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Background: After childhood acute lymphoblastic leukemia (ALL), sequelae include overweight and obesity, yet with conflicting evidence. We compared the prevalence of overweight and obesity between ≥5‐year ALL survivors from the North American Childhood Cancer Survivor Study (CCSS) and the Swiss Childhood Cancer Survivor Study (SCCSS) and described risk factors. Methods: We included adult childhood ALL survivors diagnosed between 1976 and 1999. We matched CCSS participants (3:1) to SCCSS participants by sex and attained age. We calculated body mass index (BMI) from self‐reported height and weight for 1287 CCSS and 429 SCCSS participants; we then compared those with siblings (2034) in North America and Switzerland (678) siblings. We assessed risk factors for overweight (BMI 25–29.9 kg/m2) and obesity (≥30 kg/m2) using multinomial regression. Results: We found overweight and obesity significantly more common among survivors in North America when compared with survivors in Switzerland [overweight: 30%, 95% confidence interval (CI): 27–32 vs. 24%, 21–29; obesity: 29%, 27–32 vs. 7%, 5–10] and siblings (overweight: 30%, 27–32 vs. 25%, 22–29; obesity: 24%, 22–26 vs. 6%, 4–8). Survivors in North America [odds ratio (OR) = 1.24, 1.01–1.53] and Switzerland (1.27, 0.74–2.21) were slightly more often obese than siblings. Among survivors, risk factors for obesity included residency in North America (5.8, 3.7–9.0); male (1.7, 1.3–2.3); attained age (≥45 years: 5.1, 2.4–10.8); Non‐Hispanic Black (3.4, 1.6–7.0); low household income (2.3, 1.4–3.5); young age at diagnosis (1.6, 1.1–2.2). Cranial radiotherapy ≥18 Gray was only a risk factor for overweight (1.4, 1.0–1.8); steroids were not associated with overweight or obesity. Interaction tests found no evidence of difference in risk factors between cohorts. Conclusions: Although treatment‐related risk for overweight and obesity were similar between regions, higher prevalence among survivors in North America identifies important sociodemographic drivers for informing health policy and targeted intervention trials. Like with the general population, our study confirms obesity as a prevalent health hazard—driven mainly by sociodemographic factors—among survivors of childhood acute lymphoblastic leukemia and their siblings. Since cancer survivors are particularly susceptible to cardiovascular disease and other late sequelae of overweight and obesity, we recommend a two‐pronged approach: health policies for reducing overweight among the general population and interventions targeting physical activity and diet during and after cancer treatment. [ABSTRACT FROM AUTHOR]

Four individuals from two families presented with a multisystemic condition of suspected genetic origin that was diagnosed only after genome analysis. The main phenotypic features were immune system dysregulation (severe immunodeficiency with autoimmunity) and intellectual disability. The four individuals were found to be homozygous for a 4.4 Kb deletion removing exons 20–23 (NM_003291.4) of the TPP2 gene, predicting a frameshift with premature termination of the protein. The deletion was located on a shared chromosome 13 haplotype indicating a Swiss founder mutation. Tripeptidyl peptidase 2 (TPP2) is a protease involved in HLA/antigen complex processing and amino acid homeostasis. Biallelic variants in TPP2 have been described in 10 individuals with variable features including immune deficiency, autoimmune cytopenias, and intellectual disability or chronic sterile brain inflammation mimicking multiple sclerosis. Our observations further delineate this severe condition not yet included in the OMIM catalog. Timely recognition of TPP2 deficiency is crucial since (1) immune surveillance is needed and hematopoietic stem cell transplantation may be necessary, and (2) for provision of genetic counselling. Additionally, enzyme replacement therapy, as already established for TPP1 deficiency, might be an option in the future. [ABSTRACT FROM AUTHOR]

In childhood-onset acute myeloid leukaemia (AML) the clinical value of karyotypic aberrations is now acknowledged, although there is still debate concerning the prognostic significance of some events. To add to this knowledge, cytogenetic analysis was performed on a consecutive series of 84 childhood AML patients diagnosed in Switzerland. A result was obtained for all patients, with 69 (82%) showing a clonal karyotypic aberration. In the remaining 15 (18%), no karyotypic aberration was seen by either conventional or fluorescence in situ hybridisation analyses. The most frequent aberrations observed were t(11q23) (19% of all patients), t(8;21) (12%) and +8 (11%). Except for cytogenetics, no clinical parameter was shown to be significantly associated with outcome. The analysis of individual cytogenetic subgroups demonstrated that aberrations involving chromosome 16q were the strongest predictor of a good prognosis, while +8 and complex karyotypes represented the strongest predictors of a poor prognosis. It was also noteworthy that patients with the rare aberrations of del(11q) ( n = 4) and t(16;21)(p11;q22) ( n = 3) had a poor outcome. The results support the importance of cytogenetic analysis in childhood AML, but show that further work is required in the classification of the poor prognosis aberrations. [ABSTRACT FROM AUTHOR]