| 1. |
- Abildgaard, Lotte, et al.
(författare)
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Optimal treatment intensity in children with Down syndrome and myeloid leukaemia: data from 56 children treated on NOPHO-AML protocols and a review of the literature.
- 2006
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Ingår i: Annals of hematology. - : Springer Science and Business Media LLC. - 0939-5555 .- 1432-0584. ; 85:5, s. 275-80
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Tidskriftsartikel (refereegranskat)abstract
- Children with Down syndrome (DS) and myeloid leukaemia have a significantly higher survival rate than other children, but they also experience considerable treatment-related toxicity. We analysed data on 56 children with DS who were treated on the Nordic Society for Paediatric Haematology and Oncology-acute myeloid leukaemia (NOPHO-AML)88 and NOPHO-AML93 protocols and reviewed the literature. In the dose-intensive NOPHO-AML88 protocol, 8 out of 15 patients (53%) experienced an event. In the less dose-intensive NOPHO-AML93 protocol, 7 out of 41 patients (17%) had an event. Therapy was reduced in 29 patients (52%) with in average 75% and 67% of the scheduled dose of anthracycline and cytarabine, respectively. Treatment-related death occurred in seven who all received full treatment. Relapse and resistant disease occurred at a similar rate in those receiving full and reduced treatment. Review of major series of myeloid leukaemia of DS showed no clear relationship between dose and survival; however, it appears that both a reduction in treatment dose and a less intensively timed treatment regimen improved the outcome. Further studies are needed to define the optimal regimen for treating myeloid leukaemia of DS.
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| 2. |
- Abrahamsson, Jonas, 1954, et al.
(författare)
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Improved outcome after relapse in children with acute myeloid leukaemia.
- 2007
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Ingår i: British journal of haematology. - : Wiley. - 0007-1048 .- 1365-2141. ; 136:2, s. 229-236
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Tidskriftsartikel (refereegranskat)abstract
- In the Nordic Society for Paediatric Haematology and Oncology paediatric study acute myeloid leukaemia (AML) 93, event-free survival was 50% and overall survival was 66%, indicating that many patients were cured following relapse. Factors influencing outcome in children with relapsed AML were investigated. The study included all 146 children in the Nordic countries diagnosed with AML between 1988 and 2003, who relapsed. Data on disease characteristics and relapse treatment were related to outcome. Sixty-six percentage achieved remission with survival after relapse (5 years) 34 +/- 4%. Of 122 patients who received re-induction therapy, 77% entered remission with 40 +/- 5% survival. Remission rates were similar for different re-induction regimens but fludarabine, cytarabine, granulocyte colony-stimulating factor-based therapy had low treatment-related mortality. Prognostic factors for survival were duration of first complete remission (CR1) and stem cell transplantation (SCT) in CR1. In early relapse (<1 year in CR1), survival was 21 +/- 5% compared with 48 +/- 6% in late relapse. For children receiving re-induction therapy, survival in early relapse was 29 +/- 6% and 51 +/- 6% in late. Patients treated in CR1 with SCT, autologous SCT or chemotherapy had a survival of 18 +/- 9, 5 +/- 5 and 41 +/- 5%, respectively. Survival was 62 +/- 6% in 64 children given SCT as part of their relapse therapy. A significant proportion of children with relapsed AML can be cured, even those with early relapse. Children who receive re-induction therapy, enter remission and proceed to SCT can achieve a cure rate of 60%.
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| 3. |
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| 4. |
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| 5. |
- Johannsdottir, Inga M. R., et al.
(författare)
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Increased prevalence of chronic fatigue among survivors of childhood cancers: A population-based study
- 2012
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Ingår i: Pediatric Blood & Cancer. - : Wiley. - 1545-5017 .- 1545-5009. ; 58:3, s. 415-420
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Tidskriftsartikel (refereegranskat)abstract
- Background Fatigue is prevalent in adult cancer survivors but less studied in childhood cancer survivors. Aims were to assess fatigue levels, prevalence of chronic fatigue (CF) and the association of CF with health-related quality of life (HRQoL) in survivors of acute myeloid leukemia (AML), infratentorial astrocytoma (IA), and Wilms tumor (WT) in childhood.
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| 6. |
- Johannsdottir, Inga M. R., et al.
(författare)
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Social outcomes in young adult survivors of low incidence childhood cancers
- 2010
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Ingår i: Journal of Cancer Survivorship. - : Springer Science and Business Media LLC. - 1932-2267 .- 1932-2259. ; 4:2, s. 110-118
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Tidskriftsartikel (refereegranskat)abstract
- 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 1934), 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.
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| 7. |
- Lie, Sverre O, et al.
(författare)
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Treatment stratification based on initial in vivo response in acute myeloid leukaemia in children without Down's syndrome: results of NOPHO-AML trials.
- 2003
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Ingår i: British journal of haematology. - : Wiley. - 0007-1048. ; 122:2, s. 217-25
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Tidskriftsartikel (refereegranskat)abstract
- Three consecutive protocols for childhood acute myeloid leukaemia (AML) have been used in the Nordic countries since 1984: the Nordic Society for Paediatric Haematology and Oncology (NOPHO)-AML84 was of moderate intensity, NOPHO-AML88 of high intensity with upfront loading and aggressive consolidation. NOPHO-AML93 utilized the same treatment blocks as NOPHO-AML88, but after the first block those children with a hypoplastic non-leukaemic bone marrow were allowed to recover from aplasia. Poor responders received intensified induction therapy. Between January 1993 and December 2000, 219 children without Down's syndrome were entered on NOPHO-AML93. Compared with NOPHO-AML88, the event-free survival (EFS) at 7 years increased from 41% to 49% (P = 0.06) and 7-year overall survival increased from 47% to 64% (P < 0.01). Toxic death during induction was reduced from 10% to 3%. Survival was similar in patients receiving stem cell transplantation or chemotherapy only in first remission. The major prognostic factors in NOPHO-AML93 were response to therapy and cytogenetics. A total of 67% of patients achieved remission after the first induction course and showed an EFS of 56% compared with 35% in those not in remission (P < 0.01). Cytogenetic results were obtained in 95% of patients. Patients with t(9;11) (p22;q23) (n = 16) experienced a significantly better EFS (86%) than other cytogenetic groups. The overall outcome was improved by employing the previous toxic protocol with different timings, and through individualizing therapy according to the initial response of the patient.
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| 8. |
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| 9. |
- Milani, Lili, et al.
(författare)
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Allele-specific gene expression patterns in primary leukemic cells reveal regulation of gene expression by CpG site methylation
- 2009
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Ingår i: Genome Research. - : Cold Spring Harbor Laboratory. - 1088-9051 .- 1549-5469. ; 19:1, s. 1-11
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Tidskriftsartikel (refereegranskat)abstract
- To identify genes that are regulated by cis-acting functional elements in acute lymphoblastic leukemia (ALL) we determined the allele-specific expression (ASE) levels of 2, 529 genes by genotyping a genome-wide panel of single nucleotide polymorphisms in RNA and DNA from bone marrow and blood samples of 197 children with ALL. Using a reproducible, quantitative genotyping method and stringent criteria for scoring ASE, we found that 16% of the analyzed genes display ASE in multiple ALL cell samples. For most of the genes, the level of ASE varied largely between the samples, from 1.4-fold overexpression of one allele to apparent monoallelic expression. For genes exhibiting ASE, 55% displayed bidirectional ASE in which overexpression of either of the two SNP alleles occurred. For bidirectional ASE we also observed overall higher levels of ASE and correlation with the methylation level of these sites. Our results demonstrate that CpG site methylation is one of the factors that regulates gene expression in ALL cells.
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| 10. |
- Milani, Lili, et al.
(författare)
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DNA methylation for subtype classification and prediction of treatment outcome in patients with childhood acute lymphoblastic leukemia.
- 2010
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Ingår i: Blood. - : American Society of Hematology. - 0006-4971 .- 1528-0020. ; 115:6, s. 1214-25
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 11. |
- Molgaard-Hansen, Lene, et al.
(författare)
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Early and treatment-related deaths in childhood acute myeloid leukaemia in the Nordic countries: 1984-2003.
- 2010
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Ingår i: British journal of haematology. - : Wiley. - 1365-2141 .- 0007-1048. ; 151:5, s. 447-59
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Tidskriftsartikel (refereegranskat)abstract
- Despite major improvements in the cure rate of childhood acute myeloid leukaemia (AML), 5-15% of patients still die from treatment-related complications. In a historical prospective cohort study, we analysed the frequency, clinical features and risk factors for early deaths (ED) and treatment-related deaths (TRD) in 525 children included in the Nordic Society of Paediatric Haematology and Oncology (NOPHO)-AML-84, -88 and -93 trials. Seventy patients (13%) died before starting treatment or from treatment-related complications. The death rate rose from 11% in NOPHO-AML-84 to 29% in -88, but then fell to 8% in -93. Sixteen patients (3%) died within the first 2 weeks, mainly from bleeding or leucostasis. Hyperleucocytosis, age <2 or ≥10 years were risk factors. After day 15, 10% of patients died from treatment-related complications with infection as the main cause of death. Risk factors were age <2 or ≥10 years and treatment according to the NOPHO-AML-88 protocol. The number of EDs and TRDs in AML is high. Therefore optimal antifungal prophylaxis is essential, and studies on the benefit of antibacterial prophylaxis and individual risk factors for ED and TRD are needed.
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| 12. |
- Molgaard-Hansen, Lene, et al.
(författare)
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Quality of health in survivors of childhood acute myeloid leukemia treated with chemotherapy only : a NOPHO-AML study
- 2011
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Ingår i: Pediatric Blood & Cancer. - : Wiley. - 1545-5009 .- 1545-5017. ; 57:7, s. 1222-1229
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: More than 60% of children with acute myeloid leukemia (AML) become long-term survivors, and approximately 50% are cured with chemotherapy only. Limited data exist about their long-term morbidity and social outcomes. The aim of the study was to compare the self-reported use of health care services, health experience, social outcomes, and lifestyle behavior of AML survivors with that of their sibling controls. METHODS: This population-based study included 138 children treated for AML according to the Nordic Society of Pediatric Hematology and Oncology (NOPHO)-AML-84, -88, and -93 trials, and alive by June 30, 2007. Patients treated with hematopoietic stem cell transplantation (HSCT) or relapse were not included. Altogether, 102 (74%) survivors and 91% of their siblings completed a questionnaire. RESULTS: The median follow-up was 11 (range 4-25) years after diagnosis. AML survivors had no increased rate of hospitalization compared with sibling controls, but were more often receiving prescription drugs, especially for asthma (23% vs. 9%, P = 0.03). Self-reported health experience was excellent or very good in 77% and comparable with that of siblings. Educational achievement, employment, and marital status were comparable in the two groups. Among surviving AML patients, 23% were current smokers and 24% of their siblings were current smokers. CONCLUSIONS: The self-reported health of children treated on NOPHO-AML protocols without HSCT was good, and their use of health care services was limited. Reported health and social outcomes were comparable to those of their siblings. Many survivors were smoking which may increase the risk of late effects.
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| 13. |
- Molgaard-Hansen, Lene, et al.
(författare)
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Treatment-related deaths in second complete remission in childhood acute myeloid leukaemia.
- 2011
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Ingår i: British journal of haematology. - : Wiley. - 1365-2141 .- 0007-1048. ; 152:5, s. 623-30
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Tidskriftsartikel (refereegranskat)abstract
- The frequency and causes of treatment-related deaths (TRD) in second complete remission (CR2) in acute myeloid leukaemia (AML) were investigated in a historical, prospective cohort study of 429 children included in the Nordic Society of Paediatric Haematology and Oncology (NOPHO)-AML-88 and -93 trials. Relapse occurred in 158 children (39%). Seventeen (18%) of the 96 patients entering CR2 suffered TRD. The main causes were infection (59%) and complications from graft-versus-host disease (22%). Fourteen (82%) of 17 TRDs occurred in children undergoing haematopoietic stem cell transplantations (HSCT). Optimal supportive care after HSCT is essential, and studies on risk factors for TRD are needed.
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| 14. |
- Olsen, Jørgen H, et al.
(författare)
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Lifelong Cancer Incidence in 47 697 Patients Treated for Childhood Cancer in the Nordic Countries.
- 2009
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Ingår i: Journal of the National Cancer Institute. - : Oxford University Press (OUP). - 1460-2105 .- 0027-8874. ; 101, s. 806-813
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Tidskriftsartikel (refereegranskat)abstract
- Background The pattern of cancer in long-term survivors from childhood cancer has not been investigated comprehensively. Methods We obtained a cohort of 47 697 children and adolescents aged 0-19 years with cancer as defined by the country-wide cancer registries of Denmark, Finland, Iceland, Norway, and Sweden during 1943-2005. Cohort members were followed through age 79 years for subsequent primary cancers notified to the registries, and the age-specific risk pattern of the survivors was compared with that of the national populations using country and sex standardized incidence ratios (SIRs). We used a multiplicative Poisson regression model to estimate relative risk of cancer for attained age, with adjustment for calendar period and age at diagnosis of primary cancer. We also calculated excess absolute risk (EAR) attributable to status as childhood cancer survivor and determined the cumulative incidence of second primary cancer as a function of attained age for three subcohorts defined by period of treatment for childhood cancer. Results A total of 1180 asynchronous second primary cancers were observed in 1088 persons, yielding an overall SIR of 3.3 (95% confidence interval = 3.1 to 3.5). The relative risk was statistically significantly increased in all age groups, even for cohort members approaching 70 years of age. The EAR for second primary cancer among survivors increased gradually from one additional case per 1000 person-years of observation in early life to six additional cases per 1000 person-years in the age group 60-69 years. For children treated in the prechemotherapy era (1943-1959), the cumulative risk for a second primary cancer reached 18%, 34%, and 48% at ages 60, 70, and 80 years, respectively. The age-specific incidence rates were highest for cohort members treated in the era of intensive, multiple-agent chemotherapy (1975-2005). Conclusion Survivors of childhood cancer have a persistent excess risk for a second primary cancer throughout their lives, accompanied by continuous changes in the risk of cancers at specific sites.
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| 17. |
- Skou, Anne-Sofie, et al.
(författare)
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Renal, gastrointestinal, and hepatic late effects in survivors of childhood acute myeloid leukemia treated with chemotherapy only--a NOPHO-AML study.
- 2014
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Ingår i: Pediatric Blood & Cancer. - : Wiley. - 1545-5009 .- 1545-5017. ; 61:9, s. 1638-1643
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: We investigated the spectrum, frequency, and risk factors for renal, gastrointestinal, and hepatic late adverse effects in survivors of childhood acute myeloid leukemia (AML) without relapse treated with chemotherapy alone according to three consecutive AML trials by the Nordic Society of Pediatric Hematology and Oncology (NOPHO).METHODS: A population-based cohort of children treated for AML according to the NOPHO-AML-84, -88, and -93 trials included 138 eligible survivors of whom 102 (74%) completed a questionnaire and 104 (75%) had a clinical examination and blood sampling performed. Eighty-five of 94 (90%) eligible sibling controls completed a similar questionnaire. Siblings had no clinical examination or blood sampling performed.RESULTS: At a median of 11 years (range 4-25) after diagnosis, renal, gastrointestinal, and hepatic disorders were rare both in survivors of childhood AML and in sibling controls, with no significant differences. Ferritin was elevated in 21 (21%) AML survivors but none had biochemical signs of liver damage. Viral hepatitis was present in three and cholelithiasis in two AML survivors. One adult survivor had hypertension, two had slightly elevated systolic blood pressure, and eight survivors had slightly elevated diastolic blood pressure. These persons all had normal creatinine and cystatin C levels. Marginal abnormalities in potassium, magnesium, calcium, or bicarbonate levels were found in 34 survivors.CONCLUSION: Survivors of childhood AML treated with chemotherapy only experienced few renal, gastrointestinal, and hepatic late effects.
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| 18. |
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| 19. |
- Wendtland Edslev, Pernille, et al.
(författare)
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Age and Prognosis in Pediatric AML
- 2008
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Ingår i: Blood. - 1528-0020 .- 0006-4971. ; 112:11
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Konferensbidrag (refereegranskat)
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