Landspitalinn

Reykjavík, Iceland

Landspitalinn

Reykjavík, Iceland

Time filter

Source Type

Sandahl J.D.,Aarhus University Hospital | Kjeldsen E.,Aarhus University Hospital | Ha S.-Y.,Queen Mary Hospital and Hong Kong Paediatric Haematology and Oncology Study Group HKPHOSG | Heldrup J.,Lund University | And 7 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.


Laursen A.C.L.,Aarhus University Hospital | Sandahl J.D.,Aarhus University Hospital | Kjeldsen E.,Aarhus University Hospital | Asdahl P.,Aarhus University Hospital | And 9 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.


Hasle H.,Aarhus University Hospital | Forestier E.,Umeå University | Ha S.-Y.,Queen Mary Hospital | Heldrup J.,Lund University | And 5 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.


Sandahl J.D.,Aarhus University Hospital | Kjeldsen E.,Aarhus University Hospital | Ha S.-Y.,Queen Mary Hospital and Hong Kong Paediatric Haematology and Oncology Study Group HKPHOSG | Heldrup J.,Lund University | And 7 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.


Johannsdottir I.M.R.,University of Oslo | Hjermstad M.J.,University of Oslo | Hjermstad M.J.,Norwegian University of Science and Technology | Moum T.,University of Oslo | And 6 more authors.
Journal of Cancer Survivorship | Year: 2010

Introduction: The intensity and duration of childhood cancer treatment may disrupt psychosocial development and thereby cause difficulties in transition into adulthood. The study objective was to assess social outcomes in early adulthood after successful treatment for childhood acute myeloid leukemia (AML), Wilms tumor (WT) and infratentorial astrocytoma (IA). Methods: Nordic patients treated for AML, WT and IA from 1985 to 2001 identified from a database administered by NOPHO (Nordic Society of Paediatric Haematology and Oncology) were invited to participate in a postal survey. All cancer-free survivors treated at age >1 year who were >19 years at time of study were eligible. Seventy-four percent; 247/335 responded. An age-equivalent group (N = 1,814) from a Norwegian Census Study served as controls. Results: Mean age of survivors was 23 years (range 19-34), 55% females. The proportion with academic education (≥4 years) was similar in survivors and controls (28 vs. 32%). Fifty-nine percent of survivors were employed compared to 77% among controls (p<.01). More survivors were recipients of social benefits (6.7 vs. 3.1%, p<.01). There were no differences in marital status but parenthood was more common among controls (37 vs. 27%, p=.01). Controls lived longer in their parental homes (p=.01). Cancer type or treatment intensity had no statistically significant impact on results, except for parenthood. Conclusions and Implications for Cancer Survivors: The study revealed important differences in social outcomes between survivors and controls early in adult life. Specific difficulties pertain to studying social status in early adulthood because of the natural transition characteristics for this age group. Therefore, longer follow-up is warranted. © 2010 Springer Science+Business Media, LLC.


PubMed | Copenhagen University, University of Oslo, University of Helsinki, Uppsala University and 8 more.
Type: Journal Article | Journal: Pediatric blood & cancer | Year: 2015

Studies on adolescents and young adults with acute lymphoblastic leukemia suggest better results when using pediatric protocols for adult patients, while corresponding data for acute myeloid leukemia (AML) are limited.We investigated disease characteristics and outcome for de novo AML patients 10-30 years old treated in pediatric or adult departments. We included 166 patients 10-18 years of age with AML treated according to the pediatric NOPHO-protocols (1993-2009) compared with 253 patients aged 15-30 years treated in hematology departments (1996-2009) in the Nordic countries.The incidence of AML was 4.9/million/year for the age group 10-14 years, 6.5 for 15-18 years, and 6.9 for 19-30 years. Acute promyelocytic leukemia (APL) was more frequent in adults and in females of all ages. Pediatric patients with APL had similar overall survival as pediatric patients without APL. Overall survival at 5 years was 60% (52-68%) for pediatric patients compared to 65% (58-70%) for adult patients. Cytogenetics and presenting white blood cell count were the only independent prognostic factors for overall survival. Age was not an independent prognostic factor.No difference was found in outcome for AML patients age 10-30 years treated according to pediatric as compared to adult protocols.


PubMed | Copenhagen University, University of Oslo, University of Helsinki, Uppsala University and 5 more.
Type: Journal Article | Journal: Genes, chromosomes & 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.


PubMed | Copenhagen University, University of Oslo, University of Helsinki, Uppsala University and 5 more.
Type: Journal Article | Journal: British journal of haematology | Year: 2015

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, 0-18years 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=002), and 5-year overall survival 51% vs. 90%, (P=004). 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.


Lonnerholm G.,Uppsala University | Thorn I.,Uppsala University | Sundstrom C.,Uppsala University | Frost B.-M.,Uppsala University | And 12 more authors.
Leukemia Research | Year: 2011

Leukemic cells from 230 children with newly diagnosed B-cell precursor ALL were tested for in vitro drug resistance to a panel of anti-cancer drugs. Minimal residual disease (MRD) was measured by RQ-PCR. During follow-up, 24 relapses occurred in the 159 children with MRD <0.1% day 29. The risk of any relapse was correlated to vincristine and doxorubicin resistance, with a relative risk of 3.7 (95% CI 1.3-10.5; p = 0.016) for patients resistant to both drugs. There was a significant correlation also for the subgroup with extra-medullary relapses. Our findings indicate that analysis of drug resistance can add prognostic information to other known risk-factors including MRD. © 2010 Elsevier Ltd.


Milani L.,Uppsala University | Lundmark A.,Uppsala University | Kiialainen A.,Uppsala University | Nordlund J.,Uppsala University | And 10 more authors.
Blood | Year: 2010

Despite improvements in the prognosis of childhood acute lymphoblastic leukemia (ALL), subgroups of patients would benefit from alternative treatment approaches. Our aim was to identify genes with DNA methylation profiles that could identify such groups. We determined the methylation levels of 1320 CpG sites in regulatory regions of 416 genes in cells from 401 children diagnosed with ALL. Hierarchical clustering of 300 CpG sites distinguished between T-lineage ALL and B-cell precursor (BCP) ALL and between the main cytogenetic subtypes of BCP ALL. It also stratified patients with high hyperdiploidy and t(12;21) ALL into 2 subgroups with different probability of relapse. By using supervised learning, we constructed multivariate classifiers by external cross-validation procedures. We identified 40 genes that consistently contributed to accurate discrimination between the main subtypes of BCP ALL and gene sets that discriminated between subtypes of ALL and between ALL and controls in pairwise classification analyses. We also identified 20 individual genes with DNA methylation levels that predicted relapse of leukemia. Thus, methylation analysis should be explored as a method to improve stratification of ALL patients. The genes highlighted in our study are not enriched to specific pathways, but the gene expression levels are inversely correlated to the methylation levels. (Blood. 2010;115:1214-1225) © 2010 by The American Society of Hematology.

Loading Landspitalinn collaborators
Loading Landspitalinn collaborators