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Relapsed acute myeloid leukemia

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https://www.readbyqxmd.com/read/27902595/prognostic-impact-of-viral-reactivations-in-acute-myeloid-leukemia-patients-undergoing-allogeneic-stem-cell-transplantation-in-first-complete-response
#1
Sarah Guenounou, Cécile Borel, Emilie Bérard, Edwige Yon, Marylise Fort, Catherine Mengelle, Sarah Bertoli, Audrey Sarry, Suzanne Tavitian, Françoise Huguet, Michel Attal, Christian Récher, Anne Huynh
Cytomegalovirus (CMV) serological status of donor and recipient as well as CMV reactivation have been associated with a lower risk of relapse in acute myeloid leukemia (AML) patients after allogeneic stem cell transplantation (alloSCT). Since immunosuppression following transplant allows resurgence of many other viruses, we retrospectively evaluated the impact of viral reactivations on relapse and survival in a cohort of 136 AML patients undergoing alloSCT in first remission from sibling (68%) or unrelated (32%) donors...
November 2016: Medicine (Baltimore)
https://www.readbyqxmd.com/read/27893163/sorafenib-and-azacitidine-as-salvage-therapy-for-relapse-of-flt3-itd-mutated-aml-after-allo-sct
#2
Christina Rautenberg, Kathrin Nachtkamp, Ariane Dienst, Pia Verena Schmidt, Claudia Heyn, Mustafa Kondakci, Ulrich Germing, Rainer Haas, Guido Kobbe, Thomas Schroeder
OBJECTIVE: Patients with acute myeloid leukemia (AML) carrying FLT3-ITD mutations (FLT3-ITD+) who relapse after allogeneic 3transplantation (allo-SCT) have a very dismal prognosis with the currently available treatment options. METHODS: We treated 8 patients with FLT3-ITD+ AML who had relapsed in median 91 days (range, 28 - 249) following allo-SCT with a combination of the multikinase inhibitor Sorafenib and the DNA methyltransferase inhibitor Azacitidine (Aza)...
November 28, 2016: European Journal of Haematology
https://www.readbyqxmd.com/read/27890261/consolidation-chemotherapy-prior-to-hematopoietic-cell-transplantation-for-adults-with-acute-myeloid-leukemia-in-first-remission
#3
REVIEW
Frederick R Appelbaum
Whether patients with acute myeloid leukemia (AML) should receive routine consolidation chemotherapy prior to transplant remains a significant question. Consolidation therapy may be advisable in the face of transplant delays, such as donor identification, insurance clearance, or transplant center scheduling, to prevent relapse prior to transplant. However, in cases where physicians have a choice, the question of the value of consolidation chemotherapy continues to be debated. This paper reviews the value of consolidation therapy in 4 different transplant settings...
December 2016: Best Practice & Research. Clinical Haematology
https://www.readbyqxmd.com/read/27890254/why-are-there-so-few-randomized-trials-for-patients-with-primary-refractory-acute-myeloid-leukemia
#4
REVIEW
Elihu Estey
Fewer patients with primary refractory AML ("PREF") are entered into phase 3 trials than are patients with relapsed AML. This is particularly noteworthy because data from phase 3 trials for newly diagnosed AML indicated PREF and relapse are equally common. Here I discuss three possible reasons for this discrepancy. First, there is disagreement whether the criterion for PREF AML should be failure of one or two courses of initial induction therapy. Second, there may be an impression that PREF AML is qualitatively worse than relapsed AML...
December 2016: Best Practice & Research. Clinical Haematology
https://www.readbyqxmd.com/read/27890252/aml-in-2016-where-we-are-now
#5
REVIEW
Jacob M Rowe
A high relapse rate for patients with acute myeloid leukemia (AML) is still a major barrier to the long-term survival of these patients. Nevertheless, considerable progress has been made both in the biology and therapy of the disease. Specifically, progress has been made in the areas of integrated genomic analysis for prognosis, the widening application of minimal residual disease (MRD) monitoring in clinical practice, the development of new agents, and the increasing use of drugs, such as IDH and FLT3 inhibitors, as a bridge to transplant...
December 2016: Best Practice & Research. Clinical Haematology
https://www.readbyqxmd.com/read/27884166/tigar-cooperated-with-glycolysis-to-inhibit-the-apoptosis-of-leukemia-cells-and-associated-with-poor-prognosis-in-patients-with-cytogenetically-normal-acute-myeloid-leukemia
#6
Sixuan Qian, Jianyong Li, Ming Hong, Yu Zhu, Huihui Zhao, Yue Xie, Jiayu Huang, Yun Lian, Yanru Li, Shuai Wang, Jianping Mao, Yaoyu Chen
BACKGROUND: Cancer cells show increased glycolysis and take advantage of this metabolic pathway to generate ATP. The TP53-induced glycolysis and apoptosis regulator (TIGAR) inhibits aerobic glycolysis and protects tumor cells from intracellular reactive oxygen species (ROS)-associated apoptosis. However, the function of TIGAR in glycolysis and survival of acute myeloid leukemia cells remains unclear. METHODS: We analyzed TIGAR expression in cytogenetically normal (CN-) AML patients and the correlations with clinical and biological parameters...
November 25, 2016: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/27883945/recent-advances-in-the-treatment-of-lower-risk-non-del-5q-myelodysplastic-syndromes-mds
#7
REVIEW
Antonio Almeida, Pierre Fenaux, Alan F List, Azra Raza, Uwe Platzbecker, Valeria Santini
Patients with lower-risk myelodysplastic syndromes (MDS) are affected primarily by symptoms of chronic anemia and fatigue rather than progression to acute myeloid leukemia. Severe thrombocytopenia, although less common in lower-risk MDS, is associated with increased risk of bleeding. For anemic patients, the principal aim of treatment is to improve anemia and decrease red blood cell transfusions. For transfusion-dependent patients with lower-risk MDS without chromosome 5q deletion [non-del(5q) MDS], there are limited effective treatments...
November 13, 2016: Leukemia Research
https://www.readbyqxmd.com/read/27881874/acute-myeloid-leukemia-derived-from-lympho-myeloid-clonal-hematopoiesis
#8
F Thol, S Klesse, L Köhler, R Gabdoulline, A Kloos, A Liebich, M Wichman, A Chaturvedi, J Fabisch, V I Gaidzik, P Paschka, L Bullinger, G Bug, H Serve, G Göhring, B Schlegelberger, M Lübbert, H Kirchner, M Wattad, D Kraemer, B Hertenstein, G Heil, W Fiedler, J Krauter, R Schlenk, K Döhner, H Döhner, A Ganser, M Heuser
We studied acute myeloid leukemia (AML) patients with lympho-myeloid clonal hematopoiesis (LM-CH), defined by the presence of DNA methyltransferase 3A (DNMT3A) mutations in both the myeloid and lymphoid T-cell compartment. Diagnostic, CR and relapse samples were sequenced for 34 leukemia-related genes in 171 DNMT3A mutated adult AML patients. AML with LM-CH was found in 40 patients (23%) and was associated with clonal haematopoiesis of indeterminate potential (CHIP) years prior to AML, older age, secondary AML, and more frequent MDS-type co-mutations (TET2, RUNX1 and EZH2)...
November 24, 2016: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/27881579/a-mirnas-dnmt1-axis-is-involved-in-azacitidine-resistance-and-predicts-survival-in-higher-risk-myelodysplastic-syndrome-and-low-blast-count-acute-myeloid-leukemia
#9
Françoise Solly, Catherine Koering, Aminetou Mint-Mohamed, Delphinne Maucort-Boulch, Guillaume Robert, Patrick Auberger, Pascale Flandrin-Gresta, Lionel Ades, Pierre Fenaux, Olivier Kosmider, Emmanuelle Tavernier-Tardy, Jerome Cornillon, Denis Guyotat, Lydia Lydia Campos, Franck Mortreux, Eric Wattel
PURPOSE: Azacitidine (AZA) inhibits DNA methyltransferases, including DNMT1, and is currently the standard of care for patients with higher risk myelodysplastic syndrome (HRMDS) or low blast count AML (AML). EXPERIMENTAL DESIGN: The expression of 754 microRNAs (miRNAs) was compared in AZA-resistant and AZA-sensitive MDS cells. We investigated the role of differentially expressed miRNAs on DNMT1 expression and AZA-resistance in vitro. We next evaluated anti-DNMT1 miRNAs expression in pretreatment bone marrow samples deriving from 75 patients treated with AZA for HRMDS or AML...
November 23, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/27880933/immunological-effects-of-nilotinib-prophylaxis-after-allogeneic-stem-cell-transplantation-in-patients-with-advanced-chronic-myeloid-leukemia-or-philadelphia-chromosome-positive-acute-lymphoblastic-leukemia
#10
Nira Varda-Bloom, Ivetta Danylesko, Roni Shouval, Shiran Eldror, Atar Lev, Jacqueline Davidson, Esther Rosenthal, Yulia Volchek, Noga Shem-Tov, Ronit Yerushalmi, Avichai Shimoni, Raz Somech, Arnon Nagler
Allogeneic stem cell transplantation remains the standard treatment for resistant advanced chronic myeloid leukemia and Philadelphia chromosome-positive acute lymphoblastic leukemia. Relapse is the major cause of treatment failure in both diseases. Post-allo-SCT administration of TKIs could potentially reduce relapse rates, but concerns regarding their effect on immune reconstitution have been raised. We aimed to assess immune functions of 12 advanced CML and Ph+ ALL patients who received post-allo-SCT nilotinib...
November 18, 2016: Oncotarget
https://www.readbyqxmd.com/read/27872732/minimal-residual-disease-in-acute-myeloid-leukemia-of-adults-determination-prognostic-impact-and-clinical-applications
#11
REVIEW
Maria Ilaria Del Principe, Francesco Buccisano, Luca Maurillo, Giuseppe Sconocchia, Mariagiovanna Cefalo, Maria Irno Consalvo, Chiara Sarlo, Consuelo Conti, Giovanna De Santis, Eleonora De Bellis, Ambra Di Veroli, Patrizia Palomba, Cristina Attrotto, Annagiulia Zizzari, Giovangiacinto Paterno, Maria Teresa Voso, Giovanni Del Poeta, Francesco Lo-Coco, William Arcese, Sergio Amadori, Adriano Venditti
Pretreatment assessment of cytogenetic/genetic signature of acute myeloid leukemia (AML) has been consistently shown to play a major prognostic role but also to fail at predicting outcome on individual basis, even in low-risk AML. Therefore, we are in need of further accurate methods to refine the patients' risk allocation process, distinguishing more adequately those who are likely to recur from those who are not. In this view, there is now evidence that the submicroscopic amounts of leukemic cells (called minimal residual disease, MRD), measured during the course of treatment, indicate the quality of response to therapy...
2016: Mediterranean Journal of Hematology and Infectious Diseases
https://www.readbyqxmd.com/read/27872058/a-randomised-assessment-of-adding-the-kinase-inhibitor-lestaurtinib-to-1st-line-chemotherapy-for-flt3-mutated-aml
#12
Steven Knapper, Nigel Russell, Amanda Gilkes, Robert K Hills, Rosemary E Gale, James D Cavenagh, Gail Jones, Lars Kjeldsen, Michael R Grunwald, Ian Thomas, Heiko Konig, Mark J Levis, Alan K Burnett
The clinical benefit of adding FLT3-directed small molecule therapy to standard first-line treatment of acute myeloid leukemia (AML) has not yet been established. As part of the UK AML15 and 17 trials, patients with previously-untreated AML and confirmed FLT3-activating mutations, mostly aged <60 years, were randomised to receive oral Lestaurtinib (CEP701), or not, following each of four cycles of induction and consolidation chemotherapy. Lestaurtinib was commenced 2 days after completing chemotherapy and administered in cycles of up to 28 days...
November 21, 2016: Blood
https://www.readbyqxmd.com/read/27865463/molecular-changes-during-acute-myeloid-leukemia-aml-evolution-and-identification-of-novel-treatment-strategies-through-molecular-stratification
#13
E Karjalainen, G A Repasky
Acute myeloid leukemia (AML) is a hematopoietic malignancy characterized by impaired differentiation and uncontrollable proliferation of myeloid progenitor cells. Due to high relapse rates, overall survival for this rapidly progressing disease is poor. The significant challenge in AML treatment is disease heterogeneity stemming from variability in maturation state of leukemic cells of origin, genetic aberrations among patients, and existence of multiple disease clones within a single patient. Disease heterogeneity and the lack of biomarkers for drug sensitivity lie at the root of treatment failure as well as selective efficacy of AML chemotherapies and the emergence of drug resistance...
2016: Progress in Molecular Biology and Translational Science
https://www.readbyqxmd.com/read/27863523/oligoclonal-expansion-of-tcr-v%C3%AE-t-cells-may-be-a-potential-immune-biomarker-for-clinical-outcome-of-acute-myeloid-leukemia
#14
Zhenyi Jin, Qiang Luo, Shuai Lu, Xinyu Wang, Zifan He, Jing Lai, Shaohua Chen, Lijian Yang, Xiuli Wu, Yangqiu Li
BACKGROUND: Recent data have shown that γδ T cells can act as mediators for immune defense against tumors. Our previous study has demonstrated that persisting clonally expanded TRDV4 T cells might be relatively beneficial for the outcome of patients with T cell acute lymphoblastic leukemia after hematopoietic stem cell transplantation (HSCT). However, little is known about the distribution and clonality of the TRDV repertoire in T cell receptor (TCR) of γδ T cells and their effects on the clinical outcome of patients with acute myeloid leukemia (AML)...
November 18, 2016: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/27856368/haploidentical-transplantation-with-post-transplant-cyclophosphamide-for-high-risk-acute-lymphoblastic-leukemia
#15
Samer A Srour, Denái R Milton, Asad Bashey, Amado Karduss-Urueta, Monzr Al Malki, Rizwan Romee, Scott Solomon, Stacey Brown, Michael Slade, Rosendo Perez, Gabriela Rondon, Stephan J Forman, Richard E Champlin, Partow Kebriaei, Stefan O Ciurea
Haploidentical transplantation performed with post-transplantation cyclophosphamide (PTCy)-based graft-versus-host disease (GVHD) prophylaxis has been associated with favorable outcomes for patients with acute myeloid leukemia and lymphomas. However, it remains unclear if such approach is effective for patients with acute lymphoblastic leukemia (ALL). We analyzed outcomes of 109 consecutively treated ALL patients 18 years of age and older at 5 institutions. The median age was 32 years and the median follow-up for survivors was 13 months...
November 14, 2016: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/27837251/mcm7-polymorphisms-associated-with-the-aml-relapse-and-overall-survival
#16
Jin Sol Lee, Hyun Sub Cheong, Youngil Koh, Kwang-Sung Ahn, Hyoung Doo Shin, Sung-Soo Yoon
The minichromosome maintenance complex component 7 (MCM7) encodes a member of MCM complex, which plays a critical role in the initiation of gene replication. Due to the importance of MCM complex, MCM7 gene has been regarded as a candidate gene for cancer development. In the present study, seven MCM7 polymorphisms were genotyped in 344 subjects composed of 103 acute myeloid leukemia (AML) patients and 241 normal controls to examine the possible associations between MCM7 polymorphisms and the risk of AML. MCM7 polymorphisms were not associated with the risk of AML (P > 0...
November 12, 2016: Annals of Hematology
https://www.readbyqxmd.com/read/27835920/-acute-myeloid-leukemia
#17
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/27833171/serum-levels-of-soluble-adhesion-molecules-in-newly-diagnosed-acute-myeloid-leukemia-and-in-complete-remission-suggest-endothelial-cell-activation-by-myeloblasts
#18
Tomas Kupsa, Jan Vanek, Zak Pavel, Ladislav Jebavy, Jan M Horacek
BACKGROUND AND AIMS: Despite high-dose multi-agent chemotherapy and allogeneic stem cell transplantation, the relapse rate of acute myeloid leukemia (AML) is high. Further, the disease is highly resistent to drugs. We speculated that deeper understanding of AML-endothelial cell interactions might provide new targets for selective modulation of the AML microenvironment and form the basis for novel treatment approaches. In this study, we evaluated levels of endothelium derived soluble adhesion molecules in active disease and in complete remission (CR) and their relationship with inflammatory cytokines...
November 10, 2016: Biomedical Papers of the Medical Faculty of the University Palacký, Olomouc, Czechoslovakia
https://www.readbyqxmd.com/read/27833094/enhanced-sensitivity-to-glucocorticoids-in-cytarabine-resistant-aml
#19
D Malani, A Murumägi, B Yadav, M Kontro, S Eldfors, A Kumar, R Karjalainen, M M Majumder, P Ojamies, T Pemovska, K Wennerberg, C Heckman, K Porkka, M Wolf, T Aittokallio, O Kallioniemi
We sought to identify drugs that could counteract cytarabine resistance in acute myeloid leukemia (AML) by generating eight resistant variants from MOLM-13 and SHI-1 AML cell lines by long-term drug treatment. These cells were compared with 66 ex vivo chemorefractory samples from cytarabine-treated AML patients. The models and patient cells were subjected to genomic and transcriptomic profiling and high-throughput testing with 250 emerging and clinical oncology compounds. Genomic profiling uncovered deletion of the deoxycytidine kinase (DCK) gene in both MOLM-13- and SHI-1-derived cytarabine-resistant variants and in an AML patient sample...
December 2, 2016: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/27833093/molecular-alterations-in-bone-marrow-mesenchymal-stromal-cells-derived-from-acute-myeloid-leukemia-patients
#20
E K von der Heide, M Neumann, S Vosberg, A R James, M P Schroeder, J O Tanchez, K Isaakidis, C Schlee, M Luther, K Jöhrens, I Anagnostopoulos, L H Mochmann, D Nowak, W-K Hofmann, P A Greif, C D Baldus
The contribution of molecular alterations in bone marrow mesenchymal stromal cells (BM-MSC) to the pathogenesis of acute myeloid leukemia (AML) is poorly understood. Thus, we assessed genome wide genetic, transcriptional and epigenetic alterations in BM-MSC derived from AML patients (AML BM-MSC). Whole exome sequencing (WES) of AML BM-MSC samples from 21 patients revealed a non-specific pattern of genetic alterations in the stromal compartment. The only mutation present in AML BM-MSC at serial time points of diagnosis, complete remission and relapse was a mutation in the PLEC gene encoding for cytoskeleton key player Plectin in one AML patient...
November 11, 2016: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
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