Impact of asparaginase discontinuation on outcome in childhood ALL: A report from the Children’s Oncology Group (COG).
Bibliographic record
Abstract
10005 Background: Asparaginase (ASP) is an important component of acute lymphoblastic leukemia (ALL) treatment, but is often discontinued due to toxicity. For allergic reactions, but not other toxicities, Erwinia Asparaginase (EA) is often substituted. The majority of treatment protocols use discrete, discontinuous periods of asparagine depletion. In the context of such protocols, the impact of EA substitution or complete ASP discontinuation is unknown. Methods: Patients age 1-30.99 years enrolled on frontline COG trials for B-ALL [standard risk (NCI SR): AALL0331; high risk (NCI HR) AALL0232] were included. The number of prescribed pegaspargase (PEG) doses varied by trial, risk strata, and randomization (Table). Maintenance therapy did not contain ASP. Landmark analyses starting at Maintenance compared event free survival (EFS) between those receiving all prescribed doses of PEG vs. those switched to EA but receiving all doses vs. those not receiving all ASP doses. Results: This study included 5,195 AALL0331 and 3,001 AALL0232 patients. The cumulative incidence of PEG discontinuation was 12.2±4.6% on AALL0331 and 25.4%±0.8% on AALL0232. In multivariable analyses adjusted for patient and disease variables, NCI HR patients who did not receive all prescribed ASP doses had inferior EFS [hazard ratio (HR) 1.5, 95% confidence interval (95CI) 1.2-1.9; p=0.002] compared to those receiving all prescribed PEG doses. Patients with EA substitution who completed their courses were not at increased risk (HR 1.1, 95CI 0.7-1.6; p=0.69). Sensitivity analyses excluding patients discontinuing ASP due to pancreatitis or thrombosis yielded similar results. NCI SR patients who discontinued ASP were not at elevated risk (HR 1.2, 95CI 0.9-1.6; p=0.23), except when analyses were restricted to NCI SR patients with slow early response (HR 1.7, 95CI 1.1-2.7; p=0.03). Conclusions: Discontinuation of ASP doses is associated with significantly inferior EFS and must be balanced against the risks of ASP re-challenge. Our results also illustrate the potentially severe consequences of EA shortages. Prescribed pegasparagase doses. [Table: see text]
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How this classification was reachedexpand
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 | 0.007 | 0.014 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.002 | 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 | 0.001 | 0.002 |
| 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 itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".