Outcomes with reduced intensity therapy in a low-risk subset of children with National Cancer Institute (NCI) standard-risk (SR) B-lymphoblastic leukemia (B-ALL): A report from Children’s Oncology Group (COG) AALL0932.
Bibliographic record
Abstract
10509 Background: Post-hoc analysis of COG P9904 identified a low risk (LR) group of SR B-ALL patients aged 1-9.99 years with WBC < 50,000/µL, no CNS3, and either ETV6/RUNX1 or double trisomies (DT) of chromosomes 4 and 10 with day 8 peripheral blood (PB) and day 29 marrow (BM) minimal residual disease (MRD) < 0.01% who had a 5-year event-free survival (EFS) of 97±2% and overall survival (OS) 98.8±0.8%. Outstanding results were also obtained for LR patients on COG AALL0331 using CCG-based ALL therapy. AALL0932 tested prospectively whether LR B-ALL patients could attain a 5-year EFS ≥95% with these regimens. Methods: Following a 3-drug induction, eligible AALL0932 LR patients had NCI SR B-ALL (no testicular leukemia, unfavorable genetics or Down syndrome) with DT or ETV6/RUNX1 fusion, CNS1, no steroid pre-treatment, with Day 8 PB and Day 29 BM MRD < 0.01%. Between 2010-16, 603 LR patients were randomized to P9904-based regimen LR-M (n = 301) or CCG 1991/COG AALL0331-based regimen LR-C (n = 302). LR-M included 6 24-hour infusions of 1 gm/m 2 of methotrexate (MTX) with leucovorin rescue, but no anthracyclines or alkylating agents. Maintenance followed with daily 6-mercaptopurine (6-MP) and weekly oral MTX, and every 16 week 7-day pulses of dexamethasone (DEX) with vincristine (VCR) on days 1 and 8. Boys and girls were treated for 2.5 years from diagnosis. LR-C had no 24-hour MTX infusions, but included 2 Interim Maintenance (IM) phases with VCR and escalating IV MTX without leucovorin rescue given every 10 days for 5 doses, flanking an 8-week Delayed Intensification (DI) phase that included DEX, VCR, pegasparagase, doxorubicin (75 mg/m 2 ), cyclophosphamide (1 gm/m 2 ) and 8 doses of low-dose cytarabine (75 mg/m2/dose). LR-C Maintenance included daily 6-MP and weekly oral MTX with 5-day pulses of DEX and 1 dose of VCR given every 12 weeks. Girls received 2 years and boys 3 years of therapy from the start of IM I. Results: Both regimens achieved outstanding outcomes: 5-yr disease-free survival (±SE) 98.8%±0.8% for LR-M and 98.5%±0.9% for LR-C (p = 0.67). Both had 5-yr OS 100%. Therapies were well tolerated with higher rates of mucositis (12.9 vs 6.3%; p = 0.008) and allergic reactions (2.3% vs 0%; p = 0.02) on LR-C. Conclusions: AALL0932 demonstrated that application of stringent risk criteria can identify a favorable B-ALL subgroup almost certain to be cured with either LR-M or LR-C, allowing physicians and families to select the optimal treatment approach in the future. Clinical trial information: NCT01190930.
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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 | 0.004 | 0.012 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.004 | 0.001 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.003 |
| 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".