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https://www.readbyqxmd.com/read/28428668/prognostic-parameters-of-acute-myeloid-leukaemia-at-presentation
#1
Azra Jahic, Ermina Iljazovic, Samira Hasic, Aida Custovic Arnautovic, Damir Sabitovic, Semir Mesanovic, Haris Sahovic, Vlastimir Simendic
INTRODUCTION: The treatment response and outcome in acute myeloid leukaemia (AML) is heterogeneous. AIM: To analyze the prognostic parameters of AML at presentation. METHODS: The total sample of 44 AML patients was analyzed on the basis of age <55 and ≥55 years, sex, WBC count <50x10/(9)/l and ≥50x10/(9)/l, the Hb concentration <100 g/l and ≥100 g/l, PLT count <100x10/(9)/l and ≥100x10/(9)/l, Karnofsky score <60% and >60%, cytogenetics, CD56 expression, morphological type and types of treatment (standard and reduced induction chemotherapy, high-dose chemotherapy/stem cell transplantation - autologous and HLA matched, related, allogeneic, together and separately)...
February 2017: Medical Archives
https://www.readbyqxmd.com/read/28419965/chidamide-in-flt3-itd-positive-acute-myeloid-leukemia-and-the-synergistic-effect-in-combination-with-cytarabine
#2
Xia Li, Xiao Yan, Wenjian Guo, Xin Huang, Jiansong Huang, Mengxia Yu, Zhixin Ma, Yu Xu, ShuJuan Huang, Chenying Li, Yile Zhou, Jie Jin
Chidamide, a novel histone deacetylase inhibitor (HDACi), has been approved for treatment of T-cell lymphomas in multiple clinical trials. It has been demonstrated that chidamide can inhibit cell cycle, promote apoptosis and induce differentiation in leukemia cells, whereas its effect on acute myeloid leukemia (AML) patients with FLT3-ITD mutation has not been clarified. In this study, we found that chidamide specifically induced G0/G1 arrest and apoptosis in FLT3-ITD positive AML cells in a concentration and time-dependent manner...
April 15, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28415689/targeting-cd157-in-aml-using-a-novel-fc-engineered-antibody-construct
#3
Christina Krupka, Felix S Lichtenegger, Thomas Köhnke, Jan Bögeholz, Veit Bücklein, Michael Roiss, Torben Altmann, To Uyen Do, Rachel Dusek, Keith Wilson, Arnima Bisht, Jon Terrett, Dee Aud, Esteban Pombo-Villar, Christian Rohlff, Wolfgang Hiddemann, Marion Subklewe
Antibody-based immunotherapy represents a promising strategy to eliminate chemorefractory leukemic cells in acute myeloid leukemia (AML). In this study, we evaluated a novel Fc-engineered antibody against CD157 (MEN1112) for its suitability as immunotherapy in AML. CD157 was expressed in 97% of primary AML patient samples. A significant, albeit lower expression level of CD157 was observed within the compartment of leukemia-initiating cells, which are supposed to be the major source of relapse. In healthy donor bone marrow, CD157 was expressed on CD34+ cells...
March 9, 2017: Oncotarget
https://www.readbyqxmd.com/read/28411282/genomic-architecture-and-treatment-outcome-in-pediatric-acute-myeloid-leukemia-a-children-s-oncology-group-report
#4
Marijana Vujkovic, Edward F Attiyeh, Rhonda E Ries, Elizabeth K Goodman, Yang Ding, Marko Kavcic, Todd A Alonzo, Yi-Cheng Wang, Robert B Gerbing, Lillian Sung, Betsy Hirsch, Susana Raimondi, Alan S Gamis, Soheil Meshinchi, Richard Aplenc
Childhood acute myeloid leukemia (AML) is frequently characterized by chromosomal instability. Approximately 50% of patients have disease relapse, and novel prognostic markers are needed to improve risk stratification. We performed genome-wide genotyping in 446 pediatric patients with de novo AML enrolled on Children's Oncology Group (COG) studies, AAML0531 (NCT01407757), AAML03P1 (NCT00070174), and CCG2961 (NCT00003790). Affymetrix and Illumina Omni 2.5 platforms were used to evaluate copy number alterations (CNAs) and determine their associations with treatment outcome...
April 14, 2017: Blood
https://www.readbyqxmd.com/read/28400376/therapy-reduction-in-patients-with-down-syndrome-myeloid-leukemia-the-international-ml-ds-2006-trial
#5
Madita Uffmann, Mareike Rasche, Martin Zimmermann, Christine von Neuhoff, Ursula Creutzig, Michael Dworzak, Lenie Scheffers, Henrik Hasle, C Michel Zwaan, Dirk Reinhardt, Jan-Henning Klusmann
Children with Down syndrome and myeloid leukemia (ML-DS) have a superior outcome compared to non-DS patients, but suffer from higher constitutional susceptibility to cytotoxic drugs. We analyzed the outcome of 170 pediatric patients with ML-DS enrolled in the prospective, multi-center, open-label, non-randomized ML-DS 2006 trial, by the NOPHO, DCOG and AML-BFM study groups. In comparison to the historical control arm (reduced intensity protocol for ML-DS patients from the AML-BFM 98 trial) treatment intensity was reduced by lowering the cumulative dose of etoposide (950 mg/m(2) to 450 mg/m(2)) and intrathecal CNS-prophylaxis while omitting maintenance therapy...
April 11, 2017: Blood
https://www.readbyqxmd.com/read/28396161/isolated-extramedullary-relapse-of-acute-leukemia-after-allogeneic-stem-cell-transplantation-different-kinetics-and-better-prognosis-than-systemic-relapse
#6
Noga Shem-Tov, Francesco Saraceni, Ivetta Danylesko, Roni Shouval, Ronit Yerushalmi, Arnon Nagler, Avichai Shimoni
Allogeneic stem-cell transplantation (SCT) is curative treatment in patients with acute leukemia and MDS. However, recurrent disease is the major cause of treatment failure. Isolated extramedullary-relapse (iEMR) after SCT is relatively rare and not well characterized. We performed retrospective analysis of 566 consecutive patients with AML (n=446) and ALL (n=120) following SCT to study the incidence, risk factors, treatment options and outcome of iEMR. The 5-year cumulative incidence of bone-marrow relapse (BMR) and iEMR was 41...
April 7, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/28395440/-prognostic-significance-of-blood-count-at-the-time-of-achieving-morphologic-leukemia-free-state-in-adults-with-acute-myeloid-leukemia
#7
X Ren, T Zhao, J Wang, H H Zhu, H Jiang, J S Jia, S M Yang, B Jiang, D B Wang, X J Huang, Q Jiang
Objective: To explore prognostic significance of blood count at the time of achieving first morphologic leukemia-free state[complete remission (CR, ANC ≥1×10(9)/L and PLT ≥100×10(9)/L) , CR with incomplete PLT recovery (CRp) and CR with incomplete ANC and PLT recovery (CRi) ]in adult patients with de novo acute myeloid leukemia (AML) . Methods: From January 2008 to February 2016, data of consecutive newly-diagnosed AML (non-APL) adults who received continuous chemotherapy in our hospital were analyzed retrospectively...
March 14, 2017: Zhonghua Xue Ye Xue za Zhi, Zhonghua Xueyexue Zazhi
https://www.readbyqxmd.com/read/28394581/dna-methyltransferases-demonstrate-reduced-activity-against-arabinosylcytosine-implications-for-epigenetic-instability-in-acute-myeloid-leukemia
#8
Christopher S Nabel, Jamie E DeNizio, Martin Carroll, Rahul M Kohli
Arabinosylcytosine (araC) is a mainstay in the initial treatment of acute myeloid leukemia (AML), although relapses are common. Given the recent recognition of altered DNA methylation patterns in relapsed AML, we considered whether araC, which acts by incorporation into DNA, could itself perturb methylation dynamics. To explore this possibility, we examined several DNA methyltransferases and find that araC embedded in DNA is consistently methylated with an efficiency diminished relative to that of deoxycytidine...
April 12, 2017: Biochemistry
https://www.readbyqxmd.com/read/28370903/impact-of-post-transplant-minimal-residual-disease-on-the-clinical-outcome-of-pediatric-acute-leukemia
#9
Katsutsugu Umeda, Atsushi Iwai, Koji Kawaguchi, Masamitsu Mikami, Seishiro Nodomi, Satoshi Saida, Hidefumi Hiramatsu, Toshio Heike, Katsuyuki Ohmori, Souichi Adachi
This retrospective study examined the clinical significance of FCM-MRD in 36 patients with ALL and 29 patients with AML after their first allogeneic HSCT. Hematological (FCM-MRD ≥5.0%) and molecular relapse (FCM-MRD <5.0%) were first detected in 10 and two patients with ALL and in seven and eight patients with AML, respectively. Eight of 10 patients with molecular relapse eventually progressed to hematological relapse, although most were treated with immunological intervention by aggressive discontinuation of immunosuppressive therapy or donor lymphocyte infusion...
March 31, 2017: Pediatric Transplantation
https://www.readbyqxmd.com/read/28370201/a-phase-1-study-of-amg-900-an-orally-administered-pan-aurora-kinase-inhibitor-in-adult-patients-with-acute-myeloid-leukemia
#10
Hagop M Kantarjian, Michael W Schuster, Nitin Jain, Anjali Advani, Elias Jabbour, Erick Gamelin, Erik Rasmussen, Gloria Juan, Abraham Anderson, Vincent F Chow, Greg Friberg, Florian D Vogl, Mikkael A Sekeres
Aurora kinases are involved in the pathophysiology of several cancers including acute myeloid leukemia (AML). In this phase 1 study, we investigated the safety and efficacy of AMG 900, an orally administered, highly potent, selective, small-molecule inhibitor of both Aurora kinase A and B, in patients with AML. Patients with pathologically documented AML who either declined standard treatments or had relapsed from or were refractory to previous therapies were enrolled. Two every-2-week dose-escalation schedules using a modified 3 + 3+3 design were used: AMG 900 given daily for 4 days with 10 days off (4/10 schedule), and AMG 900 given daily for 7 days with 7 days off (7/7 schedule)...
March 28, 2017: American Journal of Hematology
https://www.readbyqxmd.com/read/28350519/outcome-of-lower-risk-patients-with-myelodysplastic-syndromes-without-5q-deletion-after-failure-of-erythropoiesis-stimulating-agents
#11
Sophie Park, Jean-François Hamel, Andrea Toma, Charikleia Kelaidi, Sylvain Thépot, Maria Diez Campelo, Valeria Santini, Mikkael A Sekeres, Enrico Balleari, Jennifer Kaivers, Rosa Sapena, Katharina Götze, Catharina Müller-Thomas, Odile Beyne-Rauzy, Aspasia Stamatoullas, Ioannis Kotsianidis, Rami Komrokji, David P Steensma, Jaime Fensterl, Gail J Roboz, Teresa Bernal, Fernando Ramos, Marisa Calabuig, Agnès Guerci-Bresler, Dominique Bordessoule, Pascale Cony-Makhoul, Stéphane Cheze, Eric Wattel, Christian Rose, Norbert Vey, Daniela Gioia, Dario Ferrero, Gianluca Gaidano, Giovanni Cametti, Fabrizio Pane, Alessandro Sanna, Ulrich Germing, Guillermo F Sanz, François Dreyfus, Pierre Fenaux
Purpose Most anemic patients with non-deleted 5q lower-risk myelodysplastic syndromes (MDS) are treated with erythropoiesis-stimulating agents (ESAs), with a response rate of approximately 50%. Second-line treatments, including hypomethylating agents (HMAs), lenalidomide (LEN), and investigational drugs, may be used after ESA failure in some countries, but their effect on disease progression and overall survival (OS) is unknown. Here, we analyzed outcome after ESA failure and the effect of second-line treatments...
March 28, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28337888/decitabine-treatment-for-acute-myeloid-leukemia-relapse-after-allogeneic-hematopoietic-stem-cell-transplantation
#12
X L Liu, X Zhao, C Wang, S J Gao, Y H Tan
Therapeutic options for patients with relapse of acute myeloid leukemia (AML) after allo-SCT are limited. Here, we present a case of a 49-year female with AML who underwent myeloablative allo-SCT from a matched sibling donor. Seven months after transplantation she developed cGVHD and suffered from extramedullary plus concurrent medullary relapse. The presence of CNS extramedullary disease is unique. Our patient was treated with decetabine. After one cycle the patient achieved complete remission and full donor chimerism without severe side effects or the occurrence of GVHD...
January 2017: Journal of Biological Regulators and Homeostatic Agents
https://www.readbyqxmd.com/read/28318761/the-bone-marrow-microenvironment-home-of-the-leukemic-blasts
#13
REVIEW
Manar S Shafat, Bruno Gnaneswaran, Kristian M Bowles, Stuart A Rushworth
Acute Myeloid Leukaemia (AML) is a genetically, biologically and clinically heterogeneous set of diseases, which are characterised by an increased growth of abnormal myeloid progenitor cells within the bone marrow (BM). Ex-vivo AML exhibits a high level of spontaneous apoptosis. Furthermore, relapse for patients achieving remission occurs from minimal residual disease harboured within the BM microenvironment. Taken together, these observations illustrate the importance of the BM microenvironment in sustaining AML...
March 12, 2017: Blood Reviews
https://www.readbyqxmd.com/read/28286924/treatment-of-relapsed-refractory-acute-myeloid-leukemia
#14
REVIEW
Prithviraj Bose, Pankit Vachhani, Jorge E Cortes
Approximately 40-45% of younger and 10-20% of older adults with acute myeloid leukemia (AML) will be cured with current standard chemotherapy. The outlook is particularly gloomy for patients with relapsed and/or refractory disease (cure rates no higher than 10%). Allogeneic hematopoietic stem cell transplantation (HSCT), the only realistic hope of cure for these patients, is an option for only a minority. In recent years, much has been learned about the genomic and epigenomic landscapes of AML, and the clonal architecture of both de novo and secondary AML has begun to be unraveled...
March 2017: Current Treatment Options in Oncology
https://www.readbyqxmd.com/read/28283965/treatment-of-acute-myeloid-leukemia-with-the-flt3-gene-mutation
#15
REVIEW
Carlos Best-Aguilera, O Rodrigo Gómez-Vázquez, A Elizabeth Guzmán-Hernández, R Monserrat Rojas-Sotelo
In acute myeloid leukemia (AML), mutations of the Fms-like tyrosine kinase 3 receptor (FLT3) and its overexpression are related with hyperleukocytosis, higher risk of relapse, and decrease of both disease-free survival and overall survival. It has been suggested that this phenomenon confers proliferative and survival advantages to the malignant blast cells. As a consequence, it is an attractive therapeutic target. As the best treatment strategy for mutated FLT3 AML remains to be defined, the addition of FLT3 inhibitor drugs to chemotherapy or to the bone marrow transplant approach has become a growing strategy...
March 2017: Current Oncology Reports
https://www.readbyqxmd.com/read/28278716/efficacy-of-single-agent-decitabine-in-relapsed-and-refractory-acute-myeloid-leukemia
#16
Niloufer Khan, Andrew Hantel, Randall W Knoebel, Andrew Artz, Richard A Larson, Lucy A Godley, Michael J Thirman, Hongtao Liu, Jane E Churpek, Darren King, Olatoyosi Odenike, Wendy Stock
Improving therapy for relapsed/refractory AML remains a challenge. We performed a retrospective analysis of outcomes following decitabine treatment in 34 patients with relapsed/refractory AML (median age, 62; median Charlson comorbidity score, 6). Decitabine, 20 mg/m(2) daily, was given in 5- (25%) or 10-day (75%) cycles. Overall response rate (OR) was 30% with 21% complete remission and 9% partial remission rate. Patients with therapy-related myeloid neoplasm (t-MN) and secondary AML had a significantly higher OR compared to those with de novo AML (70 vs...
February 20, 2017: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/28270496/jab1-csn5-thioredoxin-signaling-in-relapsed-acute-monocytic-leukemia-under-oxidative-stress
#17
Fuling Zhou, Yunbao Pan, Yongchang Wei, Ronghua Zhang, Gaigai Bai, Qiuju Shen, Shan Meng, Xiao-Feng Le, Michael Andreeff, Francois X Claret
PURPOSE: High levels of ROS and ineffective antioxidant systems contribute to oxidative stress, which affects the function of hematopoietic cells in acute myeloid leukemia (AML); however, the mechanisms by which ROS lead to malignant transformation in relapsed AML-M5 are not completely understood. We hypothesized that alterations in intracellular ROS would trigger AML-M5 relapse by activating the intrinsic pathway. EXPERIMENTAL DESIGN: We studied ROS levels and conducted JAB1/COPS5 and TRX gene expression analyses with blood samples obtained from 60 matched AML-M5 patients at diagnosis and relapse and conducted mechanism studies of Jab1's regulation of Trx in leukemia cell lines...
March 7, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28261562/inhibition-of-dna-and-histone-methylation-by-5-aza-2-deoxycytidine-decitabine-and-3-deazaneplanocin-a-on-antineoplastic-action-and-gene-expression-in-myeloid-leukemic-cells
#18
Richard L Momparler, Sylvie Côté, Louise F Momparler, Youssef Idaghdour
Epigenetic alterations play an important role in the development of acute myeloid leukemia (AML) by silencing of genes that suppress leukemogenesis and differentiation. One of the key epigenetic changes in AML is gene silencing by DNA methylation. The importance of this alteration is illustrated by the induction of remissions in AML by 5-aza-2'-deoxycytidine (5-AZA-CdR, decitabine), a potent inhibitor of DNA methylation. However, most patients induced into remission by 5-AZA-CdR will relapse, suggesting that a second agent should be sought to increase the efficacy of this epigenetic therapy...
2017: Frontiers in Oncology
https://www.readbyqxmd.com/read/28246275/correlation-between-isocitrate-dehydrogenase-gene-aberrations-and-prognosis-of-patients-with-acute-myeloid-leukemia-a-systematic-review-and-meta-analysis
#19
Qingyu Xu, Yan Li, Na Lv, Yu Jing, Yihan Xu, Yuyan Li, Wenjun Li, Zilong Yao, Xiaosu Chen, Sai Huang, Li Li Wang, Yonghui Li, Li Yu
PURPOSE: Whether isocitrate dehydrogenase (IDH) gene aberrations affected prognosis of patients with acute myeloid leukemia (AML) was controversial. Here, we conducted a meta-analysis to evaluate their prognostic value. EXPERIMENTAL DESIGN: PubMed, Embase, Cochrane and Chinese databases were searched to identify studies exploring how IDH gene aberrations affected AML outcome. Pooled hazard ratios (HR) and relative risks (RR) were calculated, along with 95% confidence intervals (CI)...
February 28, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28245400/-autologous-peripheral-blood-hematopoietic-stem-cell-transplantation-with-ibu-precondition-regimen-in-treatment-for-11-patients-with-low-to-intermediate-risk-acute-myeloid-leukemia
#20
Wei Wu, Wei-Ying Gu, Wei-Min Dong, Biao Wang, Xiao-Mei Zhang, Zhuo-Jun Zheng, Xiao-Bao Xie
OBJECTIVE: To evaluate safety and efficacy of autologous peripheral blood hematopoietic stem cell transplantation (auto-PBHSCT) with IBu precondition regimen consisting of high-dose idarubicin (IDA) and busulphan (Bu) for treatment of patients with low and intermediate risk acute myeloid leuekmia (AML). METHODS: A total of 11 patients with AML (5 low and 6 intermediate risk patients) treated with auto-PBHSCT with IBu precondition regimen (IDA 20 mg/m(2), continuous i...
February 2017: Zhongguo Shi Yan Xue Ye Xue za Zhi
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