| 1. |
- Bonnesen, Trine Gade, et al.
(author)
-
Long-term risk of renal and urinary tract diseases in childhood cancer survivors : A population-based cohort study
- 2016
-
In: European Journal of Cancer. - : Elsevier BV. - 0959-8049. ; 64, s. 52-61
-
Journal article (peer-reviewed)abstract
- Background Childhood cancer has been associated with long-term risk of urinary tract diseases, but risk patterns remain to be comprehensively investigated. We analysed the lifetime risk of urinary tract diseases in survivors of childhood cancer in the Nordic countries. Methods We identified 32,519 one-year survivors of childhood cancer diagnosed since the 1940s and 1950s in the five Nordic cancer registries and selected 211,156 population comparisons of a corresponding age, sex, and country of residence from the national population registries. To obtain information on all first-time hospitalizations for a urinary tract disease, we linked all study subjects to the national hospital registry of each country. Relative risks (RRs) and absolute excess risks (AERs) and associated 95% confidence intervals (CIs) for urinary tract diseases among cancer survivors were calculated with the appropriate morbidity rates among comparisons as reference. Results We observed 1645 childhood cancer survivors ever hospitalized for urinary tract disease yielding an RR of 2.5 (95% CI 2.4-2.7) and an AER of 229 (95% CI 210-248) per 100,000 person-years. The cumulative risk at age 60 was 22% in cancer survivors and 10% in comparisons. Infections of the urinary system and chronic kidney disease showed the highest excess risks, whereas survivors of neuroblastoma, hepatic and renal tumours experienced the highest RRs. Conclusion Survivors of childhood cancer had an excess risk of urinary tract diseases and for most diseases the risk remained elevated throughout life. The highest risks occurred following therapy of childhood abdominal tumours.
|
|
| 2. |
- Norsker, Filippa Nyboe, et al.
(author)
-
Neurologic disorders in long-term survivors of neuroblastoma–a population-based cohort study within the Adult Life after Childhood Cancer in Scandinavia (ALiCCS) research program
- 2020
-
In: Acta Oncologica. - 0284-186X. ; 59:2, s. 134-140
-
Journal article (peer-reviewed)abstract
- Background: Neuroblastoma is the commonest extracranial solid tumor of childhood, yet rare, and with poor survival before 1990, especially for high-risk disease; thus, information on late effects is sparse. With great advances in cancer treatment, survival has reached 80% in the Nordic countries. The aim of the study was to investigate the risk of developing neurologic disorders after neuroblastoma. Material and methods: Through population-based cancer registries of four Nordic countries we identified 654 5-year survivors of neuroblastoma (diagnosed 1959–2008) and 133,668 matched population comparisons. We grouped neurologic diagnoses from national hospital registries into 11 main diagnostic categories and 56 disease-specific sub-categories and calculated relative risks (RRs), absolute excess risks (AERs), cumulative incidence and mean cumulative count (MCC). Information on cancer treatment was available for 49% of survivors. Results: A hospital contact for a neurologic disorder was observed in 181 survivors 5 years or more from cancer diagnosis with 59 expected, yielding a RR of 3.1 (95% CI 2.7–3.6) and an AER of 16 per 1,000 person-years (95% CI 12–19). The most frequent disorders included epilepsy, paralytic syndromes, diseases of the eyes and ears and hearing loss. The cumulative incidence of any neurologic disorder was 31% in survivors 20 years after cancer diagnosis with a MCC of 0.5 unique diagnoses. All risks were highest in survivors of high-risk neuroblastoma. Conclusion: Neuroblastoma survivors represent a population with a high risk of developing neurologic disorders. Our results should contribute to improving health care planning and underscores the need for systematic follow-up care of this vulnerable group of survivors.
|
|
| 3. |
- Norsker, Filippa Nyboe, et al.
(author)
-
Risk of late health effects after soft-tissue sarcomas in childhood–a population-based cohort study within the Adult Life after Childhood Cancer in Scandinavia research programme
- 2020
-
In: Acta Oncologica. - 0284-186X. ; 59:10, s. 1-11
-
Journal article (peer-reviewed)abstract
- Background: In the 1960s only 1/3 of children with soft-tissue sarcomas survived, however with improved treatments survival today has reached 70%. Given the previous poor survival and the rarity of soft-tissue sarcomas, the risk of somatic late effects in a large cohort of Nordic soft-tissue sarcoma survivors has not yet been assessed. Methods: In this population-based cohort study we identified 985 five-year soft-tissue sarcoma survivors in Nordic nationwide cancer registries and late effects in national hospital registries covering the period 1964–2012. Information on tumour site and radiotherapy was available for Danish and Finnish survivors (N = 531). Using disease-specific rates of first-time hospital contacts for somatic diseases in survivors and in 4,830 matched comparisons we calculated relative rates (RR) and rate differences (RD). Results: Survivors had a RR of 1.5 (95% CI 1.4–1.7) and an absolute RD of 23.5 (17.7–29.2) for a first hospital contact per 1,000 person-years. The highest risks in both relative and absolute terms were of endocrine disorders (RR = 2.5; RD = 7.6), and diseases of the nervous system (RR = 1.9; RD = 6.6), digestive organs (RR = 1.7; RD = 5.4) and urinary system (RR = 1.7; RD = 5.6). By tumour site, excess risk was lower after extremity tumours. Irradiated survivors had a 2.6 (1.2–5.9) times higher risk than non-irradiated. Conclusions: Soft-tissue sarcoma survivors have an increased risk of somatic late effects in 5 out of 10 main diagnostic groups of diseases, and the risk remains increased up to 40 years after cancer diagnosis. Risks were slightly lower for those treated for tumours in the extremities, and radiotherapy increased the risk by more than two-fold.
|
|
| 4. |
- Norsker, Filippa Nyboe, et al.
(author)
-
Somatic late effects in 5-year survivors of neuroblastoma : a population-based cohort study within the Adult Life after Childhood Cancer in Scandinavia study
- 2018
-
In: International Journal of Cancer. - : Wiley. - 0020-7136. ; 143:12, s. 3083-3096
-
Journal article (peer-reviewed)abstract
- Because of the rarity of neuroblastoma and poor survival until the 1990s, information on late effects in neuroblastoma survivors is sparse. We comprehensively reviewed the long-term risk for somatic disease in neuroblastoma survivors. We identified 721 5-year survivors of neuroblastoma in Nordic population-based cancer registries and identified late effects in national hospital registries covering the period 1977–2012. Detailed treatment information was available for 46% of the survivors. The disease-specific rates of hospitalization of survivors and of 152,231 randomly selected population comparisons were used to calculate standardized hospitalization rate ratios (SHRRs) and absolute excess risks (AERs). During 5,500 person-years of follow-up, 501 5-year survivors had a first hospital contact yielding a SHRR of 2.3 (95% CI 2.1–2.6) and a corresponding AER of 52 (95% CI 44–60) per 1,000 person-years. The highest relative risks were for diseases of blood and blood-forming organs (SHRR 3.8; 95% CI 2.7–5.4), endocrine diseases (3.6 [3.1–4.2]), circulatory system diseases (3.1 [2.5–3.8]), and diseases of the nervous system (3.0 [2.6–3.3]). Approximately 60% of the excess new hospitalizations of survivors were for diseases of the nervous system, urinary system, endocrine system, and bone and soft tissue. The relative risks and AERs were highest for the survivors most intensively treated. Survivors of neuroblastoma have a highly increased long-term risk for somatic late effects in all the main disease groups as compared to background levels. Our results are useful for counseling survivors and should contribute to improving health care planning in post-therapy clinics.
|
|
| 5. |
- Abildgaard, Lotte, et al.
(author)
-
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
-
In: Annals of hematology. - : Springer Science and Business Media LLC. - 0939-5555 .- 1432-0584. ; 85:5, s. 275-80
-
Journal article (peer-reviewed)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.
|
|
| 6. |
- Abrahamsson, Jonas, 1954, et al.
(author)
-
Associations between neutrophil recovery time, infections and relapse in pediatric acute myeloid leukemia
- 2018
-
In: Pediatric Blood & Cancer. - : John Wiley & Sons. - 1545-5009 .- 1545-5017. ; 65:9
-
Journal article (peer-reviewed)abstract
- BackgroundChildren with acute myeloid leukemia (AML) treated similarly show different toxicity and leukemic responses. We investigated associations between neutrophil recovery time after the first induction course, infection and relapse in children treated according to NOPHO-AML 2004 and DB AML-01. ProcedureNewly diagnosed patients with AML with bone marrow blast<5% between day 15 after the start of the treatment and the start of second induction course, and in complete remission after the second induction course were included (n=279). Neutrophil recovery time was defined as the time from the start of the course to the last day with absolute neutrophil count<0.5x10(9)/l. Linear and Cox regressions were used to investigate associations. ResultsNeutrophil recovery time after the first induction course was positively associated with neutrophil recovery time after the remaining courses, and longer neutrophil recovery time (25 days) was associated with increased risk of grade 3-4 infections (hazard ratio 1.4, 95% confidence interval [CI], 1.1-1.8). Longer neutrophil recovery time after the first induction (>30 days) was associated with the increased risk of relapse (5-year cumulative incidence: 48% vs. 42%, hazard ratio 1.7, 95% CI, 1.1-2.6) for cases not treated with hematopoietic stem cell transplantation in first complete remission. ConclusionLonger neutrophil recovery time after the first induction course was associated with grade 3-4 infections and relapse. If confirmed, this knowledge could be incorporated into risk stratification strategies in pediatric AML.
|
|
| 7. |
- Abrahamsson, Jonas, 1954, et al.
(author)
-
Improved outcome after relapse in children with acute myeloid leukaemia.
- 2007
-
In: British journal of haematology. - : Wiley. - 0007-1048 .- 1365-2141. ; 136:2, s. 229-236
-
Journal article (peer-reviewed)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%.
|
|
| 8. |
|
|
| 9. |
- Abrahamsson, Jonas, 1954, et al.
(author)
-
Use of granulocyte colony-stimulating factor and risk of relapse in pediatric patients treated for acute myeloid leukemia according to NOPHO-AML 2004 and DB AML-01.
- 2019
-
In: Pediatric blood & cancer. - : Wiley. - 1545-5017 .- 1545-5009. ; 66:6
-
Journal article (peer-reviewed)abstract
- Supportive-care use of granulocyte colony-stimulating factor (G-CSF) in pediatric acute myeloid leukemia (AML) remains controversial due to a theoretical increased risk of relapse and limited impact on neutropenic complications. We describe the use of G-CSF in patients treated according to NOPHO-AML 2004 and DB AML-01 and investigated associations with relapse.Patients diagnosed with de novo AML completing the first week of therapy and not treated with hematopoietic stem cell transplantation in the first complete remission were included (n=367). Information on G-CSF treatment after each course (yes/no) was registered prospectively in the study database and detailed information was gathered retrospectively from each center. Descriptive statistics were used to describe G-CSF use and Cox regression to assess the association between G-CSF and risk of relapse.G-CSF as supportive care was given to 128 (35%) patients after 268 (39%) courses, with a large variation between centers (0-93%). The use decreased with time-the country-adjusted odds ratio was 0.8/diagnostic year (95% confidence interval [CI] 0.7-0.9). The median daily dose was 5 μg/kg (range 3-12 μg/kg) and the median cumulative dose was 75 μg/kg (range 7-1460 μg/kg). Filgrastim was used in 82% of G-CSF administrations and infection was the indication in 44% of G-CSF administrations. G-CSF was associated with increased risk of relapse-the adjusted hazard ratio was 1.5 (95% CI 1.1-2.2).G-CSF as supportive care was used in a third of patients, and use decreased with time. Our results indicate that the use of G-CSF may be associated with an increased risk of relapse.
|
|
| 10. |
- Adolfsen Løhmann, DJ, et al.
(author)
-
Associations between Pre-therapeutic Body Mass Index, Outcome and Cytogenetic Abnormalities in Pediatric Acute Myeloid Leukemia
- 2019
-
In: 38th NOPHO Annual meeting. Aalborg, Denmark 3-7 May.
-
Conference paper (other academic/artistic)abstract
- Introduction: Associations between body mass index (BMI), outcome and leukemia-related factors in children with acute myeloid leukemia (AML) are unclear. Aim: To investigate associations between pre-therapeutic BMI, cytogenetic abnormalities, and outcome in a large multinational cohort of children with AML. Methods: We included patients age 2–17 years, diagnosed with de novo AML from the five Nordic countries (2004–2016), Hong Kong (2007–2016), the Netherlands and Belgium (2010–2016), and Canada and USA (1995–2012). Cases with Down syndrome, acute promyelocytic leukemia, or isolated granulocytic sarcoma were excluded. Cases with missing data on pre-therapeutic BMI (n=7) were also excluded. BMI standard deviations score for age and sex was calculated and categorized according to the World Health Organization. Cumulative incidence functions, Cox regression and logistic regression were used to investigate associations. Results: In total, 867 patients were included. The median age was 10 years (range 2–17 years) and 53% were male. At diagnosis, 4% were underweight, 73% were healthy weight, 15% were overweight, and 9% were obese. Patients were treated on 17 different protocols with AAML0531, COG9421, NOPHO-AML 2004, DB AML-01 and NOPHO-DBH AML 2012 accounting for 79%. There was no difference in relapse risk, treatment-related mortality or overall mortality across BMI groups. The frequency of t(8;21) and inv(16) increased with increasing BMI. For obese patients, the sex, age and country adjusted odds ratio of having t(8;21) or inv(16) were 1.9 (95% confidence interval (CI) 1.1–3.4) and 2.8 (95% CI 1.3–5.8) respectively compared to healthy weight patients. Conclusion: This multi-institutional study of 867 pediatric patients with de novo AML did not confirm previous reports of associations between overweight and increased treatment-related or overall mortality in children. Obesity was associated with a higher frequency of t(8;21) and inv(16). AML cytogenetics appear to differ by BMI status.
|
|
| 11. |
|
|
| 12. |
- Arad-Cohen, Nira, et al.
(author)
-
Supportive care in pediatric acute myeloid leukemia:Expert-based recommendations of the NOPHO-DB-SHIP consortium
- 2022
-
In: Expert Review of Anticancer Therapy. - : Taylor & Francis Group. - 1473-7140 .- 1744-8328. ; 22:11, s. 1183-1196
-
Research review (peer-reviewed)abstract
- Introduction Pediatric acute myeloid leukemia (AML) is the second most common type of pediatric leukemia. Patients with AML are at high risk for several complications such as infections, typhlitis, and acute and long-term cardiotoxicity. Despite this knowledge, there are no definite supportive care guidelines as to what the best approach is to manage or prevent these complications. Area covered The NOPHO-DB-SHIP (Nordic-Dutch-Belgian-Spain-Hong-Kong-Israel-Portugal) consortium, in preparation for a new trial in pediatric AML patients, had dedicated meetings for supportive care. In this review, the authors discuss the available data and outline recommendations for the management of children and adolescents with AML with an emphasis on hyperleukocytosis, tumor lysis syndrome, coagulation abnormalities and bleeding, infection, typhlitis, malnutrition, cardiotoxicity, and fertility preservation. Expert opinion Improved supportive care has significantly contributed to increased cure rates. Recommendations on supportive care are an essential part of treatment for this highly susceptible population and will further improve their outcome.
|
|
| 13. |
- Asdahl, Peter Haubjerg, et al.
(author)
-
Gastrointestinal and liver disease in Adult Life After Childhood Cancer in Scandinavia : A population-based cohort study
- 2016
-
In: International Journal of Cancer. - : Wiley. - 0020-7136. ; 139:7, s. 1501-1511
-
Journal article (peer-reviewed)abstract
- Survival after childhood cancer diagnosis has remarkably improved, but emerging evidence suggests that cancer-directed therapy may have adverse gastrointestinal late effects. We aimed to comprehensively assess the frequency of gastrointestinal and liver late effects among childhood cancer survivors and compare this frequency with the general population. Our population-based cohort study included all 1-year survivors of childhood and adolescent cancer in Denmark, Finland, Iceland, Norway and Sweden diagnosed from the 1940s and 1950s. Our outcomes of interest were hospitalization rates for gastrointestinal and liver diseases, which were ascertained from national patient registries. We calculated standardized hospitalization rate ratios (RRs) and absolute excess rates comparing hospitalizations of any gastrointestinal or liver disease and for specific disease entities between survivors and the general population. The study included 31,132 survivors and 207,041 comparison subjects. The median follow-up in the hospital registries were 10 years (range: 0-42) with 23% of the survivors being followed at least to the age of 40 years. Overall, survivors had a 60% relative excess of gastrointestinal or liver diseases [RR: 1.6, 95% confidence interval (CI): 1.6-1.7], which corresponds to an absolute excess of 360 (95% CI: 330-390) hospitalizations per 100,000 person-years. Survivors of hepatic tumors, neuroblastoma and leukemia had the highest excess of gastrointestinal and liver diseases. In addition, we observed a relative excess of several specific diseases such as esophageal stricture (RR: 13; 95% CI: 9.2-20) and liver cirrhosis (RR: 2.9; 95% CI: 2.0-4.1). Our findings provide useful information about the breadth and magnitude of late complications among childhood cancer survivors and can be used for generating hypotheses about potential exposures related to these gastrointestinal and liver late effects.
|
|
| 14. |
- Asdahl, Peter H, et al.
(author)
-
The adult life after childhood cancer in scandinavia (ALiCCS) study: Design and characteristics.
- 2015
-
In: Pediatric Blood & Cancer. - : Wiley. - 1545-5017 .- 1545-5009. ; 62:12, s. 2204-2210
-
Journal article (peer-reviewed)abstract
- During the last five decades, survival of childhood cancer has increased from 25% to 80%. At the same time, however, it has become evident that survivors experience a broad range of therapy-related late adverse health effects. The aim of the Adult Life after Childhood Cancer in Scandinavia (ALiCCS) study is to investigate long-term health consequences of past and current therapies in order to improve follow-up care of survivors and to reduce treatment-related morbidity of future patients.
|
|
| 15. |
|
|
| 16. |
- Bager, Ninna, et al.
(author)
-
Complex and monosomal karyotype are distinct cytogenetic entities with an adverse prognostic impact in paediatric acute myeloid leukaemia : A NOPHO-DBH-AML study
- 2018
-
In: British Journal of Haematology. - : Wiley. - 0007-1048 .- 1365-2141. ; 183:4, s. 618-628
-
Journal article (peer-reviewed)abstract
- Data on occurrence, genetic characteristics and prognostic impact of complex and monosomal karyotype (CK/MK) in children with acute myeloid leukaemia (AML) are scarce. We studied CK and MK in a large unselected cohort of childhood AML patients diagnosed and treated according to Nordic Society for Paediatric Haematology and Oncology (NOPHO)-AML protocols 1993-2015. In total, 800 patients with de novo AML were included. CK was found in 122 (15%) and MK in 41 (5%) patients. CK and MK patients were young (median age 2.1 and 3.3 years, respectively) and frequently had FAB M7 morphology (24% and 22%, respectively). Refractory disease was more common in MK patients (15% vs. 4%) and stem cell transplantation in first complete remission was more frequent (32% vs. 19%) compared with non-CK/non-MK patients. CK showed no association with refractory disease but was an independent predictor of an inferior event-free survival (EFS; hazard ratio [HR] 1.43, P = 0.03) and overall survival (OS; HR 1.48, P = 0.01). MK was associated with a poor EFS (HR 1.57, P = 0.03) but did not show an inferior OS compared to non-MK patients (HR 1.14, P = 0.62). In a large paediatric cohort, we characterized AML with non-recurrent abnormal karyotype and unravelled the adverse impact of CK and MK on prognosis.
|
|
| 17. |
|
|
| 18. |
- Balgobind, Brian V, et al.
(author)
-
Novel prognostic subgroups in childhood 11q23/MLL-rearranged acute myeloid leukemia : results of an international retrospective study.
- 2009
-
In: Blood. - : American Society of Hematology. - 0006-4971 .- 1528-0020. ; 114:12, s. 2489-2496
-
Journal article (peer-reviewed)abstract
- Translocations involving chromosome 11q23 frequently occur in pediatric acute myeloid leukemia (AML) and are associated with poor prognosis. In most cases, the MLL gene is involved, and more than 50 translocation partners have been described. Clinical outcome data of the 11q23-rearranged subgroups are scarce because most 11q23 series are too small for meaningful analysis of subgroups, although some studies suggest that patients with t(9;11)(p22;q23) have a more favorable prognosis. We retrospectively collected outcome data of 756 children with 11q23- or MLL-rearranged AML from 11 collaborative groups to identify differences in outcome based on translocation partners. All karyotypes were centrally reviewed before assigning patients to subgroups. The event-free survival of 11q23/MLL-rearranged pediatric AML at 5 years from diagnosis was 44% (+/- 5%), with large differences across subgroups (11% +/- 5% to 92% +/- 5%). Multivariate analysis identified the following subgroups as independent prognostic predictors: t(1;11)(q21;q23) (hazard ratio [HR] = 0.1, P = .004); t(6;11)(q27;q23) (HR = 2.2, P < .001); t(10;11)(p12;q23) (HR = 1.5, P = .005); and t(10;11)(p11.2;q23) (HR = 2.5, P = .005). We could not confirm the favorable prognosis of the t(9;11)(p22;q23) subgroup. We identified large differences in outcome within 11q23/MLL-rearranged pediatric AML and novel subgroups based on translocation partners that independently predict clinical outcome. Screening for these translocation partners is needed for accurate treatment stratification at diagnosis.
|
|
| 19. |
|
|
| 20. |
- Blink, Marjolein, et al.
(author)
-
Normal karyotype is a poor prognostic factor in myeloid leukemia of Down syndrome : a retrospective, international study
- 2014
-
In: Haematologica. - : Ferrata Storti Foundation. - 0390-6078 .- 1592-8721. ; 99:2, s. 299-307
-
Journal article (peer-reviewed)abstract
- Myeloid leukemia of Down syndrome has a better prognosis than sporadic pediatric acute myeloid leukemia. Most cases of myeloid leukemia of Down syndrome are characterized by additional cytogenetic changes besides the constitutional trisomy 21, but their potential prognostic impact is not known. We, therefore, conducted an international retrospective study of clinical characteristics, cytogenetics, treatment, and outcome of 451 children with myeloid leukemia of Down syndrome. All karyotypes were centrally reviewed before assigning patients to subgroups. The overall 7-year event-free survival for the entire cohort was 78% (± 2%), with the overall survival rate being 79% (± 2%), the cumulative incidence of relapse 12% (± 2%), and the cumulative incidence of toxic death 7% (± 1%). Outcome estimates showed large differences across the different cytogenetic subgroups. Based on the cumulative incidence of relapse, we could risk-stratify patients into two groups: cases with a normal karyotype (n=103) with a higher cumulative incidence of relapse (21%± 4%) than cases with an aberrant karyotype (n=255) with a cumulative incidence of relapse of 9% (± 2%) (P=0.004). Multivariate analyses revealed that white blood cell count ≥ 20 × 10(9)/L and age >3 years were independent predictors for poor event-free survival, while normal karyotype independently predicted inferior overall survival, event-free survival, and relapse-free survival. In conclusion, this study showed large differences in outcome within patients with myeloid leukemia of Down syndrome and identified novel prognostic groups that predicted clinical outcome and hence may be used for stratification in future treatment protocols.
|
|
| 21. |
- Bonnesen, Trine G., et al.
(author)
-
Disease-specific Hospitalizations among 5-Year Survivors of Hepatoblastoma : A Nordic Population-based Cohort Study
- 2019
-
In: Journal of Pediatric Hematology/Oncology. - 1077-4114. ; 41:3, s. 181-186
-
Journal article (peer-reviewed)abstract
- Introduction: The long-term risk of somatic disease in hepatoblastoma survivors has not been thoroughly evaluated in previous studies. In this population-based study of 86 five-year HB survivors, we used inpatient registers to evaluate the risk for a range of somatic diseases.Methods: In total, 86 five-year survivors of hepatoblastoma were identified in the Nordic cancer registries from 1964 to 2008 and 152,231 population comparisons were selected. Study subjects were followed in national hospital registries for somatic disease classified into 12 main diagnostic groups. Standardized hospitalization rate ratios (RRs) and absolute excess risks were calculated.Results: After a median follow-up of 11 years, 35 of the 86 five-year hepatoblastoma survivors had been hospitalized with a total of 69 hospitalizations, resulting in an RR of 2.7 (95% confidence interval [CI], 2.2-3.5) and an overall absolute excess risk of 4.2 per 100 person-years. Highest risk was seen for benign neoplasms (RR=16) with 6 hospitalizations for benign neoplasms in the colon and one in rectum.Conclusions: The pattern of hospitalizations found in this first comprehensive follow-up of hepatoblastoma survivors seems reassuring. Less than 50% of the 5-year survivors had been hospitalized and often for diseases that were not severe or life-threatening.
|
|
| 22. |
- Bonnesen, Trine Gade, et al.
(author)
-
Liver diseases in Adult Life after Childhood Cancer in Scandinavia (ALiCCS) : A population-based cohort study of 32,839 one-year survivors
- 2018
-
In: International Journal of Cancer. - : Wiley. - 0020-7136. ; 142:4, s. 702-708
-
Journal article (peer-reviewed)abstract
- Information on late onset liver complications after childhood cancer is scarce. To ensure an appropriate follow-up of childhood cancer survivors and reducing late liver complications, the need for comprehensive and accurate information is presented. We evaluate the risk of liver diseases in a large childhood cancer survivor cohort. We included all 1-year survivors of childhood cancer treated in the five Nordic countries. A Cox proportional hazards model was used to estimate hospitalisation rate (hazard) ratios (HRs) for each liver outcome according to type of cancer. We used the risk among survivors of central nervous system tumour as internal reference. With a median follow-up time of 10 years, 659 (2%) survivors had been hospitalised at least once for a liver disease. The risk for hospitalisation for any liver disease was high after hepatic tumour (HR = 6.9) and leukaemia (HR = 1.7). The Danish sub-cohort of leukaemia treated with haematopoietic stem cell transplantation had a substantially higher risk for hospitalisation for all liver diseases combined (HR = 3.8). Viral hepatitis accounted for 286 of 659 hospitalisations corresponding to 43% of all survivors hospitalised for liver disease. The 20-year cumulative risk of viral hepatitis was 1.8% for survivors diagnosed with cancer before 1990 but only 0.3% for those diagnosed after 1990. The risk of liver disease was low but significantly increased among survivors of hepatic tumours and leukaemia. Further studies with focus on the different treatment modalities are needed to further strengthen the prevention of treatment-induced late liver complications.
|
|
| 23. |
|
|
| 24. |
- Borg Hammer, Anne Sofie, et al.
(author)
-
Hypodiploidy has unfavorable impact on survival in pediatric acute myeloid leukemia : An I-BFM Study Group collaboration
- 2023
-
In: Blood Advances. - : American Society of Hematology. - 2473-9529 .- 2473-9537. ; 7:6, s. 1045-1055
-
Journal article (peer-reviewed)abstract
- Hypodiploidy, defined as modal numbers (MNs) 45 or lower, has not been independently investigated in pediatric acute myeloid leukemia (AML) but is a well-described high-risk factor in pediatric acute lymphoblastic leukemia. We aimed to characterize and study the prognostic impact of hypodiploidy in pediatric AML. In this retrospective cohort study, we included children below 18 years of age with de novo AML and a hypodiploid karyotype diagnosed from 2000 to 2015 in 14 childhood AML groups from the International Berlin-Frankfurt-Münster (I-BFM) framework. Exclusion criteria comprised constitutional hypodiploidy, monosomy 7, composite karyotype, and t(8;21) with concurring sex chromosome loss. Hypodiploidy occurred in 81 patients (1.3%) with MNs, 45 (n = 66); 44 (n = 10) and 43 (n = 5). The most frequently lost chromosomes were chromosome 9 and sex chromosomes. Five-year event-free survival (EFS) and overall survival (OS) were 34% and 52%, respectively, for the hypodiploid cohort. Children with MN≤44 (n = 15) had inferior EFS (21%) and OS (33%) compared with children with MN = 45 (n = 66; EFS, 37%; OS, 56%). Adjusted hazard ratios (HRs) were 4.9 (P = .001) and 6.1 (P = .003). Monosomal karyotype or monosomy 9 had particular poor OS (43% and 15%, respectively). Allogeneic stem cell transplantation (SCT) in first complete remission (CR1) (n = 18) did not mitigate the unfavorable outcome of hypodiploidy (adjusted HR for OS was 1.5; P = .42). We identified pediatric hypodiploid AML as a rare subgroup with an inferior prognosis even in the patients treated with SCT in CR1.
|
|
| 25. |
- Borgstedt-Bendixen, Sofie E., et al.
(author)
-
Abdominal Complications During Treatment for Pediatric Acute Myeloid Leukemia
- 2022
-
In: Journal of Pediatric Hematology/Oncology. - : Ovid Technologies (Wolters Kluwer Health). - 1077-4114 .- 1536-3678. ; 44:5, s. 220-229
-
Journal article (peer-reviewed)abstract
- Acute myeloid leukemia (AML) accounts for 15% to 20% of childhood leukemias. Because of high-intensive therapy, up to 5% of patients suffer from treatment-related mortality (TRM). Abdominal complications are frequent, however, literature on this subject is sparse. We aimed to characterize severe abdominal pain (AP) and hyperbilirubinemia experienced by pediatric AML patients treated according to the Nordic Society of Pediatric Hematology and Oncology (NOPHO)-AML 2004 protocol (n=313). Patients were censored at hematopoietic stem cell transplantation and relapse. Toxicity information was collected prospectively. Additional information was requested retrospectively from the treating centers. Sixteen episodes of hyperbilirubinemia and 107 episodes of AP were reported. The treating centers deemed infection (30%) and typhlitis (18%) as the most frequent causes of AP. Six patients developed appendicitis (2%). Patients experiencing concurrent AP and sepsis had a high risk of TRM (36%, n=4). Eighty percent of episodes with hyperbilirubinemia fulfilled the European Society for Bone and Marrow Transplantation criteria for sinusoidal obstruction syndrome. In conclusion, abdominal complications were frequent with infection considered the predominate cause. Most patients with hyperbilirubinemia fulfilled the criteria for sinusoidal obstruction syndrome. AML treatment might be associated with appendicitis. Patients suffering from concurrent AP and sepsis had a high risk of TRM indicating that high awareness of abdominal complications is essential to reduce mortality, especially during sepsis.
|
|
