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Acute promyelocytic leukemia high risk

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https://www.readbyqxmd.com/read/29572500/basophil-lineage-commitment-in-acute-promyelocytic-leukemia-predicts-for-severe-bleeding-after-starting-therapy
#1
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
#2
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
#3
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
#4
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
#5
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
#6
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
#7
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
#8
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
#9
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
#10
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
#11
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
#12
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
https://www.readbyqxmd.com/read/28954349/-prediction-of-outcome-in-acute-myeloid-leukemia-by-measurement-of-wt1-expression-as-a-basic-marker-of-minimal-residual-disease
#13
N Zhao, H Wei, Y Wang, D Lin, C L Zhou, B C Liu, K Q Liu, G J Zhang, S N Wei, B F Gong, X Y Gong, W Li, Y Li, Y T Liu, S W Qiu, R X Gu, Y C Mi, J X Wang
Objective: To probe the potential utility of Wilms tumor 1 (WT1) as a marker of minimal residual disease (MRD) in acute myeloid leukemia (AML) to estimate the relapse-predicting cut-off value. Methods: Quantitative assessment of bone marrow WT1 mRNA level was preformed using real-time quantitative reverse transcription polymerase chain reaction (RQ-RT-PCR) assay. The expression levels of WT1 dynamically measured with RQ-RT-PCR were retrospectively analyzed in 121 AML cases (not including acute promyelocytic leukemia) achieving complete remission (CR) after induction therapy followed by consolidation therapy...
August 14, 2017: Zhonghua Xue Ye Xue za Zhi, Zhonghua Xueyexue Zazhi
https://www.readbyqxmd.com/read/28940056/causes-and-prognostic-factors-for-early-death-in-patients-with-acute-promyelocytic-leukemia-treated-with-single-agent-arsenic-trioxide
#14
Jinxiao Hou, Shuye Wang, Yingmei Zhang, Dachuan Fan, Haitao Li, Yiju Yang, Fei Ge, Wenyi Hou, Jinyue Fu, Ping Wang, Hongli Zhao, Jiayue Sun, Kunpeng Yang, Jin Zhou, Xiaoxia Li
Early death (ED) is one of the most critical issues involved in the current care of patients with acute promyelocytic leukemia (APL). Factors identified as independent predictors of ED varied among published studies. We retrospectively analyzed the incidence, causes, and prognostic factors of ED in a series of 216 patients with newly diagnosed APL who received arsenic trioxide (ATO) as induction therapy. Multivariate logistic regression analysis was used to determine the association of clinical factors with overall ED, hemorrhagic ED, death within 7 days, and death within 8-30 days...
December 2017: Annals of Hematology
https://www.readbyqxmd.com/read/28934679/the-kinetics-of-white-blood-cell-and-the-predictive-factors-of-leukocytosis-under-oral-or-intravenous-arsenic-as-the-first-line-treatment-for-acute-promyelocytic-leukemia
#15
Fang Wang, Jin-Song Jia, Jing Wang, Ting Zhao, Qian Jiang, Hao Jiang, Hong-Hu Zhu
OBJECTIVE: We aimed to compare the kinetics of white blood cell (WBC) and explore predictive factors of leukocytosis in non-high-risk acute promyelocytic leukemia (APL), with oral arsenic plus all-trans retinoic acid (ATRA) or intravenous arsenic trioxide (ATO) plus ATRA as a first-line treatment. METHODS: The absolute count, doubling time and peak time of WBC were analyzed in 64 newly diagnosed non-high-risk APL patients who were treated with different induction regimens containing either oral Realgar-indigo naturalis formula (RIF) (n=35) or ATO (n=29)...
October 2017: Leukemia Research
https://www.readbyqxmd.com/read/28923666/validation-of-a-molecular-risk-score-for-prognosis-of-patients-with-acute-promyelocytic-leukemia-treated-with-all-trans-retinoic-acid-and-chemotherapy-containing-regimens
#16
Anna Hecht, Seraphina Doll, Heidi Altmann, Daniel Nowak, Eva Lengfelder, Christoph Röllig, Gerhard Ehninger, Karsten Spiekermann, Wolfgang Hiddemann, Christel Weiß, Wolf-Karsten Hofmann, Florian Nolte, Uwe Platzbecker
INTRODUCTION: Although treatment of acute promyelocytic leukemia (APL) has evolved dramatically during the past decades, especially with the introduction of all-trans retinoic acid, risk stratification remains an important issue. To date, relapse risk can be predicted by leukocyte and platelet counts only. In the present report, we present a validation study on 3 candidate genes and a newly developed molecular risk score for APL in 2 independent patient cohorts. PATIENTS AND METHODS: An integrative risk score combining the expression levels of BAALC, ERG, and WT1 was calculated for 79 de novo APL patients from the original cohort and 76 de novo APL patients from a validation cohort...
December 2017: Clinical Lymphoma, Myeloma & Leukemia
https://www.readbyqxmd.com/read/28823055/effectivity-of-a-modified-sanz-risk-model-for-early-death-prediction-in-patients-with-newly-diagnosed-acute-promyelocytic-leukemia
#17
MULTICENTER STUDY
Yinjun Lou, Yafang Ma, Jianai Sun, Sansan Suo, Hongyan Tong, Wenbin Qian, Wenyuan Mai, Haitao Meng, Jie Jin
Early death is the main obstacle for the cure of patients with acute promyelocytic leukemia (APL). We have analyzed risk factors of early death from 526 consecutive newly diagnosed APL patients between 2004 and 2016. The overall incidence of early death was 7.2% (38/526). The peak hazard of early death occurred in the first 0-3 days. Multivariate logistic analysis demonstrated white blood cell (WBC) counts [odds ratio (OR) = 1.039; 95% confidence interval (CI): 1.024-1.055; P < 0.001], age (OR = 1...
November 2017: Annals of Hematology
https://www.readbyqxmd.com/read/28814164/cpx-351-in-acute-myeloid-leukemia-can-a-new-formulation-maximize-the-efficacy-of-old-compounds
#18
REVIEW
Claudia Brunetti, Luisa Anelli, Antonella Zagaria, Giorgina Specchia, Francesco Albano
The management of Acute Myeloid Leukemia (AML) (with the exception of acute promyelocytic leukemia) has remained largely unchanged over the past 40 years. In particular, patients defined as high-risk, according to the 2017 European Leukemia Net recommendations, represent a subgroup with poor response to current therapies that are frequently associated with high-grade toxicity and potentially fatal complications. Areas covered: Preliminary results from an ongoing phase III clinical trial suggest that CPX-351 could represent an interesting treatment option in both induction and 'bridge-to-transplant' settings...
October 2017: Expert Review of Hematology
https://www.readbyqxmd.com/read/28810326/-the-analysis-of-prognosis-associated-factors-in-adults-with-acute-promyelocytic-leukemia
#19
R J Ma, Z M Zhu, X L Yuan, L Jiang, S W Yang, J Yang, J M Guo, J Shi, P C Lei, L Zhang, B J Shang, K Sun, Y P Zhai, W Li, Y Zhang
Objective: To explore the prognostic value of CD34, CD2, CD56 expressions and FLT3-ITD mutation in adults with acute promyelocytic leukemia (APL) . Methods: The immuno-phenotypic and molecular characteristics of 137 adult patients with APL (from January 2010 to March 2016, in Henan Provincial People's Hospital) were investigated. And the relationships between CD34, CD2, CD56 expressions, FLT3-ITD mutation and the outcomes of high WBC counts at onset, complete remission (CR) rate, early mortality, relapse rate (RR) , overall survival (OS) , disease free survival (DFS) were explored...
July 14, 2017: Zhonghua Xue Ye Xue za Zhi, Zhonghua Xueyexue Zazhi
https://www.readbyqxmd.com/read/28767288/arsenic-trioxide-consolidation-allows-anthracycline-dose-reduction-for-pediatric-patients-with-acute-promyelocytic-leukemia-report-from-the-children-s-oncology-group-phase-iii-historically-controlled-trial-aaml0631
#20
MULTICENTER STUDY
Matthew A Kutny, Todd A Alonzo, Robert B Gerbing, Yi-Cheng Wang, Susana C Raimondi, Betsy A Hirsch, Cecilia H Fu, Soheil Meshinchi, Alan S Gamis, James H Feusner, John J Gregory
Purpose The Children's Oncology Group AAML0631 trial for newly diagnosed pediatric acute promyelocytic leukemia (APL) was a phase III historically controlled trial to determine the survival of patients receiving arsenic trioxide (ATO) consolidation and reduced doses of anthracyclines. Patients and Methods Patients age 2 to 21 years with de novo APL confirmed by PML-RARα polymerase chain reaction were stratified as standard risk (SR) or high risk (HR) on the basis of diagnostic WBC count. All patients received all-trans retinoic acid (ATRA) during induction, each consolidation course, and maintenance...
September 10, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
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