A Report of the Event-Free Survival (EFS) and Neurotoxicity for Children with Newly Diagnosed Standard Risk Acute Lymphoblastic Leukemia (ALL) on Pediatric Oncology Group (POG) Protocol 9405.
Bibliographic record
Abstract
Abstract POG 9405, a randomized phase III study for children with standard risk ALL, opened in 1994. The primary objectives were to determine effects on event-free survival (EFS) of: 1) higher (2.5g/m2) vs. standard (1g/m2) dose methotrexate (MTX) infusions during consolidation (in an attempt to obtain a plasma MTX target of 12 μmol) and (2) once vs. twice daily 6- mercaptopurine (MP) dosing during continuation (to improve the efficacy of MP based on its short half-life and S-phase dependence). Following remission induction, patients were randomized to: Regimens (Reg) A/B (MTX 1 g/m2 IV) or C/D (MTX 2.5 g/m2), all with MP 1g/m2 IV, q2 weeks (wk) x 12. Leucovorin 5 mg/m2 q6h x 5 began at hour 48 and continued until MTX level was <0.3μmol. MTX 20 mg/m2/wk IM and MP 75 mg/m2/day p.o. were given on alternate wks. Continuation was MTX 20 mg/m2/wk IM for all patients and MP 75 mg/m2 daily p.o. for A/C and 37.5 mg/m2 p.o. b.i.d for B/D. CNS prophylaxis was age-adjusted triple intrathecal therapy (TIT) for a total of 14–19 doses due to protocol modifications made because of concerns about neurotoxicity. Total treatment duration was 130 wks. 295 patients entered consolidation therapy. Reg A: 77, Reg B: 77, Reg C: 70, Reg D: 71. The overall 6 year EFS for the study was 80% ±2.4% (s.e.). The study closed prematurely in 1996 due to issues pertaining to neurotoxicity. There was no significant difference in EFS between the two 6-MP dosing regimens [once-daily 78% vs. twice-daily 83%; p = 0.222]. Only 36% of patients on Reg C/D received the full 12 courses of higher dose MTX due to above noted protocol modifications. Neither the efficacy nor the toxicity of higher dose MTX can be fully evaluated for this study. 57 Patients (19%) reported one or more grade 2–4 neurotoxicity event using the Common Toxicity Criteria (CTC) version 2.0. These events included: cortical toxicity 37 events (including 33 seizures), cerebellar 15, cognitive dysfunction 6, headaches 4, motor 3, and significant fatigue in 3 children. Preliminary review indicates no difference in neurotoxicity incidence based on MTX dose. This antimetabolite based study highlights the importance of monitoring for neurotoxicity, as well as other unexpected adverse events on subsequent leukemia treatment protocols.
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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 | 0.001 | 0.002 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| 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".