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| 2. |
- Holmqvist, Anna Sällfors, et al.
(författare)
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Late morbidity and mortality after autologous blood or marrow transplantation for lymphoma in children, adolescents and young adults—a BMTSS report
- 2024
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Ingår i: Leukemia. - 0887-6924. ; 38:3, s. 601-609
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Tidskriftsartikel (refereegranskat)abstract
- We determined the risk of late morbidity and mortality after autologous blood or marrow transplantation (BMT) for lymphoma performed before age 40. The cohort included autologous BMT recipients who had survived ≥2 years after transplantation (N = 583 [HL = 59.9%; NHL = 40.1%]) and a comparison cohort (N = 1070). Participants self-reported sociodemographics and chronic health conditions. A severity score (grade 3 [severe], 4 [life threatening] or 5 [fatal]) was assigned to the conditions using CTCAE v5.0. Logistic regression estimated the odds of grade 3–4 conditions in survivors vs. comparison subjects. Proportional subdistribution hazards models identified predictors of grade 3–5 conditions among BMT recipients. Median age at BMT was 30.0 years (range: 2.0–40.0) and median follow-up was 9.8 years (2.0–32.1). Survivors were at a 3-fold higher adjusted odds for grade 3–4 conditions (95% CI = 2.3–4.1) vs. comparison subjects. Factors associated with grade 3–5 conditions among BMT recipients included age at BMT (>30 years: adjusted hazard ratio [aHR] = 2.31; 95% CI = 1.27–4.19; reference: ≤21 years), pre-BMT radiation (aHR = 1.52; 95% CI = 1.13–2.03; reference: non-irradiated), and year of BMT (≥2000: aHR = 0.54; 95% CI = 0.34–0.85; reference: <1990). The 25 years cumulative incidence of relapse-related and non-relapse-related mortality was 18.2% and 25.9%, respectively. The high risk for late morbidity and mortality after autologous BMT for lymphoma performed at age <40 calls for long-term anticipatory risk-based follow-up.
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| 3. |
- Holmqvist, Anna Sällfors, et al.
(författare)
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Severe, life-threatening, and fatal chronic health conditions after allogeneic blood or marrow transplantation in childhood
- 2023
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Ingår i: Cancer. - : Wiley. - 0008-543X .- 1097-0142. ; 129:4, s. 624-633
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Tidskriftsartikel (refereegranskat)abstract
- Background: A comprehensive assessment of morbidity after allogeneic bone marrow transplantation (BMT) performed in childhood remains understudied. Methods: Seven hundred eighty-nine allogeneic BMT recipients who had survived ≥2 years after BMT performed between 1974 and 2014 at age <22 years and 690 siblings completed a 255-item survey self-reporting sociodemographics and chronic health conditions. A severity score (grade 3 [severe], 4 [life-threatening], or 5 [fatal]) was assigned to the conditions using Common Terminology Criteria for Adverse Events, version 5.0. For the BMT cohort, the cumulative incidence of chronic health conditions was calculated as a function of time from BMT. Proportional subdistribution hazards models were used to determine predictors of grade 3–5 conditions. Logistic regression was used to estimate the risk of grade 3–4 conditions in BMT recipients who were alive at the time of this study compared with siblings. Results: The median age at transplantation was 11.3 years (range, 0.4–22.0 years), and the median length of follow-up was 11.7 years (range, 2.0–45.3 years). The most prevalent primary diagnoses were acute lymphoblastic leukemia (30.7%), and acute myeloid leukemia/myelodysplastic syndrome (26.9%). At age 35 years, the cumulative incidence of a grade 3–4 condition was 53.8% (95% CI, 46.7%–60.3%). The adjusted odds ratio of a grade 3–4 condition was 15.1 in survivors (95% CI, 9.5–24.0) compared with siblings. The risk of a grade 3–5 condition increased with age at BMT (hazard ratio [HR], 1.03; 95% CI, 1.01–1.05) and was higher among females (HR, 1.27; 95% CI, 1.02–1.59), patients who received total body irradiation (HR, 1.71; 95% CI, 1.27–2.31), and those reporting chronic graft-versus-host disease (HR, 1.38; 95% CI, 1.09–1.74). Conclusions: Two-year survivors of allogeneic BMT in childhood have an increased risk of grade 3–4 chronic health conditions compared with siblings, suggesting the need for long-term follow-up.
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| 4. |
- Oskarsson, T., et al.
(författare)
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Osteoporotic Fractures in Childhood Cancer Survivors - ALICCS Cohort Study
- 2018
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Ingår i: Pediatric Blood & Cancer. - : John Wiley & Sons. - 1545-5009 .- 1545-5017. ; 65:Suppl.2, s. S693-S694
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Background/Objectives: Children and adolescents undergoing treatment for cancer are exposed to multiple factors that impact the development of peak bone mass and bone quality. The aims of this study were to examine the risks and cumulative incidence of osteoporotic fractures in childhood cancer survivors and identify subgroups at higher risk.Design/Methods: In the national cancer registries of Denmark, Finland, Iceland and Sweden we identified patients diagnosed with cancer before 20 years of age from the start of registration in the 1940s and 1950s through 2008. We compared 26.334 one‐year survivors with a cohort of 162.372 age‐ and sex‐matched population comparison subjects selected from the national population registries. With data derived from national hospital registries we estimated the standardized hospitalization rate ratios (SHRR) and the mean cumulative count (MCC) of hospital admissions for osteoporotic fractures. To identify subgroups at risk we used Cox regression models to generate hazard ratios (HR) for osteoporotic fractures. Death and new cancer were treated as competing risks.Results: The estimated SHRR for the first osteoporotic fracture was 1.41 (95% CI; 1.27‐1.58) but the MCC for recurrent osteoporotic fractures did not differ between the survivors and the comparison group. The SHRR for isolated hip fractures was 2.90 (2.32‐3.63). The adjusted HR for osteoporotic fracture as the first event was 1.53 (1.09‐2.16) if cancer was diagnosed 15‐19 years and 2.10 (1.48‐2.98) for long‐term survivors of CNS tumors. Survivors 15‐19 years at cancer diagnosis and long‐term survivors of CNS tumors were also at higher risk of experiencing a second fracture, HR 3.29 (1.65‐6.55) and HR 2.71 (1.45‐5.05), respectively.Conclusions: Childhood cancer survivors are at higher risk of being hospitalized for osteoporotic fractures but the burden of recurrent fractures is not higher. For subgroups at risk, surveillance of bone health and measures to increase bone strength and prevent fractures should be encouraged.
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| 5. |
- Schleiermacher, G., et al.
(författare)
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Emergence of New ALK Mutations at Relapse of Neuroblastoma
- 2014
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Ingår i: Journal of Clinical Oncology. - : American Society of Clinical Oncology (ASCO). - 0732-183X .- 1527-7755. ; 32:25, s. 2727-2734
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Tidskriftsartikel (refereegranskat)abstract
- Purpose In neuroblastoma, the ALK receptor tyrosine kinase is activated by point mutations. We investigated the potential role of ALK mutations in neuroblastoma clonal evolution. We analyzed ALK mutations in 54 paired diagnosis-relapse neuroblastoma samples using Sanger sequencing. When an ALK mutation was observed in one paired sample, a minor mutated component in the other sample was searched for by more than 100,000 x deep sequencing of the relevant hotspot, with a sensitivity of 0.17%. All nine ALK-mutated cases at diagnosis demonstrated the same mutation at relapse, in one case in only one of several relapse nodules. In five additional cases, the mutation seemed to be relapse specific, four of which were investigated by deep sequencing. In two cases, no mutation evidence was observed at diagnosis. In one case, the mutation was present at a subclonal level (0.798%) at diagnosis, whereas in another case, two different mutations resulting in identical amino acid changes were detected, one only at diagnosis and the other only at relapse. Further evidence of clonal evolution of ALK-mutated cells was provided by establishment of a fully ALK-mutated cell line from a primary sample with an ALK-mutated cell population at subclonal level (6.6%). In neuroblastoma, subclonal ALK mutations can be present at diagnosis with subsequent clonal expansion at relapse. Given the potential of ALK-targeted therapy, the significant spatiotemporal variation of ALK mutations is of utmost importance, highlighting the potential of deep sequencing for detection of subclonal mutations with a sensitivity 100-fold that of Sanger sequencing and the importance of serial samplings for therapeutic decisions.
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| 6. |
- Asdahl, Peter H, et al.
(författare)
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The adult life after childhood cancer in scandinavia (ALiCCS) study: Design and characteristics.
- 2015
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Ingår i: Pediatric Blood & Cancer. - : Wiley. - 1545-5017 .- 1545-5009. ; 62:12, s. 2204-2210
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Tidskriftsartikel (refereegranskat)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.
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| 9. |
- Bonnesen, Trine G., et al.
(författare)
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Disease-specific Hospitalizations among 5-Year Survivors of Hepatoblastoma : A Nordic Population-based Cohort Study
- 2019
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Ingår i: Journal of Pediatric Hematology/Oncology. - 1077-4114. ; 41:3, s. 181-186
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Tidskriftsartikel (refereegranskat)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.
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| 10. |
- Bonnesen, Trine Gade, et al.
(författare)
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Liver diseases in Adult Life after Childhood Cancer in Scandinavia (ALiCCS) : A population-based cohort study of 32,839 one-year survivors
- 2018
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Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136. ; 142:4, s. 702-708
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Tidskriftsartikel (refereegranskat)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.
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