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Acute promyelocytic leukemia high risk

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https://www.readbyqxmd.com/read/28814164/cpx-351-in-acute-myeloid-leukemia-can-a-new-formulation-maximize-the-efficacy-of-old-compounds
#1
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...
August 17, 2017: Expert Review of Hematology
https://www.readbyqxmd.com/read/28810326/-the-analysis-of-prognosis-associated-factors-in-adults-with-acute-promyelocytic-leukemia
#2
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
#3
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...
August 2, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28694043/risk-factors-and-clinical-characteristics-of-non-promyelocytic-acute-myeloid-leukemia-of-intracerebral-hemorrhage-a-single-center-study-in-china
#4
Qiaolei Zhang, Xueying Li, Zhangyue Wei, Xiujin Ye, Lixia Zhu, Mixue Xie, Wanzhuo Xie, Jingjing Zhu, Li Li, De Zhou, Yanlong Zheng, Xiudi Yang, Mingyu Zhu, Jianai Sun
BACKGROUND: Although high mortality in patients with acute leukemia (AL) is associated with intracranial hemorrhage (ICH), the clinical features and pathogenesis of AL patients with cerebral hemorrhage are not well known. METHODS: We diagnosed 90 patients with ICH from a total of 1467 patients with non-promyelocytic AL who had been hospitalized in the First Affiliated Hospital of Medical School of Zhejiang University from January 2010 to October 2015. Moreover, the risk factors of ICH death were evaluated...
July 8, 2017: Journal of Clinical Neuroscience: Official Journal of the Neurosurgical Society of Australasia
https://www.readbyqxmd.com/read/28654205/driving-toward-precision-medicine-for-acute-leukemias-are-we-there-yet
#5
Clement Chung, Hilary Ma
Despite recent progress in the understanding of the molecular basis of acute leukemias, treatment options for these diseases have not shown significant changes over the last few decades. In this review, we present a nonexhaustive key summary of the current cytogenetic and molecular changes associated with acute leukemias in disease prognostication and potential targeted therapies. An emerging paradigm is that many genetic or molecular alterations target similar signal transduction, transcriptional, and epigenetic pathways...
June 27, 2017: Pharmacotherapy
https://www.readbyqxmd.com/read/28598536/characteristics-and-outcome-in-patients-with-central-nervous-system-involvement-treated-in-european-pediatric-acute-myeloid-leukemia-study-groups
#6
Ursula Creutzig, Michael N Dworzak, Martin Zimmermann, Dirk Reinhardt, Lucie Sramkova, Jan Pierre Bourquin, Henrik Hasle, Jonas Abrahamsson, Gertjan Kaspers, Mary M van den Heuvel, Ardine M J Reedijk, Barbara De Moerloose, Franco Locatelli, Riccardo Masetti
BACKGROUND: There is no consensus on the treatment for pediatric patients with acute myeloid leukemia and initial central nervous system (CNS) involvement. METHODS: To evaluate different CNS-directed treatment options (intrathecal [IT] therapy, CNS irradiation, hematopoietic stem cell transplantation [HSCT]), 261 patients (excluding acute promyelocytic leukemia) with initial CNS involvement treated in trials with similar intensive chemotherapy by four cooperative European study groups (1998-2013) were studied and compared with CNS-negative patients from the Berlin-Frankfurt-Münster group...
June 9, 2017: Pediatric Blood & Cancer
https://www.readbyqxmd.com/read/28446274/-efficacy-of-idarubicin-based-stratified-therapy-for-acute-promyelocytic-leukemia
#7
Wei Guan, Wen-Jun Li, Lan Yang, Yu Jing, Li Yu
OBJECTIVE: To investigate the remission rate of all-transretinoic acid (ATRA) combined with arsenics acid(ATO) on acute promyelocytic leukemia, and the efficacy and safety of sequential consolidation therapy with idarubicin, all-trans retinoic acid and arsenic trioxide/compound Huangdai tablet. METHODS: Between January 2011 and January 2016 years 22 patients with newly diagnosed acute promyelocytic leukemia who received ATRA combined with ATO till complete remission in our hospital were retrospectively analyzed...
April 2017: Zhongguo Shi Yan Xue Ye Xue za Zhi
https://www.readbyqxmd.com/read/28352191/retinoic-acid-and-arsenic-trioxide-in-the-treatment-of-acute-promyelocytic-leukemia-current-perspectives
#8
REVIEW
Derek McCulloch, Christina Brown, Harry Iland
Acute promyelocytic leukemia (APL) is a distinct subtype of acute myeloid leukemia (AML) with a unique morphological appearance, associated coagulopathy and canonical balanced translocation of genetic material between chromosomes 15 and 17. APL was first described as a distinct subtype of AML in 1957 by Dr Leif Hillestad who recognized the pattern of an acute leukemia associated with fibrinolysis, hypofibrinogenemia and catastrophic hemorrhage. In the intervening years, the characteristic morphology of APL has been described fully with both classical hypergranular and variant microgranular forms...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28293819/characteristics-features-and-factors-influencing-early-death-in-acute-promyelocytic-leukemia-experience-from-united-arab-emirates-uae
#9
Inaam Bashir Hassan, Mariam R Al Zaabi, Arif Alam, Mohammed Jawad Hashim, Martin S Tallman, Jorgen Kristensen
Although acute promyelocytic leukemia (APL) is a curable hematologic malignancy, early death (ED) remains a significant cause of treatment failure especially in developing countries. In a retrospective data analysis of 67 adult APL patients diagnosed in United Arab Emirates we report an ED rate of 11.9% which is comparable to that reported from more developed countries. We identified the following parameters at presentation as significant predictor of increased ED: Age >40 years (P = 0.015), fever (P = 0...
July 2017: International Journal of Hematology
https://www.readbyqxmd.com/read/28270346/molecular-and-hematologic-relapses-in-adult-patients-with-acute-promyelocytic-leukemia-a-cohort-study
#10
Ilana de França Azevedo, Michelline Gomes Magalhães, Fernanda Ribeiro Souto, Washington Batista das Neves, Fárida Coeli de Barros Correia Melo, Eduardo Magalhães Rego, Raul Antônio Morais Melo
OBJECTIVE: To evaluate factors predictive for relapse in a cohort of adult patients with acute promyelocytic leukemia monitored by molecular methods during consolidation and during at least one month of maintenance therapy. METHODS: The charts and laboratory data of 65 adult patients with acute promyelocytic leukemia treated according to the International Consortium on Acute Promyelocytic Leukemia 2006 protocol were reviewed. The identification of the promyelocytic leukemia-retinoic acid receptor-alpha gene rearrangement at diagnosis, post-induction, post-consolidation and during maintenance treatment was performed by qualitative and quantitative reverse transcription polymerase chain reaction...
January 2017: Revista Brasileira de Hematologia e Hemoterapia
https://www.readbyqxmd.com/read/28268092/droplet-digital-pcr-is-a-reliable-tool-for-monitoring-minimal-residual-disease-in-acute-promyelocytic-leukemia
#11
Claudia Brunetti, Luisa Anelli, Antonella Zagaria, Angela Minervini, Crescenzio F Minervini, Paola Casieri, Nicoletta Coccaro, Cosimo Cumbo, Giuseppina Tota, Luciana Impera, Paola Orsini, Giorgina Specchia, Francesco Albano
Nested RT-PCR (nPCR) and real-time quantitative PCR (qPCR) are well-established methods for monitoring minimal residual disease (MRD) in acute promyelocytic leukemia (APL). Despite their remarkable sensitivity and specificity, both methods have inherent limitations, such as qualitative MRD evaluation and relative quantification. Herein, we used droplet digital PCR (ddPCR) to monitor MRD in 21 APL patients and compared its performance with nPCR and qPCR. After assessing the limit of detection (LOD) for each technique on serial dilutions of PML-RARA bcr1 and bcr3 transcripts, a total of 48 follow-up samples were analyzed and the results compared...
May 2017: Journal of Molecular Diagnostics: JMD
https://www.readbyqxmd.com/read/28194055/treatment-of-acute-promyelocytic-leukemia-with-single-agent-arsenic-trioxide-experience-from-a-tertiary-care-center-in-india
#12
Karthik Udupa, Joseph Thomas, Chethana Babu Udupa, V S Binu, Prahlad Sharan
APML is a highly curable hematological malignancy which is treated with differentiation agents and chemotherapy. The morbidity caused by chemotherapy in the treatment of APML is a great cause of concern. We treated 12 patients with newly diagnosed APML with single agent arsenic trioxide between 2010 and 2014 irrespective of risk stratification. Out of 12 patient 2 patients died during induction. All the ten patients who completed induction, completed their consolidation and maintenance without any delays. One out of these ten patients relapsed 10 months after treatment...
March 2017: Indian Journal of Hematology & Blood Transfusion
https://www.readbyqxmd.com/read/28125133/acute-wt1-positive-promyelocytic-leukemia-with-hypogranular-variant-morphology-bcr-3-isoform-of-pml-rar%C3%AE-and-flt3-itd-mutation-a-rare-case-report
#13
Xi Zhang, Cheng Yang, Xiangui Peng, Xinghua Chen, Yimei Feng
CONTEXT: Acute promyelocytic leukemia (APL) accounts for 8% to 10% of cases of acute myeloid leukemia (AML). Remission in cases of high-risk APL is still difficult to achieve, and relapses occur readily. CASE REPORT: Here, we describe a case of APL with high white blood cell counts in blood tests and hypogranular variant morphology in bone marrow, together with fms-like tyrosine kinase-3 with internal tandem duplication mutations (FLT3-ITD), and bcr-3 isoform of PML-RARα...
March 2017: São Paulo Medical Journal, Revista Paulista de Medicina
https://www.readbyqxmd.com/read/28111878/first-experience-of-the-aml-berlin-frankfurt-m%C3%A3-nster-group-in-pediatric-patients-with-standard-risk-acute-promyelocytic-leukemia-treated-with-arsenic-trioxide-and-all-trans-retinoid-acid
#14
Ursula Creutzig, Michael N Dworzak, Konrad Bochennek, Jörg Faber, Christian Flotho, Norbert Graf, Udo Kontny, Claudia Rossig, Irene Schmid, Arend von Stackelberg, Jans-Enno Mueller, Christine von Neuhoff, Dirk Reinhardt, Nils von Neuhoff
Recently, studies in adults with acute promyelocytic leukemia (APL) showed high cure rates in low-risk patients treated with all-trans retinoid acid (ATRA) and arsenic trioxide (ATO), while toxicities were significantly reduced compared to the standard treatment with ATRA and chemotherapy. Here we report about first experience with 11 pediatric patients with low-risk APL treated with ATRA and ATO. All patients stayed in molecular remission. All suffered from hyperleukocytosis. Two patients experienced reversible severe side effects...
January 23, 2017: Pediatric Blood & Cancer
https://www.readbyqxmd.com/read/28053193/promyelocytic-extracellular-chromatin-exacerbates-coagulation-and-fibrinolysis-in-acute-promyelocytic-leukemia
#15
Muhua Cao, Tao Li, Zhangxiu He, Lixiu Wang, Xiaoyan Yang, Yan Kou, Lili Zou, Xue Dong, Valerie A Novakovic, Yayan Bi, Junjie Kou, Bo Yu, Shaohong Fang, Jinghua Wang, Jin Zhou, Jialan Shi
Despite routine treatment of unselected acute promyelocytic leukemia (APL) with all-trans-retinoic acid (ATRA), early death because of hemorrhage remains unacceptably common, and the mechanism underlying this complication remains elusive. We have recently demonstrated that APL cells undergo a novel cell death program, termed ETosis, which involves release of extracellular chromatin. However, the role of promyelocytic extracellular chromatin in APL-associated coagulation remains unclear. Our objectives were to identify the novel role of ATRA-promoted extracellular chromatin in inducing a hypercoagulable and hyperfibrinolytic state in APL and to evaluate its interaction with fibrin and endothelial cells (ECs)...
March 30, 2017: Blood
https://www.readbyqxmd.com/read/28024465/-flt3-itd-mutation-in-newly-diagnosed-patients-with-acute-promyelocytic-leukemia
#16
Ben-Fa Gong, Ying Wang, Dong Lin, Hui Wei, Wei Li, Chun-Lin Zhou, Bing-Cheng Liu, Kai-Qi Liu, Guang-Ji Zhang, Yun-Tao Liu, Yan Li, Shu-Ning Wei, Xiao-Yuan Gong, Xing-Li Zhao, Shao-Wei Qiu, Run-Xia Gu, Ying-Chang Mi, Jian-Xiang Wang
OBJECTIVE: To evaluate the influence of FLT3-ITD mutation on long term survival of newly diagnosed patients with acute promyelocytic leukemia (APL). METHODS: Long term survival of 170 newly diagnosed APL patients was retrospective analyzed. Mutation rate of FLT3-ITD was assayed, and its influence on disease-free survival(DFS) or overall survival (OS) was analyzed. RESULTS: The mutation rate of FLT3-ITD in newly diagnosed patients with APL was 14...
December 2016: Zhongguo Shi Yan Xue Ye Xue za Zhi
https://www.readbyqxmd.com/read/28003274/long-term-outcome-of-acute-promyelocytic-leukemia-treated-with-all-trans-retinoic-acid-arsenic-trioxide-and-gemtuzumab
#17
Yasmin Abaza, Hagop Kantarjian, Guillermo Garcia-Manero, Elihu Estey, Gautam Borthakur, Elias Jabbour, Stefan Faderl, Susan O'Brien, William Wierda, Sherry Pierce, Mark Brandt, Deborah McCue, Rajyalakshmi Luthra, Keyur Patel, Steven Kornblau, Tapan Kadia, Naval Daver, Courtney DiNardo, Nitin Jain, Srdan Verstovsek, Alessandra Ferrajoli, Michael Andreeff, Marina Konopleva, Zeev Estrov, Maria Foudray, David McCue, Jorge Cortes, Farhad Ravandi
The combination of all-trans-retinoic acid (ATRA) plus arsenic trioxide (ATO) has been shown to be superior to ATRA plus chemotherapy in the treatment of standard-risk patients with newly diagnosed acute promyelocytic leukemia (APL). A recent study demonstrated the efficacy of this regimen with added gemtuzumab ozogamicin (GO) in high-risk patients. We examined the long-term outcome of patients with newly diagnosed APL treated at our institution on 3 consecutive prospective clinical trials, using the combination of ATRA and ATO, with or without GO...
March 9, 2017: Blood
https://www.readbyqxmd.com/read/27863754/survival-and-treatment-response-in-adults-with-acute-promyelocytic-leukemia-treated-with-a-modified-international-consortium-on-acute-promyelocytic-leukemia-protocol
#18
Erick Crespo-Solis, Jorge Contreras-Cisneros, Roberta Demichelis-Gómez, Adriana Rosas-López, Juan Mauricio Vera-Zertuche, Alvaro Aguayo, Xavier López-Karpovitch
Acute promyelocytic leukemia has good prognosis in view of the high complete remission and survival rates achieved with therapies containing all-trans retinoic acid or arsenic trioxide. However, there is a significant risk of death during induction due to hemorrhage secondary to disseminated intravascular coagulation. This has contributed to a gap in the prognosis of patients between developed and developing countries. The International Consortium on Acute Promyelocytic Leukemia was created in 2005 and proposed a treatment protocol based on daunorubicin and all-trans retinoic acid stratified by risk geared toward developing countries...
October 2016: Revista Brasileira de Hematologia e Hemoterapia
https://www.readbyqxmd.com/read/27835920/-acute-myeloid-leukemia
#19
REVIEW
Jan Braess
Acute myeloid leukemia (AML) has been genetically characterized extensively and can now be subdivided into 9 to 11 pathogenetically different subtypes according to their profile of driver mutations. In clinical practice karyotyping and molecular analysis of NPM1, cEBPa and FLT3-ITD are required for treatment stratification and potentially genotype specific treatment. Some markers such as NPM1 not only offer prognostic information but can also serve as markers of minimal residual disease and thus have the potential to guide therapy in the future...
November 2016: Deutsche Medizinische Wochenschrift
https://www.readbyqxmd.com/read/27736291/clinical-significance-of-galectin-3-in-patients-with-adult-acute-myeloid-leukemia-a-retrospective-cohort-study-with-long-term-follow-up-and-formulation-of-risk-scoring-system
#20
Na Gao, Wen-Zheng Yu, Nong-Jian Guo, Xue-Xia Wang, Jian-Rong Sun
Galectin-3 plays an increasingly important role in development and progression of tumor. However, little is known about the clinical impact of galectin-3 in non-acute promyelocytic leukemia (non-M3 AML). Peripheral blood of 298 patients with primary non-M3 AML and 30 normal donors was collected for measurement of galectin-3. Galectin-3 levels were significantly higher compared with the control group (p < .001). Patients with higher galectin-3 levels had lower CR rates (p = .001) and 1-year overall survival (OS) rates (p = ...
October 13, 2016: Leukemia & Lymphoma
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