Karolinska Inst, Dept Oncol Pathol, Stockholm, Sweden.;Karolinska Univ Hosp, Reprod Med, Stockholm, Sweden..
Karolinska Univ Hosp, Astrid Lindgren Childrens Hosp, Paediat Oncol Unit, Stockholm, Sweden.;Karolinska Inst, Dept Womens & Childrens Hlth, Stockholm, Sweden..
Objective: The aim of this study was to investigate practice behaviours of Swedish physicians with regard to discussing the impact of cancer treatment on fertility with paediatric oncology patients and their parents, and to identify factors associated with such discussions.
Methods: A cross-sectional survey study was conducted targeting all physicians in Sweden working in paediatric oncology care settings. Participants responded to a questionnaire measuring practice behaviour, attitudes, barriers, and confidence in knowledge. Multivariable logistic regression was used to determine factors associated with seldom discussing fertility.
Results: More than half of the physicians routinely talked with their patients/parents about the treatment's potential impact on fertility (male patients: 62%; female patients: 57%; P = 0.570). Factors associated with less frequently discussing fertility with patients/parents were working at a non-university hospital (male patients: OR 11.49, CI 1.98-66.67; female patients: OR 33.18, CI 4.06-271.07), concerns that the topic would cause worry (male patients: OR 8.23, CI 1.48-45.89; female patients: OR 12.38, CI 1.90-80.70), and perceiving the parents as anxious (male patients: OR 7.18, CI 1.20-42.85; female patients: OR 11.65, CI 1.32-103.17).
Conclusions: Based on our findings, we recommend structured training in how to communicate about fertility issues in stressful situations, which in turn might increase fertility-related discussions in paediatric oncology.
Boyne Res Inst, 5 Bolton Sq East, Drogheda A92 RY6K, Louth, Ireland..
Univ Turin, Citta Salute & Sci Hosp, Canc Epidemiol Unit, Childhood Canc Registry Piedmont, Via Santena 7, I-10126 Turin, Italy.;Ctr Canc Prevent CPO, Via Santena 7, I-10126 Turin, Italy..
Univ Paris Saclay, Gustave Roussy, Canc & Radiat, Unit INSERM 1018, 39 Rue Camille Desmoulins, F-94805 Villejuif, France..
Ist Giannina Gaslini, Epidemiol & Biostat Unit, Italian Off Therapy Registry OTR, Via Gerolamo Gaslini 5, I-16148 Genoa, Italy..
Semmelweis Univ, Dept Pediat 2, Budapest, Hungary.;Kepler Univ Klinikum, Linz, Austria..
Danish Canc Soc, Res Ctr, Strandboulevarden 49, DK-2100 Copenhagen, Denmark..
Univ Birmingham, Inst Appl Hlth Res, Ctr Childhood Canc Survivor Studies, Birmingham B15 2TT, W Midlands, England..
Newcastle Univ, Inst Hlth & Soc, Newcastle Upon Tyne NE4 5PL, Tyne & Wear, England..
Acad Med Ctr Amsterdam, Emma Childrens Hosp, Dept Pediat Oncol, Meibergdreef 9, NL-1105 AZ Amsterdam, Netherlands.;Princess Maxima Ctr Paediat Oncol, Utrecht, Netherlands..
WHO, Sect Canc Surveillance, Int Agcy Res Canc, F-69372 Lyon 08, France..
St Anna Childrens Hosp, Kinderspitalgasse 6, A-1090 Vienna, Austria..
Lund Univ, Dept Clin Sci, Pediat, Skane Univ Hosp, Lund, Sweden..
Univ Med Ctr, Inst Med Biostat Epidemiol & Informat, GCCR, Mainz, Germany..
Reg Canc Ctr South, Lund, Sweden..
Univ Bern, Inst Social & Prevent Med, Swiss Childhood Canc Registry, Bern, Switzerland.;Univ Bern, Univ Childrens Hosp Bern, Dept Paediat, Bern, Switzerland..
Semmelweis Univ, Dept Pediat 2, Hungarian Childhood Canc Registry, Budapest, Hungary..
Univ Milano Bicocca, Fdn MBBM Monza, Pediat Clin, Monza, Italy.;Italian Off Therapy Register OTR, Monza, Italy..
Univ Bern, Inst Social & Prevent Med, Swiss Childhood Canc Registry, Bern, Switzerland..
Med Univ, St Anna Childrens Canc Res Inst, Dept Paediat, Vienna, Austria..
Turku Univ, Dept Pediat & Adolescent Med, Turku, Finland.;Turku Univ Hosp, Turku, Finland..
Great Ormond St Hosp Children NHS Fdn Trust, Dept Oncol, London WCIN3JH, England..
Univ Lucerne, Dept Hlth Sci & Hlth Policy, Luzern, Switzerland..
Royal Victoria Infirm, Great North Childrens Hosp, Dept Paediat & Adolescent Haematol & Oncol, Childrens BMT Unit, Newcastle Upon Tyne NE1 4LP, Tyne & Wear, England.;Newcastle Univ, Northern Inst Canc Res, Newcastle Upon Tyne NE4 5PL, Tyne & Wear, England..
van der Pal, Helena J.
Princess Maxima Ctr Paediat Oncol, Utrecht, Netherlands..
Norwegian Canc Register, Oslo, Norway.;Oslo Univ Hosp, Dept Pediat Med, Oslo, Norway.;Univ Oslo, Fac Med, Inst Clin Med, Oslo, Norway..
Danish Canc Soc, Res Ctr, Strandboulevarden 49, DK-2100 Copenhagen, Denmark.;Aarhus Univ, Fac Hlth, Dept Clin Med, Palle Juul Jensens Blvd 82, DK-8200 Aarhus, Denmark..
Inst Oncol, Div Radiotherapy, Zaloska Cesta 2, SI-1000 Ljubljana, Slovenia..
Background: Second malignant neoplasms and cardiotoxicity are among the most serious and frequent adverse health outcomes experienced by childhood and adolescent cancer survivors (CCSs) and contribute significantly to their increased risk of premature mortality. Owing to differences in health-care systems, language and culture across the continent, Europe has had limited success in establishing multi-country collaborations needed to assemble the numbers of survivors required to clarify the health issues arising after successful cancer treatment. PanCareSurFup (PCSF) is the first pan-European project to evaluate some of the serious long-term health risks faced by survivors. This article sets out the overall rationale, methods and preliminary results of PCSF. Methods: The PCSF consortium pooled data from 13 cancer registries and hospitals in 12 European countries to evaluate subsequent primary malignancies, cardiac disease and late mortality in survivors diagnosed between ages 0 and 20 years. In addition, PCSF integrated radiation dosimetry to sites of second malignancies and to the heart, developed evidence-based guidelines for long-term care and for transition services, and disseminated results to survivors and the public. Results: We identified 115,596 individuals diagnosed with cancer, of whom 83,333 were 5-year survivors and diagnosed from 1940 to 2011. This single data set forms the basis for cohort analyses of subsequent malignancies, cardiac disease and late mortality and case-control studies of subsequent malignancies and cardiac disease in 5-year survivors. Conclusions: PCSF delivered specific estimates of risk and comprehensive guidelines to help survivors and care-givers. The expected benefit is to provide every European CCS with improved access to care and better long-term health.
Univ Gothenburg, Dept Rheumatol & Inflammat Res, Gothenburg, Sweden..
Guizhou Med Univ, Affiliated Hosp, Cent Lab, Guiyang, Peoples R China..
Univ Gothenburg, Dept Microbiol & Immunol, Gothenburg, Sweden..
Sahlgrens Univ Hosp, Dept Clin Chem, Gothenburg, Sweden.;Univ Gothenburg, Dept Clin Chem & Transfus Med, Gothenburg, Sweden..
Department of Anesthesiology, Perioperative and Pain Medicine, Stanford University, Palo Alto, California, USA.
Paediatric Intensive Care Unit, Starship Childrens Hospital, Auckland, New Zealand.
Paediatric Palliative Care, Department of Paediatrics, IWK Health Centre, Dalhousie University, Halifax, Canada.
BACKGROUND: Pain is a common feature of childhood and adolescence around the world, and for many young people, that pain is chronic. The World Health Organization (WHO) guidelines for pharmacological treatments for persisting pain in children acknowledge that pain in children is a major public health concern of high significance in most parts of the world. Views on children's pain have changed over time and relief of pain is now seen as important. In the past, pain was largely dismissed and was frequently left untreated, and it was assumed that children quickly forgot about painful experiences.We designed a suite of seven reviews in chronic non-cancer pain and cancer pain (looking at antidepressants, antiepileptic drugs, non-steroidal anti-inflammatory drugs, opioids, and paracetamol as priority areas) to review the evidence for children's pain using pharmacological interventions.As one of the leading causes of mortality and morbidity for children and adolescents in the world today, childhood cancer (and its associated pain) is a major health concern. Specific mortality and morbidity data relating to children are not currently identified. All childhood cancer rates are on the rise; for example, in the USA approximately 10,380 children aged under 15 years were expected to be diagnosed with cancer by the end of 2016. However, with survival rates also increasing, over 80% of paediatric cancer patients are expected to survive for five years or more, thus identifying the need to address pain management in this population.Cancer pain in infants, children, and adolescents is primarily nociceptive pain with negative long term effects. Cancer-related pain is generally caused directly by the tumour itself such as compressing on the nerve or inflammation of the organs. Cancer-related pain generally occurs as a result of perioperative procedures, nerve damage caused by radiation or chemotherapy treatments, or mucositis. However, this review focused on pain caused directly by the tumour itself such as nerve infiltration, external nerve compression, and other inflammatory events.Non-steroidal anti-inflammatory drugs (NSAIDs) are used to treat pain, reduce fever, and for their anti-inflammatory properties. They are commonly used within paediatric pain management. NSAIDs are currently licensed for use in western countries, however not approved for infants aged under three months. Primary adverse effects include gastrointestinal issues and possible renal impairment with long term use. Other adverse effects in children include diarrhoea, headache, nausea, constipation, rash, dizziness, and abdominal pain.
OBJECTIVES: To assess the analgesic efficacy, and adverse events, of non-steroidal anti-inflammatory drugs (NSAIDs) used to treat cancer-related pain in children and adolescents aged from birth and 17 years, in any setting.
SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) via the Cochrane Register of Studies Online, MEDLINE via Ovid, and Embase via Ovid from inception to 21 February 2017. We also searched the reference lists of retrieved studies and reviews, and searched online clinical trial registries.
SELECTION CRITERIA: Randomised, double-blind trials of any dose, and any route, treating cancer-related pain in children and adolescents, comparing NSAIDs with placebo or an active comparator.
DATA COLLECTION AND ANALYSIS: Two review authors independently assessed studies for eligibility. We planned to use dichotomous data to calculate risk ratio and number needed to treat for one additional event, using standard methods. We assessed GRADE (Grading of Recommendations Assessment, Development and Evaluation) and planned to create a 'Summary of findings' table.
MAIN RESULTS: No studies were eligible for inclusion in this review (very low quality evidence). We downgraded the quality of evidence by three levels due to the lack of data reported for any outcome.
AUTHORS' CONCLUSIONS: There is no evidence from randomised controlled trials that non-steroidal anti-inflammatory drugs (NSAIDs) reduce cancer-related pain in children and adolescents. This means that no reliance or conclusions can be made about efficacy or harm in the use of NSAIDs to treat chronic cancer-related pain in children and adolescents.
Aim: To give a detailed description of the long-term outcome of a cohort of children with glioneuronal tumors regarding pre-and postsurgical factors, including "dual" and "double" pathology, seizure freedom, and psychosocial outcome.
Methods: During a fifteen-year period (1995-2009), all patients (age 0-17.99 years) with a glioneuronal brain tumor diagnosed and treated at Uppsala University Children's Hospital were identified from the National Brain Tumor Registry and the National Epilepsy Surgery Registry. Hospital medical records were reviewed and neuroradiological and neuropathological findings were re-evaluated. A cross-sectional long-term follow-up prospective evaluation, including an interview, neurologic examination, and electroencephalogram, was accomplished in patients accepting participants in the study.
Results: A total of 25 out of 28 (89%) eligible patientswere included. The M: F ratiowas 1.5: 1. Mean follow-up time after surgery was 12.1 years (range 5.0-19.3). Twenty patients were adults (N18 years) at follow-up. Seizure freedomwas achieved in 64%. Gross total resection (GTR) was the only preoperative factor significantly correlating to seizure freedom (p= 0.027). Thirty-eight percent were at some time postoperatively admitted for a psychiatric evaluation. There was a trend towards both higher educational level and employment status in adults who became seizure free.
Conclusion: Long-termoutcome is good regarding seizure freedom if GTR can be achieved, but late seizure recurrence can occur. "Dual" and "double" pathology is uncommon and does not influence seizure outcome. Obtaining seizure freedomseems to be important for psychosocial outcome, but there is a risk for psychiatric comorbidities and long-term follow-up by a multi-professional team is advisable.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Neuropediatrics/Paediatric oncology. Uppsala Univ, Childrens Hosp, Uppsala, Sweden.
Aims: The aim of this study was to investigate long-term cognitive outcome, health-related quality of life (HRQoL), and psychiatric symptoms in children and young adults diagnosed with a glioneuronal tumor in childhood.
Methods: Twenty-eight children and adolescents (0-17.99 years) with a minimum postoperative follow-up time of five years were eligible for the study; four persons declined participation. A cross-sectional long-term follow-up evaluation was performed using the following study measures: Wechsler Intelligence Scale for Children (WISC-IV) or Wechsler Adult Intelligence Scale (WAIS-IV), Reys Complex Figure Test (RCFT), Short Form 36 version 2 (SF-36v2), Short Form 10 (SF-10), Quality of Life in Epilepsy 31 (QOLIE-31), Hospital Anxiety Depression Scale (HADS) or Beck Youth Inventory Scales (BYI), and Rosenberg Self-Esteem Scale. Historical WISC-III and RCFT data were used to compare cognitive longitudinal data.
Results: Mean follow-up time after surgery was 12.1 years. Sixty-three percent (15/24) were seizure-free. Despite a successive postoperative gain in cognitive function, a significant reduction relative to norms was seen in the seizure-free group with respect to perceptual reasoning index (PRI), working memory index (WMI), and full-scale intelligence quotient (FSIQ). Seizure freedom resulted in acceptable HRQoL. Thirty-two percent and 16% exceeded the threshold level of possible anxiety and depression, respectively, despite seizure freedom.
Conclusion: Although lower than in corresponding reference groups, cognitive outcome and HRQoL are good provided that seizure freedom or at least a low seizure severity can be achieved. There is a risk of elevated levels of psychiatric symptoms. Long-term clinical follow-up is advisable.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology. Karolinska Inst, Dept Med Solna, Clin Epidemiol Unit, Stockholm.
Statens Serum Inst, Dept Epidemiol Res, Copenhagen.
Karolinska Inst, Dept Med Solna, Clin Epidemiol Unit, Stockholm; Karolinska Univ Hosp, Hematol Ctr, Stockholm.
Karolinska Inst, Dept Med Solna, Clin Epidemiol Unit, Stockholm.
Aarhus Univ Hosp, Dept Haematol, Aarhus C.
Statens Serum Inst, Dept Epidemiol Res, Copenhagen; Rigshosp, Dept Haematol, Copenhagen.
Statens Serum Inst, Dept Epidemiol Res, Copenhagen; Rigshosp, Dept Paediat & Adolescent Med, Copenhagen.
Background: Hodgkin lymphoma (HL) treatment protocols for children, adolescents and young adults traditionally differ, but the biological and clinical justification for this remains uncertain.
Material and methods: We compared age-dependent clinical presentation and treatment and outcome for 1072 classical HL patients 0–24 years diagnosed in Denmark (1990–2010) and Sweden (1992–2009) in pediatric (n = 315, Denmark <15 years, Sweden <18 years) or adult departments (n = 757). Distribution of clinical characteristics was assessed with Pearson's chi2-test and Mantel–Haenszel trend test. The Kaplan–Meier method was used for survival analyses. Hazard ratios (HR) were used to compare the different treatment groups and calculated using Cox regression.
Results: Children (0–9 years) less often presented with advanced disease than adolescents (10–17 years) and young adults (18–24 years) (stage IIB-IV: children 32% vs. adolescents 50%, and adults 55%; p < .005). No variation in overall survival (OS) was seen between pediatric and adult departments or by country. Danish pediatric patients received radiotherapy (36%) less frequently than Swedish pediatric patients (71%) (p < .0001). Ten-year event-free survival (EFS) was lower among Danish pediatric patients (0–14 years) (0.79; 95% confidence interval (CI) 0.70–0.86) than among Swedish pediatric patients (0–17 years) (0.88; 95% CI 0.83–0.92), HR (1.93; 95% CI 1.08–3.46). A similar pattern was seen between adult patients in the two countries: Denmark 10-year EFS 0.85 (95% CI 0.81–0.88), Sweden 0.88 (95% CI 0.84–0.91), adjusted HR 1.51 (95% CI 1.03–2.22).
Conclusion: Adolescents and young adults shared similar clinical presentation suggesting a rationale of harmonized treatment for these groups. Both adult and pediatric protocols provided high OS with no significant difference between the departments. The less frequent use of radiotherapy in Danish pediatric patients corresponded to a lower EFS, but comparable OS in all groups confirmed effective rescue strategies for the relapsing patients.
Department of Radiation Sciences, Umea University, Umea, Sweden.
BACKGROUND: Children can experience distress when undergoing radiotherapy as a reaction to being scared of and unfamiliar with the procedure. The aim was to evaluate children's experiences and responses towards an intervention for psychological preparation for radiotherapy.
METHODS: A case control design with qualitative content analysis of semi-structured interviews and statistical analysis of anxiety ratings were used for evaluating a strategy for psychological preparation and distraction. Fifty-seven children aged 2 to 18 years and their parents participated - 30 children in the baseline group and 27 in the intervention group. Child interviews were performed and the child and their parents rated the child's anxiety.
RESULTS: The intervention was most appropriate for the younger children, who enjoyed the digital story, the stuffed animal and training with their parents. There were some technical problems and the digital story was not detailed enough to fit exactly with various cancer diagnoses. Children described suggestions for improvement of the intervention. The ratings of the child's anxiety during radiation treatment showed no differences between the baseline group and the intervention group.
CONCLUSIONS: The children of all the age groups experienced their interventions as positive. The strength of the intervention was that it encouraged interaction within the family and provided an opportunity for siblings and peers to take part in what the child was going through. Future research on children's experiences to interventions should be encouraged. The intervention and the technical solutions could improve by further development.
Aarhus Univ Hosp Skejby, Dept Pediat, Aarhus, Denmark..
Umea Univ Hosp, Dept Pediat, Umea, Sweden..
Queen Silvia Childrens Hosp, Dept Pediat, Inst Clin Sci, Gothenburg, Sweden..
Queen Mary Hosp, Dept Pediat, Hong Kong, Hong Kong, Peoples R China.;HKPHOSG, Hong Kong, Hong Kong, Peoples R China..
Univ Hosp, Dept Pediat, Lund, Sweden..
Univ Helsinki, Childrens Hosp, Helsinki, Finland.;Univ Helsinki, Cent Hosp, Helsinki, Finland..
Landspitalinn, Dept Pediat, Reykjavik, Iceland..
Univ Copenhagen, Rigshosp, Dept Pediat & Adolescent Med, Copenhagen, Denmark..
Oslo Univ Hosp, Div Pediat & Adolescent Med, Oslo, Norway..
Univ Gothenburg, Sahlgrenska Acad, Inst Biomed, Dept Clin Chem & Transfus Med, Gothenburg, Sweden..
The t(7;12)(q36;p13) (MNX1/ETV6) is not included in the WHO classification but has been described in up to 30% of acute myeloid leukemia (AML) in children <2 years and associated with a poor prognosis. We present the clinical and cytogenetics characteristics of AML cases with t(7;12)(p36;p13). A literature review identified 35 patients with this translocation, published between 2000 and 2015. Outcome data were available in 22 cases. The NOPHO-AML (Nordic Society for Pediatric Hematology and Oncology) database contained 651 patients with AML from 1993 to 2014 and seven (1.1%) had the translocation. The t(7;12) was only present in patients <2 years of age (median age 6 months) but none was diagnosed as newborn. These patients constituted 4.3% of the patients <2 years of age. There was a strong association with trisomy 19 (literature: 86%, NOPHO: 100%) and +8 (literature: 19%, NOPHO: 14%). Seventeen of 22 patients from the literature with t(7;12) and four of seven patients from the NOPHO database suffered from relapse. The patients with t(7;12) had a 3-year event free survival of 24% (literature) vs. 43% (NOPHO) and a 3-year overall survival of 42% (literature) vs. 100% (NOPHO). None of the NOPHO patients was treated with hematopoietic stem cell transplantation (HSCT) in first complete remission. Relapse was frequent but the salvage rate using HSCT was high. We conclude that t(7;12)(q36;13) is a unique subgroup of childhood AML with presentation before 2 years of age with most cases being associated with +19.
Neuroblastoma (NB) is one of the most common childhood cancers. Patients with low stage tumor have high survival rate, while those with advanced stage and/or unfavorable molecular biology have poor prognosis. A correct histopathological diagnosis, clinical stage, and identified genetic aberrations are crucial for treatment stratification according to current protocol. The tumor sample is obtained either by fine needle aspiration, cutting needle biopsy or open biopsy. NB exhibits neuroendocrine differentiation by showing immunoreactivity for chromogranin A (CgA), synaptophysin (syn), and neuron specific enolase (NSE) and 90% of the patients have increased levels of urine catecholamine metabolites.
2. Chromogranin A and neuron-specific enolase in neuroblastoma: Correlation to stage and prognostic factors.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Neuropediatrics/Paediatric oncology. Karolinska Inst, Dept Clin Intervent & Technol CLINTEC, Stockholm, Sweden.;Childrens Univ Hosp, Dept Womens & Childrens Hlth, Pediat Oncol, Uppsala, Sweden..
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Neuropediatrics/Paediatric oncology. Childrens Univ Hosp, Dept Womens & Childrens Hlth, Pediat Oncol, Uppsala, Sweden.
Karolinska Univ Hosp, Dept Pathol & Cytol, Stockholm, Sweden..
Karolinska Inst, Dept Lab Med, Div Therapeut Immunol, Stockholm, Sweden..
Severe aGvHD is a life-threatening complication after allogeneic HSCT. The GI tract is considered to play a key role in aGvHD, where the disease process can start and is one of the major target organs. Here, we present a case of a one-year-old child with a life-threatening GI-aGvHD stage IV, post-HSCT, resistant to steroids and MMF for 4 weeks. He was successfully treated with placenta-derived DSC.
Karolinska Inst, CLINTEC, Dept Clin Sci Intervent & Technol, SE-14186 Stockholm, Sweden.
Karolinska Inst, Dept Microbiol Tumor & Cell Biol, Stockholm, Sweden;Karolinska Univ Hosp, Dept Clin Microbiol, Stockholm, Sweden.
Karolinska Inst, CLINTEC, Dept Clin Sci Intervent & Technol, SE-14186 Stockholm, Sweden;Karolinska Univ Hosp, Liljeholmen Child & Adolescent Med Facil, Dept Paediat, Stockholm, Sweden.
Karolinska Inst, CLINTEC, Dept Clin Sci Intervent & Technol, SE-14186 Stockholm, Sweden;Karolinska Univ Hosp, Astrid Lindgrens Children s Hosp, Dept Pediat Hematol Immunol & Stem Cell Transplan, Stockholm, Sweden.
Inst Canc Res, Div Mol Pathol, Ctr Evolut & Canc, London, England.
SCL/TAL1 interrupting locus (STIL)-T-cell acute leukaemia (TAL1) fusion genes are present in approximately 11-27% of children with paediatric T-cell acute lymphoblastic leukaemia (T-ALL), but the developmental timing of the rearrangement is still unknown. To investigate whether the fusion gene can be detected in neonatal blood spots (NBSs) from paediatric patients diagnosed with T-cell ALL, we analysed DNA from 38 paediatric patients with T-ALL by nested polymerase chain reaction and electrophoresis. The STIL-TAL1 fusion gene was not detected in NBSs from any of the 38 patients with T-ALL, suggesting that STIL-TAL1 fusion genes are most probably postnatal events in paediatric T-ALL.
Stockholm Univ, Dept Special Educ, S-11418 Stockholm, Sweden.;Linkoping Univ, Dept Social & Welf Studies, S-58183 Norrkoping, Sweden..
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Research in Disability and Habilitation. Swedish Natl Ctr Rett Syndrome & Related Disorder, S-83223 Froson, Sweden.
Linkoping Univ, Dept Social & Welf Studies, S-58183 Norrkoping, Sweden..
Linkoping Univ, Dept Social & Welf Studies, S-58183 Norrkoping, Sweden.;Orebro Univ, Fac Med & Hlth, Sch Hlth Sci, S-70281 Orebro, Sweden..
Assistive technology (AT) can be used as early intervention in order to reduce activity limitations in play and communication. This longitudinal case study examines eye-gaze control technology as early intervention for a young child with high spinal cord injury without the ability to make sounds. The young child was followed by repeated measures concerning performance and communication from baseline at 9 months to 26 months, and finalized at 36 months by field observations in the home setting. The results showed eye-gaze performance and frequency of use of eye-gaze control technology increased over time. Goals set at 15 months concerning learning and using the AT; naming objects and interactions with family was successfully completed at 26 months. Communicative functions regarding obtaining objects and social interaction increased from unintentional actions to purposeful choices and interactions. At 36 months, the toddler was partly independent in eye gazing, used all activities provided, and made independent choices. In conclusion, the results show that a 9-month-old child with profound motor disabilities can benefit from eye-gaze control technology in order to gradually perform activities, socially interact with family members, and make choices.
Astrid Lindgren Childrens Hosp, Dept Neuropediat, Q302, S-17176 Stockholm, Sweden..
Astrid Lindgren Childrens Hosp, Dept Neuropediat, Q302, S-17176 Stockholm, Sweden.;Karolinska Inst, Dept Womens & Childrens Hlth, Stockholm, Sweden..
Background: X-linked adrenoleukodystrophy (X-ALD) is a genetic peroxisomal disorder associated with tissue accumulation of very long chain fatty acids (VLCFAs). In approximately one third of affected males, this causes progressive and irreversible damage to the brain white matter. Progress is often rapid with upper motor neuron damage leading to severe spasticity and dystonia. The increased muscle tone is frequently difficult to alleviate with oral drugs. Here, we describe two patients with X-ALD who have received treatment with intrathecal baclofen pumps (ITB). Case study: Both boys had a rapidly progressive cerebral form of the disorder resulting, among other things, in escalating spasticity and dystonia causing severe pain, dramatically reducing their quality of life. Both were treated with a variety of oral medications without adequate relief. Both patients tolerated ITB surgery without complications and the positive clinical effects of treatment with ITB became clear in the following weeks and months, with significantly reduced muscle tone, less pain and better sleep. Moreover, general caretaking became easier. Conclusion: The treatment of spasticity and dystonia in these patients is difficult partly due to the relentless nature of this progressive disorder. In our two patients, ITB has been effective from both a symptomatic and palliative perspective. We recommend that such treatment be considered as an early option for increased muscle tone in boys with the cerebral form of X-ALD. (C) 2017 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.
Aarhus Univ Hosp, Child & Adolescent Hlth, Aarhus, Denmark.
Univ Hosp Rigshosp, Dept Paediat & Adolescent Med, Copenhagen, Denmark.
Univ Gothenburg, Sahlgrenska Acad, Inst Clin Sci, Dept Paediat, Gothenburg, Sweden.
Tech Univ Denmark, Dept Bio & Hlth Informat, Lyngby, Denmark.
Karolinska Univ Hosp, Childhood Canc Res Unit, Dept Womens & Childrens Hlth, Stockholm, Sweden; Karolinska Inst, Stockholm, Sweden.
Landspitali Univ Hosp, Childrens Hosp, Reykjavik, Iceland.
Turku Univ Hosp, Dept Paediat & Adolescent Med, Turku, Finland; Turku Univ, Turku, Finland.
St Olavs Hosp, Dept Paediat, Trondheim, Norway.
Univ Childrens Hosp, Dept Oncol & Haematol, Tallinn, Estonia.
Vilnius Univ, Fac Med, Clin Childrens Dis, Vilnius, Lithuania.
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.
Copenhagen Univ Hosp, Rigshosp, Dept Paediat & Adolescent Med, Blegdamsvej 9, DK-2100 Copenhagen, Denmark.
Rigshosp, Copenhagen Univ Hosp, Dept Clin Immunol, Tissue Typing Lab, Copenhagen, Denmark.
Karolinska Univ Hosp, Astrid Lindgren Childrens Hosp & Clintec, Stockholm, Sweden.
Oslo Univ Hosp, Dept Paediat Haematol & Oncol, Oslo, Norway.
Queen Silvia Childrens Hosp, Dept Paediat, Inst Clin Sci, Gothenburg, Sweden.
Vilnius Univ Hosp, Childrens Hosp, Ctr Paediat Oncol & Haematol, Vilnius, Lithuania.
Tallin Childrens Hosp, Tallinn, Estonia.
St Olavs Univ Hosp Trondheim, Dept Paediat, Trondheim, Norway;NTNU, Dept Clin & Mol Med, Trondheim, Norway.
Landspitali Univ Hosp, Reykjavik, Iceland.
Karolinska Inst, Childhood Canc Res Unit, Astrid Lindgrens Childrens Hosp, Karolinska Univ Hosp, Stockholm, Sweden.
Copenhagen Univ Hosp, Rigshosp, Dept Paediat & Adolescent Med, Blegdamsvej 9, DK-2100 Copenhagen, Denmark;Univ Copenhagen, Inst Clin Med, Copenhagen, Denmark.
Univ Helsinki, Dept Paediat, Helsinki, Finland.
The population-based Nordic/Baltic acute lymphoblastic leukaemia (ALL) Nordic Society for Paediatric Haematology and Oncology (NOPHO) ALL2008 protocol combined minimal residual disease (MRD)-driven treatment stratification with very intense first line chemotherapy for patients with high risk ALL. Patients with MRD >= 5% at end of induction or >= 10(-3) at end of consolidation or following two high risk blocks were eligible for haematopoietic cell transplantation (HCT) in first remission. After at least three high risk blocks a total of 71 children received HCT, of which 46 had MRD >= 5% at end of induction. Ten patients stratified to HCT were not transplanted; 12 received HCT without protocol indication. Among 69 patients with evaluable pre-HCT MRD results, 22 were MRD-positive, one with MRD >= 10(-3). After a median follow-up of 5 center dot 5 years, the cumulative incidence of relapse was 23 center dot 5% (95% confidence interval [CI]: 10 center dot 5-47 center dot 7) for MRD-positive versus 5 center dot 1% (95% CI: 1 center dot 3-19 center dot 2), P = 0 center dot 02) for MRD-negative patients. MRD was the only variable significantly associated with relapse (hazard ratio 9 center dot 1, 95% CI: 1 center dot 6-51 center dot 0, P = 0 center dot 012). Non-relapse mortality did not differ between the two groups, resulting in disease-free survival of 85 center dot 6% (95% CI: 75 center dot 4-97 center dot 2) and 67 center dot 4% (95% CI: 50 center dot 2-90 center dot 5), respectively. In conclusion, NOPHO block treatment efficiently reduced residual leukaemia which, combined with modern transplant procedures, provided high survival rates, also among pre-HCT MRD-positive patients.
Univ Oulu, Res Unit Med Imaging Phys & Technol, Fac Med, Oulu, Finland;Univ Oulu, Med Res Ctr, Oulu, Finland.
Oulu Univ Hosp, Dept Pediat & Adolescence, Oulu, Finland;Oulu Univ Hosp, PEDEGO Res Unit, Oulu, Finland;Univ Oulu, Oulu, Finland.
Univ Oulu, Res Unit Med Imaging Phys & Technol, Fac Med, Oulu, Finland;Univ Oulu, Med Res Ctr, Oulu, Finland;Univ Oulu, Oulu, Finland;Oulu Univ Hosp, Dept Diagnost Radiol, Oulu, Finland.
Kuopio Univ Hosp, Dept Clin Radiol, Kuopio, Finland.
Univ Helsinki, Dept Pediat Radiol, HUS Med Imaging Ctr, Radiol, Helsinki, Finland;Helsinki Univ Hosp, Helsinki, Finland.
Kuopio Univ Hosp, Dept Pediat & Adolescence, Kuopio, Finland;Univ Eastern Finland, Kuopio, Finland.
Tampere Univ Hosp, Dept Pediat, Tampere, Finland;Univ Tampere, Fac Med & Life Sci, Tampere, Finland.
Turku Univ Hosp, Dept Pediat & Adolescent Med, Turku, Finland;Turku Univ, Turku, Finland.
Helsinki Univ Hosp, Dept Pediat & Adolescence, Helsinki, Finland.
Univ Oulu, Med Res Ctr, Oulu, Finland;Oulu Univ Hosp, Dept Pediat & Adolescence, Oulu, Finland;Oulu Univ Hosp, PEDEGO Res Unit, Oulu, Finland;Univ Oulu, Oulu, Finland.
Purpose: Long-term side effects of the treatments are common in survivors of irradiated pediatric brain tumors. Ionizing radiation in combination with surgery and chemotherapy during childhood may reduce vertebral height and bone mineral density (BMD), and cause growth failure. The aim of this study was to evaluate the late consequences of tumor treatments on vertebrae in survivors of childhood brain tumors.
Methods: 72 adult survivors (mean age 27.8 years, standard deviation 6.7) of irradiated childhood brain tumor were studied by spinal magnetic resonance imaging (MRI) for vertebral abnormalities from the national cohort of Finland. Patients were treated in five university hospitals in Finland between the years 1970 and 2008. Subject height and weight were measured and body mass index (BMI) was calculated. The morphology and height/ depth ratio of the vertebrae in the middle of the kyphotic thoracic curvature (Th8) and lumbar lordosis (L3) were examined. Vertebrae were analyzed by Genant's semiquantative (SQ) method and spinal deformity index (SDI) was calculated. BMD was measured by using dual X-ray absorptiometry.
Results: 4.2% (3/72) of the patients had undiagnosed asymptomatic vertebral fracture and 5.6% (4/72) of patients had radiation- induced decreased vertebral body height. Male patients had flatter vertebrae compared with females. Patient age at the time of irradiation, BMI and irradiation area correlated to vertebral morphology differentially in males and females. BMD had no association with the vertebral shape. Patients who had received craniospinal irradiation were shorter than the general population.
Conclusion: Childhood brain tumor survivors had a high number of vertebral abnormalities in young adulthood. Irradiation was associated with abnormal vertebral morphology and compromised final height. Male gender may predispose vertebrae to the side effects of irradiation.