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Childhood leukemia

Mervi Taskinen, Trausti Oskarsson, Mette Levinsen, Matteo Bottai, Marit Hellebostad, Olafur Gisli Jonsson, Päivi Lähteenmäki, Kjeld Schmiegelow, Mats Heyman
BACKGROUND: Central nervous system irradiation (CNS-RT) has played a central role in the cure of acute lymphoblastic leukemia (ALL), but due to the risk of long-term toxicity, it is now considered a less-favorable method of CNS-directed therapy. PROCEDURES: Retrospectively, we estimated the effect of CNS involvement and CNS-RT on events and overall survival (OS) in 835 children treated for high-risk ALL in the Nordic Society of Paediatric Haematology and Oncology (NOPHO) ALL-92 and ALL-2000 trials...
October 17, 2016: Pediatric Blood & Cancer
Anita F Oliveira, Aline Tansini, Daniel O Vidal, Luiz F Lopes, Konradin Metze, Irene Lorand-Metze
BACKGROUND: Immunophenotyping of bone marrow (BM) hemopoietic precursors is useful for diagnosis of adult myelodysplastic syndrome (MDS), but data concerning pediatric patients are limited. We analyzed immunophenotypic features of BM cells at diagnosis of children who were referred to the Brazilian Pediatric Cooperative Group of Myelodysplastic Syndromes. METHODS: Diagnosis was based on clinical information, peripheral blood counts, BM cytology and cytogenetics...
October 17, 2016: Pediatric Blood & Cancer
Yueqin Han, Yanping Zhu, Jinshen Wang, Yanqin Han, Daogang Qin, Qiaozhi Yang, Xiaojing Sun, Lijun Chen
OBJECTIVES: To investigate the efficacy of interleukin 11 (IL-11) towards the high dose methotrexate (HDMTX)-concurrent rat small intestinal mucositis and its impacts on the proliferation of the human T-lymphoblastic leukemia (CEM) cell line. MATERIALS AND METHODS: 95 Wistar rats were randomly divided into five groups, the normal control group (A), the methotrexate (MTX) control group (B), the IL-11-pre-treated high-dose group (C), the post-IL-11-treatment high-dose group (D) and the post-IL-11-treatment low-dose group (E)...
August 2016: Iranian Journal of Basic Medical Sciences
P Pardes-Chavanes, M Afanetti, C Boyer, M Poirée
Intracerebral hemorrhage (ICH) remains a cause of death in hematologic malignancies. Asparaginase represents a key agent in the treatment of acute lymphoblastic leukemia (ALL). The toxicity of asparaginase includes coagulopathy such as thrombotic or bleeding tendency. We report a case of fatal cerebral hemorrhage in a 12-year-old girl treated for ALL. Cerebral hemorrhage occurred after three injections of L-asparaginase. The patient presented with hypofibrinogenemia (0.36g/L), associated with thrombocytopenia (24,000/mm(3))...
October 12, 2016: Archives de Pédiatrie: Organe Officiel de la Sociéte Française de Pédiatrie
Marina Kunstreich, Sebastian Kummer, Hans-Juergen Laws, Arndt Borkhardt, Michaela Kuhlen
The morbidity and toxicity associated with current intensive treatment protocols for acute lymphoblastic leukemia in childhood become even more important as the vast majority of children can be cured and become long-term survivors. Osteonecrosis is one of the most common therapy-related and debilitating side effects of anti-leukemic treatment and can adversely affect long-term quality of life. Incidence and risk factors vary substantially between study groups and therapeutic regimens. We therefore analyzed 22 clinical trials of childhood acute lymphoblastic leukemia in terms of osteonecrosis incidence and risk factors...
October 14, 2016: Haematologica
Eva Rettinger, Michael Merker, Emilia Salzmann-Manrique, Hermann Kreyenberg, Thomas Krenn, Matthias Dürken, Jörg Faber, Sabine Huenecke, Claudia Cappel, Melanie Bremm, Andre Willasch, Shahrzad Bakhtiar, Andrea Jarisch, Jan Soerensen, Thomas Klingebiel, Peter Bader
Monitoring of minimal residual disease (MRD) or chimerism may help guide pre-emptive immunotherapy (IT) with a view to preventing relapse in childhood acute lymphoblastic leukemia (ALL) post-transplant. ALL-patients consecutively transplanted in Frankfurt/Main, Germany between January 1(st), 2005, and July 1(st), 2014, were included in this retrospective study. Chimerism monitoring was performed in all, MRD assessment in 58 of 89 patients. IT was guided in 19 of 24 patients with mixed chimerism (MC) and MRD and by MRD only in another 4 patients with complete chimerism (CC)...
October 11, 2016: Biology of Blood and Marrow Transplantation
Xiang Wang, Dongjian Zuo, Yufang Yuan, Xiaochun Yang, Ze Hong, Rongrong Zhang
PURPOSE: The aim of this study was to investigate roles of microRNA (miR)-183 in pediatric acute myeloid leukemia (AML). METHODS: miR-183 expression in bone marrow and patients' sera of childhood AML was detected by real-time quantitative PCR. Functions of miR-183 in malignant phenotypes of two leukemia cell lines were then evaluated. Additionally, putative targets of miR-183 were predicted using three miRNA target prediction algorithms and validated by luciferase reporter assay...
October 13, 2016: Journal of Cancer Research and Clinical Oncology
M-W Jin, S-M Xu, Q An, P Wang
OBJECTIVE: Leukemia is the most common cancer of childhood, with AML, CML, ALL and CLL being the most common. Environmental and genetic factors have been studied extensively in children with childhood leukemia. Other factors, such as the prenatal parental use of controlled substances, have not been investigated to the same degree. We review what is currently known about environmental and parental factors and the occurrence of leukemia in children. MATERIALS AND METHODS: Electronic databases were searched for studies correlated pediatric leukemia with (1) ionizing radiation; (2) benzene; (3) parental drug use (4) parental alcohol use; (5) genetic factors...
September 2016: European Review for Medical and Pharmacological Sciences
E Waanders, B Scheijen, M C J Jongmans, H Venselaar, S V van Reijmersdal, A H A van Dijk, A Pastorczak, R D A Weren, C E van der Schoot, M van de Vorst, E Sonneveld, N Hoogerbrugge, V H J van der Velden, B Gruhn, P M Hoogerbrugge, J J M van Dongen, A G van Kessel, F N van Leeuwen, R P Kuiper
The contribution of genetic predisposing factors to the development of pediatric acute lymphoblastic leukemia (ALL), the most frequently diagnosed cancer in childhood, has not been fully elucidated. Children presenting with multiple de novo leukemias are more likely to suffer from genetic predisposition. Here, we selected five of these patients and analyzed the mutational spectrum of normal and malignant tissues. In two patients, we identified germline mutations in TYK2, a member of the JAK tyrosine kinase family...
October 13, 2016: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
Stephen A Sands, Brian T Harel, Mirko Savone, Kara Kelly, Veena Vijayanathan, Jennifer Greene Welch, Lynda Vrooman, Lewis B Silverman, Peter D Cole
PURPOSE: Neurocognitive impairment is frequently observed among acute lymphoblastic leukemia (ALL) survivors within the domains of intelligence, attention, processing speed, working memory, learning, and memory. However, few have investigated treatment-induced changes in neurocognitive function during the first months of treatment. Additionally, dysfunction during treatment may be preceded by changes in biomarkers measured within cerebrospinal fluid (CSF). Identification of acute declines in neurocognitive function, as well as predictive genotypes or biomarkers, could guide therapeutic trials of protective interventions...
October 10, 2016: Supportive Care in Cancer: Official Journal of the Multinational Association of Supportive Care in Cancer
Prashant R Tembhare, Sitaram Ghogale, Nisha Ghatwai, Yajamanam Badrinath, Nikesh Kunder, Nikhil V Patkar, Asma R Bibi, Gaurav Chatterjee, Brijesh Arora, Gaurav Narula, Shripad Banawali, Nilesh Deshpande, Prathibha Amare, Sumeet Gujral, Papagudi G Subramanian
BACKGROUND: Multiparametric flow cytometry (MFC) is a popular technique for minimal residual disease (MRD) analysis. However, its applicability is still limited to 90% of B-cell precursor acute lymphoblastic leukemia (BCPALL) due to two major issues, i.e. a proportion of cases do not express adequate leukemia associated immunophenotype (LAIPs) with currently used markers and drug-induced antigen-modulation. Hence, the incorporation of additional reliable markers is required for the further improvement of MFC-based MRD evaluation...
October 7, 2016: Cytometry. Part B, Clinical Cytometry
Mareike Doerrenberg, Andreas Kloetgen, Kebria Hezaveh, Wilhelm Wössmann, Kirsten Bleckmann, Martin Stanulla, Martin Schrappe, Alice C McHardy, Arndt Borkhardt, Jessica I Hoell
For reasons not yet understood, nearly all infants with acute lymphoblastic leukemia (ALL) are diagnosed with the B-cell type, with T-ALL in infancy representing a very rare exception. Clinical and molecular knowledge about infant T-ALL is still nearly completely lacking and it is also still unclear whether it represents a distinct disease compared to childhood T-ALL. To address this, we performed exome sequencing of three infant cases, which enabled the detection of mutations in NOTCH2, NOTCH3, PTEN, and KRAS...
September 26, 2016: Genes, Chromosomes & Cancer
Ritva Ahomäki, Arja Harila-Saari, Jaakko Matomäki, Päivi M Lähteenmäki
BACKGROUND: In order to assess neurocognitive and social outcomes after childhood cancer, we explored the educational and vocational attainments of Finnish survivors in comparison to matched population controls. METHODS: From national registries, we identified survivors (n = 3243) born from 1960 to 1992 and aged below 16 at cancer diagnosis (years 1964-2009) as well as their controls (n = 16,215). Data on educational achievements, yearly income, employment status, and retirement were retrieved from Statistics Finland...
October 6, 2016: Journal of Cancer Survivorship: Research and Practice
Heidrun Boztug, Nora Mühlegger, Ulrike Pötschger, Andishe Attarbaschi, Christina Peters, Georg Mann, Michael Dworzak
Intensive chemotherapy directed against acute myeloid leukemia of childhood is followed by profound neutropenia and high risk for bacterial and fungal infections, including viridans group streptococci as a common cause for gram-positive septicemia. Few retrospective studies have shown the efficacy of various antibiotic prophylactic regimens in children. We retrospectively studied 50 pediatric patients treated on the AML-BFM 2004 protocol between 2005 and 2015 at St. Anna Children's Hospital and assessed the effect of antibiotic prophylaxis on the frequency of febrile neutropenia and bacterial sepsis...
October 4, 2016: Annals of Hematology
M Kato, S Ishimaru, M Seki, K Yoshida, Y Shiraishi, K Chiba, N Kakiuchi, Y Sato, H Ueno, H Tanaka, T Inukai, D Tomizawa, D Hasegawa, T Osumi, Y Arakawa, T Aoki, M Okuya, K Kaizu, K Kato, Y Taneyama, H Goto, T Taki, M Takagi, M Sanada, K Koh, J Takita, S Miyano, S Ogawa, A Ohara, M Tsuchida, A Manabe
In the treatment of childhood acute lymphoblastic leukemia (ALL), excess shortening of maintenance therapy resulted in high relapse rate, as shown by our previous trial, TCCSG L92-13, in which maintenance therapy was terminated at one year from initiation of treatment. In this study, we aimed to confirm the long-term outcome of L92-13, and to identify who can or cannot be cured by shorter duration of maintenance therapy. To obtain sentinel cytogenetics information which had been missed before, we performed genetic analysis with genomic microarray and target intron-capture sequencing from diagnostic bone marrow smear...
October 4, 2016: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
Lauren K Williams, Maria C McCarthy, Kylie Burke, Vicki Anderson, Nicole Rinehart
PURPOSE: Child emotional and behavioral problems constitute significant sequelae of acute lymphoblastic leukemia (ALL) treatment. The aims of this study were to a) examine the feasibility, acceptability and satisfaction of a parenting intervention amongst parents of children with ALL and b) explore whether participation in a parenting intervention shows promise for improvements in child behavior. METHODS: 12 parents with a child aged between 2 and 8 years receiving maintenance phase treatment for ALL participated in a phase 2 randomized controlled trial comparing eight weeks of group online participation in Triple P: Positive Parenting Program with no intervention...
October 2016: European Journal of Oncology Nursing: the Official Journal of European Oncology Nursing Society
Simone Hearps, Marc Seal, Vicki Anderson, Maria McCarthy, Madeleine Connellan, Peter Downie, Cinzia De Luca
Cognitive late-effects have been identified in patients treated with chemotherapy-only protocols for childhood acute lymphoblastic leukemia (ALL), yet the underlying neuropathology is not well understood. This review synthesized recent findings from eight articles investigating the relationship between neurocognitive and neuroimaging outcomes for patients treated for ALL with chemotherapy-only protocols. Reported cognitive domains, imaging methods, and neuroanatomy examined were variable. Despite this, 62.5% (n = 5) of the reviewed studies found a significant relationship between cognitive and imaging outcomes...
October 3, 2016: Pediatric Blood & Cancer
Meng-Ju Li, Hsi-Che Liu, Hsiu-Ju Yen, Tang-Her Jaing, Dong-Tsamn Lin, Chao-Ping Yang, Kai-Hsin Lin, Iou-Jih Hung, Shiann-Tarng Jou, Meng-Yao Lu, Chih-Cheng Hsiao, Ching-Tien Peng, Tai-Tsung Chang, Shih-Chung Wang, Ming-Tsan Lin, Jiann-Shiuh Chen, Te-Kau Chang, Giun-Yi Hung, Kang-Hsi Wu, Yung-Li Yang, Hsiu-Hao Chang, Shih-Hsiang Chen, Ting-Chi Yeh, Chao-Neng Cheng, Pei-Chin Lin, Shyh-Shin Chiou, Jiunn-Ming Sheen, Shin-Nan Cheng, Shu-Huey Chen, Yu-Hsiang Chang, Wan-Ling Ho, Yu-Hua Chao, Rong-Long Chen, Bow-Wen Chen, Jinn-Li Wang, Yuh-Lin Hsieh, Yu-Mei Liao, Shang-Hsien Yang, Wan-Hui Chang, Yu-Mei Y Chao, Der-Cherng Liang
BACKGROUND: Reinduction therapy has improved the outcomes in children with acute lymphoblastic leukemia (ALL). We sought to determine the optimal course(s) of reinduction therapy for standard-risk (SR, or "low-risk" in other groups) patients. Also, we evaluated outcomes using triple intrathecal therapy without cranial radiation (CrRT) for central nervous system (CNS) preventive therapy. PROCEDURE: From 2002 to 2012, all newly diagnosed children with ALL in Taiwan were enrolled in Taiwan Pediatric Oncology Group ALL-2002 protocol...
October 3, 2016: Pediatric Blood & Cancer
J Vijayakrishnan, R Kumar, M Y R Henrion, A V Moorman, P S Rachakonda, I Hosen, M I da Silva Filho, A Holroyd, S E Dobbins, R Koehler, H Thomsen, J A Irving, J M Allan, T Lightfoot, E Roman, S E Kinsey, E Sheridan, P D Thompson, P Hoffmann, M M Nöthen, S Heilmann-Heimbach, J Karl-Heinz, M Greaves, C J Harrison, C R Bartram, M Schrappe, M Stanulla, K Hemminki, R S Houlston
Genome-wide association studies (GWASs) have shown that common genetic variation contributes to the heritable risk of childhood acute lymphoblastic leukemia (ALL). To identify new susceptibility loci for the largest subtype of ALL, B-cell precursor ALL (BCP-ALL), we conducted a meta-analysis of two GWAS with imputation using 1000 Genomes and UK10K Project data as reference (totaling 1658 cases and 7224 controls). After genotyping an additional 2525 cases and 3575 controls we identify new susceptibility loci for BCP-ALL mapping to 10q26...
October 3, 2016: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
Antonis Dagklis, Sofie Demeyer, Jolien De Bie, Enrico Radaelli, Daphnie Pauwels, Sandrine Degryse, Olga Gielen, Carmen Vicente, Roel Vandepoel, Ellen Geerdens, Anne Uyttebroeck, Nancy Boeckx, Charles E de Bock, Jan Cools
T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive childhood leukemia that is caused by the accumulation of multiple genomic lesions resulting in transcriptional deregulation and increased cell proliferation and survival. Through analysis of gene expression data, we provide evidence that the hedgehog pathway is activated in 20% of T-ALL samples. Hedgehog pathway activation is associated with ectopic expression of the hedgehog ligands SHH or IHH, and with upregulation of the transcription factor GLI1...
September 30, 2016: Blood
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