| 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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| 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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| 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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