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https://www.readbyqxmd.com/read/29156196/familial-myelodysplastic-syndrome-acute-myeloid-leukemia
#1
REVIEW
Jane E Churpek
A growing number of inherited genetic loci that contribute to myelodysplastic syndrome/acute myeloid leukemia (MDS/AML) development in both children as well as adults are rapidly being identified. In recognition of the clinical impact of this emerging field, the World Health Organization, National Comprehensive Cancer Network, and European LeukemiaNet have all added consideration of inherited predisposition to MDS/AML classification and management. Study of these disorders is providing unique insight into the biology of both sporadic and familial MDS/AML...
December 2017: Best Practice & Research. Clinical Haematology
https://www.readbyqxmd.com/read/29155426/cd22-targeted-car-t-cells-induce-remission-in-b-all-that-is-naive-or-resistant-to-cd19-targeted-car-immunotherapy
#2
Terry J Fry, Nirali N Shah, Rimas J Orentas, Maryalice Stetler-Stevenson, Constance M Yuan, Sneha Ramakrishna, Pamela Wolters, Staci Martin, Cindy Delbrook, Bonnie Yates, Haneen Shalabi, Thomas J Fountaine, Jack F Shern, Robbie G Majzner, David F Stroncek, Marianna Sabatino, Yang Feng, Dimiter S Dimitrov, Ling Zhang, Sang Nguyen, Haiying Qin, Boro Dropulic, Daniel W Lee, Crystal L Mackall
Chimeric antigen receptor (CAR) T cells targeting CD19 mediate potent effects in relapsed and/or refractory pre-B cell acute lymphoblastic leukemia (B-ALL), but antigen loss is a frequent cause of resistance to CD19-targeted immunotherapy. CD22 is also expressed in most cases of B-ALL and is usually retained following CD19 loss. We report results from a phase 1 trial testing a new CD22-targeted CAR (CD22-CAR) in 21 children and adults, including 17 who were previously treated with CD19-directed immunotherapy...
November 20, 2017: Nature Medicine
https://www.readbyqxmd.com/read/29155316/influence-of-age-on-acute-and-chronic-gvhd-in-children-receiving-hla-identical-sibling-bmt-for-acute-leukemia-implications-for-prophylaxis
#3
Muna Qayed, Tao Wang, Michael T Hemmer, Stephen Spellman, Mukta Arora, Daniel Couriel, Amin Alousi, Joseph Pidala, Hisham Abdel-Azim, Mahmoud Aljuf, Mouhab Ayas, Menachem Bitan, Mitchell Cairo, Sung Won Choi, Christopher Dandoy, David Delgado, Robert Peter Gale, Gregory Hale, Haydar Frangoul, Rammurti T Kamble, Mohamed Kharfan-Dabaja, Leslie Lehman, John Levine, Margaret MacMillan, David I Marks, Taiga Nishihori, Richard F Olsson, Peiman Hematti, Olov Ringden, Ayman Saad, Prakash Satwani, Bipin N Savani, Kirk R Schultz, Sachiko Seo, Shalini Shenoy, Edmund K Waller, Lolie Yu, Mary M Horowitz, John Horan
Relapse remains the major cause of mortality post hematopoietic cell transplantation (HCT) for pediatric acute leukemia. Previous research suggests that reducing the intensity of calcineurin inhibitor based graft versus host disease (GVHD) prophylaxis may be an effective strategy in abrogating the risk of relapse in pediatric patients undergoing matched sibling donor (MSD) HCT. We reasoned that benefits of this strategy could be maximized by selectively applying it to those patients least likely to develop GVHD...
November 16, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/29150106/reactions-related-to-asparaginase-infusion-in-a-10-year-retrospective-cohort
#4
Amanda Cabral Dos Santos, Marcelo Gerardin Poirot Land, Nathalia Peroni da Silva, Kelly Oliveira Santos, Elisangela da Costa Lima-Dellamora
INTRODUCTION: Although it is an essential component of the treatment of acute lymphoid leukemia in children, asparaginase causes adverse reactions that sometimes make it impossible to use it fully. Hypersensitivity reactions are the most frequent and may lead to early discontinuation of treatment. The present study aimed to investigate suspicions of adverse reactions during the infusion of asparaginase in a pediatric cohort. METHODS: A retrospective observational study was carried out at a university pediatric institute in the state of Rio de Janeiro...
October 2017: Revista Brasileira de Hematologia e Hemoterapia
https://www.readbyqxmd.com/read/29149980/incidence-of-infectious-complications-in-children-with-acute-lymphoblastic-leukemia-treated-with-hematopoietic-stem-cell-transplantation
#5
A Zaucha-Prażmo, J R Kowalczyk, K Drabko, K Czyżewski, J Goździk, O Zając-Spychała, J Wachowiak, J Frączkiewicz, E Gorczyńska, K Kałwak, J Styczyński
OBJECTIVE: We analyzed incidence and profile of infections in children with acute lymphoblastic leukemia (ALL) treated with hematopoietic stem cell transplantation (HSCT) in Polish pediatric HSCT departments, over a 2-year period. PATIENTS AND METHODS: Hospital records of 67 patients, who underwent allogeneic HSCT for ALL, were analyzed retrospectively for microbiologically documented infection: bacterial infection (BI), viral infection (VI), and fungal infection (FI)...
November 2017: Transplantation Proceedings
https://www.readbyqxmd.com/read/29143289/agents-in-development-for-childhood-acute-lymphoblastic-leukemia
#6
REVIEW
Kelly W Maloney, Lia Gore
Acute lymphoblastic leukemia (ALL) is the most common cancer in childhood. Standard chemotherapy has afforded outstanding outcomes for many patients; however, there remain some sub-groups with high-risk features, refractory disease, and patients that  relapse who have a poor prognosis with conventional treatments. Over the past decade, there have been significant advances in newer treatment options, including improved monoclonal antibody therapies, T cell engagers, and chimeric antigen T-cell receptor products, all of which have changed the landscape for patients who relapse...
November 15, 2017: Paediatric Drugs
https://www.readbyqxmd.com/read/29141316/-a-clinical-analysis-of-micafungin-treatment-of-pulmonary-invasive-fungal-infection-in-pediatric-patients-with-acute-leukemia-or-post-hematopoietic-stem-cells-transplantation
#7
K Huang, K Y Qiu, L L Deng, J P Fang, Y Li, H X Guo, D H Zhou
Objective: To investigate the efficacy and safety of micafungin (MCF) for pulmonary invasive fungal disease (PIFD) in pediatric patients with acute leukemia or post hematopoietic stem cells transplantation. Method: Twenty-five neutropenic PIFD children with acute leukemia or post hematopoietic stem cells transplantation in Sun Yat-sen Memorial Hospital of Sun Yat-sen University were selected from January 2012 to June 2015, including 12 males and 13 females, age range 2-15 (average 6.2±2.0) years. There were 12 cases of acute leukemia (AL) after chemotherapy, 4 cases of acute leukemia (AL) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) and 9 cases of β-thalassemia major after allo-HSCT...
November 2, 2017: Zhonghua Er Ke za Zhi. Chinese Journal of Pediatrics
https://www.readbyqxmd.com/read/29140934/response-of-symptomatic-persistent-chronic-disseminated-candidiasis-to-corticosteroid-therapy-in-immunosuppressed-pediatric-patients-case-study-and-review-of-the-literature
#8
Vered Shkalim-Zemer, Itzhak Levi, Salvador Fischer, Hannah Tamary, Joanne Yakobovich, Gali Avrahami, Gil Gilad, Sara Elitzur, Isaac Yaniv, Ronit Elhasid, Michal Manistersky, Itamar Shalit
BACKGROUND: Chronic disseminated candidiasis (CDC) is a severe invasive fungal infection principally observed during neutrophil recovery in patients with acute leukemia treated with intensive chemotherapy. Its pathophysiology remains unclear. We describe the management of six children with symptomatic CDC who did not respond to antifungal therapy. METHODS: The databases of the hematology-oncology departments of two tertiary pediatric medical centers were searched for all patients diagnosed with CDC from 2003 to 2015 who responded to corticosteroids after failing antifungal therapy...
November 14, 2017: Pediatric Infectious Disease Journal
https://www.readbyqxmd.com/read/29132472/-research-progress-in-ph-like-childhood-acute-lymphoblastic-leukemia
#9
Xue Tang, Xia Guo
Philadelphia chromosome-like acute lymphoblastic leukemia (Ph-like ALL) is a subtype of B-lineage ALL (B-ALL) that displays a gene expression profile (GEP) similar to Philadelphia chromosome-positive ALL (Ph(+) ALL). It has a diverse range of genetic alterations that activate cytokine receptor genes and kinase signaling pathways, frequently accompanied by abnormal transcription factors related to lymphatic development. Children with Ph-like ALL account for 15% of children with high-risk B-ALL. It has adverse clinical features and a poor prognosis...
November 2017: Zhongguo Dang Dai Er Ke za Zhi, Chinese Journal of Contemporary Pediatrics
https://www.readbyqxmd.com/read/29129488/dna-hypomethylating-agents-as-epigenetic-therapy-before-and-after-allogeneic-hematopoietic-stem-cell-transplantation-in-myelodysplastic-syndromes-and-juvenile-myelomonocytic-leukemia
#10
REVIEW
Christian Flotho, Sebastian Sommer, Michael Lübbert
Myelodysplastic syndrome (MDS) is a clonal bone marrow disorder, typically of older adults, which is characterized by ineffective hematopoiesis, peripheral blood cytopenias and risk of progression to acute myeloid leukemia. Juvenile myelomonocytic leukemia (JMML) is an aggressive myeloproliferative neoplasm occurring in young children. The common denominator of these malignant myeloid disorders is the limited benefit of conventional chemotherapy and a particular responsiveness to epigenetic therapy with the DNA-hypomethylating agents 5-azacytidine (azacitidine) or decitabine...
November 9, 2017: Seminars in Cancer Biology
https://www.readbyqxmd.com/read/29125853/whole-genome-dna-methylation-characteristics-in-pediatric-precursor-b-cell-acute-lymphoblastic-leukemia-bcp-all
#11
Radosław Chaber, Artur Gurgul, Grażyna Wróbel, Olga Haus, Anna Tomoń, Jerzy Kowalczyk, Tomasz Szmatoła, Igor Jasielczuk, Blanka Rybka, Renata Ryczan-Krawczyk, Ewa Duszeńko, Sylwia Stąpor, Krzysztof Ciebiera, Sylwia Paszek, Natalia Potocka, Christopher J Arthur, Izabela Zawlik
In addition to genetic alterations, epigenetic abnormalities have been shown to underlie the pathogenesis of acute lymphoblastic leukemia (ALL)-the most common pediatric cancer. The purpose of this study was to characterize the whole genome DNA methylation profile in children with precursor B-cell ALL (BCP ALL) and to compare this profile with methylation observed in normal bone marrow samples. Additional efforts were made to correlate the observed methylation patterns with selected clinical features. We assessed DNA methylation from bone marrow samples obtained from 38 children with BCP ALL at the time of diagnosis along with 4 samples of normal bone marrow cells as controls using Infinium MethylationEPIC BeadChip Array...
2017: PloS One
https://www.readbyqxmd.com/read/29120974/plasma-7-hydroxymethotrexate-levels-versus-methotrexate-to-predict-delayed-elimination-in-children-receiving-high-dose-methotrexate
#12
Nicolas Fabresse, Bénédicte Devictor, Christel Pissier, Hervé Chambost, Bruno Lacarelle, Gérard Michel, Caroline Solas
BACKGROUND: The aim of this study was to investigate the correlation between 7-hydroxymethotrexate (7-OHMTX) and creatinine and to evaluate the predictive value of 7-OHMTX levels on delayed elimination at 24 and 48 hours. In addition, differences in methotrexate (MTX), 7-OHMTX levels, and MTX metabolism using the ratio MTX/7-OHMTX were determined according to age. METHODS: The authors included a total of 106 cycles, corresponding to 33 patients (mean age: 9.8 years, range: 2-18 years) suffering from acute lymphoblastic leukemia, non-Hodgkin lymphoma and osteosarcoma and receiving high-dose MTX (HD-MTX)...
November 8, 2017: Therapeutic Drug Monitoring
https://www.readbyqxmd.com/read/29115886/severe-pegaspargase-hypersensitivity-reaction-rates-grade-%C3%A2-3-with-intravenous-infusion-vs-intramuscular-injection-analysis-of-54-280-doses-administered-to-16-534-patients-on-children-s-oncology-group-cog-clinical-trials
#13
Michael J Burke, Meenakshi Devidas, Kelly Maloney, Anne Angiolillo, Reuven Schore, Kimberly Dunsmore, Eric Larsen, Len A Mattano, Wanda Salzer, Stuart S Winter, William Carroll, Naomi J Winick, Mignon L Loh, Elizabeth Raetz, Stephen P Hunger, Archie Bleyer
PEGylated asparaginase (pegaspargase) can be administered via intramuscular (IM) injection or intravenous (IV) infusion with a hypersensitivity reaction (HSR) incidence ranging 3-41%. We evaluated grade ≥3 HSRs when given IM vs. IV on six Children's Oncology Group (COG) leukemia trials (2003-2015) to determine differences in HSR rates. 54,280 doses were administered to 16,534 patients. Considering all doses of pegaspargase during induction, consolidation, and delayed intensification, grade ≥3 HSR rate with IM injection was 5...
November 8, 2017: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/29114918/donor-age-determines-outcome-in-acute-leukemia-patients-over-40-undergoing-haploidentical-hematopoietic-cell-transplantation
#14
Jonathan Canaani, Bipin N Savani, Myriam Labopin, Xiao-Jun Huang, Fabio Ciceri, William Arcese, Yener Koc, Johanna Tischer, Didier Blaise, Zafer Gülbas, Maria Teresa Van Lint, Benedetto Bruno, Mohamad Mohty, Arnon Nagler
Haploidentical hematopoietic cell transplantation (haplo-HCT) is being increasingly used in acute leukemia patients as an alternative transplant modality when matched sibling or matched unrelated donors are unavailable. As several potential haploidentical relative donors are typically available for a given patient, optimizing donor selection to improve clinical outcome is crucial. The impact of donor age and kinship on the outcome of acute leukemia patients is not clearly established in this setting. Using the multinational registry of the acute leukemia working party of the European society for blood and marrow transplantation we retrospective analyzed the clinical outcome of 1270 acute myeloid leukemia and acute lymphoblastic leukemia patients who underwent haplo-HCT between 2005 and 2015...
November 8, 2017: American Journal of Hematology
https://www.readbyqxmd.com/read/29113332/lncrnas-downregulated-in-childhood-acute-lymphoblastic-leukemia-modulate-apoptosis-cell-migration-and-dna-damage-response
#15
Romain Gioia, Simon Drouin, Manon Ouimet, Maxime Caron, Pascal St-Onge, Chantal Richer, Daniel Sinnett
Childhood acute lymphoblastic leukemia (cALL) accounts for 25% of pediatric cancers and is one of the leading causes of disease-related death in children. Although long non-coding RNAs (lncRNAs) have been implicated in cALL etiology, progression, and treatment response, little is known about their exact functional role. We had previously sequenced the whole transcriptome of 56 cALL patients and identified lncRNA transcripts specifically silenced in tumoral cells. Here we investigated the impact of restoring the expression of three of these (RP11-624C23...
October 6, 2017: Oncotarget
https://www.readbyqxmd.com/read/29113211/aberrant-expression-of-cd133-and-cd82-in-patients-with-pediatric-acute-lymphoblastic-leukemia-and-the-clinical-significance
#16
Hongyan Ji, Li Chen, Yunpeng Dai, Xiaojun Sun, Xiuli Li, Qi Wang, Daoxin Ma, Dongdong Du, Ping Zhao, Yulin Wang
Cluster of differentiation (CD)133 is considered to be a marker of leukemia stem cells (LSCs), which are one of the primary causes of occurrence, drug resistance and relapse of acute lymphoblastic leukemia (ALL). CD82, an adhesion molecule, performs an important role in the interaction between LSCs and their niche. The purpose of the present study was to assess CD133 and CD82 expression in patients with pediatric ALL, and to evaluate the association with the clinical data. Using flow cytometric assessment and reverse transcription-polymerase chain reaction, CD133 and CD82 expression levels were measured in the bone marrow (BM) of 37 patients with newly diagnosed (ND) pediatric ALL [ALL-ND; 30 B-cell-ALL (B-ALL) and 7 T-cell-ALL (T-ALL)], in 22 patients with complete remission pediatric ALL (ALL-CR) and in 16 age-matched children without BM disease...
November 2017: Oncology Letters
https://www.readbyqxmd.com/read/29112230/longitudinal-analysis-of-quality-of-life-outcomes-in-children-during-treatment-for-acute-lymphoblastic-leukemia-a-report-from-the-children-s-oncology-group-aall0932-trial
#17
Daniel J Zheng, Xiaomin Lu, Reuven J Schore, Lyn Balsamo, Meenakshi Devidas, Naomi J Winick, Elizabeth A Raetz, Mignon L Loh, William L Carroll, Lillian Sung, Stephen P Hunger, Anne L Angiolillo, Nina S Kadan-Lottick
BACKGROUND: Children with average-risk acute lymphoblastic leukemia (AR-ALL) face many challenges that can adversely affect their quality of life (QOL). However, to the authors' knowledge, patterns and predictors of QOL impairment during therapy have not been well characterized to date. METHODS: Patients with AR-ALL who were enrolled on the Children's Oncology Group AALL0932 trial were offered participation in this prospective cohort study if they were aged ≥4 years at the time of diagnosis and had an English-speaking parent...
November 7, 2017: Cancer
https://www.readbyqxmd.com/read/29108313/skeletal-abnormalities-detected-by-spect-is-associated-with-increased-relapse-risk-in-pediatric-acute-lymphoblastic-leukemia
#18
Fen Zhou, Meiling Zhang, Juan Han, Jinjin Hao, Yan Xiao, Qin Liu, Runming Jin, Heng Mei
Objectives: Most children with acute lymphoblastic leukemia (ALL) exhibit skeletal abnormalities. This study aimed to investigate bone lesions detected by whole-body bone single-photon emission computed tomography (SPECT) and its prognostic value in children with ALL. Methods: A retrospective analysis was performed using whole-body bone SPECT scans obtained from children with ALL in our department between June 2008 and June 2012. A total of 166 children newly diagnosed with ALL were included, and the patients were divided into two groups: patients with positive and negative SPECT scans...
October 3, 2017: Oncotarget
https://www.readbyqxmd.com/read/29107745/respiratory-syncytial-virus-induces-nrf2-degradation-through-a-promyelocytic-leukemia-protein-ring-finger-protein-4-dependent-pathway
#19
Narayana Komaravelli, Maria Ansar, Roberto P Garofalo, Antonella Casola
Respiratory syncytial virus (RSV) is the most important cause of viral acute respiratory tract infections and hospitalizations in children, for which no vaccine or specific treatments are available. RSV causes airway mucosa inflammation and cellular oxidative damage by triggering production of reactive oxygen species and by inhibiting at the same time expression of antioxidant enzymes, via degradation of the transcription factor NF-E2-related factor 2 (NRF2). RSV infection induces NRF2 deacetylation, ubiquitination, and degradation through a proteasome-dependent pathway...
October 28, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/29106862/an-investigation-of-operative-outcomes-pediatric-invasive-fungal-sinusitis
#20
Curtis Hanba, Peter F Svider, Wanda Lai, Syed Naweed Raza, Anthony Sheyn, Jean Anderson Eloy, Adam J Folbe
OBJECTIVES/HYPOTHESIS: Invasive fungal sinusitis is an uncommon entity among children. Early recognition is crucial for facilitating successful treatment with minimal morbidity. The goal of this analysis was to identify patient characteristics associated with high-risk surgical disease through a population-based examination into this rare and deadly disease process. METHODS: A retrospective chart review of the 2009 and 2012 Kids' Inpatient Database (KID) was conducted...
November 2017: International Journal of Pediatric Otorhinolaryngology
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