ArticleBlood2015
Genetics of glucocorticoid-associated osteonecrosis in children with acute lymphoblastic leukemia.
Article in Blood, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 84 papers, 3 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
High Risk B-Precursor Acute Lymphoblastic Leukemia (ALL)
Total XV - Total Therapy Study XV for Newly Diagnosed Patients With Acute Lymphoblastic Leukemia
Who cites it
84 citing papers in PubMed, 3 syntheses or guidelines pooled it, 117 citations in OpenAlex.
- Novel susceptibility loci for steroid-associated osteonecrosis of the femoral head in systemic lupus erythematosus.Human molecular genetics · 2022Pooled it
- Association between genetic polymorphisms and osteonecrosis in steroid treatment populations: a detailed stratified and dose-response meta-analysis.Bioscience reports · 2019Pooled it
- Osteonecrosis of the femoral head: genetic basis.International orthopaedics · 2019Pooled it
- Development of osteonecrosis and improved survival in B-ALL: results of Children's Oncology Group Trial AALL0232.Leukemia · 2024Trial
- Whole-joint magnetic resonance imaging to assess osteonecrosis in pediatric patients with acute lymphoblastic lymphoma.Pediatric blood & cancer · 2020Trial
- An investigation of toxicities and survival in Hispanic children and adolescents with ALL: Results from the Dana-Farber Cancer Institute ALL Consortium protocol 05-001.Pediatric blood & cancer · 2018Trial
- Neurocognitive Functioning of Children Treated for High-Risk B-Acute Lymphoblastic Leukemia Randomly Assigned to Different Methotrexate and Corticosteroid Treatment Strategies: A Report From the Children's Oncology Group.Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2017Trial
- Trial
- Genetic Determinants of Treatment-Related Bone Toxicity in Pediatric Acute Lymphoblastic Leukemia.Clinical pharmacology and therapeutics · 2026Article
- Pharmacogenetic Predictors of Chemotherapy Treatment-Related Toxicities in Paediatric and Adolescent Acute Lymphoblastic Leukemia: A Systematic Review, Meta-Analysis and Literature-Based Candidate Prioritization.Pharmaceuticals (Basel, Switzerland) · 2026Review
- SHED-Exo delivery of miR-708-5p activates PI3K/AKT signaling pathway to alleviate glucocorticoid-induced osteogenic inhibition in BMSCs.Molecular and cellular biochemistry · 2026Article
- The role of pharmacogenetics in the therapy regimen of acute lymphoblastic leukemia in children: recent discoveries and future perspectives.Pharmacological reports : PR · 2026Review
- Pathogenesis and molecular mechanisms of steroid-induced femoral head necrosis in children: a narrative review.Frontiers in pediatrics · 2026Review
- Pharmacogenomics of treatment toxicities in pediatric B-Cell ALL: toward safer precision therapy.Frontiers in pharmacology · 2026Review
- Review
- The challenge of deintensifying chemotherapy for children and adolescents with B-ALL in the immunotherapy era.Hematology. American Society of Hematology. Education Program · 2025Review
- Four Pharmacogenomic Variants Strongly Linked to Corticosteroid-Induced Avascular Necrosis in Children with Cancer.Journal of clinical pharmacology · 2025Article
- Follow-up of osteonecrosis in paediatric acute lymphoblastic leukaemia patients treated with the NOPHO ALL2008 protocol.British journal of haematology · 2025Article
- Humeral head avascular necrosis: etiology, diagnosis, and management.Clinics in shoulder and elbow · 2025Article
- Defining the Differential Corticosteroid Response Basis from Multiple Omics Approaches.International journal of molecular sciences · 2024Review
24 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
28 authors at 11 institutions in 1 country.
Funding
Abstract
Glucocorticoids are important therapy for acute lymphoblastic leukemia (ALL) and their major adverse effect is osteonecrosis. Our goal was to identify genetic and nongenetic risk factors for osteonecrosis. We performed a genome-wide association study of single nucleotide polymorphisms (SNPs) in a discovery cohort comprising 2285 children with ALL, treated on the Children's Oncology Group AALL0232 protocol (NCT00075725), adjusting for covariates. The minor allele at SNP rs10989692 (near the glutamate receptor GRIN3A locus) was associated with osteonecrosis (hazard ratio = 2.03; P = 3.59 × 10(-7)). The association was supported by 2 replication cohorts, including 361 children with ALL on St. Jude's Total XV protocol (NCT00137111) and 309 non-ALL patients from Vanderbilt University's BioVU repository treated with glucocorticoids (odds ratio [OR] = 1.87 and 2.26; P = .063 and .0074, respectively). In a meta-analysis, rs10989692 was also highest ranked (P = 2.68 × 10(-8)), and the glutamate pathway was the top ranked pathway (P = 9.8 × 10(-4)). Osteonecrosis-associated glutamate receptor variants were also associated with other vascular phenotypes including cerebral ischemia (OR = 1.64; P = 2.5 × 10(-3)), and arterial embolism and thrombosis (OR = 1.88; P = 4.2 × 10(-3)). In conclusion, osteonecrosis was associated with inherited variations near glutamate receptor genes. Further understanding this association may allow interventions to decrease osteonecrosis. These trials are registered at www.clinicaltrials.gov as #NCT00075725 and #NCT00137111.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.