenesis. Blood or bone marrow samples from 216 patients with AML (158 AML patients in the first stage, and 58 more patients with AML-M3 for further verification), and 146 healthy controls were collected. Sanger sequencing was performed for the D-loop region ranging between nucleotide (nt)15811 and nt 775. With the exception of mitochondrial microsatellite instability (mtMSI) variations, a total of 2,630 variations in 232 loci were identified with similar variation rates/person in patients with AML and controls when compared with the revised Cambridge reference sequence (8...
November 2017: Oncology Letters
https://www.readbyqxmd.com/read/29062237/low-platelet-count-is-potentially-the-most-important-contributor-to-severe-bleeding-in-patients-newly-diagnosed-with-acute-promyelocytic-leukemia
#20
Yu-Hua Song, Peng Peng, Chun Qiao, Run Zhang, Jian-Yong Li, Hua Lu
The objective of the current study was to provide more appropriate therapeutic strategies for reducing severe hemorrhaging by assessing the recovery of abnormal coagulation indexes in patients with acute promyelocytic leukemia (APL) during induction therapy. Retrospective analyses of 112 patients newly diagnosed with APL were performed during initial treatment. In our study, the early death rate was 5.36%. Hemorrhage was the leading cause of death during the induction period (4/6). The values of white blood cell count, lactate dehydrogenase, prothrombin time (PT), fibrinogen (Fbg), hemoglobin, and bone marrow leukemic promyelocytes were significantly different in the high-risk group compared to the low/intermediate-risk groups...
2017: OncoTargets and Therapy
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