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pediatric aml

Mareike Rasche, Martin Zimmermann, Lisa Borschel, Jean-Pierre Bourquin, Michael Dworzak, Thomas Klingebiel, Thomas Lehrnbecher, Ursula Creutzig, Jan-Henning Klusmann, Dirk Reinhardt
Overall survival (OS) of pediatric patients with acute myeloid leukemia (AML) increased in recent decades. However, it remained unknown whether advances in first-line treatment, supportive care, or second-line therapy mainly contributed to this improvement. Here, we retrospectively analyzed outcome and clinical data of 1940 pediatric AML patients (younger than 18 years of age), enrolled in the population-based AML-BFM trials between 1987 and 2012. While 5-year probability of OS (pOS) increased from 49 ± 3% (1987-1992) to 76 ± 4% (2010-2012; p < 0...
February 22, 2018: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
Genki Yamato, Norio Shiba, Kenichi Yoshida, Yusuke Hara, Yuichi Shiraishi, Kentaro Ohki, Jun Okubo, Myoung-Ja Park, Manabu Sotomatsu, Hirokazu Arakawa, Nobutaka Kiyokawa, Daisuke Tomizawa, Souichi Adachi, Takashi Taga, Keizo Horibe, Satoru Miyano, Seishi Ogawa, Yasuhide Hayashi
No abstract text is available yet for this article.
March 14, 2018: Blood
Julie C Fitzgerald, Yimei Li, Brian T Fisher, Yuan-Shung Huang, Tamara P Miller, Rochelle Bagatell, Alix E Seif, Richard Aplenc, Neal J Thomas
OBJECTIVES: To evaluate hospital-level variability in resource utilization and mortality in children with new leukemia who require ICU support, and identify factors associated with variation. DESIGN: Retrospective cohort study. SETTING: Children's hospitals contributing to the Pediatric Health Information Systems administrative database from 1999 to 2011. PATIENTS: Inpatients less than 25 years old with newly diagnosed acute lymphocytic leukemia or acute myeloid leukemia requiring ICU support (n = 1,754)...
March 9, 2018: Pediatric Critical Care Medicine
José Carlos Jaime-Pérez, José Ramón Padilla-Medina, Lucía Teresa Fernández, José Luis Herrera-Garza, César Homero Gutiérrez-Aguirre, Luz Tarín-Arzaga, David Gómez-Almaguer
INTRODUCTION: The outcomes for adolescents and young adults (AYAs) with acute myeloid leukemia (AML) have been poorly characterized in Hispanics in low- to middle-income countries. The results are influenced by biologic and socioeconomic factors. The clinical paths for AYA patients with AML are reported. PATIENTS AND METHODS: A retrospective analysis of AYA and pediatric AML patients aged 1 to 39 years during 2003 to 2016 from a single reference center in Northeast Mexico treated with a 7+3 standard protocol was performed...
February 8, 2018: Clinical Lymphoma, Myeloma & Leukemia
Emily Y Jen, Chia-Wen Ko, Jee Eun Lee, Pedro L Del Valle, Antonina Aydanian, Charles Jewell, Kelly J Norsworthy, Donna Przepiorka, Lei Nie, Jiang Liu, Christopher M Sheth, Marjorie Shapiro, Ann T Farrell, Richard Pazdur
On September 1, 2017, FDA granted approval for gemtuzumab ozogamicin (GO) (Mylotarg; Pfizer, Inc) in combination with daunorubicin and cytarabine (DA) and as a monotherapy for the treatment of adult patients with newly-diagnosed CD33-positive acute myeloid leukemia (AML). GO is a CD33-targeted antibody-drug conjugate joined to calicheamicin. Approval of GO combination treatment was based on a randomized trial of 271 patients with newly-diagnosed AML treated with DA with or without 3 mg/m2 fractionated GO, which resulted in an event-free survival (EFS) of 13...
February 23, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
M Begum, A Islam, A A Rahman, M Akter, S T Alam, R Tasmeen
Acute leukemias are the most common child hood malignancy, of which acute myeloid leukemia (AML) are 15 to 20%. Abandonment is one of the most important causes of treatment failure in AML in developing countries. Lost to follow-up is also a big problem in low income countries. Many patients stop therapy soon after diagnosis due to cost, distance and ignorance. To determine the abandonment, outcome and treatment related mortality (TRM) and morbidity among children with AML. This prospective observational study was conducted in the Department of Pediatric hematology and Oncology, Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka from February 2013 to January 2014...
January 2018: Mymensingh Medical Journal: MMJ
Pei-Fang Xiao, Yan-Fang Tao, Shao-Yan Hu, Lan Cao, Jun Lu, Jian Wang, Xing Feng, Jian Pan, Yi-Huan Chai
Histone modification is dysregulated in various types of cancers, including hematological malignancies. However, the expression profile of histone-modifying enzymes in pediatric acute monoblastic leukemia (AML FAB M5) has not been investigated. In this study, we evaluated the mRNA expression profile of 85 genes that encode enzymes involved in histone-modification in 27 pediatric AML FAB M5 samples by using a novel real-time PCR array. We obtained a gene cluster consisting of a total of 28 genes (15 up-regulated genes and 13 down-regulated genes)...
March 1, 2017: Die Pharmazie
Özlem Tüfekçi, Melek Erdem, Hale Ören, Şebnem Yilmaz
Cup-like phenotype is defined in some subtypes of acute myeloid leukemia (AML) and have been associated with NPM-1 and/or FLT3-ITD positivity in the presence of normal karyotype in >60% of patients. Herein we present two pediatric AML-M1 patients with cuplike nuclear morphology and NPM-1 positivity. Both patients were negative for FLT3-ITD mutation. NPM-1 mutation and FLT3-ITD mutation should be kept in mind in AML patients with cup-like blast morphology as these two mutations are important molecular markers for prognosis, risk group classification and also for response to treatment...
February 9, 2018: Journal of Pediatric Hematology/oncology
Raj Bhayadia, Kathrin Krowiorz, Nadine Haetscher, Razan Jammal, Stephan Emmrich, Askar Obulkasim, Jan Fiedler, Adrian Schwarzer, Arefeh Rouhi, Michael Heuser, Susanne Wingert, Sabrina Bothur, Konstanze Döhner, Tobias Mätzig, Michelle Ng, Dirk Reinhardt, Hartmut Döhner, C Michel Zwaan, Marry van den Heuvel Eibrink, Dirk Heckl, Maarten Fornerod, Thomas Thum, R Keith Humphries, Michael A Rieger, Florian Kuchenbauer, Jan-Henning Klusmann
Purpose Dysregulated microRNAs are implicated in the pathogenesis and aggressiveness of acute myeloid leukemia (AML). We describe the effect of the hematopoietic stem-cell self-renewal regulating miR-193b on progression and prognosis of AML. Methods We profiled miR-193b-5p/3p expression in cytogenetically and clinically characterized de novo pediatric AML (n = 161) via quantitative real-time polymerase chain reaction and validated our findings in an independent cohort of 187 adult patients. We investigated the tumor suppressive function of miR-193b in human AML blasts, patient-derived xenografts, and miR-193b knockout mice in vitro and in vivo...
February 12, 2018: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
Mathieu Roussy, Mélanie Bilodeau, Loubna Jouan, Pauline Tibout, Louise Laramée, Emmanuelle Lemyre, Sophie Cardin, Camille Sauvageau, Françoise Couture, Aurélien Choblet, Natalie Patey, Patrick Gendron, Michel Duval, Pierre Teira, Josée Hébert, Brian T Wilhelm, John K Choi, Tanja A Gruber, Henrique Bittencourt, Sonia Cellot
The advent of large scale genomic sequencing technologies significantly improved the molecular classification of acute megakaryoblastic leukaemia (AMKL). AMKL represents a subset (∼10%) of high fatality pediatric acute myeloid leukemia (AML). Recurrent and mutually exclusive chimeric gene fusions associated with pediatric AMKL are found in 60-70% of cases and include RBM15-MKL1, CBFA2T3-GLIS2, NUP98-KDM5A and MLL rearrangements. In addition, another 4% of AMKL harbor NUP98 rearrangements (NUP98r), with yet undetermined fusion partners...
February 10, 2018: Genes, Chromosomes & Cancer
Elena Zerkalenkova, Agnesa Panfyorova, Anna Kazakova, Pavel Baryshev, Larisa Shelihova, Irina Kalinina, Galina Novichkova, Michael Maschan, Aleksey Maschan, Yulia Olshanskaya
T(16;21)(p11;q22)/FUS-ERG is a rare but recurrent translocation in acute leukemias and in some types of solid tumors. Due to multiple types of FUS-ERG transcripts, PCR-based minimal residual disease detection is impeded. In this study, we evaluated a cohort of pediatric patients with t(16;21)(p11;q22)/FUS-ERG and revealed fusion gene breakpoints. We implemented next-generation sequencing (NGS) on long PCR amplicons for the detection of fusion genes with unknown partners or DNA breakpoints. That allowed us to describe different fusion variants of FUS/ERG in different patients and to detect MRD on both RNA and DNA levels...
February 9, 2018: Annals of Hematology
Jingbo Wang, Lei Yuan, Haoyu Cheng, Xinhong Fei, Yumin Yin, Jiangying Gu, Song Xue, Junbao He, Fan Yang, Xiaocan Wang, Yixin Yang, Weijie Zhang
There is an ongoing debate concerning the performance of salvaged allogeneic hematopoietic stem cell transplantation (allo-HSCT) in pediatric patients with acute refractory leukemia, in whom the prognosis is quite dismal. Few studies have ever been conducted on this subject. This may be partly due to missed opportunities by majority of the patients in such situations. To investigate the feasibility, evaluate the efficiency, and identify the prognostic factors of allo-HSCT in this sub-setting, the authors performed a single institution-based retrospective analysis...
January 9, 2018: Oncotarget
Kelly D Getz, Tamara P Miller, Alix E Seif, Yimei Li, Yuan-Shung V Huang, Brian T Fisher, Richard Aplenc
PURPOSE: A cohort of pediatric patients with AML treated at hospitals contributing to the Pediatric Health Information System was used to evaluate differences in opioid utilization by sex, age, race, and insurance. METHODS: Billing data were used to compute the prevalence of opioid exposure and to quantify rates of utilization among those exposed to opioids as days of use per 1000 inpatient days. Multivariable regressions were used to compare opioid prevalence, and rates of utilization among those exposed...
2018: PloS One
Chintan Vyas, Sandeep Jain, Gauri Kapoor
Therapy-related acute myeloid leukemia/myelodysplastic syndrome (t-AML/MDS) is a devastating late effect of cancer treatment. There is limited data on incidence of t-AML/MDS from India. We retrospectively studied pediatric t AML/MDS at our institute between January 1996 and December 2015. Among 1285 children, 8 patients developed t-AML with a median age of 15.5 years. Overall incidence of t-AML/MDS was 0.62% [0.99% (4/402) in solid tumours and 0.45% (4/883) in leukemia/lymphoma, P = 0.26] with 6390 patient years of follow up...
January 2018: Indian Journal of Hematology & Blood Transfusion
Agnieszka Zaucha-Prazmo, Jolanta Gozdzik, Robert Debski, Katarzyna Drabko, Elzbieta Sadurska, Jerzy R Kowalczyk
The aim of the study was to assess the risk of TRM in pediatric patients treated for malignant disorders with allogeneic HSCT, according to different risk factors. The treatment outcome was analyzed in 299 pediatric patients treated in pediatric transplant departments from 2006 to 2015. To compare the outcome, patients were analyzed all together and in groups according to the diagnosis, age at transplant, donor type, disease status, stem cell source, and pediatric TRM score. At the end of the observation time, 82 patients were alive, 82 died, of which 40 due to transplant-related reasons...
February 3, 2018: Pediatric Transplantation
Erin L Marcotte, Michaela Richardson, Michelle Roesler, Logan G Spector
BACKGROUND: Studies have reported increased risks of pediatric acute lymphoblastic leukemia (ALL) among children born by cesarean delivery (CD). However, no previous study has examined the impact of CD on risk of infant leukemia specifically. METHODS: 443 infants diagnosed with acute leukemia, including both ALL and acute myeloid leukemia (AML), were identified at Children's Oncology Group institutions between January 1996 and December 2006. 324 controls frequency matched by year of birth were identified though random digit dialing and random selection from US birth registries...
January 22, 2018: Cancer Epidemiology, Biomarkers & Prevention
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
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
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
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
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