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Pediatric leukemias

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https://www.readbyqxmd.com/read/29334537/isolated-central-nervous-system-chloroma-as-a-presenting-sign-of-relapsed-pediatric-acute-lymphoblastic-leukemia
#1
Jessica L Heath, Waitman K Aumann, Charles M Maxfield, Daniel S Wechsler
Central nervous system (CNS) chloromas are an exceedingly rare presentation of CNS relapse in acute lymphoblastic leukemia (ALL). We report a relapsed ALL patient who presented with 2 separate chloromas and cerebrospinal fluid lymphoblastocytosis, and outline a treatment plan of systemic chemotherapy and CNS-directed radiation therapy. A review of the literature indicates that multiagent chemotherapy combined with CNS radiotherapy is effective, with hematopoietic stem cell transplantation used in half of reported cases...
January 12, 2018: Journal of Pediatric Hematology/oncology
https://www.readbyqxmd.com/read/29334534/symptomatic-hyperammonemia-with-erwinia-chrysanthemi-derived-asparaginase-in-pediatric-leukemia-patients
#2
Nathan Gossai, Michael Richards, Lara Boman, Yoav Messinger, Sara Gernbacher, Joanna Perkins, Bruce Bostrom
Erwinia chrysanthemi-derived asparaginase is increasingly integral to acute lymphoblastic leukemia therapy. In our series, 16% of patients developed symptomatic hyperammonemia following Erwinia administration with symptoms including refractory nausea, vomiting, profound fatigue, malaise, and coma. This series of patients receiving Erwinia indicates higher than expected incidence of hyperammonemia, correlation between ammonia and asparaginase levels and therapeutic asparaginase activity levels despite dose reduction...
January 12, 2018: Journal of Pediatric Hematology/oncology
https://www.readbyqxmd.com/read/29334255/ngs-based-methylation-profiling-differentiates-tcf3-hlf-and-tcf3-pbx1-positive-b-cell-acute-lymphoblastic-leukemia
#3
Priyadarshini Kachroo, Silke Szymczak, Femke-Anouska Heinsen, Michael Forster, Jörn Bethune, Georg Hemmrich-Stanisak, Lewis Baker, Martin Schrappe, Martin Stanulla, Andre Franke
AIM: To determine whether methylation differences between mostly fatal TCF3-HLF and curable TCF3-PBX1 pediatric acute lymphoblastic leukemia subtypes can be associated with differential gene expression and remission. MATERIALS & METHODS: Five (extremely rare) TCF3-HLF versus five (very similar) TCF3-PBX1 patients were sampled before and after remission and analyzed using reduced representation bisulfite sequencing and RNA-sequencing. RESULTS: We identified 7000 differentially methylated CpG sites between subtypes, of which 78% had lower methylation levels in TCF3-HLF...
January 15, 2018: Epigenomics
https://www.readbyqxmd.com/read/29333004/drosha-rs642321-polymorphism-influence-susceptibility-to-childhood-acute-lymphoblastic-leukemia-a-preliminary-report
#4
Mohammad Hashemi, Seyed-Shahaboddin Hasani, Majid Naderi
Introduction: It has been well known that the microRNA biogenesis is involved in the pathogenesis of various diseases. We investigated the possible association between DROSHA rs642321 variant and risk of acute lymphocytic leukemia (ALL). Materials and Methods: We genotyped 75 children diagnosed with ALL and 115 age- and sex-matched children with no history of cancer of any type (as the control group) by the tetra amplification refractory mutation system-polymerase chain reaction...
October 2017: Indian Journal of Medical and Paediatric Oncology
https://www.readbyqxmd.com/read/29330417/high-stap1-expression-in-dux4-rearranged-cases-is-not-suitable-as-therapeutic-target-in-pediatric-b-cell-precursor-acute-lymphoblastic-leukemia
#5
Elisabeth M P Steeghs, Marjolein Bakker, Alex Q Hoogkamer, Judith M Boer, Quirine J Hartman, Femke Stalpers, Gabriele Escherich, Valerie de Haas, Hester A de Groot-Kruseman, Rob Pieters, Monique L den Boer
Approximately 25% of the pediatric B-cell precursor acute lymphoblastic leukemia (BCP-ALL) cases are genetically unclassified. More thorough elucidation of the pathobiology of these genetically unclassified ('B-other') cases may identify novel treatment options. We analyzed gene expression profiles of 572 pediatric BCP-ALL cases, representing all major ALL subtypes. High expression of STAP1, an adaptor protein downstream of the B-cell receptor (BCR), was identified in BCR-ABL1-like and non-BCR-ABL1-like B-other cases...
January 12, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29325825/-thromboembolic-disease-in-pediatric-oncology
#6
A Theron, C Biron-Andreani, S Haouy, L Saumet, M Saguintah, E Jeziorski, N Sirvent
The survival rate of children with cancer is now close to 80 %, as a result of continuous improvement in diagnostic and treatment procedures. Prevention and treatment of treatment-associated complications is now a major challenge. Thromboembolic venous disease, due to multifactorial pathogenesis, is a frequent complication (up to 40 % asymptomatic thrombosis in children with cancer), responsible for significant morbidity. Predominantly in children with acute lymphoblastic leukemia, lymphoma, or sarcoma, thromboembolic disease justifies primary prophylaxis in certain populations at risk, whether genetic or environmental...
January 8, 2018: Archives de Pédiatrie: Organe Officiel de la Sociéte Française de Pédiatrie
https://www.readbyqxmd.com/read/29319209/effectiveness-of-antibacterial-prophylaxis-during-induction-chemotherapy-in-children-with-acute-lymphoblastic-leukemia
#7
M L Sulis, T M Blonquist, K E Stevenson, S K Hunt, S Kay-Green, U H Athale, L A Clavell, P D Cole, K M Kelly, C Laverdiere, J M Leclerc, B Michon, M A Schorin, J G Welch, D S Neuberg, S E Sallan, L B Silverman
BACKGROUND: Pediatric patients receiving induction chemotherapy for newly diagnosed acute lymphoblastic leukemia (ALL) are at high risk of developing life-threatening infections. We investigated whether uniform antibacterial guidelines, including mandatory antibacterial prophylaxis in afebrile patients during induction, decreases the incidence of microbiologically documented bacteremia. METHODS: Between 2012 and 2015, 230 patients with newly diagnosed ALL (aged 1-21) were enrolled on Dana-Farber Cancer Institute ALL Consortium Protocol 11-001 (DFCI 11-001)...
January 10, 2018: Pediatric Blood & Cancer
https://www.readbyqxmd.com/read/29314654/exercise-program-for-children-and-adolescents-with-leukemia-and-lymphoma-during-treatment-a-comprehensive-review
#8
REVIEW
Giulia Zucchetti, Francesca Rossi, Carolina Chamorro Vina, Nicoletta Bertorello, Franca Fagioli
An exercise program (EP) during cancer treatment seems to be a valid strategy against physiological and quality-of-life impairments, but scientific evidence of benefits among pediatric patients is still limited. This review summarizes the literature focused on randomized controlled trials of EP offered to patients during leukemia and lymphoma treatment. Studies published up to June 2017 were selected from multiple databases and assessed by three independent reviewers for methodological validity. The review identified eight studies, but several types of bias have to be avoided to provide evidence-based recommendations accessible to patients, families, and professionals...
January 4, 2018: Pediatric Blood & Cancer
https://www.readbyqxmd.com/read/29305692/cd99-at-the-crossroads-of-physiology-and-pathology
#9
REVIEW
Michela Pasello, Maria Cristina Manara, Katia Scotlandi
CD99 is a cell surface protein with unique features and only partly defined mechanisms of action. This molecule is involved in crucial biological processes, including cell adhesion, migration, death, differentiation and diapedesis, and it influences processes associated with inflammation, immune responses and cancer. CD99 is frequently overexpressed in many types of tumors, particularly pediatric tumors including Ewing sarcoma and specific subtypes of leukemia. Engagement of CD99 induces the death of malignant cells through non-conventional mechanisms...
January 6, 2018: Journal of Cell Communication and Signaling
https://www.readbyqxmd.com/read/29305553/preclinical-efficacy-of-daratumumab-in-t-cell-acute-lymphoblastic-leukemia-t-all
#10
Karen L Bride, Tiffaney L Vincent, Soo-Yeon Im, Richard Aplenc, David M Barrett, William L Carroll, Robin Carson, Yunfeng Dai, Meenakshi Devidas, Kimberly P Dunsmore, Tori Fuller, Tina Glisovic-Aplenc, Terzah M Horton, Stephen P Hunger, Mignon L Loh, Shannon L Maude, Elizabeth A Raetz, Stuart S Winter, Stephan A Grupp, Michelle L Hermiston, Brent L Wood, David T Teachey
As a consequence of acquired or intrinsic disease resistance, the prognosis for patients with relapsed or refractory T-cell acute lymphoblastic leukemia (T-ALL) is dismal. Novel, less toxic drugs are clearly needed. One of the most promising emerging therapeutic strategies for cancer treatment is targeted immunotherapy. Immune therapies have improved outcomes for patients with other hematologic malignancies including B-ALL, however no immune therapy has been successfully developed for T-ALL. We hypothesize targeting CD38 will be effective against T-ALL...
January 5, 2018: Blood
https://www.readbyqxmd.com/read/29299118/identification-of-a-cytogenetic-and-molecular-subgroup-of-acute-myeloid-leukemias-showing-sensitivity-to-l-asparaginase
#11
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
#12
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/29296818/genetic-association-with-b-cell-acute-lymphoblastic-leukemia-in-allogeneic-transplant-patients-differs-by-age-and-sex
#13
Alyssa I Clay-Gilmour, Theresa Hahn, Leah M Preus, Kenan Onel, Andrew Skol, Eric Hungate, Qianqian Zhu, Christopher A Haiman, Daniel O Stram, Loreall Pooler, Xin Sheng, Li Yan, Qian Liu, Qiang Hu, Song Liu, Sebastiano Battaglia, Xiaochun Zhu, AnneMarie W Block, Sheila N J Sait, Ezgi Karaesmen, Abbas Rizvi, Daniel J Weisdorf, Christine B Ambrosone, David Tritchler, Eva Ellinghaus, David Ellinghaus, Martin Stanulla, Jacqueline Clavel, Laurent Orsi, Stephen Spellman, Marcelo C Pasquini, Philip L McCarthy, Lara E Sucheston-Campbell
The incidence and mortality rates of B-cell acute lymphoblastic leukemia (B-ALL) differ by age and sex. To determine if inherited genetic susceptibility contributes to these differences we performed 2 genome-wide association studies (GWAS) by age, sex, and subtype and subsequent meta-analyses. The GWAS included 446 B-ALL cases, and 3027 healthy unrelated blood and marrow transplant (BMT) donors as controls from the Determining the Influence of Susceptibility Conveying Variants Related to One-Year Mortality after BMT (DISCOVeRY-BMT) study...
September 12, 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
#14
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/29296717/homeobox-protein-tlx3-activates-mir-125b-expression-to-promote-t-cell-acute-lymphoblastic-leukemia
#15
Laurent Renou, Pierre-Yves Boelle, Caroline Deswarte, Salvatore Spicuglia, Aissa Benyoucef, Julien Calvo, Benjamin Uzan, Mohamed Belhocine, Agata Cieslak, Judith Landman-Parker, Andre Baruchel, Vahid Asnafi, Françoise Pflumio, Paola Ballerini, Irina Naguibneva
The oncogenic mechanisms driven by aberrantly expressed transcription factors in T-cell acute leukemia (T-ALL) are still elusive. MicroRNAs (miRNAs) play an important role in normal development and pathologies. Here, we examined the expression of 738 miRNA species in 41 newly diagnosed pediatric T-ALLs and in human thymus-derived cells. We found that expression of 2 clustered miRNAs, miR-125b/99a, peaks in primitive T cells and is upregulated in the T leukemia homeobox 3 (TLX3)-positive subtype of T-ALL. Using loss- and gain-of-function approaches, we established functional relationships between TLX3 and miR-125b...
May 9, 2017: Blood Advances
https://www.readbyqxmd.com/read/29288817/low-body-mass-index-is-associated-with-increased-risk-of-acute-gvhd-after-umbilical-cord-blood-transplantation-in-children-and-young-adults-with-acute-leukemia-a-study-on-behalf-of-eurocord-and-the-ebmt-pediatric-disease-working-party
#16
Annalisa Paviglianiti, Jean Hugues Dalle, Mouhab Ayas, Jan Jaap Boelens, Fernanda Volt, Anna Paola Iori, Mair Pedro de Souza, Miguel Angel Diaz, Gerard Michel, Franco Locatelli, Charlotte Jubert, Ibrahim Yakoub-Agha, Henrique Bittencourt, Yves Bertrand, Chantal Kenzey, Karina Tozatto Maio, Hiromi Hayashi, Vanderson Rocha, Peter Bader, Eliane Gluckman, Annalisa Ruggeri
Body mass index (BMI) might influence outcomes after allogeneic stem cell transplantation (HSCT). However, the impact of BMI on survival in children undergoing HSCT is not well defined, with conflicting results being reported on this issue. We analyzed 855 patients aged 2 to 20 years with diagnosis of acute leukemia who underwent umbilical cord blood transplantation (UCBT) from 1990 to 2015. Patients were classified according to BMI as normal (5th-85th percentile), underweight (<5th percentile), overweight (85th-95th percentile) and obese (>95th percentile) using growth charts for age and gender...
December 27, 2017: Biology of Blood and Marrow Transplantation
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
#17
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
#18
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
#19
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/29284681/a-novel-aggf1-pdgfr%C3%AE-fusion-in-pediatric-t-cell-acute-lymphoblastic-leukemia
#20
Matthew S Zabriskie, Orlando Antelope, Anupam R Verma, Lauren R Draper, Christopher A Eide, Anthony D Pomicter, Thai Hoa Tran, Brian J Druker, Jeffrey W Tyner, Rodney R Miles, James M Graham, Jae-Yeon Hwang, Katherine E Varley, Reha M Toydemir, Michael W Deininger, Elizabeth A Raetz, Thomas O'Hare
No abstract text is available yet for this article.
December 28, 2017: Haematologica
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