Pharmacogenetic Risk Factors for Osteonecrosis of the Hip Among Children With Leukemia
Why this work is in the frame
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Bibliographic record
Abstract
PURPOSE: One of the adverse effects of therapy for acute lymphoblastic leukemia (ALL) is osteonecrosis of the hip. Putative risk factors for osteonecrosis have included being female, white race, and older age. Our goal was to define possible genetic risk factors for osteonecrosis among children treated for newly diagnosed ALL. METHODS: Using a candidate gene approach, we determined the genotypes for 16 common polymorphisms in genes likely to affect the pharmacokinetics or pharmacodynamics of antileukemic medications in 64 children with ALL. Therapy included glucocorticoids and antifolates. Magnetic resonance imaging of both hips was used to diagnose osteonecrosis, and was performed at similar times from the start of ALL therapy (P =.61) in the 25 patients with and the 39 patients without osteonecrosis (median, 447 days and 443 days, respectively). RESULTS: In addition to age older than 10 years (odds ratio [OR], 24.2; P =.0001) and white race (OR, 11.1; P =.037), host factors for osteonecrosis included the vitamin D receptor FokI start site CC genotype (OR, 4.5; P =.045), and the thymidylate synthase low activity 2/2 enhancer repeat genotype (OR, 7.4; P =.049). CONCLUSION: Because folate-related and vitamin D-receptor genetic variants have been associated with bone and vasculature morbidity, these pharmacogenetic associations likely reflect the interaction of antileukemic medications with germline sensitivity to drug actions, and might identify ALL patients at highest risk to develop osteonecrosis.
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Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.002 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it