Induction Failure in Childhood and Young Adult T-cell Acute Lymphoblastic Leukemia
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PROVIDER: EGAS00001006411 | EGA |
REPOSITORIES: EGA
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Project description:We carried out WGS and RNAseq on a cohort of 48 children and young adults with induction failure in T-cell Acute Lymphoblastic Leukemia (T-ALL) to identify genomic drivers of treatment resistance. The study includes WGS for 33 tumour/normal pairs and 15 tumour-only samples. In addition, there is RNAseq data for 37 cases.
| EGAD00001009058 | EGA
Project description:BACKGROUND:Failure of remission-induction therapy is a rare but highly adverse event in children and adolescents with acute lymphoblastic leukemia (ALL). METHODS:We identified induction failure, defined by the persistence of leukemic blasts in blood, bone marrow, or any extramedullary site after 4 to 6 weeks of remission-induction therapy, in 1041 of 44,017 patients (2.4%) 0 to 18 years of age with newly diagnosed ALL who were treated by a total of 14 cooperative study groups between 1985 and 2000. We analyzed the relationships among disease characteristics, treatments administered, and outcomes in these patients. RESULTS:Patients with induction failure frequently presented with high-risk features, including older age, high leukocyte count, leukemia with a T-cell phenotype, the Philadelphia chromosome, and 11q23 rearrangement. With a median follow-up period of 8.3 years (range, 1.5 to 22.1), the 10-year survival rate (±SE) was estimated at only 32±1%. An age of 10 years or older, T-cell leukemia, the presence of an 11q23 rearrangement, and 25% or more blasts in the bone marrow at the end of induction therapy were associated with a particularly poor outcome. High hyperdiploidy (a modal chromosome number >50) and an age of 1 to 5 years were associated with a favorable outcome in patients with precursor B-cell leukemia. Allogeneic stem-cell transplantation from matched, related donors was associated with improved outcomes in T-cell leukemia. Children younger than 6 years of age with precursor B-cell leukemia and no adverse genetic features had a 10-year survival rate of 72±5% when treated with chemotherapy only. CONCLUSIONS:Pediatric ALL with induction failure is highly heterogeneous. Patients who have T-cell leukemia appear to have a better outcome with allogeneic stem-cell transplantation than with chemotherapy, whereas patients who have precursor B-cell leukemia without other adverse features appear to have a better outcome with chemotherapy. (Funded by Deutsche Krebshilfe and others.).
| S-EPMC3374496 | biostudies-literature
Project description:BackgroundGrowth failure is associated with adverse consequences, but studies need to control adequately for confounding.ObjectiveWe related height-for-age z scores (HAZs) and stunting at age 24 mo to adult human capital, marriage, fertility, health, and economic outcomes.DesignIn 2002-2004, we collected data from 1338 Guatemalan adults (aged 25-42 y) who were studied as children in 1969-1977. We used instrumental variable regression to correct for estimation bias and adjusted for potentially confounding factors.ResultsA 1-SD increase in HAZ was associated with more schooling (0.78 grades) and higher test scores for reading and nonverbal cognitive skills (0.28 and 0.25 SDs, respectively), characteristics of marriage partners (1.39 y older, 1.02 grade more schooling, and 1.01 cm taller) and, for women, a higher age at first birth (0.77 y) and fewer number of pregnancies and children (0.63 and 0.43, respectively). A 1-SD increase in HAZ was associated with increased household per capita expenditure (21%) and a lower probability of living in poverty (10 percentage points). Conversely, being stunted at 2 y was associated with less schooling, a lower test performance, a lower household per capita expenditure, and an increased probability of living in poverty. For women, stunting was associated with a lower age at first birth and higher number of pregnancies and children. There was little relation between either HAZ or stunting and adult health.ConclusionGrowth failure in early life has profound adverse consequences over the life course on human, social, and economic capital.
| S-EPMC3798075 | biostudies-literature
Project description:Microarray analyses of induction failure in T-ALL
| PRJNA112317 | ENA
Project description:Attention-deficit/hyperactivity disorder (ADHD) often persists into adulthood, but it remains unclear which childhood factors predict future outcome.To identify childhood predictors of ADHD outcome using both dimensional and categorical approaches.116 adolescents and young adults with childhood ADHD were followed up on average 6.6 years later. ADHD outcome variables were interview-based parent-reported ADHD symptoms and impairment. Childhood predictors included parent- and teacher-rated ADHD symptoms and co-occurring behaviours; actigraph measures of activity level; socio-economic status (SES); and cognitive measures previously associated with ADHD.Of the sample, 79% continued to meet clinical criteria of ADHD in adolescence and young adulthood. Higher parent-rated ADHD symptoms and movement intensity in childhood, but not teacher-rated symptoms, predicted ADHD symptoms at follow up. Co-occurring symptoms of oppositional behaviours, anxiety, social and emotional problems were also significant predictors, but these effects disappeared after controlling for ADHD symptoms. IQ and SES were significant predictors of both ADHD symptoms and impairment at follow up, but no other cognitive measures significantly predicted outcome.SES and IQ emerge as potential moderators for the prognosis of ADHD. Childhood severity of ADHD symptoms, as measured by parent ratings and actigraph movement intensity, also predicts later ADHD outcome. These factors should be considered when identifying ADHD children at most risk of poor long-term outcomes and for the development of interventions to improve prognosis.
| S-EPMC4480336 | biostudies-literature
Project description:BackgroundThe relationship between obesity and asthma is an area of debate.ObjectiveTo investigate the association of elevated body mass index (BMI) at a young age and young adult asthma.MethodsBMI, questionnaires, and serologic tests results were analyzed in participants of a predominantly white, middle-class, population-based birth cohort from Detroit, Michigan at 6 to 8 and 18 years of age. Asthma diagnosis was based on medical record data. Allergen specific IgE was analyzed using UniCAP, with atopy defined as 1 or more allergen specific IgE levels of 0.35 kU/L or higher. Overweight was defined as a BMI in 85th percentile or higher.ResultsA total of 10.6% of overweight males at 6 to 8 years of age had current asthma at 18 to 20 years of age compared with 3.2% of males who were normal or underweight (relative risk [RR], 3.3; 95% confidence interval [CI], 1.0-11.0; P=.048). A total of 19.6% of females who were overweight at 6 to 8 years of age had asthma compared with 10.3% of females who were normal or underweight (RR, 1.9; 95% CI, 0.9-3.9; P=.09). After adjustment for atopy at 6 to 8 years of age, overweight males had an adjusted RR of 4.7 (95% CI, 1.4-16.2; P=.01), and overweight females had an adjusted RR of 1.7 (95% CI, 0.8-3.3; P=.15). Change in BMI between 6 to 8 years of age and 18 to 20 years of age was also examined. Patients with persistently elevated BMI exhibited increased risk of asthma as young adults (RR, 2.4; 95% CI, 1.2-4.7) but not with an increasing BMI (RR, 0.8; 95% CI, 0.3-2.2) or a decreasing BMI (RR, 0.8; 95% CI, 0.3-2.2).ConclusionOverweight males 6 to 8 years of age have increased risk of asthma as young adults. Being overweight remains a predictor of asthma after adjustment for early atopy. A similar but not statistically significant trend was also seen among overweight females. Overweight body habitus throughout childhood is a risk factor for young adult asthma.
| S-EPMC3769639 | biostudies-literature
Project description:The 6th International Symposium on Childhood, Adolescent and Young Adult (CAYA) Non-Hodgkin Lymphoma (NHL) was held in Rotterdam, Netherlands, 26-29 September, 2018. This summary manuscript is a perspective on the presentations from the plenary scientific sessions, including wellness and survivorship, B-cell NHL, AYA lymphoma, translational NHL biology, lymphoma immunology, bone marrow transplantation and cell therapy, T/Natural Killer cell lymphoma, anaplastic large cell lymphoma, lymphoblastic lymphoma, novel lymphoma therapeutics and Hodgkin lymphoma. The symposium was attended by over 260 registrants from 42 different countries and included young, middle and senior investigators. Finally, the Angelo Rosolen, MD, Memorial Lecture was delivered by Alfred Reiter, MD.
| S-EPMC6897376 | biostudies-literature
Project description:Genome wide DNA methylation profiling of samples from adult survivors of childhood and young adult cancer, using the Illumina Infinium Human MethylationEPIC Beadchip arrays. Samples included 32 samples, all sampled at least 10 years after diagnosis . Specific therapies and duration between sampling and diagnosis varied.
2020-12-31 | GSE162559 | GEO
Project description:Comprehensive genomic analysis (WXS, WGS, RNAseq) identifies shared pathways of progression between human and mouse myeloma.
2024-04-04 | GSE255233 | GEO
Project description:OBJECTIVE:While individuals with 22q11.2 deletion syndrome (22q11DS) are at increased risk for a variety of functional impairments and psychiatric disorders, including psychosis, not all individuals with 22q11DS experience negative outcomes. Efforts to further understand which childhood variables best predict adult functional outcomes are needed, especially those that investigate childhood executive functioning abilities. METHODS:This longitudinal study followed 63 individuals with 22q11DS and 43 control participants over 9 years. Childhood executive functioning ability was assessed using both rater-based and performance-based measures and tested as predictors of young adult outcomes. RESULTS:Childhood global executive functioning abilities and parent report of child executive functioning abilities were the most consistent predictors of young adult outcomes. The study group moderated the relationship between child executive functioning and young adult outcomes for several outcomes such that the relationships were stronger in the 22q11DS sample. CONCLUSION:Rater-based and performance-based measures of childhood executive functioning abilities predicted young adult outcomes in individuals with and without 22q11DS. Executive functioning could be a valuable target for treatment in children with 22q11DS for improving not only childhood functioning but also adult outcomes. (JINS, 2018, 24, 905-916).
| S-EPMC6211806 | biostudies-literature