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

Associations of widespread pain sensitivity, comorbid chronic pain and psychological distress with Irritable Bowel Syndrome and abdominal pain

This is the first report documenting widespread hyperalgesia among adolescent and adult individuals with symptoms of IBS in the general population. Results were found to be independent of sex, comorbid pain and psychological distress. Increased pain sensitivity may contribute in triggering and maintaining chronic pain, but prospective studies are needed to examine these possible causal relationships. The prevalence of depression is considerably increased among adolescents with AP and IBS in the general population, in particular among adolescents with AP reporting severe and widespread abdominal pain, and among adolescents reporting comorbid chronic pain in other body sites. Evaluating these pain symptom dimensions may be of value for identifying subgroups adolescents with AP and IBS that have greater risk of depression

Chronic iron deficiency and anaemia were highly prevalent in a population-based longitudinal study among adolescent girls

Aim: The combination of iron deficiency and anaemia is a major health problem, and adolescents are an at- risk group. The main aim of this study was to explore the mag-nitude of these conditions among adolescents aged 15–19 and identify possible as-sociated risk factors. Methods: This population- based longitudinal study of adolescents in North Norway was conducted in 2010–2011, with a follow-up two years later. Repeated measure-ments of iron deficiency and anaemia and its possible risk factors were studied in 309 girls and 273 boys. Results: Iron deficiency and anaemia were found in 18.1% and 19.9% of girls and 1.6% and 2.9% of boys in the first study and about half of the cases were chronic two years later. Most girls had moderate iron deficiency (14.5%) and mild anaemia (16.0%). Daily milk consumption was associated with increased iron deficiency in girls (odds ratio 2.3, 95% confidence interval 1.1–4.9), and the most physically active girls had the lowest levels of iron deficiency (odds ratio 0.4, 95% confidence intervaI 0.2–0.9). Iron deficiency was the most important risk factor for chronic anaemia in girls. Conclusion: The results of this study highlight the importance of iron deficiency screening and treatment for adolescent girls

Obesity as a predictor of treatment-related toxicity in children with acute lymphoblastic leukaemia.

To access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked DownloadObesity 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 2·0-17·9 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/m2 ; healthy weight, 17 to <25 kg/m2 ; overweight, 25 to <30 kg/m2 ; and obese, ≥30 kg/m2 . Obese children had a higher incidence rate ratio (IRR) for severe toxic events {IRR: 1·55 [95% confidence interval (CI) 1·07-2·50]}, 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 2·87 (95% CI 1·00-8·21)] and anaphylactic reactions [IRR 7·95 (95% CI 2·15-29·37)] as well as higher risk for truncation of asparaginase [IRR 3·54 (95% CI 1·67-7·50)]. 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.Barncancerfonden (Swedish Childhood Cancer Fund

Obesity as a predictor of treatment-related toxicity in children with acute lymphoblastic leukaemia

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, &lt;17 kg/m(2); healthy weight, 17 to &lt;25 kg/m(2); overweight, 25 to &lt;30 kg/m(2); and obese, &gt;= 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 &gt;= 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 &gt;= 10 years with ALL

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

Abstract 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

Obesity as a predictor of treatment-related toxicity in children with acute lymphoblastic leukaemia

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 2·0–17·9 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, &lt;17 kg/m²; healthy weight, 17 to &lt;25 kg/m² overweight 25 to &lt;30 kg/m²; and obese, ≥30 kg/m². Obese children had a higher incidence rate ratio (IRR) for severe toxic events {IRR: 1·55 [95% confidence interval (CI) 1·07–2·50]}, 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 2·87 (95% CI 1·00–8·21)] and anaphylactic reactions [IRR 7·95 (95% CI 2·15–29·37)] as well as higher risk for truncation of asparaginase [IRR 3·54 (95% CI 1·67–7·50)]. 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

Widespread hyperalgesia in adolescents with symptoms of irritable bowel syndrome: results from a large population-based study

Widespread hyperalgesia is well documented among adult patients with Irritable Bowel Syndrome (IBS), but little is known about pain sensitivity among adolescents with IBS. We examined pain sensitivity in 961 adolescents from the general population (mean age 16.1 years), including pain threshold and tolerance measurements of heat (forearm) and pressure pain (fingernail and shoulder), and cold-pressor tolerance (hand). Adolescents with IBS symptoms (Rome III criteria) had lower heat pain thresholds compared to controls after adjustments for sex, co-morbid pain and psychological distress (mean difference = -0.8 oC; 95% CI = -1.6 to -0.04). Similar results were found for pressure pain threshold at the shoulder (mean difference = -46 kPa; 95% CI = -78 to -13) and fingernail (mean difference = -62 kPa; 95% CI = -109 to -15), and for an aggregate of all three threshold measures (z-score difference = -0.4; 95% CI = -0.6 to -0.2), though pressure pain threshold differences were non-significant after the final adjustments for psychological distress. No difference of pain tolerance was found between the IBS cases and controls. Our results indicate that adolescents in the general population with IBS symptoms, like adults, have widespread hyperalgesia

Age and DNA-methylation subgroup as potential independent risk factors for treatment stratification in children with Atypical Teratoid/Rhabdoid Tumors

BACKGROUND Controversy exists as to what may be defined as standard of care (including markers for stratification) for patients with Atypical Teratoid Rhabdoid Tumors (ATRT). The European Rhabdoid Registry, EU-RHAB, recruits uniformly treated patients and offers standardized genetic and DNA methylation analyses. METHODS Clinical, genetic and treatment data of 143 patients from 13 European countries were analyzed (2009 - 2017). Therapy consisted of surgery, anthracycline-based induction and either radiotherapy or high dose chemotherapy following a consensus among European experts. FISH, MLPA and sequencing were employed for assessment of somatic and germline mutations in SMARCB1. Molecular subgroups (ATRT-SHH, -TYR and -MYC) were determined using DNA-methylation arrays resulting in profiles of 84 tumors. RESULTS Median age at diagnosis of 67 girls and 76 boys was 29.5 months. 5-year overall survival (OS) and event-free survival (EFS) were 34.7±4.5% and 30.5±4.2%. Tumors displayed allelic partial/whole gene deletions (66%; 122/186 alleles) or single nucleotide variants (34%; 64/186 alleles) of SMARCB1. Germline mutations were detected in 26% of ATRT (30/117). The patient cohort consisted of 47% ATRT-SHH (39/84), 33% ATRT-TYR (28/84), and 20% ATRT-MYC 17/84). Age <1 year, non-TYR signature (ATRT-SHH or -MYC), metastatic or synchronous tumors, germline mutation, incomplete remission and omission of radiotherapy were negative prognostic factors in univariate analyses (p<0.05). An adjusted multivariate model identified age <1 year and a non-TYR signature as independent negative predictors of OS: high risk (<1 year + non-TYR; 5-year OS = 0%), intermediate risk (<1 year + ATRT-TYR or ≥1 year + non-TYR; 5-year OS = 32.5±8.7%) and standard risk (≥1 year + ATRT-TYR, 5-year OS = 71.5±12.2%). CONCLUSIONS Age and molecular subgroup status are independent risk factors for survival in children with ATRT. Our model warrants validation within future clinical trials