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Acute promyelocytic leukemia high risk

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https://www.readbyqxmd.com/read/28446274/-efficacy-of-idarubicin-based-stratified-therapy-for-acute-promyelocytic-leukemia
#1
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
#2
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
#3
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...
March 14, 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
#4
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
#5
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
#6
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
#7
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
#8
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
#9
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
#10
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
#11
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
#12
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
#13
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
#14
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
https://www.readbyqxmd.com/read/27708545/chromosomal-abnormality-of-acute-promyelocytic-leukemia-other-than-pml-rara-a-case-report-of-acute-promyelocytic-leukemia-with-del-5q
#15
Osamu Imataki, Makiko Uemura
BACKGROUND: The recent study described a better outcome in acute promyelocytic leukemia patients treated with all-trans retinoic acid and arsenic oxide compared to those treated with all-trans retinoic acid combined with conventional chemotherapy. The pivotal study indicated that favorable-risk acute promyelocytic leukemia patients can be cured without any cytotoxic chemotherapy. Even high-risk patients are treatable with cytotoxic agents. Acute promyelocytic leukemia does not develop only by the dedifferentiation caused by PML-RARA...
2016: BMC Clinical Pathology
https://www.readbyqxmd.com/read/27632567/telomere-length-recovery-a-strong-predictor-of-overall-survival-in-acute-promyelocytic-leukemia
#16
RANDOMIZED CONTROLLED TRIAL
Muhamed Baljevic, Bogdan Dumitriu, Ju-Whei Lee, Elisabeth M Paietta, Peter H Wiernik, Janis Racevskis, Christina Chen, Eytan M Stein, Robert E Gallagher, Jacob M Rowe, Frederick R Appelbaum, Bayard L Powell, Richard A Larson, Steven E Coutré, Jeffrey Lancet, Mark R Litzow, Selina M Luger, Neal S Young, Martin S Tallman
Telomeres are the capping ends of chromosomes that protect the loss of genetic material and prevent chromosomal instability. In human tissue-specific stem/progenitor cells, telomere length (TL) is maintained by the telomerase complex, which consists of a reverse transcriptase catalytic subunit (TERT) and an RNA template (TERC). Very short telomeres and loss-of-function mutations in the TERT and TERC genes have been reported in acute myeloid leukemia, but the role of telomeres in acute promyelocytic leukemia (APL) has not been well established...
2016: Acta Haematologica
https://www.readbyqxmd.com/read/27626069/evolution-of-a-flt3-tkd-mutated-subclone-at-meningeal-relapse-in-acute-promyelocytic-leukemia
#17
Tilmann Bochtler, Stefan Fröhling, Wilko Weichert, Volker Endris, Christian Thiede, Barbara Hutter, Michael Hundemer, Anthony D Ho, Alwin Krämer
Here, we report the case of an acute promyelocytic leukemia (APL) patient who-although negative for FLT3 mutations at diagnosis-developed isolated FLT3 tyrosine kinase II domain (FLT3-TKD)-positive meningeal relapse, which, in retrospect, could be traced back to a minute bone marrow subclone present at first diagnosis. Initially, the 48-yr-old female diagnosed with high-risk APL had achieved complete molecular remission after standard treatment with all-trans retinoic acid (ATRA) and chemotherapy according to the AIDA (ATRA plus idarubicin) protocol...
September 2016: Cold Spring Harbor Molecular Case Studies
https://www.readbyqxmd.com/read/27560113/rationale-and-efficacy-of-proteasome-inhibitor-combined-with-arsenic-trioxide-in-the-treatment-of-acute-promyelocytic-leukemia
#18
S Ganesan, A A Alex, E Chendamarai, N Balasundaram, H K Palani, S David, U Kulkarni, M Aiyaz, R Mugasimangalam, A Korula, A Abraham, A Srivastava, R A Padua, C Chomienne, B George, P Balasubramanian, V Mathews
Arsenic trioxide (ATO) mediates PML-RARA (promyelocytic leukemia-retinoic acid receptor-α) oncoprotein degradation via the proteasome pathway and this degradation appears to be critical for achieving cure in acute promyeloytic leukemia (APL). We have previously demonstrated significant micro-environment-mediated drug resistance (EMDR) to ATO in APL. Here we demonstrate that this EMDR could be effectively overcome by combining a proteasome inhibitor (bortezomib) with ATO. A synergistic effect on combining these two agents in vitro was noted in both ATO-sensitive and ATO-resistant APL cell lines...
November 2016: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/27538433/connect-mds-aml-design-of-the-myelodysplastic-syndromes-and-acute-myeloid-leukemia-disease-registry-a-prospective-observational-cohort-study
#19
David P Steensma, Medrdad Abedi, Rafael Bejar, Christopher R Cogle, Kathryn Foucar, Guillermo Garcia-Manero, Tracy I George, David Grinblatt, Rami Komrokji, Xiaomei Ma, Jaroslaw Maciejewski, Daniel A Pollyea, Michael R Savona, Bart Scott, Mikkael A Sekeres, Michael A Thompson, Arlene S Swern, Melissa Nifenecker, Mary M Sugrue, Harry Erba
BACKGROUND: Myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML) are myeloid neoplasms in which outgrowth of neoplastic clones disrupts normal hematopoiesis. Some patients with unexplained persistent cytopenias may not meet minimal diagnostic criteria for MDS but an alternate diagnosis is not apparent; the term idiopathic cytopenia of undetermined significance (ICUS) has been used to describe this state. MDS and AML occur primarily in older patients who are often treated outside the clinical trial setting...
August 19, 2016: BMC Cancer
https://www.readbyqxmd.com/read/27436336/npm1-flt3-and-cebpa-mutations-in-pediatric-patients-with-aml-from-argentina-incidence-and-prognostic-value
#20
Patricia Rubio, B Campos, J A Digiorge, M S Gallego, A Medina, J G Rossi, M S Felice, C N Alonso
Mutations in NPM1, FLT3 and CEBPA genes are found in 25-35 % of adult acute myeloblastic leukemia (AML) cases and correlate with prognosis. To date, there have been no reports about these mutations in pediatric AML from Argentina. The aims of the present study were to describe the incidence of NPM1, FLT3 and CEBPA mutations and to analyze their prognostic impact in this population. The incidences of these mutations within a population of 216 pediatric AML cases were: NPM1-mutated 4.2 %, CEBPA-mutated 1.9 %, FLT3-ITD 10...
November 2016: International Journal of Hematology
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