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Relapsed acute myeloid leukemia

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https://www.readbyqxmd.com/read/28435324/symptomatic-central-nervous-system-involvement-in-adult-patients-with-acute-myeloid-leukemia
#1
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/28420416/emerging-therapies-for-acute-myeloid-leukemia
#2
REVIEW
Caner Saygin, Hetty E Carraway
Acute myeloid leukemia (AML) is characterized by clinical and biological heterogeneity. Despite the advances in our understanding of its pathobiology, the chemotherapy-directed management has remained largely unchanged in the past 40 years. However, various novel agents have demonstrated clinical activity, either as single agents (e.g., isocitrate dehydrogenase (IDH) inhibitors, vadastuximab) or in combination with standard induction/consolidation at diagnosis and with salvage regimens at relapse. The classes of agents described in this review include novel cytotoxic chemotherapies (CPX-351 and vosaroxin), epigenetic modifiers (guadecitabine, IDH inhibitors, histone deacetylase (HDAC) inhibitors, bromodomain and extraterminal (BET) inhibitors), FMS-like tyrosine kinase receptor 3 (FLT3) inhibitors, and antibody-drug conjugates (vadastuximab), as well as cell cycle inhibitors (volasertib), B-cell lymphoma 2 (BCL-2) inhibitors, and aminopeptidase inhibitors...
April 18, 2017: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/28419965/chidamide-in-flt3-itd-positive-acute-myeloid-leukemia-and-the-synergistic-effect-in-combination-with-cytarabine
#3
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
#4
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
#5
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/28409853/a-phase-1-study-of-the-cxcr4-antagonist-plerixafor-in-combination-with-high-dose-cytarabine-and-etoposide-in-children-with-relapsed-or-refractory-acute-leukemias-or-myelodysplastic-syndrome-a-pediatric-oncology-experimental-therapeutics-investigators-consortium
#6
Todd M Cooper, Edward Allan Racela Sison, Sharyn D Baker, Lie Li, Amina Ahmed, Tanya Trippett, Lia Gore, Margaret E Macy, Aru Narendran, Keith August, Michael J Absalon, Jessica Boklan, Jessica Pollard, Daniel Magoon, Patrick A Brown
BACKGROUND: Plerixafor, a reversible CXCR4 antagonist, inhibits interactions between leukemic blasts and the bone marrow stromal microenvironment and may enhance chemosensitivity. A phase 1 trial of plerixafor in combination with intensive chemotherapy in children and young adults with relapsed or refractory acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML), and myelodysplastic syndrome (MDS) was performed to determine a tolerable and biologically active dose. PROCEDURE: Plerixafor was administered daily for 5 days at four dose levels (6, 9, 12, and 15 mg/m(2) /dose) followed 4 hr later by high-dose cytarabine (every 12 hr) and etoposide (daily)...
April 14, 2017: Pediatric Blood & Cancer
https://www.readbyqxmd.com/read/28397012/live-kinase-b1-maintains-cd34-cd38-aml-cell-proliferation-and-self-renewal
#7
Huihan Wang, Xiaobin Wang, Na Xin, Lin Qi, Aijun Liao, Wei Yang, Zhuogang Liu, Chenghai Zhao
Live kinase B1 (LKB1) has been recognized as a tumor suppressor in many human cancers; however, LKB1 maintains self-renewal of hematopoietic stem cells (HSCs). The existence of leukemia stem cells (LSCs) is responsible for drug resistance and leukemia relapse. In acute myeloid leukemia (AML), CD34(+)CD38(-) fraction is the most enriched compartment for LSCs. We found that LKB1 was upregulated in CD34(+)CD38(-) AML cells. LKB1 downregulation suppressed the long-term proliferation of CD34(+)CD38(-) AML cells, induced CD34(+)CD38(-) AML cells into G2/M phase, and enhanced the sensitivity of CD34(+)CD38(-) AML cells to chemotherapy...
April 10, 2017: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/28395444/-prognostic-value-of-dynamic-monitoring-of-runx1-runx1t1-transcript-in-pediatric-acute-myeloid-leukemia
#8
H T Gao, Y Zhang, K Sun, J M Guo, Y Q Chen, X L Chen, J Shi, X N Niu, F Wang, L Huo
Objective: To investigate the prognostic value of dynamic monitoring of RUNX1-RUNX1T1 transcript in pediatric patients with t (8;21) acute myeloid leukemia (AML) . Methods: The clinical features and RUNX1-RUNX1T1 transcript levels of 55 pediatric t (8;21) AML patients, newly diagnosed from Jan. 2010 to Apr. 2016, were analyzed retrospectively. The relationship between the minimal residual disease (MRD) and prognosis was analysed by dynamic monitoring of RUNX1-RUNX1T1 transcript levels using real-time quantitative PCR (RQ-PCR) technology...
March 14, 2017: Zhonghua Xue Ye Xue za Zhi, Zhonghua Xueyexue Zazhi
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
#9
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
#10
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/28391645/hematopoietic-stem-cell-transplantation-in-advanced-cutaneous-t-cell-lymphoma
#11
Hiroshi Saruta, Chika Ohata, Ikko Muto, Taichi Imamura, Eijiro Oku, Koichi Ohshima, Koji Nagafuji, Takekuni Nakama
We retrospectively reviewed data pertaining to five patients with cutaneous T-cell lymphoma (CTCL) who had received hematopoietic stem cell transplantation (HSCT) between 2004 and 2015 at Kurume University Hospital, along with their clinical data until March 2016. For patients with advanced CTCL eligible for HSCT, autologous HSCT was performed when they responded well to chemotherapy, and allogeneic HSCT was selected for patients with advanced mycosis fungoides (MF)/Sézary syndrome (SS) and CTCL other than MF/SS with poor chemosensitivity...
April 9, 2017: Journal of Dermatology
https://www.readbyqxmd.com/read/28391288/cd33-cd96-and-death-associated-protein-kinase-dapk-expression-are-associated-with-the-survival-rate-and-or-response-to-the-chemotherapy-in-the-patients-with-acute-myeloid-leukemia-aml
#12
Yongfang Jiang, Ping Xu, Dandan Yao, Xi Chen, Haibin Dai
BACKGROUND Leukemia stem cells (LSC) are involved in the incidence, drug resistance, and relapse of leukemia while LSC-related antigen CD33, CD96, and DAPK expression in AML and its prognosis is still unclear. This study explored LSC-related antigens expression in acute myeloid leukemia (AML) and its prognosis. MATERIAL AND METHODS A total of 156 cases of AML patients were enrolled in the experiment. The expression of CD33, CD96, and DAPK in CD34+CD38-CD123+ LSC were tested by flow cytometry. The survival curve was established using the Kaplan-Meier method...
April 9, 2017: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/28386105/measurable-residual-disease-testing-in-acute-myeloid-leukaemia
#13
REVIEW
C S Hourigan, R P Gale, N J Gormley, G J Ossenkoppele, R B Walter
There is considerable interest in developing techniques to detect and/or quantify remaining leukaemia cells termed measurable or, less precisely, minimal residual disease (MRD) in persons with acute myeloid leukaemia (AML) in complete remission defined by cytomorphological criteria. An important reason for AML MRD-testing is the possibility of estimating the likelihood (and timing) of leukaemia relapse. A perfect MRD-test would precisely quantify leukaemia cells biologically able and likely to cause leukaemia relapse within a defined interval...
April 21, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28380315/myeloablative-versus-reduced-intensity-hematopoietic-cell-transplantation-for-acute-myeloid-leukemia-and-myelodysplastic-syndromes
#14
Bart L Scott, Marcelo C Pasquini, Brent R Logan, Juan Wu, Steven M Devine, David L Porter, Richard T Maziarz, Erica D Warlick, Hugo F Fernandez, Edwin P Alyea, Mehdi Hamadani, Asad Bashey, Sergio Giralt, Nancy L Geller, Eric Leifer, Jennifer Le-Rademacher, Adam M Mendizabal, Mary M Horowitz, H Joachim Deeg, Mitchell E Horwitz
Purpose The optimal regimen intensity before allogeneic hematopoietic cell transplantation (HCT) is unknown. We hypothesized that lower treatment-related mortality (TRM) with reduced-intensity conditioning (RIC) would result in improved overall survival (OS) compared with myeloablative conditioning (MAC). To test this hypothesis, we performed a phase III randomized trial comparing MAC with RIC in patients with acute myeloid leukemia or myelodysplastic syndromes. Patients and Methods Patients age 18 to 65 years with HCT comorbidity index ≤ 4 and < 5% marrow myeloblasts pre-HCT were randomly assigned to receive MAC (n = 135) or RIC (n = 137) followed by HCT from HLA-matched related or unrelated donors...
April 10, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28378367/clonal-evolution-detected-with-conventional-cytogenetic-analysis-is-a-potent-prognostic-factor-in-adult-patients-with-relapsed-aml
#15
Hiroaki Shimizu, Akihiko Yokohama, Takuma Ishizaki, Nahoko Hatsumi, Satoru Takada, Takayuki Saitoh, Toru Sakura, Yoshihisa Nojima, Hiroshi Handa
We retrospectively investigated 144 patients with relapsed acute myeloid leukemia (AML) to clarify predisposing factors and the prognostic impact of acquisition of additional cytogenetic abnormalities (ACA) at the first relapse. Additional cytogenetic abnormalities are recognized as clonal evolution at the cytogenetic level. Fifty-nine patients (41%) acquired ACA at the first relapse. The incidences of ACA acquisition varied depending on cytogenetic abnormalities at initial diagnosis. Multivariate analysis identified t(8;21), complex karyotype, and a duration of fewer than 12 months of complete remission as independent predisposing factors for ACA acquisition...
April 4, 2017: Hematological Oncology
https://www.readbyqxmd.com/read/28370339/long-term-impact-of-hyperleukocytosis-in-newly-diagnosed-acute-myeloid-leukemia-patients-undergoing-allogeneic-stem-cell-transplantation-an-analysis-from-the-acute-leukemia-working-party-of-the-ebmt
#16
Jonathan Canaani, Myriam Labopin, Gerard Socié, Anne Nihtinen, Anne Huynh, Jan Cornelissen, Eric Deconinck, Tobias Gedde-Dahl, Edouard Forcade, Patrice Chevallier, Jean Henri Bourhis, Didier Blaise, Mohamad Mohty, Arnon Nagler
Up to 20% of acute myeloid leukemia (AML) patients present initially with hyperleukocytosis, placing them at increased risk for early mortality during induction. Yet, it is unknown whether hyperleukocytosis still retains prognostic value for AML patients undergoing hematopoietic stem cell transplantation (HSCT). Furthermore, it is unknown whether hyperleukocytosis holds prognostic significance when modern molecular markers such as FLT3-ITD and NPM1 are accounted for. To determine whether hyperleukocytosis is an independent prognostic factor influencing outcome in transplanted AML patients we performed a retrospective analysis using the registry of the acute leukemia working party of the EBMT...
March 28, 2017: American Journal of Hematology
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
#17
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/28368379/therapy-related-acute-myeloid-leukemia-and-myelodysplastic-syndrome-after-hematopoietic-cell-transplantation-for-lymphoma
#18
S Yamasaki, R Suzuki, K Hatano, K Fukushima, H Iida, S Morishima, Y Suehiro, T Fukuda, N Uchida, H Uchiyama, H Ikeda, A Yokota, K Tsukasaki, H Yamaguchi, J Kuroda, H Nakamae, Y Adachi, K-I Matsuoka, Y Nakamura, Y Atsuta, J Suzumiya
Therapy-related acute myeloid leukemia and myelodysplastic syndrome (t-AML/MDS) represent severe late effects in patients receiving hematopoietic cell transplantation (HCT) for lymphoma. The choice between high-dose therapy with autologous HCT and allogeneic HCT with reduced-intensity conditioning remains controversial in patients with relapsed lymphoma. We retrospectively analyzed incidence and risk factors for the development of t-AML/MDS in lymphoma patients treated with autologous or allogeneic HCT. A total of 13 810 lymphoma patients who received autologous (n=9963) or allogeneic (n=3847) HCT between 1985 and 2012 were considered...
April 3, 2017: Bone Marrow Transplantation
https://www.readbyqxmd.com/read/28363872/novel-therapeutic-strategies-to-target-leukemic-cells-that-hijack-compartmentalized-continuous-hematopoietic-stem-cell-niches
#19
REVIEW
Vashendriya V V Hira, Cornelis J F Van Noorden, Hetty E Carraway, Jaroslaw P Maciejewski, Remco J Molenaar
Acute myeloid leukemia and acute lymphoblastic leukemia cells hijack hematopoietic stem cell (HSC) niches in the bone marrow and become leukemic stem cells (LSCs) at the expense of normal HSCs. LSCs are quiescent and resistant to chemotherapy and can cause relapse of the disease. HSCs in niches are needed to generate blood cell precursors that are committed to unilineage differentiation and eventually production of mature blood cells, including red blood cells, megakaryocytes, myeloid cells and lymphocytes...
March 28, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28360149/notch1-mutation-tp53-alteration-and-myeloid-antigen-expression-predict-outcome-heterogeneity-in-children-with-first-relapse-of-t-cell-acute-lymphoblastic-leukemia
#20
Jana Hof, Corinne Kox, Stefanie Groeneveld-Krentz, Obul R Bandapalli, Leonid Karawajew, Katharina Schedel, Joachim B Kunz, Cornelia Eckert, Wolf-Dieter Ludwig, Richard Ratei, Peter Rhein, Günter Henze, Martina U Muckenthaler, Andreas E Kulozik, Arend von Stackelberg, Renate Kirschner-Schwabe
No abstract text is available yet for this article.
March 30, 2017: Haematologica
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