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Relapsed acute myeloid leukemia

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https://www.readbyqxmd.com/read/28550184/reduced-hematopoietic-stem-cells-frequency-predicts-outcome-in-acute-myeloid-leukemia
#1
Wenwen Wang, Thomas Stiehl, Simon Raffel, Van T Hoang, Isabel Hoffmann, Laura Poisa-Beiro, Borhan R Saeed, Rachel Blume, Linda Manta, Volker Eckstein, Tilmann Bochtler, Patrick Wuchter, Marieke Essers, Anna Jauch, Andreas Trumpp, Anna Marciniak-Czochra, Anthony D Ho, Christoph Lutz
In patients with acute myeloid leukemia and low percentages of aldehyde-dehydrogenase-positive cells, non-leukemic hematopoietic stem cells can be separated from leukemic cells. By relating hematopoietic stem cell frequencies to outcome we detected poor overall- and disease-free survival of patients with low hematopoietic stem cell frequencies. Serial analysis of matched diagnostic and follow-up samples further demonstrated that hematopoietic stem cells increased after chemotherapy in patients that achieved durable remissions...
May 26, 2017: Haematologica
https://www.readbyqxmd.com/read/28548938/nkp30-expression-is-a-prognostic-immune-biomarker-for-stratification-of-patients-with-intermediate-risk-acute-myeloid-leukemia
#2
Anne-Sophie Chretien, Cyril Fauriat, Florence Orlanducci, Jerome Rey, Gaelle Bouvier Borg, Emmanuel Gautherot, Samuel Granjeaud, Clemence Demerle, Jean-François Hamel, Adelheid Cerwenka, Elke Pogge von Strandmann, Norbert Ifrah, Catherine Lacombe, Pascale Cornillet-Lefebvre, Jacques Delaunay, Antoine Toubert, Christine Arnoulet, Norbert Vey, Daniel Olive
Cytogenetics and European Leukemia Net (ELN) genetic classification predict patients at increased risk of relapse in acute myeloid leukemia (AML) except in the intermediate risk group for which further prognostic determinants are required. We have previously shown that Natural Killer (NK) cell defects in AML are predictors of poor overall survival (OS). This study aimins at validating NKp30, a receptor that mediates NK activation, as a prognostic biomarker for AML patients with intermediate prognosis.NKp30 expression was prospectively assessed at diagnosis on NK cells from peripheral blood by flow cytometry (N = 201 patients)...
May 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/28540755/persistent-cytogenetic-abnormalities-in-patients-undergoing-intensive-chemotherapy-for-acute-myeloid-leukemia
#3
Lalit Saini, Joseph Brandwein, Artur Szkotak, Sunita Ghosh, Irwindeep Sandhu
We evaluated the impact of bone marrow sample characteristics on the detection of persistent cytogenetic abnormalities (PCA) following induction chemotherapy for acute myeloid leukemia (AML). PCA's were identified in 20.4% of patients and were more common with complete remission without count recovery (CRi) vs. those with count recovery (CR, 45.8 vs. 13.5%, p = .001), with  >2% blasts vs.  ≤2% blasts (42 vs. 12%, p =  .001) and with hypocellular trephine biopsies relative to those with normo/hypercellular biopsies (42...
May 25, 2017: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/28538504/clofarabine-dosing-in-a-patient-with-acute-myeloid-leukemia-on-intermittent-hemodialysis-case-report-and-review-of-the-literature
#4
Lydia L Benitez, Katherine Gharibian, David Frame, Rajen Mody, Erika Mora
Clofarabine containing chemotherapeutic regimens have demonstrated efficacy in the treatment of relapsed refractory acute myeloid leukemia. Nonetheless, there are limited data on the use of clofarabine in patients with renal failure. The present report describes the use of clofarabine in a patient with renal failure undergoing intermittent dialysis. We describe our rationale for dosing, clofarabine plasma levels obtained, and discuss our findings in the context of other available literature. Consistent with previous findings, intermittent hemodialysis was not found to be a reliable method of removing clofarabine in patients with renal insufficiency...
May 22, 2017: Journal of Pediatric Hematology/oncology
https://www.readbyqxmd.com/read/28537666/up-regulation-of-serum-mir-4262-predicts-clinical-outcome-of-patients-with-acute-myeloid-leukemia
#5
G-T Han, Z-L Sun
OBJECTIVE: The aim of this study was to investigate whether miR-4262 was associated with the prognosis of acute myeloid leukemia (AML) patients. PATIENTS AND METHODS: Serum and bone marrow miR-4262 expression were investigated in 186 AML patients and 115 healthy normal controls by using Real-time PCR. Associations between miR-4262 expressions and various clinicopathological characteristics were analyzed. Overall survival and relapse-free survival were evaluated using the Kaplan-Meier method...
May 2017: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/28529313/impact-of-killer-immunoglobulin-like-receptor-and-human-leukocyte-antigen-genotypes-on-the-efficacy-of-immunotherapy-in-acute-myeloid-leukemia
#6
E Bernson, A Hallner, F E Sander, O Wilsson, O Werlenius, A Rydström, R Kiffin, M Brune, R Foà, J Aurelius, A Martner, K Hellstrand, F B Thorén
Interactions between killer-immunoglobulin-like receptors (KIRs) and their HLA class I ligands are instrumental in natural killer (NK) cell regulation and protect normal tissue from NK cell attack. Human KIR haplotypes comprise genes encoding mainly inhibitory receptors (KIR A) or activating and inhibitory receptors (KIR B). A substantial fraction of humans lack ligands for inhibitory KIRs (iKIRs), i.e. a 'missing ligand' genotype. KIR B/x and missing ligand genotypes may thus give rise to potentially autoreactive, unlicensed NK cells...
May 22, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28521413/chromosome-t-7-11-p15-p15-translocation-in-acute-myeloid-leukemia-coexisting-with-multilineage-dyspoiesis-and-mutations-in-nras-and-wt1-a-case-report-and-literature-review
#7
Jingke Yang, Xiaodong Lyu, Xinghu Zhu, Xiangguang Meng, Wenli Zuo, Hao Ai, Mei Deng
The chromosomal translocation t(7;11)(p15;p15) and the resulting nucleoporin 98-homeobox A9 (NUP98-HOXA9) gene fusion is rare but recurrent genetic abnormity in acute myeloid leukemia (AML). The present study describes a case of AML plus maturation (-M2) with multilineage dyspoiesis in a 30-year-old male in whom a 46,XY,t(7;11)(p15;p15) karyotype was detected through chromosome analysis. Subsequent molecular and sequencing analysis demonstrated a NUP98-HOXA9 fusion gene with a type I fusion between NUP98 exon 12 and HOXA9 exon 1b, and mutations in neuroblastoma V-Ras oncogene homolog and Wilms tumor 1...
May 2017: Oncology Letters
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
#8
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/28509593/impact-of-pharmacokinetics-on-the-toxicity-and-efficacy-of-clofarabine-in-patients-with-relapsed-or-refractory-acute-myeloid-leukemia
#9
Bozena Büttner, Holger Knoth, Michael Kramer, Reinhard Oertel, Andreas Seeling, Katja Sockel, Malte von Bonin, Friedrich Stölzel, Nael Alakel, Uwe Platzbecker, Christoph Röllig, Gerhard Ehninger, Martin Bornhäuser, Johannes Schetelig, Jan Moritz Middeke
Common side effects of clofarabine (CFB) are liver toxicity, particularly a transient elevation of transaminases and skin toxicity. We studied the correlation of pharmacokinetic (PK) parameters with these toxicities and the efficacy of CFB in patients with relapsed or refractory acute myeloid leukemia. Clofarabine PK parameters showed large inter-individual variability. A higher CFB area under the curve was significantly associated with higher transaminase levels (p = .011 for aspartate aminotransferase (AST), adjusted for age, sex, cumulated CFB dosage, baseline AST, and glomerular filtration rate (GFR))...
May 16, 2017: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/28509405/opportunities-for-expanding-clinical-trial-enrollment-for-relapsed-and-refractory-pediatric-acute-myeloid-leukemia-in-the-united-states-and-canada
#10
Thomas B Alexander, Nickhill Bhakta, E Anders Kolb, Jeffrey E Rubnitz
No abstract text is available yet for this article.
May 16, 2017: Pediatric Blood & Cancer
https://www.readbyqxmd.com/read/28508228/relationship-between-white-blood-cell-count-elevation-and-clinical-response-after-g-csf-priming-chemotherapy-for-acute-myeloid-leukemia
#11
Daisuke Minakata, Shin-Ichiro Fujiwara, Takashi Ikeda, Yumiko Toda, Shoko Ito, Kiyomi Mashima, Kento Umino, Hirofumi Nakano, Ryoko Yamasaki, Kaoru Morita, Yasufumi Kawasaki, Miyuki Sugimoto, Chihiro Yamamoto, Masahiro Ashizawa, Kaoru Hatano, Kazuya Sato, Iekuni Oh, Ken Ohmine, Kazuo Muroi, Yoshinobu Kanda
We retrospectively analyzed the relationship between white blood cell (WBC) count elevation after priming and clinical response in 115 patients with AML (61 untreated and 54 relapsed or refractory) treated with low-dose cytarabine, aclarubicin, and G-CSF priming. Receiver operating characteristic curve analysis showed that the ratio of maximum WBC count to pretreatment WBC count (WBCratio) was most strongly associated with complete remission (CR) in previously untreated patients among several parameters we analyzed in this study; however, the prediction accuracy was not clinically significant considering the area under the curve of 0...
May 15, 2017: International Journal of Hematology
https://www.readbyqxmd.com/read/28504666/conditioning-regimens-for-allogeneic-hematopoietic-stem-cell-transplants-in-acute-myeloid-leukemia
#12
REVIEW
Y S Jethava, S Sica, B Savani, F Socola, M Jagasia, M Mohty, A Nagler, A Bacigalupo
AML is currently the first indication for allogeneic hematopoietic stem cell transplantation (allo-HSCT), as shown by international transplant registries. The conditioning regimens are classified as myeloablative conditioning, non-myeloablative or reduced intensity conditioning. Targeted radioimmunotherapy such as anti-CD45 antibody have also been added to the conditioning regimen in an attempt to improve tumor cell kill. Refinement of standard regimens has led to a reduction of non-relapse mortality, also in the older age group over 60 or 70 years of age...
May 15, 2017: Bone Marrow Transplantation
https://www.readbyqxmd.com/read/28504025/the-preclinical-discovery-of-vosaroxin-for-the-treatment-of-acute-myeloid-leukemia
#13
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
#14
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/28498435/plumbagin-enhances-trail-induced-apoptosis-of-human-leukemic-kasumi%C3%A2-1-cells-through-upregulation-of-trail-death-receptor-expression-activation-of-caspase-8-and-inhibition-of-cflip
#15
Xiaoyang Kong, Jing Luo, Tongpeng Xu, Yunjiao Zhou, Zengkai Pan, Yinghua Xie, Limin Zhao, Yingting Lu, Xiyao Han, Zhixiong Li, Ligen Liu
Although the patients with t(8;21) acute myeloid leukemia (AML) have a favorable prognosis compared with other non-acute promyelocytic leukemia AML patients, only ~50% patients with this relatively favorable subtype can survive for 5 years and refractory/relapse is common in clinical practice. So it is necessary to find novel agents to treat this type of AML. In this study, the effects and the mechanisms of plumbagin and recombinant soluble tumor necrosis factor‑α-related apoptosis-inducing ligand (rsTRAIL) on leukemic Kasumi‑1 cells were primarily investigated...
May 4, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28494506/minimal-residual-disease-eradication-with-epigenetic-therapy-in-core-binding-factor-acute-myeloid-leukemia
#16
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/28490935/characteristics-predicting-outcomes-of-allogeneic-stem-cell-transplantation-in-relapsed-acute-myelogenous-leukemia
#17
J Frazer, S Couban, S Doucette, S Shivakumar
BACKGROUND: Allogeneic hematopoietic stem-cell transplantation (ahsct) is associated with significant morbidity and mortality, but it can cure carefully selected patients with acute myeloid leukemia (aml) in second remission (cr2). In a cohort of patients with aml who underwent ahsct in cr2, we determined the pre-transplant factors that predicted for overall survival (os), relapse, and non-relapse mortality. We also sought to validate the prognostic risk groups derived by Michelis and colleagues in this independent population...
April 2017: Current Oncology
https://www.readbyqxmd.com/read/28475434/enhancing-acute-myeloid-leukemia-therapy-monitoring-response-using-residual-disease-testing-as-a-guide-to-therapeutic-decision-making
#18
Benjamin Tomlinson, Hillard M Lazarus
Current standards for monitoring the response of acute myeloid leukemia (AML) are based on morphologic assessments of the bone marrow and recovery of peripheral blood counts. A growing experience is being developed to enhance the detection of small amounts of AML, or minimal residual disease (MRD). Areas covered: Available techniques include multi-color flow cytometry (MFC) of leukemia associated immunophenotypes (LAIP), quantitative reverse transcriptase polymerase chain reaction (QRT-PCR) for detecting fusion and mutated genes (RUNX1-RUNX1T1, CBFB-MYH11, and NPM1), overexpression of genes such as WT1, and next generation sequencing (NGS) for MRD...
May 12, 2017: Expert Review 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
#19
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/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
#20
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
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