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https://www.readbyqxmd.com/read/29345177/prognostic-significance-of-cathepsin-l-expression-in-pediatric-acute-myeloid-leukemia
#1
Garima Pandey, Sameer Bakhshi, Bhaskar Thakur, Prerna Jain, Shyam S Chauhan
Overexpression of cathepsin L (CTSL), an endolysosomal cysteine protease, is associated with inferior survival of patients with various human malignancies. We evaluated the expression/activity of CTSL in peripheral blood mononuclear cells (PBMCs) and bone marrow mononuclear cells (BMMCs) of 103 pediatric acute myeloid leukemia (AML) patients to assess its prognostic significance in this malignancy. Thirty-five healthy siblings of patients served as controls. Our results revealed significantly higher CTSL activity (p < ...
January 18, 2018: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/29339403/a-phase-1-study-of-azacitidine-combined-with-chemotherapy-in-childhood-leukemia-a-report-from-tacl-consortium
#2
Weili Sun, Timothy Triche, Jemily Malvar, Paul Gaynon, Richard Sposto, Xiaojing Yang, Henrique Bittencourt, Andrew E Place, Yoav Messinger, Chris Fraser, Luciano Dalla-Pozza, Bodour Salhia, Peter Jones, Alan S Wayne, Lia Gore, Todd M Cooper, Gangning Liang
Growing evidence indicates that aberrant DNA hypermethylation is associated with leukemogenesis, chemotherapy resistance, and relapse. DNA methyltransferase inhibitors such as azacitidine and decitabine have been shown to reverse drug resistance and prime leukemia cells to cytotoxic agents in vitro. Here we report the first pediatric phase 1 study using azacitidine in sequence with chemotherapy in patients with relapsed/refractory leukemia. Fourteen patients were enrolled, twelve with acute myeloid leukemia (AML) and two with acute lymphoblastic leukemia (ALL)...
January 16, 2018: Blood
https://www.readbyqxmd.com/read/29338495/clinical-challenges-in-de-novo-pediatric-acute-myeloid-leukemia
#3
Kim Klein, Valérie de Haas, Gertjan J L Kaspers
Although the prognosis of pediatric acute myeloid leukemia (pAML) has improved, with current survival rates up to 75%, relapse rates remain high. Areas covered: The low number of patients, the heterogeneous genomic landscape of AML, novel diagnostic techniques, divergent available treatment protocols, and dose-limiting toxicity of conventional agents all contribute to the complexity of AML treatment. This review gives an overview of the current clinical challenges with respect to diagnostics, treatment, and supportive care in pAML...
January 17, 2018: Expert Review of Anticancer Therapy
https://www.readbyqxmd.com/read/29299118/identification-of-a-cytogenetic-and-molecular-subgroup-of-acute-myeloid-leukemias-showing-sensitivity-to-l-asparaginase
#4
Salvatore Nicola Bertuccio, Salvatore Serravalle, Annalisa Astolfi, Annalisa Lonetti, Valentina Indio, Anna Leszl, Andrea Pession, Fraia Melchionda
L-Asparaginase (L-Asp) is an enzyme that catalyzes the hydrolysis of L-asparagine to L-aspartic acid, and its depletion induces leukemic cell death. L-Asp is an important component of treatment regimens for Acute Lymphoblastic Leukemia (ALL). Sensitivity to L-Asp is due to the absence of L-Asparagine synthetase (ASNS), the enzyme that catalyzes the biosynthesis of L-asparagine. ASNS gene is located on 7q21.3, and its increased expression in ALLs correlates with L-Asp resistance. Chromosome 7 monosomy (-7) is a recurrent aberration in myeloid disorders, particularly in adverse-risk Acute Myeloid Leukemias (AMLs) and therapy-related myeloid neoplasms (t-MN), that leads to a significant downregulation of the deleted genes, including ASNS...
December 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/29296959/somatic-mutations-in-children-with-gata2-associated-myelodysplastic-syndrome-who-lack-other-features-of-gata2-deficiency
#5
Kevin E Fisher, Amy P Hsu, Christopher L Williams, Hadi Sayeed, Brian Y Merritt, M Tarek Elghetany, Steven M Holland, Alison A Bertuch, Maria Monica Gramatges
Approximately 10% of children with primary myelodysplastic syndrome (MDS) have germ line GATA2 mutations, leading to the proposal that all children with primary MDS and certain cytogenetic findings, including monosomy 7, be tested for germ line GATA2 mutations regardless of family history or other clinical features associated with GATA2 deficiency. In adults with familial GATA2-MDS, those with somatic mutations in ASXL1 experience rapid disease progression to acute myeloid leukemia (AML) and poor prognosis after stem cell transplantation; however, the prevalence of somatic mutations in primary pediatric GATA2-MDS is unclear...
February 28, 2017: Blood Advances
https://www.readbyqxmd.com/read/29296780/interleukin-6-levels-predict-event-free-survival-in-pediatric-aml-and-suggest-a-mechanism-of-chemotherapy-resistance
#6
Alexandra M Stevens, Jennifer M Miller, Jaime O Munoz, Amos S Gaikwad, Michele S Redell
The tumor microenvironment can protect cancer cells from conventional anticancer therapies. Thus, targeting these protective mechanisms could eradicate therapy-resistant cancer cells and improve outcomes. Interleukin-6 (IL-6) provides extrinsic protection for several solid tumors and multiple myeloma. In pediatric acute myeloid leukemia (AML), IL-6-induced STAT3 signaling frequently becomes stronger at relapse, and increases in IL-6-induced STAT3 activity are associated with inferior survival after relapse...
August 8, 2017: Blood Advances
https://www.readbyqxmd.com/read/29286570/identifying-patient-and-family-centered-outcomes-relevant-to-inpatient-versus-at-home-management-of-neutropenia-in-children-with-acute-myeloid-leukemia
#7
Julia E Szymczak, Kelly D Getz, Rachel Madding, Brian Fisher, Elizabeth Raetz, Nobuko Hijiya, Maria M Gramatges, Meret Henry, Amir Mian, Staci D Arnold, Catherine Aftandilian, Anderson B Collier, Richard Aplenc
Efficacy of therapeutic strategies relative to patient- and family-centered outcomes in pediatric oncology must be assessed. We sought to identify outcomes important to children with acute myeloid leukemia and their families related to inpatient versus at-home management of neutropenia. We conducted qualitative interviews with 32 children ≥8 years old and 54 parents. Analysis revealed the impact of neutropenia management strategy on siblings, parent anxiety, and child sleep quality as being outcomes of concern across respondents...
December 29, 2017: Pediatric Blood & Cancer
https://www.readbyqxmd.com/read/29286559/high-incidence-of-acute-kidney-injury-during-chemotherapy-for-childhood-acute-myeloid-leukemia
#8
Liezl Du Plessis, Shahrad Rod Rassekh, Cherry Mammen
BACKGROUND/OBJECTIVES: Childhood acute myeloid leukemia (AML) is a rare and heterogeneous disease. Pediatric data on the epidemiology of acute kidney injury (AKI) in AML are limited. We report on the incidence of AKI in childhood AML and the risk factors associated with AKI episodes. METHODS: A retrospective cohort of 53 patients (≤18 years), with de novo AML, receiving chemotherapy over a 10-year period. All serum creatinine (SCr) levels during therapy-related hospitalizations were assessed to stage AKI episodes as per Kidney Disease: Improving Global Outcomes criteria...
December 29, 2017: Pediatric Blood & Cancer
https://www.readbyqxmd.com/read/29285951/seifem-2017-from-real-life-to-an-agreement-on-the-use-of-granulocyte-transfusions-and-colony-stimulating-factors-for-prophylaxis-and-treatment-of-infectious-complications-in-patients-with-hematologic-malignant-disorders
#9
Alessandro Busca, Simone Cesaro, Luciana Teofili, Mario Delia, Chiara Cattaneo, Marianna Criscuolo, Francesco Marchesi, Nicola Stefano Fracchiolla, Caterina Giovanna Valentini, Francesca Farina, Roberta Di Blasi, Lucia Prezioso, Angelica Spolzino, Anna Candoni, Maria Ilaria Del Principe, Luisa Verga, Annamaria Nosari, Franco Aversa, Livio Pagano
The rapid spread of severe infections mainly due to resistant pathogens, justifies the search for therapies aiming to restore immune functions severely compromised in patients with hematologic malignancies. Areas covered: The present review summarizes the current knowledge on the role of granulocyte transfusions and colony-stimulating factors as treatment strategy for hematologic patients with serious infectious complications. In addition, a survey among 21 hematologic centers, to evaluate the clinical practice for the use of G-CSF originator and biosimilars was performed...
December 29, 2017: Expert Review of Hematology
https://www.readbyqxmd.com/read/29239497/clinical-outcomes-of-unrelated-cord-blood-transplantation-in-children-with-malignant-and-non-malignant-diseases-multicenter-experience-in-china
#10
Xiangfeng Tang, Jianpei Fang, Jie Yu, Zhiguang Li, Jing Chen, Xin Sun, Yiping Zhu, Shaoyan Hu, Maoquan Qin, Yongmin Tang, Zuo Luan
This multicenter retrospective study included 184 children with malignant and non-malignant diseases who underwent UCBT between January 1998 and August 2012. The malignant disease group included 101 children with ALL, AML, CML, JMML, and MDS, and the non-malignant disease group included 83 children with PID, β-thalassemia, IMD BMF, and HLH. The median duration to neutrophil and platelet engraftment was 16 and 35 days in the malignant disease group vs 15 and 38 days in the non-malignant disease group. The cumulative incidence of grade II-IV aGVHD and cGVHD was 25...
December 14, 2017: Pediatric Transplantation
https://www.readbyqxmd.com/read/29229640/adverse-effects-of-intravenous-vancomycin-based-prophylaxis-during-therapy-for-pediatric-acute-myeloid-leukemia
#11
Yilun Sun, Rachael L Huskey, Li Tang, Hiroto Inaba, Aditya H Gaur, Raul Ribeiro, Jeffrey E Rubnitz, Joshua Wolf
Background Children and adolescents with acute myeloid leukemia (AML) are at risk of life-threatening bacterial infection, especially with viridans group streptococci. Primary antibacterial prophylaxis with vancomycin-based regimens reduces this risk, but might increase risk of renal or liver toxicity, or Clostridium difficile infection (CDI).Methods A retrospective review was conducted of patients treated for newly diagnosed AML at St. Jude Children's Research Hospital from 2002 to 2008. Nephrotoxicity was classified according to pediatric Risk, Injury, Failure, Loss, End Stage Renal Disease (RIFLE) criteria, and hepatotoxicity according to Common Terminology Criteria for Adverse Events criteria...
December 11, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/29227476/the-molecular-landscape-of-pediatric-acute-myeloid-leukemia-reveals-recurrent-structural-alterations-and-age-specific-mutational-interactions
#12
Hamid Bolouri, Jason E Farrar, Timothy Triche, Rhonda E Ries, Emilia L Lim, Todd A Alonzo, Yussanne Ma, Richard Moore, Andrew J Mungall, Marco A Marra, Jinghui Zhang, Xiaotu Ma, Yu Liu, Yanling Liu, Jaime M Guidry Auvil, Tanja M Davidsen, Patee Gesuwan, Leandro C Hermida, Bodour Salhia, Stephen Capone, Giridharan Ramsingh, Christian Michel Zwaan, Sanne Noort, Stephen R Piccolo, E Anders Kolb, Alan S Gamis, Malcolm A Smith, Daniela S Gerhard, Soheil Meshinchi
We present the molecular landscape of pediatric acute myeloid leukemia (AML) and characterize nearly 1,000 participants in Children's Oncology Group (COG) AML trials. The COG-National Cancer Institute (NCI) TARGET AML initiative assessed cases by whole-genome, targeted DNA, mRNA and microRNA sequencing and CpG methylation profiling. Validated DNA variants corresponded to diverse, infrequent mutations, with fewer than 40 genes mutated in >2% of cases. In contrast, somatic structural variants, including new gene fusions and focal deletions of MBNL1, ZEB2 and ELF1, were disproportionately prevalent in young individuals as compared to adults...
December 11, 2017: Nature Medicine
https://www.readbyqxmd.com/read/29227167/diagnosis-of-platelet-function-disorders-a-standardized-rational-and-modular-flow-cytometric-approach
#13
Oliver Andres, Katja Henning, Gabriele Strauß, Annerose Pflug, Georgi Manukjan, Harald Schulze
A high proportion of patients with mucocutaneous bleeding diathesis and suspected inherited or acquired platelet disorder remain without diagnosis even after comprehensive laboratory testing. Since flow cytometry allows investigation of resting and activated platelets on the single cell level by requiring only minimal amounts of blood, this method has become an important assay within the diagnostic algorithm, especially in pediatrics. We therefore developed a standardized and modular flow cytometric approach that contributes to clarify impaired platelet function in a rational step-by-step manner...
December 11, 2017: Platelets
https://www.readbyqxmd.com/read/29226854/diagnostic-and-prognostic-relevance-of-serum-mir-195-in-pediatric-acute-myeloid-leukemia
#14
Ze Hong, Rongrong Zhang, Haixiao Qi
BACKGROUND: MicroRNA-195 acts as a tumor suppressor in a variety of cancers. However, its clinical significance in pediatric acute myeloid leukemia (AML) remains largely undefined. OBJECTIVE: To investigate the diagnostic and prognostic relevance of miR-195 in this malignancy. METHODS: Expression levels of miR-195 in peripheral blood and bone marrow samples of patients with pediatric AML and normal controls were detected by real-time quantitative PCR...
November 27, 2017: Cancer Biomarkers: Section A of Disease Markers
https://www.readbyqxmd.com/read/29222240/old-and-new-tools-in-the-clinical-diagnosis-of-inherited-bone-marrow-failure-syndromes
#15
REVIEW
Allison H West, Jane E Churpek
Patients with inherited bone marrow failure syndromes (IBMFSs) classically present with specific patterns of cytopenias along with congenital anomalies and/or other physical features that are often recognizable early in life. However, increasing application of genomic sequencing and clinical awareness of subtle disease presentations have led to the recognition of IBMFS in pediatric and adult populations more frequently than previously realized, such as those with early onset myelodysplastic syndrome (MDS). Given the well-defined differences in clinical management needs and outcomes for aplastic anemia, acute myeloid leukemia, and MDS in patients with an IBMFS vs those occurring sporadically, as well as nonhematologic comorbidities in patients with IBMFSs, it is critical for hematologists to understand how to approach screening for the currently known IBMFSs...
December 8, 2017: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/29212418/clinical-characteristics-and-outcome-of-childhood-acute-promyelocitic-leukemia-apl-in-saudi-arabia-a-multicenter-saphos-leukemia-group-study
#16
Wasil Jastaniah, Abdulrahman Alsultan, Saad Al Daama, Walid Ballourah, Mohamed Bayoumy, Faisal Al-Anzi, Omar Al Shareef, Mohammed Burhan Abrar, Reem Al Sudairy, Ibrahim Al Ghemlas
BACKGROUND: Acute promyelocytic leukemia (APL) is a rare form of acute myelogenous leukemia (AML). Survival rates exceed 80% in developed countries. Successful treatments rely on all-trans retinoic acid with anthracycline-based chemotherapy. Availability of modern care and public knowledge play important roles in pediatric APL survival. METHOD: A cytogenetic diagnosis of APL was confirmed in 30 (14.5%) out of 207 children consecutively diagnosed with de novo AML between January 2005 and December 2012 at nine cancer care centers in Saudi Arabia...
December 7, 2017: Hematology (Amsterdam, Netherlands)
https://www.readbyqxmd.com/read/29209600/targeting-flt3-signaling-in-childhood-acute-myeloid-leukemia
#17
REVIEW
Amy N Sexauer, Sarah K Tasian
Acute myeloid leukemia (AML) is the second most common leukemia of childhood and is associated with high rates of chemotherapy resistance and relapse. Clinical outcomes for children with AML treated with maximally intensive multi-agent chemotherapy lag far behind those of children with the more common acute lymphoblastic leukemia, demonstrating continued need for new therapeutic approaches to decrease relapse risk and improve long-term survival. Mutations in the FMS-like tyrosine kinase-3 receptor gene (FLT3) occur in approximately 25% of children and adults with AML and are associated with particularly poor prognoses...
2017: Frontiers in Pediatrics
https://www.readbyqxmd.com/read/29201484/intracranial-myeloid-sarcoma-metastasis-mimicking-acute-subdural-hematoma
#18
Amandip S Gill, Rabina Gill, Paul Kaloostian, Dina Elias, John S Roufail, Aurora S Cruz, Panayiotis E Pelargos, Frank P K Hsu, Ronald C Kim, Robert E Ayer, Samer Ghostine
Myeloid sarcoma, a rare consequence of myeloproliferative disorders, is rarely seen in the central nervous system, most commonly in the pediatric population. Although there are a handful of case reports detailing initial presentation of CNS myeloid sarcoma in the adult population, we have been unable to find any reports of CNS myeloid sarcoma presenting as a large mass lesion in a herniating patient. Here, we present the case of a patient transferred to our facility for a very large subdural hematoma. Based on imaging characteristics, it was felt to be a spontaneous hematoma secondary to coagulopathy...
2017: Case Reports in Surgery
https://www.readbyqxmd.com/read/29200171/reduced-neutrophil-elastase-activity-and-neutrophil-extracellular-traps-in-pediatric-acute-myeloid-leukemia-may-increase-the-rate-of-infections
#19
Sivan Berger-Achituv, Ronit Elhasid
Data on the production of neutrophil extracellular traps (NETs) in leukemia patients are scant. Phagocytosis, hydrogen peroxide, neutrophil elastase and myeloperoxidase enzymatic activity as well as NETs formation were studied in 10 pediatric acute lymphoblastic leukemia and 7 pediatric acute myeloid leukemia (AML) patients after induction chemotherapy. Median neutrophil elastase activity and NETs formation were lower in AML versus acute lymphoblastic leukemia (41% vs. 90%, P=0.005 and 51% vs. 94%, P=0.008, respectively)...
December 1, 2017: Journal of Pediatric Hematology/oncology
https://www.readbyqxmd.com/read/29200163/therapy-related-acute-myeloid-leukemia-after-the-treatment-of-primary-solid-cancer-in-children-a-single-center-experience
#20
Kyung Taek Hong, Jung Yoon Choi, Che Ry Hong, Hyoung Jin Kang, Kyung Duk Park, Hee Young Shin
Therapy-related acute myeloid leukemia (t-AML) has a dismal prognosis and is one of the most frequent second malignant neoplasms which could be encountered by pediatric oncologists. Between October 2000 and September 2016, 16 patients who had primary solid tumors were diagnosed with t-AML at the Seoul National University Children's Hospital. The median patient age at the time of diagnosis of their primary solid tumors was 9.6 years (range, 0.1 to 15.4 y), and that of t-AML was 14.0 years (range, 4.7 to 23...
December 1, 2017: Journal of Pediatric Hematology/oncology
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