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Laursen A.C.L.,Aarhus University Hospital | Sandahl J.D.,Aarhus University Hospital | Kjeldsen E.,Aarhus University Hospital | Abrahamsson J.,Institution for Clinical Science | And 10 more authors.
Genes Chromosomes and Cancer | Year: 2016

Trisomy 8 (+8) is a common cytogenetic aberration in acute myeloid leukemia (AML); however, the impact of +8 in pediatric AML is largely unknown. We retrospectively investigated 609 patients from the NOPHO-AML database to determine the clinical and cytogenetic characteristics of +8 in pediatric AML and to investigate its prognostic impact. Complete cytogenetic data were available in 596 patients (98%) aged 0–18 years, diagnosed from 1993 to 2012, and treated according to the NOPHO-AML 1993 and 2004 protocols in the Nordic countries and Hong Kong. We identified 86 patients (14%) with +8. Trisomy 8 was combined with other cytogenetic aberrations in 68 patients (11%) (+8 other) and in 18 patients (3%), it was the sole abnormality (+8 alone). Trisomy 8 was associated with FAB M5 (36%) but otherwise clinically comparable with non-trisomy 8 patients. Trisomy 8 was favorable in patients of young age and with t(9;11). Trisomy 8 alone was associated with older age (median age 10.1 years), FAB M2 (33%), and FLT3-ITD mutations (58%). The 5-year event-free survival for patients with +8 alone was 50% and 5-year overall survival was 75%. In conclusion, +8 is one of the most common cytogenetic aberrations in pediatric AML. Trisomy 8 positive AML is a heterogeneous group and the majority of cases have additional cytogenetic aberrations. Patients with +8 alone differed from patients with +8 other and were associated with older age, FAB M2, and FLT3-ITD aberrations. There were no differences in survival despite the more frequent occurrence of FLT3-ITD in +8 alone. © 2016 Wiley Periodicals, Inc. Source

Arvidsson D.,Institution for Clinical Science | Fitch M.,University of California at Berkeley | Hudes M.L.,University of California at Berkeley | Tudor-Locke C.,Pennington Biomedical Research Center | Fleming S.E.,University of California at Berkeley
Journal of Physical Activity and Health | Year: 2011

Background: Different movement efficiency in overweight children may affect accelerometer output data. The purpose was to investigate the ability of accelerometers to assess physical activity intensity and number of steps in normal-weight compared with overweight children. Methods: Eleven normal-weight and 14 overweight African American children walked at 2, 4, 5, and 6 km/h on a treadmill wearing Lifecorder, ActiGraph, RT3, and Biotrainer. Oxygen uptake was measured and steps manually counted. Fat free mass (FFM) was assessed from bioelectrical impedance analysis. Accelerometer counts and the individual linear regression lines of accelerometer counts versus VO2/FFM were evaluated, together with steps recorded by Lifecorder and Actigraph. Results: Correlations between accelerometer counts and VO2/FFM for all monitors were r ≥ .95 (P < .01). Theaccelerometer counts and their relationship to VO2/FFM did not generally differ significantly by body weight status. Lifecorder and Actigraph underestimated steps at 4, 5, and 6 km/h by less than 9%, but the error was up to -95% at 2 km/h. Conclusions: All 4 accelerometers show high ability to assess physical activity intensity, and can be used to compare physical activity between normal-weight and overweight children. The Lifecorder and the ActiGraph showed high accuracy in assessing steps, providing speed of movement exceeded 2 km/h. © 2011 Human Kinetics, Inc. Source

Sandahl J.D.,Aarhus University Hospital | Kjeldsen E.,Aarhus University Hospital | Abrahamsson J.,Institution for Clinical Science | Ha S.-Y.,Queen Mary Hospital and Hong Kong Paediatric Haematology and Oncology Study Group HKPHOSG | And 8 more authors.
British Journal of Haematology | Year: 2015

Summary: The World Health Organization (WHO) classification of myeloid leukaemia was revised in 2008. It incorporates newly recognized entities and emphasizes the pivotal role of cytogenetic abnormalities. The aim of this study was to evaluate the usability of the WHO classification when applied to a large population-based paediatric acute myeloid leukaemia (AML) cohort. We included children diagnosed with de novo AML, 0-18 years of age from the Nordic countries and Hong Kong from 1993 to 2012. Data were retrieved from the Nordic Society for Paediatric Haematology and Oncology AML database and patients classified according to the WHO 2008 classification. A successful karyotype was available in 97% of the cases. AML with recurrent genetic abnormalities were present in 262 (41%) and 94 (15%) were classified as AML with myelodysplasia-related changes (AML-MDS). WHO classifies patients with monosomy 7 and del(7q) into one group. We found that -7 (n = 14) had significantly poorer outcome than del(7q) (n = 11); 5-year event-free survival 26% vs. 67%, (P = 0·02), and 5-year overall survival 51% vs. 90%, (P = 0·04). The largest group was the highly heterogeneous AML not otherwise specified (NOS) (n = 280) (44%). In conclusion, the WHO classification allocated 15% to AML-MDS, 44% to NOS and grouped together entities with clearly different outcome, therefore limiting the applicability of the current WHO classification in children with AML. © 2015 John Wiley & Sons Ltd. Source

Hasle H.,Aarhus University Hospital | Abrahamsson J.,Institution for Clinical Science | Forestier E.,Umea University | Ha S.-Y.,Hong Kong Pediatric Hematology and Oncology Study Group | And 6 more authors.
Blood | Year: 2012

There are no data on the role of postconsolidation therapy with gemtuzumab ozogamicin (GO; Mylotarg) in children with acute myeloid leukemia (AML). The NOPHO-AML 2004 protocol studied postconsolidation randomization to GO or no further therapy. GO was administered at 5 mg/m2 and repeated after 3 weeks. We randomized 120 patients; 59 to receive GO. Survival was analyzed on an intention-to-treat basis. The median follow-up for patients who were alive was 4.2 years. Children who received GO showed modest elevation of transaminase and bilirubin without signs of venoocclusive disease. Severe neutropenia followed 95% and febrile neutropenia 40% of the GO courses. Only a moderate decline in platelet count and a minor decrease in hemoglobin occurred. Relapse occurred in 24 and 25 of those randomized to GO or no further therapy. The median time to relapse was 16 months versus 10 months (nonsignificant). The 5-year event-free survival and overall survival was 55% versus 51% and 74% versus 80% in those randomized to receive GO or no further therapy, respectively. Results were similar in all subgroups. In conclusion, GO therapy postconsolidation as given in this trial was well tolerated, showed a nonsignificant delay in time to relapse, but did not change the rate of relapse or survival (clinicaltrials.gov identifier NCT00476541). © 2012 by The American Society of Hematology. Source

Sandahl J.D.,Aarhus University Hospital | Kjeldsen E.,Aarhus University Hospital | Abrahamsson J.,Institution for Clinical Science | Ha S.-Y.,Queen Mary Hospital and Hong Kong Paediatric Haematology and Oncology Study Group HKPHOSG | And 8 more authors.
Genes Chromosomes and Cancer | Year: 2014

We report the first large series (n=596) of pediatric acute myeloid leukemia (AML) focusing on modal numbers (MN) from the population-based NOPHO-AML trials. Abnormal karyotypes were present in 452 cases (76%) and numerical aberrations were present in 40% (n=237) of all pediatric AML. Among patients with an abnormal karyotype, the MN 46 was most common (n=251; 56%) of which 36 (8%) were pseudodiploid with numerical aberrations, followed by MN 47 (n=80; 18%) and MN 43-45 (n=48; 8%). No cases had MN less than 43. Hyperdiploid AML with MN 48-65 comprised 11% of all cases and was associated with early onset (median age 2 years), female sex (57%), and a dominance of acute megakaryoblastic leukemia (AMKL) (29%). Hypodiploidy constituted 8% of all AML and was associated with older age (median age 9 years), male predominance (60%), FAB M2 (56%), and t(8;21)(q22;q22) (56%) with loss of sex chromosomes. Inferior outcome was observed for hypodiploid cases (5-year event-free survival 40% and 5-year overall survival 40%) but did not reach statistical significance. Chromosomes were gained in a nonrandom pattern, where chromosomes 8, 21, 19, and 6 were the most commonly gained. In conclusion, based on MNs, two cytogenetic subgroups with characteristic clinical features are described; hypodiploidy found in 8% and associated with high median age, male sex, t(8;21)(q22;q22), and FAB M2 and possibly associated with inferior outcome (P=0.13), and hyperdiploidy with MN 48-65 in 11% associated with early onset, female sex, and AMKL. © 2014 Wiley Periodicals, Inc. Source

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