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pediatric aml

Michael R Loken, Andrew P Voigt, Lisa Eidenschink Brodersen, Wayne Fritschle, Andrew J Menssen, Denise A Wells
The quantitative expression of cell surface antigens and light scattering properties of five cellular reference populations in stressed bone marrow specimens were compared between pediatric and adult patients treated for acute myeloid leukemia (AML). The mean intensity of each antigen as well as the within patient and between patient variability showed striking consistency between the two different age groups. The only difference between the groups of specimens was the proportion of progenitor cells in the adult cohort averaged less than three times the proportion in the pediatric cohort...
October 18, 2016: Cytometry. Part A: the Journal of the International Society for Analytical Cytology
Michael R Loken, Andrew P Voigt, Lisa Eidenschink Brodersen, Wayne Fritschle, Andrew J Menssen, Soheil Meshinchi, Denise A Wells
Five reference populations in bone marrow specimens were identified by flow cytometry using specific combinations of reagents in order define the variation of gene product expression intensities both within and between individuals. Mature lymphocytes, uncommitted progenitor cells, promyelocytes, mature monocytes and mature neutrophils can be reproducibly identified as distinct clusters of events in heterogeneous, maturing bone marrow specimens. Support Vector Machines were used to identify the reference populations in order to reduce subjective bias in manually defining boundaries of these populations since they were not discretely separated from the remainder of the cells...
October 18, 2016: Cytometry. Part A: the Journal of the International Society for Analytical Cytology
N Narayan, L Morenos, B Phipson, S N Willis, G Brumatti, S Eggers, N Lalaoui, L M Brown, H J Kosasih, R C Bartolo, L Zhou, D Catchpoole, R Saffery, A Oshlack, G J Goodall, P G Ekert
Enforced expression of miR-155 in myeloid cells has been shown to have both oncogenic or tumour suppressor functions in acute myeloid leukemia (AML). We sought to resolve these contrasting effects of miR-155 overexpression using murine models of AML and human paediatric AML datasets. We show that the highest miR-155 expression levels inhibited proliferation in murine AML models. Over time, enforced miR-155 expression in AML in vitro and in vivo, however, favors selection of intermediate miR-155 expression levels that results in increased tumour burden in mice, without accelerating the onset of disease...
October 14, 2016: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
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
Ting Yang, Qiaoxian Lin, Jinhua Ren, Ping Chen, Xiaohong Yuan, Xiaofeng Luo, Tingbo Liu, Jing Zheng, Zhihong Zheng, Xiaoyun Zheng, Xinji Chen, Langhui Zhang, Hao Zheng, Zaisheng Chen, Xueling Hua, Shaohua Le, Jian Li, Zhizhe Chen, Jianda Hu
Haplo-HSCT has been used when HLA-matched siblings are not available. Conditioning regimens aim to reduce tumor burden prior to HSCT and provide sufficient immunoablation. We report the outcome of haplo-HSCT in 63 consecutive patients from 2/2013 to 12/2015 (19 females/44 males) with high-risk or relapsed/refractory hematological malignancies (n=29-AML; 8-sAML; 19-ALL; 5-advanced-MDS; 2-CML-BC). Median age was 20 years (range: 1.1-49). Twenty-one patients achieved remission prior to transplant, while 42 did not...
October 1, 2016: Oncotarget
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
S Struski, S Lagarde, P Bories, C Puiseux, N Prade, W Cuccuini, M-P Pages, A Bidet, C Gervais, M Lafage-Pochitaloff, C Roche-Lestienne, C Barin, D Penther, N Nadal, I Radford-Weiss, M-A Collonge-Rame, B Gaillard, F Mugneret, C Lefebvre, A Petit, G Leverger, C Broccardo, I Luquet, M Pasquet, E Delabesse
Pediatric acute myeloid leukemia (AML) is a rare disease whose prognosis is highly variable according to factors such as chromosomal abnormalities. Recurrent genomic rearrangements are detected in half of pediatric AML by karyotype. NUcleoPorin 98 (NUP98) gene is rearranged with 31 different fusion partner genes. These rearrangements are frequently undetected by conventional cytogenetics, since the NUP98 gene is located at the end of the chromosome 11 short arm (11p15). By screening a series of 574 pediatric AML, we detected a NUP98 rearrangement in 22 cases (3...
October 3, 2016: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
Kiki M G J Wigny, Wendy van Dorp, Anne-Lotte L F van der Kooi, Yolanda B de Rijke, Andrica C H de Vries, Marij Smit, Saskia M F Pluijm, Erica L T van den Akker, Rob Pieters, Joop S E Laven, Marry M van den Heuvel-Eibrink
STUDY QUESTION: Are Inhibin B and testosterone levels reduced in boys with newly diagnosed cancer prior to therapy? SUMMARY ANSWER: Pretreatment serum levels of Inhibin B and testosterone are significantly reduced in boys with newly diagnosed cancer, compared to reference values. WHAT IS ALREADY KNOWN: Disease-related gonadal impairment has been demonstrated in girls and young women diagnosed with cancer, prior to therapy. STUDY DESIGN, SIZE, DURATION: We conducted a descriptive study in boys newly diagnosed with cancer between January 2006 and February 2014...
September 28, 2016: Human Reproduction
Jason C Warncke, Katie E Brodie, Erin C Grantham, Salvatore P Catarinicchia, Suhong Tong, Kimi L Kondo, Nicholas G Cost
PURPOSE: Tuberous Sclerosis Complex (TSC) is a genetic disorder characterized by the growth of hamartomas in multiple organs. Up to 80% of TSC patients will have at least one angiomyolipoma (AML) in their lifetime. In this study we aim to describe the incidence and natural history of AMLs in a pediatric TSC population, and analyze tumor growth to determine optimal renal imaging intervals in an effort to improve counseling, follow-up and treatment. METHODS: We performed a retrospective chart review of all TSC patients from 2004-2014...
September 24, 2016: Journal of Urology
Ioannis Panagopoulos, Synne Torkildsen, Ludmila Gorunova, Aina Ulvmoen, Anne Tierens, Bernward Zeller, Sverre Heim
Fluorescence in situ hybridization examination of a pediatric AML patient whose bone marrow cells carried trisomy 4 and FLT3-ITD mutation, demonstrated that part of the RUNX1 probe had unexpectedly moved to chromosome band 6q25 indicating a cryptic t(6;21)(q25;q22) translocation. RNA sequencing showed fusion of exon 7 of RUNX1 with an intergenic sequence of 6q25 close to the MIR1202 locus, something that was verified by RT-PCR together with Sanger sequencing. The RUNX1 fusion transcript encodes a truncated protein containing the Runt homology domain responsible for both heterodimerization with CBFB and DNA binding, but lacking the proline-, serine-, and threonine-rich (PST) region which is the transcription activation domain at the C terminal end...
September 22, 2016: Oncology Reports
David Schnell, Elie Azoulay, Dominique Benoit, Benjamin Clouzeau, Pierre Demaret, Stéphane Ducassou, Pierre Frange, Matthieu Lafaurie, Matthieu Legrand, Anne-Pascale Meert, Djamel Mokart, Jérôme Naudin, Frédéric Pene, Antoine Rabbat, Emmanuel Raffoux, Patricia Ribaud, Jean-Christophe Richard, François Vincent, Jean-Ralph Zahar, Michael Darmon
Neutropenia is defined by either an absolute or functional defect (acute myeloid leukemia or myelodysplastic syndrome) of polymorphonuclear neutrophils and is associated with high risk of specific complications that may require intensive care unit (ICU) admission. Specificities in the management of critically ill neutropenic patients prompted the establishment of guidelines dedicated to intensivists. These recommendations were drawn up by a panel of experts brought together by the French Intensive Care Society in collaboration with the French Group for Pediatric Intensive Care Emergencies, the French Society of Anesthesia and Intensive Care, the French Society of Hematology, the French Society for Hospital Hygiene, and the French Infectious Diseases Society...
December 2016: Annals of Intensive Care
Pooja Rao, Yimei Li, Kelly D Getz, Tamara P Miller, Yuan-Shung Huang, Jennifer J Wilkes, Alix E Seif, Rochelle Bagatell, Brian T Fisher, Clarisa Gracia, Richard Aplenc
BACKGROUND: Adolescents with cancer engage in sexual behaviors and are exposed to teratogenic chemotherapy. There are no data regarding pregnancy screening patterns for adolescents before chemotherapy exposure. METHODS: A cross-sectional study of leukemia and emergency room (ER) admissions in the Pediatric Health Information System from 1999 to 2011 was conducted. Females who were 10 to 18 years old and 1) had newly diagnosed acute lymphoblastic leukemia (ALL) or acute myeloid leukemia (AML) or 2) had ER visits with computed tomography (CT) of the abdomen/pelvis were included...
September 12, 2016: Cancer
Ashley E J Rogers, Kristen M Eisenman, Susan A Dolan, Kristin M Belderson, Jocelyn R Zauche, Suhong Tong, Jane Gralla, Joanne M Hilden, Michael Wang, Kelly W Maloney, Samuel R Dominguez
BACKGROUND: Central line-associated blood stream infections (CLABSIs) are a source of high morbidity and mortality in children with acute myelogenous leukemia (AML). PROCEDURE: To understand the epidemiology and risk factors associated with the development of CLABSI in children with AML. METHODS: We retrospectively reviewed all patients with AML over a 5-year period between 2007 and 2011 at the Children's Hospital Colorado. Cases and controls were classified on the basis of the presence of a CLABSI as defined by the National Healthcare Safety Network...
September 12, 2016: Pediatric Blood & Cancer
A Sirvent, P Auquier, C Oudin, Y Bertrand, S Bohrer, P Chastagner, M Poirée, J Kanold, S Thouvenin, Y Perel, D Plantaz, M-D Tabone, K Yakouben, V Gandemer, P Lutz, N Sirvent, C Vercasson, J Berbis, H Chambost, G Leverger, A Baruchel, G Michel
Data on post-transplant iron overload (IO) are scarce in pediatrics. We conducted a prospective multicenter cohort study (Leucémie de l'Enfant et de l'Adolescent cohort) to determine the prevalence and risk factors of IO in 384 acute leukemia survivors transplanted during childhood. Prevalence of IO (ferritin level ⩾350 ng/mL) was 42.2% (95%CI 37.2-47.2%). Factors significantly associated with IO were: 1) in univariate analysis: older age at transplant (P<0.001), allogeneic versus autologous transplantation (P<0...
September 5, 2016: Bone Marrow Transplantation
Yaping Wang, Jie Huang, Liucheng Rong, Peng Wu, Meiyun Kang, Xuejie Zhang, Qin Lu, Yongjun Fang
BACKGROUND & AIMS: Age at diagnosis is a key factor for predicting the prognosis of pediatric leukemia especially regarding the survivorship assessment. In this study, we aimed to assess the impact of this prognostic factor such as age in children with pediatric leukemia. METHODS: In this study, Surveillance, Epidemiology, and End Results Program-registered children with leukemia during 1988-2013 were analyzed. All patients were divided into five groups according to the age at the time of diagnosis (<1, 1-4, 5-9, 10-15, >15 years old)...
August 31, 2016: Oncotarget
Wasil Jastaniah, Ibrahim Al Ghemlas, Saad Al Daama, Walid Ballourah, Mohammad Bayoumy, Faisal Al-Anzi, Omar Al Shareef, Abdulrahman Alsultan, Mohammed Burhan Abrar, Reem Al Sudairy
Geographic variation and ethnicity have been implicated to influence the outcome of pediatric acute myeloid leukemia (AML). Furthermore, survival outcomes from developing countries are reported to be inferior to developed nations. We hypothesized that risk- and response-based outcome in high-income resource-rich developing countries would be comparable to developed nations as access to care and supportive measures would be similar. A total of 193 children diagnosed with de novo AML between January 2005 and December 2012 were identified, of those 175 were evaluable for outcome...
October 2016: Leukemia Research
Shinya Osone, Toshihiko Imamura, Takuyo Kanayama, Yusuke Tsuma, Sachiko Kawashima-Goto, Takuya Nakatani, Atsuya Sugimoto, Akari Takai, Mitsuru Miyachi, Shinichi Tamura, Hiroyuki Ishida, Hajime Hosoi
Sorafenib is a promising agent for treating pediatric refractory acute myeloid leukemia (AML) exhibiting FMS-like tyrosine kinase 3-internal tandem duplication (FLT3-ITD); however, its optimal use needs to be established. We report 2 cases of refractory pediatric FLT3-ITD-positive AML treated with sorafenib. Case 1 underwent stem cell transplantation (SCT) without entering remission, despite the use of chemotherapy. This patient relapsed despite receiving post-SCT sorafenib. Chemotherapy combined with sorafenib successfully achieved complete remission in case 2...
August 26, 2016: Journal of Pediatric Hematology/oncology
Kshitij Verma, Tianzhu Zang, Nehal Gupta, Trevor M Penning, Paul C Trippier
We report the design, synthesis, and evaluation of potent and selective inhibitors of aldo-keto reductase 1C3 (AKR1C3), an important enzyme in the regulatory pathway controlling proliferation, differentiation, and apoptosis in myeloid cells. Combination treatment with the nontoxic AKR1C3 inhibitors and etoposide or daunorubicin in acute myeloid leukemia cell lines, elicits a potent adjuvant effect, potentiating the cytotoxicity of etoposide by up to 6.25-fold and the cytotoxicity of daunorubicin by >10-fold...
August 11, 2016: ACS Medicinal Chemistry Letters
Marijana Vujkovic, Richard Aplenc, Todd A Alonzo, Alan S Gamis, Yimei Li
Regression analysis is commonly used in genome-wide association studies (GWAS) to test genotype-phenotype associations but restricts the phenotype to a single observation for each individual. There is an increasing need for analytic methods for longitudinally collected phenotype data. Several methods have been proposed to perform longitudinal GWAS for family-based studies but few methods are described for unrelated populations. We compared the performance of three statistical approaches for longitudinal GWAS in unrelated subjectes: (1) principal component-based generalized estimating equations (PC-GEE); (2) principal component-based linear mixed effects model (PC-LMEM); (3) kinship coefficient matrix-based linear mixed effects model (KIN-LMEM), in a study of single-nucleotide polymorphisms (SNPs) on the duration of 4 courses of chemotherapy in 624 unrelated children with de novo acute myeloid leukemia (AML) genotyped on the Illumina 2...
2016: Frontiers in Genetics
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