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| 3. |
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| 4. |
- Keune, H., et al.
(författare)
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Science-policy challenges for biodiversity, public health and urbanization : examples from Belgium
- 2013
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Ingår i: Environmental Research Letters. - : IOP Publishing. - 1748-9326. ; 8:2, s. 025015-
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Tidskriftsartikel (refereegranskat)abstract
- Internationally, the importance of a coordinated effort to protect both biodiversity and public health is more and more recognized. These issues are often concentrated or particularly challenging in urban areas, and therefore on-going urbanization worldwide raises particular issues both for the conservation of living natural resources and for population health strategies. These challenges include significant difficulties associated with sustainable management of urban ecosystems, urban development planning, social cohesion and public health. An important element of the challenge is the need to interface between different forms of knowledge and different actors from science and policy. We illustrate this with examples from Belgium, showcasing concrete cases of human-nature interaction. To better tackle these challenges, since 2011, actors in science, policy and the broader Belgian society have launched a number of initiatives to deal in a more integrated manner with combined biodiversity and public health challenges in the face of ongoing urbanization. This emerging community of practice in Belgium exemplifies the importance of interfacing at different levels. (1) Bridges must be built between science and the complex biodiversity/ecosystem-human/public health-urbanization phenomena. (2) Bridges between different professional communities and disciplines are urgently needed. (3) Closer collaboration between science and policy, and between science and societal practice is needed. Moreover, within each of these communities closer collaboration between specialized sections is needed.
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| 8. |
- Toft, N, et al.
(författare)
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Results of NOPHO ALL2008 treatment for patients aged 1-45 years with acute lymphoblastic leukemia.
- 2018
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Ingår i: Leukemia. - : Springer Science and Business Media LLC. - 1476-5551 .- 0887-6924. ; 32, s. 606-615
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Tidskriftsartikel (refereegranskat)abstract
- Adults with acute lymphoblastic leukemia (ALL) do worse than children. From 7/2008 to 12/2014, Nordic and Baltic centers treated 1509 consecutive patients aged 1-45 years with Philadelphia chromosome-negative ALL according to the NOPHO ALL2008 without cranial irradiation. Overall, 1022 patients were of age 1-9 years (A), 266 were 10-17 years (B) and 221 were 18-45 years (C). Sixteen patients (three adults) died during induction. All others achieved remission after induction or 1-3 intensive blocks. Subsequently, 45 patients (12 adults) died, 122 patients relapsed (32 adults) with a median time to relapse of 1.6 years and 13 (no adult) developed a second malignancy. Median follow-up time was 4.6 years. Among the three age groups, older patients more often had higher risk ALL due to T-ALL (32%/25%/9%, P<0.001), KMT2A rearrangements (6%/5%/3%, P<0.001) and higher day 29 residual leukemia for B-lineage (P<0.001), but not T-ALL (P=0.53). Event-free survival rates (pEFS5y) were 89±1% (A), 80±3% (B) and 74±4% (C) with significant differences only for non-high risk groups. Except for thrombosis, pancreatitis and osteonecrosis, the risk of 19 specified toxicities was not enhanced by age above 10 years. In conclusion, a pediatric-based protocol is tolerable and effective for young adults, despite their increased frequency of higher risk features.Leukemia advance online publication, 22 September 2017; doi:10.1038/leu.2017.265.
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| 9. |
- Beeckman, Dimitri, et al.
(författare)
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EPUAP classification system for pressure ulcers : european reliability study
- 2007
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Ingår i: Journal of Advanced Nursing. - 0309-2402 .- 1365-2648. - 0309-2402 ; 60:6, s. 682-691
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Tidskriftsartikel (refereegranskat)abstract
- Aim. This paper is a report of a study of the inter-observer reliability of the European Pressure Ulcer Advisory Panel pressure ulcer classification system and of the differential diagnosis between moisture lesions and pressure ulcers. Background. Pressure ulcer classification is a valuable tool to provide a common description of ulcer severity for the purposes of clinical practice, audit and research. Despite everyday use of the European Pressure Ulcer Advisory Panel system, its reliability has been evaluated in only a limited number of studies. Methods. A survey was carried out between September 2005 and February 2006 with a convenience sample of 1452 nurses from five European countries. Respondents classified 20 validated photographs as normal skin, blanchable erythema, pressure ulcers (four grades), moisture lesion or combined lesion. The nurses were familiar with the use of the European Pressure Ulcer Advisory Panel classification scale. Results. Pressure ulcers were often classified erroneously (kappa = 0.33) and only a minority of nurses reached a substantial level of agreement. Grade 3 lesions were regularly classified as grade 2. Non-blanchable erythema was frequently assessed incorrectly as blanchable erythema. Furthermore, the differential diagnosis between moisture lesions and pressure ulcers appeared to be complicated. Conclusion. Inter-observer reliability of the European Pressure Ulcer Advisory Panel classification system was low. Evaluation thus needs to focus on both the clarity and complexity of the system. Definitions and unambiguous descriptions of pressure ulcer grades and the distinction between moisture lesions will probably enhance clarity. To simplify the current classification system, a reduction in the number of grades is suggested.
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| 10. |
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| 11. |
- Kersten, CM, et al.
(författare)
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The Management of Asymptomatic Congenital Pulmonary Airway Malformation: Results of a European Delphi Survey
- 2022
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Ingår i: Children (Basel, Switzerland). - : MDPI AG. - 2227-9067. ; 9:8
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Tidskriftsartikel (refereegranskat)abstract
- Consensus on the optimal management of asymptomatic congenital pulmonary airway malformation (CPAM) is lacking, and comparison between studies remains difficult due to a large variety in outcome measures. We aimed to define a core outcome set (COS) for pediatric patients with an asymptomatic CPAM. An online, three-round Delphi survey was conducted in two stakeholder groups of specialized caregivers (surgeons and non-surgeons) in various European centers. Proposed outcome parameters were scored according to level of importance, and the final COS was established through consensus. A total of 55 participants (33 surgeons, 22 non-surgeons) from 28 centers in 13 European countries completed the three rounds and rated 43 outcome parameters. The final COS comprises seven outcome parameters: respiratory insufficiency, surgical complications, mass effect/mediastinal shift (at three time-points) and multifocal disease (at two time-points). The seven outcome parameters included in the final COS reflect the diversity in priorities among this large group of European participants. However, we recommend the incorporation of these outcome parameters in the design of future studies, as they describe measurable and validated outcomes as well as the accepted age at measurement.
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| 16. |
- Anastasopoulou, Stavroula, et al.
(författare)
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Acute central nervous system toxicity during treatment of pediatric acute lymphoblastic leukemia : phenotypes, risk factors and genotypes
- 2020
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Ingår i: Haematologica. - : Ferrata Storti Foundation. - 0390-6078 .- 1592-8721. ; 107:10, s. 2318-2328
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Tidskriftsartikel (refereegranskat)abstract
- Central nervous system (CNS) toxicity is common at diagnosis and during treatment of pediatric acute lymphoblastic leukemia (ALL). We studied CNS toxicity in 1,464 children aged 1.0-17.9 years, diagnosed with ALL and treated according to the Nordic Society of Pediatric Hematology and Oncology ALL2008 protocol. Genome-wide association studies, and a candidate single-nucleotide polymorphism (SNP; n=19) study were performed in 1,166 patients. Findings were validated in an independent Australian cohort of children with ALL (n=797) in whom two phenotypes were evaluated: diverse CNS toxicities (n=103) and methotrexate-related CNS toxicity (n=48). In total, 135/1,464 (9.2%) patients experienced CNS toxicity for a cumulative incidence of 8.7% (95% confidence interval: 7.31-10.20) at 12 months from diagnosis. Patients aged >= 10 years had a higher risk of CNS toxicity than had younger patients (16.3% vs. 7.4%; P < 0.001). The most common CNS toxicities were posterior reversible encephalopathy syndrome (n=52, 43 with seizures), sinus venous thrombosis (n=28, 9 with seizures), and isolated seizures (n=16). The most significant SNP identified by the genome-wide association studies did not reach genomic significance (lowest P-value: 1.11x10(-6)), but several were annotated in genes regulating neuronal functions. In candidate SNP analysis, ATXN1 rs68082256, related to epilepsy, was associated with seizures in patients < 10 years (P=0.01). ATXN1 rs68082256 was validated in the Australian cohort with diverse CNS toxicities (P=0.04). The role of ATXN1 as well as the novel SNP in neurotoxicity in pediatric ALL should be further explored.
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| 17. |
- Anastasopoulou, Stavroula, et al.
(författare)
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Posterior reversible encephalopathy syndrome in children with acute lymphoblastic leukemia : Clinical characteristics, risk factors, course, and outcome of disease
- 2019
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Ingår i: Pediatric Blood & Cancer. - : WILEY. - 1545-5009 .- 1545-5017. ; 66:5
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Tidskriftsartikel (refereegranskat)abstract
- Background: Posterior reversible encephalopathy syndrome (PRES) is a distinct entity with incompletely known predisposing factors. The aim of this study is to describe the incidence, risk factors, clinical course, and outcome of PRES in childhood acute lymphoblastic leukemia (ALL).Procedure: Patients aged 1.0 to 17.9 years diagnosed with ALL from July 2008 to December 2015 and treated according to the Nordic Society of Pediatric Hematology and Oncology (NOPHO) ALL2008 protocol were included. Patients with PRES were identified in the prospective NOPHO leukemia toxicity registry, and clinical data were collected from the medical records.Results: The study group included 1378 patients, of whom 52 met the criteria for PRES. The cumulative incidence of PRES at one month was 1.7% (95% CI, 1.1-2.5) and at one year 3.7% (95% CI, 2.9-4.9). Older age (hazard ratios [HR] for each one-year increase in age 1.1; 95% CI, 1.0-1.2, P = 0.001) and T-cell immunophenotype (HR, 2.9; 95% CI, 1.6-5.3, P = 0.0005) were associated with PRES. Central nervous system (CNS) involvement (odds ratios [OR] = 2.8; 95% CI, 1.2-6.5, P = 0.015) was associated with early PRES and high-risk block treatment (HR = 2.63; 95% CI, 1.1-6.4, P = 0.033) with late PRES. At follow-up of the PRES patients, seven patients had epilepsy and seven had neurocognitive difficulties.Conclusion: PRES is a neurotoxicity in the treatment of childhood ALL with both acute and long-term morbidity. Older age, T-cell leukemia, CNS involvement and high-risk block treatment are risk factors for PRES.
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| 18. |
- Anastasopoulou, Stavroula, et al.
(författare)
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Seizures during treatment of childhood acute lymphoblastic leukemia : A population-based cohort study
- 2020
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Ingår i: European journal of paediatric neurology. - : ELSEVIER SCI LTD. - 1090-3798 .- 1532-2130. ; 27, s. 72-77
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Tidskriftsartikel (refereegranskat)abstract
- Background: Seizures are common in children with acute lymphoblastic leukemia (ALL). As ALL survival rates are improving, the challenge to minimize treatment related side effects and late sequelae rises. Here, we studied the frequency, timing, etiology and risk factors of seizures in ALL patients. Methods: The study included children aged 1-17.9 years at diagnosis of B-cell-precursor and T cell ALL who were treated according to the Nordic Society of Pediatric Hematology and Oncology (NOPHO) ALL2008 protocol between 2008 and 2015. Detailed patient data were acquired from the NOPHO ALL2008 registry and by review of medical records. Results: Seizures occurred in 81/1464 (5.5%) patients. The cumulative incidence of seizures at one months was 1.7% (95% CI: 1.2-2.5) and at one year 5.3% (95% CI 4.2-6.5%). Patients aged 10-17.9 years, those with T cell immunophenotype, CNS involvement, or high-risk induction with dexamethasone had higher risk for seizures in univariable analyses. Only age remained a risk factor in multivariable analyses (the cumulative incidence of seizures for patients 10-17.9 years old at one year was 9.0% (95% CI: 6.2-12.9)). Of the 81 patients with seizures, 43 had posterior reversible encephalopathy syndrome (PRES), 15 had isolated seizures, nine had sinus venous thrombosis (SVT), three had stroke-like syndrome, and 11 had other neurotoxicities. Epilepsy diagnosis was reported in totally 11 ALL survivors at last follow up. Conclusion: Seizures are relatively common in ALL patients and occur most often in patients with PRES, SVT, or as an isolated symptom. Older children have higher risk of seizures. (C) 2020 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.
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| 19. |
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| 20. |
- Bang, Benedicte, et al.
(författare)
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A somatic UBA2 variant preceded ETV6-RUNX1 in the concordant BCP-ALL of monozygotic twins
- 2022
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Ingår i: Blood Advances. - : American Society of Hematology. - 2473-9529 .- 2473-9537. ; 6:7, s. 2275-2289
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Tidskriftsartikel (refereegranskat)abstract
- Genetic analysis of leukemic clones in monozygotic twins with concordant acute lymphoblastic leukemia (ALL) has proved a unique opportunity to gain insight into the molecular phylogenetics of leukemogenesis. Using whole-genome sequencing, we characterized constitutional and somatic single nucleotide variants/insertion-deletions (indels) and structural variants in a monozygotic twin pair with concordant ETV6-RUNX1(+) B-cell precursor ALL (BCP-ALL). In addition, digital PCR (dPCR) was applied to evaluate the presence of and quantify selected somatic variants at birth, diagnosis, and remission. A shared somatic complex rearrangement involving chromosomes 11, 12, and 21 with identical fusion sequences in leukemias of both twins offered direct proof of a common clonal origin. The ETV6-RUNX1 fusion detected at diagnosis was found to originate from this complex rearrangement. A shared somatic frameshift deletion in UBA2 was also identified in diagnostic samples. In addition, each leukemia independently acquired analogous deletions of 3 genes recurrently targeted in BCP-ALLs (ETV6, ATF7IP, and RAG1/RAG2), providing evidence of a convergent clonal evolution only explained by a strong concurrent selective pressure. Quantification of the UBA2 deletion by dPCR surprisingly indicated it persisted in remission. This, for the first time to our knowledge, provided evidence of a UBA2 variant preceding the well-established initiating event ETV6-RUNX1. Further, we suggest the UBA2 deletion exerted a leukemia predisposing effect and that its essential role in Small Ubiquitin-like Modifier (SUMO) attachment (SUMOylation), regulating nearly all physiological and pathological cellular processes such as DNA-repair by nonhomologous end joining, may hold a mechanistic explanation for the predisposition.
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| 21. |
- Beeckman, D., et al.
(författare)
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EPUAP classification system for pressure ulcers : European reliability study
- 2007
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Ingår i: Journal of Advanced Nursing. - : Wiley. - 0309-2402 .- 1365-2648. ; 60:6, s. 682-691
-
Tidskriftsartikel (refereegranskat)abstract
- AIM: This paper is a report of a study of the inter-observer reliability of the European Pressure Ulcer Advisory Panel pressure ulcer classification system and of the differential diagnosis between moisture lesions and pressure ulcers. BACKGROUND: Pressure ulcer classification is a valuable tool to provide a common description of ulcer severity for the purposes of clinical practice, audit and research. Despite everyday use of the European Pressure Ulcer Advisory Panel system, its reliability has been evaluated in only a limited number of studies. METHODS: A survey was carried out between September 2005 and February 2006 with a convenience sample of 1452 nurses from five European countries. Respondents classified 20 validated photographs as normal skin, blanchable erythema, pressure ulcers (four grades), moisture lesion or combined lesion. The nurses were familiar with the use of the European Pressure Ulcer Advisory Panel classification scale. RESULTS: Pressure ulcers were often classified erroneously (kappa = 0.33) and only a minority of nurses reached a substantial level of agreement. Grade 3 lesions were regularly classified as grade 2. Non-blanchable erythema was frequently assessed incorrectly as blanchable erythema. Furthermore, the differential diagnosis between moisture lesions and pressure ulcers appeared to be complicated. CONCLUSION: Inter-observer reliability of the European Pressure Ulcer Advisory Panel classification system was low. Evaluation thus needs to focus on both the clarity and complexity of the system. Definitions and unambiguous descriptions of pressure ulcer grades and the distinction between moisture lesions will probably enhance clarity. To simplify the current classification system, a reduction in the number of grades is suggested.
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| 22. |
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| 23. |
- Buentke, E, et al.
(författare)
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Glucocorticoid-induced cell death is mediated through reduced glucose metabolism in lymphoid leukemia cells
- 2011
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Ingår i: Blood Cancer Journal. - : Macmillan Publishers Limited. - 2044-5385. ; 1:e31, s. 9-
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Tidskriftsartikel (refereegranskat)abstract
- Malignant cells are known to have increased glucose uptake and accelerated glucose metabolism. Using liquid chromatography and mass spectrometry, we found that treatment of acute lymphoblastic leukemia (ALL) cells with the glucocorticoid (GC) dexamethasone (Dex) resulted in profound inhibition of glycolysis. We thus demonstrate that Dex reduced glucose consumption, glucose utilization and glucose uptake by leukemic cells. Furthermore, Dex treatment decreased the levels of the plasma membrane-associated glucose transporter GLUT1, thus revealing the mechanism for the inhibition of glucose uptake. Inhibition of glucose uptake correlated with induction of cell death in ALL cell lines and in leukemic blasts from ALL patients cultured ex vivo. Addition of di-methyl succinate could partially overcome cell death induced by Dex in RS4;11 cells, thereby further supporting the notion that inhibition of glycolysis contributes to the induction of apoptosis. Finally, Dex killed RS4;11 cells significantly more efficiently when cultured in lower glucose concentrations suggesting that modulation of glucose levels might influence the effectiveness of GC treatment in ALL. In summary, our data show that GC treatment blocks glucose uptake by leukemic cells leading to inhibition of glycolysis and that these effects play an important role in the induction of cell death by these drugs.
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| 24. |
- Carlsson, Fredrik, et al.
(författare)
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IgE enhances specific antibody and T cell responses in mice overexpressing CD23
- 2007
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Ingår i: Scandinavian Journal of Immunology. - : Wiley. - 0300-9475 .- 1365-3083. ; 66:2-3, s. 261-270
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Tidskriftsartikel (refereegranskat)abstract
- IgE administered with its specific antigen in vivo induces enhanced proliferation of specific T cells as well as enhanced production of specific antibodies. Both effects are dependent on the low-affinity receptor for IgE (CD23) and the underlying mechanism is thought to be increased antigen presentation following uptake of IgE/antigen complexes via CD23+ B cells. By contrast, CD23 negatively regulates antibody responses to antigens administered with alum, i.e. without IgE. This effect has been observed as low IgG1 and IgE responses in transgenic mice overexpressing CD23 (CD23Tg). The present study was designed to test whether IgE could enhance antibody and T-cell responses in CD23Tg animals or whether CD23's downregulatory effect precludes IgE-mediated enhancement. IgE-anti-TNP administered with OVA-TNP enhances the OVA-specific antibody responses in wild-type (wt) and CD23Tg mice equally well. Interestingly, the total magnitude of antibody responses to IgE + OVA-TNP and to uncomplexed OVA-TNP, as well as to sheep erythrocytes and keyhole limpet haemocyanine, were lower in the CD23Tg mice. IgE induced proliferation of OVA-specific CD4+ T cells to the same degree in wt and CD23Tg mice. The effect on T cells was dependent on CD23+ B cells as demonstrated in in vitro proliferation assays. In conclusion, CD23 does indeed have dual immunoregulatory effects in the same animal. The receptor mediates enhancement of antibody and T-cell responses to IgE-complexed antigen, most likely via increased presentation of complexed antigen, while it negatively regulates the total antibody response to a variety of antigens.
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| 25. |
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| 26. |
- Codilean, A. T., et al.
(författare)
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OCTOPUS database (v.2)
- 2022
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Ingår i: Earth System Science Data. - : Copernicus GmbH. - 1866-3508 .- 1866-3516. ; 14:8, s. 3695-3713
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Tidskriftsartikel (refereegranskat)abstract
- OCTOPUS v.2 is an Open Geospatial Consortium (OGC) compliant web-enabled database that allows users to visualise, query, and download cosmogenic radionuclide, luminescence, and radiocarbon ages and denudation rates associated with erosional landscapes, Quaternary depositional landforms, and archaeological records, along with ancillary geospatial (vector and raster) data layers. The database follows the FAIR (Findability, Accessibility, Interoperability, and Reuse) data principles and is based on open-source software deployed on the Google Cloud Platform. Data stored in the database can be accessed via a custom-built web interface and via desktop geographic information system (GIS) applications that support OGC data access protocols. OCTOPUS v.2 hosts five major data collections. CRN Denudation and ExpAge consist of published cosmogenic Be-10 and Al-26 measurements in modern fluvial sediment and glacial samples respectively. Both collections have a global extent; however, in addition to geospatial vector layers, CRN Denudation also incorporates raster layers, including a digital elevation model, gradient raster, flow direction and flow accumulation rasters, atmospheric pressure raster, and CRN production scaling and topographic shielding factor rasters. SahulSed consists of published optically stimulated luminescence (OSL) and thermoluminescence (TL) ages for fluvial, aeolian, and lacustrine sedimentary records across the Australian mainland and Tasmania. SahulArch consists of published OSL, TL, and radiocarbon ages for archaeological records, and FosSahul consists of published late-Quaternary records of direct and indirect non-human vertebrate (mega)fauna fossil ages that have been systematically quality rated. Supporting data are comprehensive and include bibliographic, contextual, and sample-preparation- and measurement-related information. In the case of cosmogenic radionuclide data, OCTOPUS also includes all necessary information and input files for the recalculation of denudation rates using the open-source program CAIRN. OCTOPUS v.2 and its associated data curation framework allow for valuable legacy data to be harnessed that would otherwise be lost to the research community. The database can be accessed at https://octopusdata.org (last access: 1 July 2022). The individual data collections can also be accessed via their respective digital object identifiers (DOIs) (see Table 1).
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| 27. |
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| 28. |
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| 29. |
- Egnell, Christina, et al.
(författare)
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Impact of body mass index on outcome and treatment-related toxicity in young adults with acute lymphoblastic leukemia
- 2023
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Ingår i: Acta Oncologica. - : Taylor & Francis. - 0284-186X .- 1651-226X. ; 62:12, s. 1723-1731
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Tidskriftsartikel (refereegranskat)abstract
- Background: Data on outcome for patients in different body mass index (BMI) categories in young adults with acute lymphoblastic leukemia (ALL) are scarce. We explored survival and toxicities in different BMI categories in young adults with ALL.Material and methods: Patients aged 18-45 years, diagnosed with ALL between July 2008 and June 2022 in the Nordic countries, Estonia, or Lithuania, and treated according to the NOPHO ALL2008 protocol, were retrospectively enrolled and classified into different BMI categories. Endpoints were overall survival (OS), event-free survival (EFS) and cumulative incidence of relapse as well as incidence rate ratio (IRR) of severe predefined toxic events, and treatment delays.Results: The group comprised 416 patients, of whom 234 (56%) were stratified to non-high-risk (non-HR) treatment. In the non-HR group, patients with severe obesity, BMI & GE;35 kg/m2 had worse EFS due to relapses but there was no effect on toxicity or treatment delays compared with the healthy-weight patients. There was no association between BMI category and OS, overall toxicity, or treatment delays in the patients with high-risk treatment.Conclusion: Severe obesity is associated with worse EFS in young adults treated according to the non-HR arms of the NOPHO ALL2008 protocol. Poorer outcome is explained with a higher risk of relapse, possibly due to under treatment, and not caused by excess therapy-related mortality.
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| 30. |
- Egnell, Christina, et al.
(författare)
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Impact of body mass index on relapse in children with acute lymphoblastic leukemia treated according to Nordic treatment protocols
- 2020
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Ingår i: European Journal of Haematology. - : WILEY. - 0902-4441 .- 1600-0609. ; 105:6, s. 797-807
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Tidskriftsartikel (refereegranskat)abstract
- Objectives High body mass index (BMI) is associated with poorer survival in childhood acute lymphoblastic leukemia (ALL), but the actual impact on the risk of relapse still needs to be clarified. We evaluated the impact of BMI at diagnosis on the risk of relapse in children with ALL treated according to Nordic Society of Paediatric Haematology and Oncology (NOPHO) protocols. Method In a multicenter study, we collected data on BMI at diagnosis and outcome of 2558 children aged 2.0-17.9 years diagnosed between 1992 and 2016. Patients were divided into four groups according to International Obesity Task Force (IOTF) childhood BMI cut-offs: underweight, <17; healthy weight, 17-25; overweight, 25-30; and obese, >= 30 kg/m(2). Results In Cox multivariate regression analyses, an increased risk of relapse was observed in children aged 10-17.9 years with unhealthy BMI at diagnosis (underweight hazard ratio HR: 2.90 [95% confidence interval: 1.24-6.78],P = .01; overweight, HR: 1.95 [1.11-3.43],P = .02, and obese HR: 4.32 [95% 2.08-8.97],P < .001), compared to children with healthy weight. BMI had no impact on relapse in children under 10 years of age. Conclusion High BMI, and especially obesity at diagnosis, is an independent adverse prognostic factor for relapse in older children with ALL.
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| 31. |
- Egnell, Christina, et al.
(författare)
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Obesity as a predictor of treatment-related toxicity in children with acute lymphoblastic leukaemia
- 2022
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Ingår i: British Journal of Haematology. - : John Wiley & Sons. - 0007-1048 .- 1365-2141. ; 196:5, s. 1239-1247
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Tidskriftsartikel (refereegranskat)abstract
- Obesity is associated with poor outcomes in childhood acute lymphoblastic leukaemia (ALL). We explored whether severe treatment-related toxicity and treatment delays could explain this observation. This study included 1 443 children aged 2 center dot 0-17 center dot 9 years with ALL treated with the Nordic Society of Pediatric Haematology and Oncology (NOPHO) ALL2008 non-high-risk protocol. Prospective treatment-related toxicities registered every three-month interval were used. Patients were classified according to sex- and age-adjusted international childhood cut-off values, corresponding to adult body mass index: underweight, <17 kg/m(2); healthy weight, 17 to <25 kg/m(2); overweight, 25 to <30 kg/m(2); and obese, >= 30 kg/m(2). Obese children had a higher incidence rate ratio (IRR) for severe toxic events {IRR: 1 center dot 55 [95% confidence interval (CI) 1 center dot 07-2 center dot 50]}, liver and kidney failures, bleeding, abdominal complication, suspected unexpected severe adverse reactions and hyperlipidaemia compared with healthy-weight children. Obese children aged >= 10 years had increased IRRs for asparaginase-related toxicities compared with healthy-weight older children: thromboses [IRR 2 center dot 87 (95% CI 1 center dot 00-8 center dot 21)] and anaphylactic reactions [IRR 7 center dot 95 (95% CI 2 center dot 15-29 center dot 37)] as well as higher risk for truncation of asparaginase [IRR 3 center dot 54 (95% CI 1 center dot 67-7 center dot 50)]. The high prevalence of toxicity and a higher risk of truncation of asparaginase may play a role in the poor prognosis of obese children aged >= 10 years with ALL.
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| 32. |
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| 33. |
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| 34. |
- Forestier, Erik, et al.
(författare)
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Clinical and cytogenetic features of pediatric dic(9;20)(p13.2;q11.2)-positive B-cell precursor acute lymphoblastic leukemias : A nordic series of 24 cases and review of the literature
- 2008
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Ingår i: Genes, Chromosomes and Cancer. - : Wiley. - 1045-2257 .- 1098-2264. ; 47:2, s. 149-158
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Forskningsöversikt (refereegranskat)abstract
- Although dic(9;20)(p13.2;q11.2) is a characteristic abnormality in childhood B-cell precursor acute lymphoblastic leukemias (BCP ALL), little is known about its clinical impact or the type and frequency of additional aberrations it may occur together with. We here review the clinical and cytogenetic features of a Nordic pediatric series of 24 patients with dic(9;20)-positive BCP ALL diagnosed 1996-2006, constituting 1.3% of the BCP ALL, as well as 47 childhood cases from the literature. Consistent immunophenotypic features of the Nordic cases included positivity for HLA-DR, CD10, CD19, CD20, and CD22 and negativity for T-cell and myeloid markers; no detailed immunophenotypes were reported for the previously published cases. In the entire cohort of 71 cases, the modal chromosome distribution was 45 (62%), 46 (21%), 47 (7%), 48 (4%), 49 (3%), 44 (1%), and 50 (1%). Additional changes were present in 63%, the most frequent of which were homozygous loss of CDKN2A (33%) and gains of chromosomes 21 (28%) and X (10%). The median patient age was 3 years, the female/male ratio was 2.0, the median white blood cell count was 24 x 10(9)/l, 11% had central nervous system involvement, and 5% had a mediastinal mass at diagnosis. Risk group stratification was nonstandard risk in 79%. The event-free survival and overall survival at 5 years for the 24 Nordic cases was 0.62 and 0.82, respectively. Thus, although relapses are quite common, postrelapse treatment of many patients is successful.
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| 35. |
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| 36. |
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| 37. |
- Hermelijn, S, et al.
(författare)
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Development of a core outcome set for congenital pulmonary airway malformations: study protocol of an international Delphi survey
- 2021
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Ingår i: BMJ open. - : BMJ. - 2044-6055. ; 11:4, s. e044544-
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Tidskriftsartikel (refereegranskat)abstract
- A worldwide lack of consensus exists on the optimal management of asymptomatic congenital pulmonary airway malformation (CPAM) even though the incidence is increasing. Either a surgical resection is performed or a wait-and-see policy is employed, depending on the treating physician. Management is largely based on expert opinion and scientific evidence is scarce. Wide variations in outcome measures are seen between studies making comparison difficult thus highlighting the lack of universal consensus in outcome measures as well. We aim to define a core outcome set which will include the most important core outcome parameters for paediatric patients with an asymptomatic CPAM.Methods and analysisThis study will include a critical appraisal of the current literature followed by a three-stage Delphi process with two stakeholder groups. One surgical group including paediatric as well as thoracic surgeons, and a non-surgeon group including paediatric pulmonologists, intensive care and neonatal specialists. All participants will score outcome parameters according to their level of importance and the most important parameters will be determined by consensus.Ethics and disseminationElectronic informed consent will be obtained from all participants. Ethical approval is not required. After the core outcome set has been defined, we intend to design an international randomised controlled trial: the COllaborative Neonatal NEtwork for the first CPAM Trial, which will be aimed at determining the optimal management of patients with asymptomatic CPAM.
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| 41. |
- Højfeldt, Sofie G., et al.
(författare)
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Genetic predisposition to PEG-asparaginase hypersensitivity in children treated according to NOPHO ALL2008
- 2019
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Ingår i: British Journal of Haematology. - : Wiley. - 0007-1048 .- 1365-2141. ; 184:3, s. 405-417
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Tidskriftsartikel (refereegranskat)abstract
- Asparaginase is essential in childhood acute lymphoblastic leukaemia (ALL) treatment, however hypersensitivity reactions to pegylated asparaginase (PEG-asparaginase) hampers anti-neoplastic efficacy. Patients with PEG-asparaginase hypersensitivity have been shown to possess zero asparaginase enzyme activity. Using this measurement to define the phenotype, we investigated genetic predisposition to PEG-asparaginase hypersensitivity in a genome-wide association study (GWAS). From July 2008 to March 2016, 1494 children were treated on the Nordic Society of Paediatric Haematology and Oncology ALL2008 protocol. Cases were defined by clinical hypersensitivity and no enzyme activity, controls had enzyme activity ≥ 100 iu/l and no hypersensitivity symptoms. PEG-asparaginase hypersensitivity was reported in 13·8% (206/1494) of patients. Fifty-nine cases and 772 controls fulfilled GWAS inclusion criteria. The CNOT3 variant rs73062673 on 19q13.42, was associated with PEG-asparaginase allergy (P = 4·68 × 10-8 ). We further identified two signals on chromosome 6 in relation to HLA-DQA1 (P = 9·37 × 10-6 ) and TAP2 (P = 1·59 × 10-5 ). This study associated variants in CNOT3 and in the human leucocyte antigen (HLA) region with PEG-asparaginase hypersensitivity, suggesting that not only genetic variations in the HLA region, but also regulation of these genes are of importance in the biology of this toxicity. Furthermore, our study emphasizes the importance of using asparaginase enzyme activity measurements to identify PEG-asparaginase hypersensitivity.
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| 42. |
- Karrman, Kristina, et al.
(författare)
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Clinical and cytogenetic features of a population-based consecutive series of 285 pediatric T-cell acute lymphoblastic leukemias: rare T-cell receptor gene rearrangements are associated with poor outcome.
- 2009
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Ingår i: Genes, chromosomes & cancer. - : Wiley. - 1098-2264 .- 1045-2257. ; 48:9, s. 795-805
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Tidskriftsartikel (refereegranskat)abstract
- Clinical characteristics and cytogenetic aberrations were ascertained and reviewed in a population-based consecutive series of 285 pediatric T-cell acute lymphoblastic leukemias (T-ALLs) diagnosed between 1992 and 2006 in the Nordic countries. Informative karyotypic results were obtained in 249 (87%) cases, of which 119 (48%) were cytogenetically abnormal. Most (62%) of the aberrant T-ALLs were pseudodiploid. Structural changes were more common than numerical ones; 86% displayed at least one structural abnormality and 41% at least one numerical anomaly. The most frequent abnormalities were T-cell receptor (TCR) gene rearrangements (20%) [TCR;11p13 (10%), TCR;10q24 (3%), TCR;other (8%)], del(9p) (17%), +8 (14%), del(6q) (12%), and 11q23 rearrangements (6%). The TCR;other group comprised the rare rearrangements t(X;14)(p11;q11), t(X;7)(q22;q34), t(1;14)(p32;q11), ins(14;5)(q11;q?q?), inv(7)(p15q34), t(8;14)(q24;q11), t(7;11)(q34;p15), and t(12;14)(p13;q11). The clinical characteristics of this Nordic patient cohort agreed well with previous larger series, with a median age of 9.0 years, male predominance (male/female ratio 3.1), median white blood cell (WBC) count of 66.5 x 10(9)/l, and a high incidence of mediastinal mass and central nervous system involvement (59% and 9.5%, respectively). These features did not differ significantly among the various genetic subgroups. 5-year event-free survival (EFS) and overall survival for all patients were 0.61 (+/-0.03) and 0.67 (+/-0.03), respectively. In a multivariate analysis, two factors affected negatively the EFS, namely a WBC count of > or =200 x 10(9)/l (P < 0.001) and the presence of rare TCR rearrangements (P = 0.001). In conclusion, in this large series of childhood T-ALLs from the Nordic countries, the cytogenetic findings were not associated with risk of therapy failure with the exception of the TCR;other group. However, further prospective and collaborative investigations of this genetically heterogeneous entity are needed to confirm these results.
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| 47. |
- Lynggaard, Line Stensig, et al.
(författare)
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Asparaginase enzyme activity levels and toxicity in childhood acute lymphoblastic leukemia : a NOPHO ALL2008 study
- 2022
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Ingår i: Blood Advances. - : American Society of Hematology. - 2473-9529 .- 2473-9537. ; 6:1, s. 138-147
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Tidskriftsartikel (refereegranskat)abstract
- Asparaginase treatment is a mainstay in contemporary treatment of acute lymphoblastic leukemia (ALL), but substantial asparaginase-related toxicity may lead to jeopardized protocol compliance and compromises survival. We investigated the association between risk of asparaginase-associated toxicities (AspTox) and asparaginase enzyme activity (AEA) levels in 1155 children aged 1.0 to 17.9 years, diagnosed with ALL between July 2008 and March 2016, and treated according to the Nordic Society of Pediatric Hematology and Oncology (NOPHO) ALL2008 protocol. Patients with >= 2 blood samples for AEA measurement drawn 14 +/- 2 days after asparaginase administration were included (6944 trough values). AEA was measurable (or >0 IU/L) in 955 patients, whereas 200 patients (17.3%) had asparaginase inactivation and few AspTox recorded. A time-dependent multiple Cox model of time to any first asparaginase-associated toxicity adjusted for sex and age was used. For patients with measurable AEA, we found a hazard ratio (HR) of 1.17 per 100 IU/L increase in median AEA (95% confidence interval [CI], 0.98-1.41; P = .09). For pancreatitis, thromboembolism, and osteonecrosis, the HRs were 1.40 (95% CI, 1.12-1.75; P = .002), 0.99 (95% CI, 0.70-1.40; P = .96), and 1.36 (95% CI, 1.04-1.77; P = .02) per 100 IU/L increase in median AEA, respectively. No significant decrease in the risk of leukemic relapse was found: HR 0.88 per 100 IU/L increase in AEA (95% CI, 0.66-1.16; P = .35). In conclusion, these results emphasize that overall AspTox and relapse are not associated with AEA levels, yet the risk of pancreatitis and osteonecrosis increases with increasing AEA levels.
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| 48. |
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| 49. |
- Martin, Rebecca K., et al.
(författare)
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Antigen Transfer from Exosomes to Dendritic Cells as an Explanation for the Immune Enhancement Seen by IgE Immune Complexes
- 2014
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 9:10, s. e110609-
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Tidskriftsartikel (refereegranskat)abstract
- IgE antigen complexes induce increased specific T cell proliferation and increased specific IgG production. Immediately after immunization, CD23(+) B cells capture IgE antigen complexes, transport them to the spleen where, via unknown mechanisms, dendritic cells capture the antigen and present it to T cells. CD23, the low affinity IgE receptor, binds IgE antigen complexes and internalizes them. In this study, we show that these complexes are processed onto B-cell derived exosomes (bexosomes) in a CD23 dependent manner. The bexosomes carry CD23, IgE and MHC II and stimulate antigen specific T-cell proliferation in vitro. When IgE antigen complex stimulated bexosomes are incubated with dendritic cells, dendritic cells induce specific T-cell proliferation in vivo, similar to IgE antigen complexes. This suggests that bexosomes can provide the essential transfer mechanism for IgE antigen complexes from B cells to dendritic cells.
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