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https://www.readbyqxmd.com/read/28527985/long-term-follow-up-and-impact-of-comorbidity-prior-to-allogeneic-hematopoietic-stem-cell-transplantation-in-patients-with-relapsed-or-refractory-aml-lessons-learned-from-the-prospective-bridge-trial-clofarabine-salvage-therapy-prior-to-allogeneic-transplantation
#1
Jan Moritz Middeke, Regina Herbst, Stefani Parmentier, Gesine Bug, Mathias Hänel, Gernot Stuhler, Kerstin Schäfer-Eckart, Wolf Rösler, Stefan Klein, Wolfgang Bethge, Ulrich Bitz, Bozena Büttner, Holger Knoth, Nael Alakel, Markus Schaich, Anke Morgner, Michael Kramer, Katja Sockel, Malte von Bonin, Friedrich Stölzel, Uwe Platzbecker, Christoph Röllig, Christian Thiede, Gerhard Ehninger, Martin Bornhäuser, Johannes Schetelig
In patients with relapsed or refractory (r/r) AML, allogeneic Hematopoietic Stem Cell Transplantation (HSCT) is considered to be the only treatment providing long-term disease control. The BRIDGE trial studied the safety and efficacy of a clofarabine-based salvage therapy prior to HSCT in patients with r/r AML. Here, we report the long-term follow up of this Phase II, multi-center trial and exploratory analyses on the impact of comorbidity on outcome. Eighty-four patients with a median age of 61 years (range 40 - 75) were enrolled...
May 17, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/28518151/disulfiram-copper-selectively-eradicates-aml-leukemia-stem-cells-in-vitro-and-in-vivo-by-simultaneous-induction-of-ros-jnk-and-inhibition-of-nf-%C3%AE%C2%BAb-and-nrf2
#2
Bing Xu, Shiyun Wang, Rongwei Li, Kai Chen, Lingli He, Manman Deng, Vinodh Kannappan, Jie Zha, Huijuan Dong, Weiguang Wang
Acute myeloid leukemia (AML) is a heterogeneous malignancy. Despite the advances in past decades, the clinical outcomes of AML patients remain poor. Leukemia stem cells (LSCs) is the major cause of the recurrence of AML even after aggressive treatment making, promoting development of LSC-targeted agents is an urgent clinical need. Although the antitumor activity of disulfiram (DS), an approved anti-alcoholism drug, has been demonstrated in multiple types of tumors including hematological malignancies such as AML, it remains unknown whether this agent would also be able to target cancer stem cells like LSCs...
May 18, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28504025/the-preclinical-discovery-of-vosaroxin-for-the-treatment-of-acute-myeloid-leukemia
#3
Etienne Paubelle, Florence Zylbersztejn, Xavier Thomas
Acute myeloid leukemia (AML) represents a disease with a very poor outcome and remains an area of significant unmet need necessitating novel therapeutic strategies. Among novel therapeutic agents, vosaroxin is a first-in-class anticancer quinolone derivative that targets topoisomerase II and induces site-selective double-strand breaks in DNA, leading to tumor cell apoptosis. Area covered: Herein, the authors provide a comprehensive review of the preclinical development of vosaroxin. This includes coverage of vosaroxin's mechanism of action in addition to its pharmacology and of the main studies reported over the past few years with vosaroxin when used to treat adult AML...
May 13, 2017: Expert Opinion on Drug Discovery
https://www.readbyqxmd.com/read/28500307/alox5-exhibits-anti-tumor-and-drug-sensitizing-effects-in-mll-rearranged-leukemia
#4
Yungui Wang, Jennifer R Skibbe, Chao Hu, Lei Dong, Kyle Ferchen, Rui Su, Chenying Li, Hao Huang, Hengyou Weng, Huilin Huang, Xi Qin, Jie Jin, Jianjun Chen, Xi Jiang
MLL-rearranged acute myeloid leukemia (AML) remains a fatal disease with a high rate of relapse and therapeutic failure due to chemotherapy resistance. In analysis of our Affymetrix microarray profiling and chromatin immunoprecipitation (ChIP) assays, we found that ALOX5 is especially down-regulated in MLL-rearranged AML, via transcription repression mediated by Polycomb repressive complex 2 (PRC2). Colony forming/replating and bone marrow transplantation (BMT) assays showed that Alox5 exhibited a moderate anti-tumor effect both in vitro and in vivo...
May 12, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28494506/minimal-residual-disease-eradication-with-epigenetic-therapy-in-core-binding-factor-acute-myeloid-leukemia
#5
Brittany Knick Ragon, Naval Daver, Guillermo Garcia-Manero, Farhad Ravandi, Jorge Cortes, Tapan Kadia, Betul Oran, Maro Ohanian, Alessandra Ferrajoli, Naveen Pemmaraju, Hagop M Kantarjian, Gautam Borthakur
Recurrent translocations, t(8;21) or inv(16), in core binding factor acute myeloid leukemia (CBF-AML) are amenable to monitoring for minimal residual disease (MRD) with reverse transcriptase polymerase chain reaction (RTPCR). Despite a favorable prognosis, disease relapse remains the single cause of treatment failure in CBF-AML. Fusion products of these translocations recruit epigenetic silencing complexes resulting in hematopoietic maturation arrest. We hypothesized that maintenance therapy with hypomethylating agents (HMA), including decitabine (DAC) and azacitidine (AZA) after induction/consolidation, can be used for MRD elimination to ultimately prolong relapse free survival...
May 11, 2017: American Journal of Hematology
https://www.readbyqxmd.com/read/28474744/outcome-of-elderly-patients-after-failure-to-hypomethylating-agents-given-as-frontline-therapy-for-acute-myeloid-leukemia-aml-single-institution-experience
#6
Rama Nanah, Kristen McCullough, William Hogan, Kebede Begna, Mrinal Patnaik, Michelle Elliott, Mark Litzow, Aref Al-Kali
Outcomes of acute myeloid leukemia (AML) in elderly patients unfit for intensive chemotherapy is challenging. Hypomethylating agents (HMAs) can be effective in these patients but responses are usually short-lived. The majority of patients will either have stable disease or progress through therapy. We hereby describe the outcome of these patients at our institution after they fail HMAs. The data on 56 AML patients at Mayo Clinic, Rochester were reviewed. Patients were considered for our study if they received HMA as frontline therapy for their AML...
May 5, 2017: American Journal of Hematology
https://www.readbyqxmd.com/read/28470536/flt3-itd-and-its-current-role-in-acute-myeloid-leukaemia
#7
REVIEW
Francisco Alejandro Lagunas-Rangel, Venice Chávez-Valencia
FMS-like tyrosine kinase 3 (FLT3) is a proto-oncogene involved in crucial steps of haematopoiesis such as proliferation, differentiation and survival. In recent years, FLT3 has been an important marker in different haematological malignancies, highlighting in acute myeloid leukaemia, where FLT3 mutations have been associated with the clinical prognosis, treatment and survival of patients. The most common form of FLT3 mutation is an internal tandem duplication (ITD) that promotes ligand-independent auto-phosphorylation and constitutive activation of the receptor...
June 2017: Medical Oncology
https://www.readbyqxmd.com/read/28470473/reduced-intensity-conditioning-of-allogeneic-hematopoietic-stem-cell-transplantation-for-myelodysplastic-syndrome-and-acute-myeloid-leukemia-in-patients-older-than-50%C3%A2-years-of-age-a-systematic-review-and-meta-analysis
#8
Zhi-Hui Zhang, Xin-Yue Lian, Dong-Ming Yao, Pin-Fang He, Ji-Chun Ma, Zi-Jun Xu, Hong Guo, Wei Zhang, Jiang Lin, Jun Qian
PURPOSE: A systematic review and meta-analysis were performed to explore the efficacy and safety of allogeneic hematopoietic stem cell transplantation with a reduced intensity conditioning regimen in elderly patients with myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML). METHODS: Overall survival (OS) and event-free survival (EFS) were established as the primary endpoints for directly assessing the efficacy, and non-relapse mortality (NRM) for safety...
May 3, 2017: Journal of Cancer Research and Clinical Oncology
https://www.readbyqxmd.com/read/28447422/minimal-residual-disease-in-acute-myelogenous-leukemia
#9
REVIEW
N M Cruz, N Mencia-Trinchant, D C Hassane, M L Guzman
Treatment of acute myelogenous leukemia (AML) over the past four decades remains mostly unchanged and the prognosis for the majority of patients remains poor. Most of the significant advances that have been observed are in defining cytogenetic abnormalities, as well as the genetic and epigenetic profiles of AML patients. While new cytogenetic and genetic aberrations such as the FLT3-ITD and NPM1 mutations are able to guide prognosis for the majority of patients with AML, outcomes are still dismal and relapse rates remain high...
May 2017: International Journal of Laboratory Hematology
https://www.readbyqxmd.com/read/28446272/-efficacy-comparison-of-different-salvage-treatment-regimens-for-patients-with-refractory-relapsed-acute-myeloid-leukemia
#10
Wen-Hui Gao, Hong-Min Li, Jing-Yi Yu, Ya-Li Zheng, Li-Hua Wu, Qing-Guo Liu, Jun-Fan Li, Chun-Hua Liu, Yi-Ming Hu, Ning Xu, Shang-Zhu Li, Ying-Chang Mi, Ping-Ping Huang
OBJECTIVE: To compare the efficacy and safety of 3 different regimens, namely MAC, FLAG and CAG, as the re-induction chemotherapy for acute myeloid leukemia(AML) patients with primary induction failure and relapse. METHODS: The clinical data of 156 AML patients with primary induction failure and relapse, except patients with acute promyelocytic leukemia(APL), treated with any of the above 3 regimens in our center from January 2008 to April 2016 were analyzed retrospectively...
April 2017: Zhongguo Shi Yan Xue Ye Xue za Zhi
https://www.readbyqxmd.com/read/28445808/treatment-results-in-children-with-myeloid-leukemia-of-down-syndrome-in-saudi-arabia-a-multicenter-saphos-leukemia-group-study
#11
Wasil Jastaniah, Abdulrahman Alsultan, Saad Al Daama, Walid Ballourah, Mohammad Bayoumy, Faisal Al-Anzi, Omar Al Shareef, Mohammed Burhan Abrar, Reem Al Sudairy, Ibrahim Al Ghemlas
Despite the high incidence of Down syndrome (DS) in Arab countires, the incidence and outcomes of myeloid leukemia of DS (ML-DS) have not been studied. We evaluated 206 pediatric acute myeloid leukemia (AML) patients diagnosed between 2005 and 2012 and identified 31 (15%) ML-DS. The incidence of ML-DS was 48 per 100,000 compared to 0.6 per 100,000 for AML in non-DS children. Thus, patients with DS had 80-fold increased risk of ML-DS compared to AML in non-DS children. The median age at diagnosis was 1.8 years, male/female ratio was 1...
April 12, 2017: Leukemia Research
https://www.readbyqxmd.com/read/28439893/outcome-after-intensive-reinduction-therapy-and-allogeneic-stem-cell-transplant-in-paediatric-relapsed-acute-myeloid-leukaemia
#12
Lene Karlsson, Erik Forestier, Henrik Hasle, Kirsi Jahnukainen, Ólafur G Jónsson, Birgitte Lausen, Ulrika Norén Nyström, Josefine Palle, Anne Tierens, Bernward Zeller, Jonas Abrahamsson
Given that 30-40% of children with acute myeloid leukaemia (AML) relapse after primary therapy it is important to define prognostic factors and identify optimal therapy. From 1993 to 2012, 543 children from the Nordic countries were treated according to two consecutive protocols: 208 children relapsed. The influence of disease characteristics, first line treatment, relapse therapy and duration of first remission on outcome was analysed. Second complete remission (CR2) was achieved in 146 (70%) patients. Estimated 5-year overall survival (OS5y ) was 39 ± 4% for the whole group and 43 ± 4% for the 190 patients given re-induction therapy, of whom 76% received regimens that included fludarabine, cytarabine (FLA) ± anthracyclines, 18% received Nordic Society for Paediatric Haematology and Oncology (NOPHO) upfront blocks and 5% received other regimens...
April 25, 2017: British Journal of Haematology
https://www.readbyqxmd.com/read/28435324/symptomatic-central-nervous-system-involvement-in-adult-patients-with-acute-myeloid-leukemia
#13
Nael Alakel, Friedrich Stölzel, Brigitte Mohr, Michael Kramer, Uta Oelschlägel, Christoph Röllig, Martin Bornhäuser, Gerhard Ehninger, Markus Schaich
INTRODUCTION: Acute myeloid leukemia (AML) rarely involves the central nervous system (CNS). Little is known about the clinical course in adult AML patients since most studies examined pediatric patients. Therefore, this study analyzed the data of patients treated in three prospective trials of the "Study Alliance Leukemia" (SAL) study group for CNS involvement. METHODS: In all, 3,261 AML patients included in the prospective AML96, AML2003, and AML60+ trials of the SAL study group were analyzed...
2017: Cancer Management and Research
https://www.readbyqxmd.com/read/28428668/prognostic-parameters-of-acute-myeloid-leukaemia-at-presentation
#14
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
#15
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...
June 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28415689/targeting-cd157-in-aml-using-a-novel-fc-engineered-antibody-construct
#16
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
#17
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
#18
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
#19
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 myelodysplastic syndrome. 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 a retrospective analysis of 566 consecutive patients with acute myeloid leukemia (n = 446) and acute lymphoblastic leukemia (ALL; n = 120) after SCT to study the incidence, risk factors, treatment options, and outcome of iEMR...
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
#20
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
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