Hyperlipidemia is a risk factor for osteonecrosis in children and young adults with acute lymphoblastic leukemia

TesisLa intoxicación con plomo es un problema de trascendental importancia para la salud pública por sus efectos en la calidad de vida de las personas, particularmente de los niños expuestos. La presente investigación fue de tipo descriptivo transversal y se realizó con la finalidad de determinar los niveles de plomo sanguíneo en los habitantes del Centro Poblado de Taca, durante los meses de junio y julio de 2013. Participaron del estudio 42 personas voluntarias: 32 varones y 10 mujeres, cuya media de edad fue de 33,23 años (rango: 21-72 años). Se tomaron muestras de sangre mediante venopunción previo consentimiento informado, utilizando tubos al vacío con anticoagulante, se mantuvieron bajo refrigeración a 8 °C, se trataron con mezcla sulfonítrica - ácido nítrico concentrado a ebullición lenta en un equipo de digestión y luego leídas en un espectrofotómetro de absorción atómica Thermo Scientific ¡CE 3300 a 217 nm. Se obtuvieron los siguientes resultados: todos los sujetos estudiados presentan algún grado de contaminación con plomo, encontrándose un nivel de plumbemia medio de 26,62 ug/dl y los niveles de plomo en sangre de varones y mujeres de 18 a 72 años de edad, encontrándose medias de 33,96 y 3,16 ug/dl, respectivamente, existiendo relación entre el género y plumbemia (p<0,05). El nivel de plomo en sangre de los habitantes del Centro Poblado de Taca, Distrito Canaria, Provincia de Víctor Fajardo, se incrementa en función del tiempo de residencia, por lo que existe relación entre estas dos variables (P<0,05)

Health care utilisation preceding relapse or second malignant neoplasm after childhood acute lymphoblastic leukaemia:a population-based matched cohort study

OBJECTIVES: To investigate health care utilisation including both primary and secondary health care 6 months before the diagnosis of a relapse or a second malignant neoplasm (SMN) in survivors of childhood acute lymphoblastic leukaemia (ALL). DESIGN AND SETTING: A Danish population-based matched cohort study linking multiple nationwide registries. PARTICIPANTS: Participants were recruited from a total of 622 childhood ALL 2.5-year event-free survivors diagnosed between 1994 and 2015. Cases were survivors developing a relapse or an SMN and references were survivors still in first remission. Each case was matched with five references on age, sex, treatment protocol and risk group. PRIMARY OUTCOME MEASURES: Consultations in general practice and hospital the last 6 months before relapse or SMN. Cases and references were compared with monthly incidence rate ratios (IRRs) from negative binomial regression models. RESULTS: Of the 622 childhood ALL survivors, 60 (9.6%) developed a relapse (49) or an SMN (11) and 295 matched references were identified. Health care utilisation in general practice increased among cases the last month before the event compared with references with an IRR of 2.71 (95% CI 1.71 to 4.28). Data showed a bimodal structure with a significantly increased number of visits 4, 5 and 6 months before the event. Hospital health care utilisation increased 2 months before the event in cases with an IRR of 5.01 (3.78 to 6.63) the last month before the event and an IRR of 1.94 (1.32 to 2.85) the second-last month comparing cases and references. CONCLUSIONS: Survivors of childhood ALL developing a relapse or an SMN have a short period of increased health care utilisation before diagnosis. At hospital, this might be explained by pre-diagnostic examinations. In general practice, data suggest a bimodal structure with children later developing a relapse having more contacts also half a year before the relapse, suggesting that there could be early warnings

Quality of life in mothers and fathers of children treated for acute lymphoblastic leukaemia in Sweden, Finland and Denmark

Acute lymphoblastic leukaemia (ALL) has a high survival rate, but treatment is lengthy with risk of severe side-effects, which may also impact parents' health-related quality of life (HRQOL). We present data on 526 parents of 310 children treated for ALL according to the NOPHO ALL2008-protocol, in Sweden, Finland and Denmark. Parents were asked to complete the 36-Item Short Form Survey (SF-36) at least 6 months after end of treatment and data were compared with Norwegian reference data. Parental background factors were collected via a study-specific questionnaire. Participating parents scored significantly lower than the reference population on both physical and mental summary indexes, but only surpassed a minimal clinically important difference for the mental summary index (Mental Component Summary [MCS]). Mothers scored lower than fathers in the MCS and stopped working and took care of the affected child more often than the fathers. Higher mental HRQOL was associated with male gender and living in Finland or Denmark (compared to Sweden). Correlations within spouses in physical and mental scores were weak to moderate. In conclusion, ALL negatively affects parental HRQOL, especially the mental domains, even after treatment. Findings suggest that mothers are more affected than fathers and may require extra support.</p

A survey on thromboprophylaxis and coagulation assessment in children and young adults with acute lymphoblastic leukaemia (ALL) in the Nordic and Baltic countries : Different practices of assessment and management

Patients undergoing treatment for acute lymphoblastic leukaemia (ALL) are at risk of coagulopathy, especially thromboembolism. We conducted a survey on practices in the assessment and management of coagulopathy during the new ALLTogether protocol in 29 (17 paediatric, 12 adult) Nordic and Baltic cancer centres. While 92% of adult centres used thromboprophylaxis with low-molecular-weight heparin, no paediatric centre did. Almost all providers performed baseline coagulation studies, but only 59% continued the assessment. Fibrinogen replacement was conducted in 59%, and antithrombin replacement in 28% of the centres. The survey highlights the need for guidelines in the management of coagulopathy during ALL therapy.Peer reviewe

Candidate single nucleotide polymorphisms and thromboembolism in acute lymphoblastic leukemia - A NOPHO ALL2008 study

Introduction: Thromboembolism is a serious toxicity of acute lymphoblastic leukemia treatment, and contributes to substantial morbidity and mortality. Several single nucleotide polymorphisms have been associated with thromboembolism in the general population; however, their impact in patients with acute lymphoblastic leukemia, particularly in children, remains uncertain. Materials and methods: We collected constitutional DNA and prospectively registered thromboembolic events in 1252 patients, 1-45 years, with acute lymphoblastic leukemia included in the Nordic Society of Pediatric Hematology and Oncology ALL2008 protocol in the Nordic and Baltic countries (7/2008-7/2016). Based on previously published data and a priori power calculations, we selected four single nucleotide polymorphisms: F5 rs6025, F11 rs2036914, FGG rs2066865, and ABO rs8176719. Results: The 2.5 year cumulative incidence of thromboembolism was 7.1% (95% confidence interval (CI) 5.6-8.5). F11 rs2036914 was associated with thromboembolism (hazard ratio (HR) 1.52, 95%CI 1.11-2.07) and there was a borderline significant association for FGG rs2066865 (HR 1.37, 95%CI 0.99-1.91), but no association for ABO rs8176719 or F5 rs6025 in multiple cox regression. A genetic risk score based on F11 rs2036914 and FGG rs2066865 was associated with thromboembolism (HR 1.45 per risk allele, 95%CI 1.15-1.81), the association was strongest in adolescents 10.0-17.9 years (HR 1.64). Conclusion: If validated, a F11 rs2036914/FGG rs2066865 risk prediction model should be tested as a stratification tool for prevention of thromboembolism in patients with acute lymphoblastic leukemia.Peer reviewe

Changes in body mass index during treatment of childhood acute lymphoblastic leukemia with the Nordic ALL2008 protocol

Funding Information: Christina Egnell is supported by funding from the Swedish Childhood Cancer Foundation (Barncancerfonden, grant numbers TJ2018‐0093; PR2019‐0075; TJ2019‐0048). This work is part of the Danish nation‐wide research program Childhood Oncology Network Targeting Research, Organisation & Life expectancy (CONTROL) and supported by the Danish Cancer Society (R‐257‐A14720) and the Danish Childhood Cancer Foundation (2019‐5934 and 2020‐5769). Publisher Copyright: © 2022 The Authors. European Journal of Haematology published by John Wiley & Sons Ltd.Objectives: Children with acute lymphoblastic leukemia (ALL) have a tendency to gain weight during treatment. As overweight and obesity associate with health problems, prophylactic interventions are warranted. Therefore, it is important to identify the children most prone to gain weight. Methods: Patients aged 2.0–17.9 years at ALL diagnosis were identified from the NOPHO ALL2008 registry. Registry data was complemented with height and weight at the end of therapy from questionnaires. Body mass index (BMI) was classified according to international age- and sex-adjusted International Obesity Task Force BMI cut-offs. BMI values were transformed into standard deviation scores (SDS) to calculate the difference in BMISDS during treatment. Results: Data on BMI change were available for 765 children. Overweight and obesity doubled during treatment: 9.7% were overweight and 2.1% obese at diagnosis and 21.8% and 5.4% at the end of therapy, respectively. The mean BMISDS change was +0.64. Younger (2.0–5.9 years) and healthy weight children were most prone to become overweight (mean change in BMI SDS +0.85 and + 0.65, respectively). Conclusions: Younger children (2.0–5.9 years) with healthy weight at diagnosis were most prone to becoming overweight and therefore are an important group to target while considering interventions.Peer reviewe

National, clinical cohort study of late effects among survivors of acute lymphoblastic leukaemia:The ALL-STAR study protocol

Introduction More than 90% of patients diagnosed with childhood acute lymphoblastic leukaemia (ALL) today will survive. However, half of the survivors are expected to experience therapy-related chronic or late occurring adverse effects, reducing quality of life. Insight into underlying risk trajectories is warranted. The aim of this study is to establish a Nordic, national childhood ALL survivor cohort, to be investigated for the total somatic and psychosocial treatment-related burden as well as associated risk factors, allowing subsequent linkage to nation-wide public health registers.Methods and analysis This population-based observational cohort study includes clinical follow-up of a retrospective childhood ALL survivor cohort (n=475), treated according to a common Nordic ALL protocol during 2008–2018 in Denmark. The study includes matched controls. Primary endpoints are the cumulative incidence and cumulative burden of 197 health conditions, assessed through self-report and proxy-report questionnaires, medical chart validation, and clinical examinations. Secondary endpoints include organ-specific outcome, including cardiovascular and pulmonary function, physical performance, neuropathy, metabolic disturbances, hepatic and pancreatic function, bone health, oral and dental health, kidney function, puberty and fertility, fatigue, and psychosocial outcome. Therapy exposure, acute toxicities, and host genome variants are explored as risk factors.Ethics and dissemination The study is approved by the Regional Ethics Committee for the Capital Region in Denmark (H-18035090/H-20006359) and by the Danish Data Protection Agency (VD-2018–519). Results will be published in peer-reviewed journals and are expected to guide interventions that will ameliorate the burden of therapy without compromising the chance of cure

Parental experiences of the informed consent process in randomized clinical trials-A Nordic study

Background Randomized clinical trials (RCTs) are an essential part of improving acute lymphoblastic leukemia (ALL) treatment. This population-based questionnaire study investigated parents' experiences of the informed consent process in the RCTs within the Nordic NOPHO (Nordic Society of Paediatric Haematology and Oncology) ALL2008 trial. Procedure Parents in Sweden, Denmark, and Finland whose child was alive and in first remission after end of therapy and who were asked to participate in any RCT in the ALL2008 protocol, were asked to complete 15 questions/items regarding their experience of the RCT consent process. Results A total of 483 parents of 279 children met the inclusion criteria and answered the study questionnaire. Most (91%) agreed/strongly agreed to having received sufficient information to make a well-informed decision, felt confidence in the study design (86%), and thought that the process was satisfactory (86%). Those who did not consent reported a generally more negative experience of the process. More than a third of all parents and over half of parents who had refused participation felt that it was burdensome to decide. Most parents (66%) in general, and one-third of those with children 8 years or older, reported that their child was not involved in the process. Conclusions Parents were in general satisfied with the informed consent process, although many parents, particularly those who refused participation, reported it as burdensome to make the decision concerning RCT. Fewer than expected of the school-aged children were involved in the decision process, which calls for attention on how children are included in the consent procedure in clinical trials