Outcomes in children with Down syndrome (DS) and B-lymphoblastic leukemia (B-ALL): A Children’s Oncology Group (COG) report.
Bibliographic record
Abstract
10510 Background: Patients with DS and B-ALL experience increased rates of relapse and toxicities. Here, we report results from 4 COG trials (2003-2018). Methods: We analyzed clinical, and outcome data for DS (n = 743) and non-DS (n = 21,703) patients age 1-30 enrolled on standard-risk (SR) trials AALL0331 and AALL0932 and high-risk (HR) trials AALL0232 and AALL1131. Initially, DS-ALL patients on AALL0232/AALL0331 experienced excess mortality, prompting enhanced supportive care and omission of induction anthracycline except for slow responders on AALL1131. Other modifications included: non-random assignment to treatment strata without investigational agents; leucovorin rescue after intrathecal methotrexate (MTX); equal maintenance length for boys and girls; every 12-week maintenance vincristine/steroid pulses; and reduced anthracycline and intravenous MTX for HR patients. Results: Across all 4 trials, DS and non-DS patients did not differ significantly in age, sex, initial WBC, or CNS status. DS-ALL patients had significantly higher end of induction (EOI) minimal residual disease (MRD) vs non-DS patients on both AALL0932 and AALL1131, but the difference persisted at end of consolidation (EOC) only on AALL1131, with fewer EOI MRD+ DS patients achieving EOC MRD < 0.01% (76.1 vs 88.0%, p = 0.001). 5-year EFS and OS were significantly poorer for DS vs non-DS across all trials (EFS 79.6+2.1% vs 86.3+0.3%, p < 0.0001; OS 86.5+1.8% vs 93.1+0.2%, p < 0.0001), as well as on each individual trial. In Cox regression analysis for all DS patients, inferior EFS was associated with several known risk factors (age > 10, EOI MRD >0.01%) but not with cytogenetics or CRLF2 status Induction death was more frequent in DS patients (3.4% vs 0.8%, p < 0.0001) as was death in remission (4.8+0.8% vs 1.8+0.1%, p < 0.0001). For death in remission, the increased frequency occurred pre-maintenance and in patients taken off protocol therapy, but not during maintenance, in contrast to prior reports. Grade >3 mucositis, infections, and hyperglycemia were significantly more frequent in DS patients on all trials. Grade >3 seizures were significantly more frequent in DS patients on HR but not SR trials (4.1% vs 1.7%. p = 0.001) and occurred in all phases pre-maintenance. Conclusions: Patients with DS and B-ALL continue to have inferior outcomes compared to non-DS, with increased relapse and toxicities. Less toxic approaches such as immunotherapies and targeted therapies hold promise to improve outcomes in both these areas.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
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 | 0.003 | 0.011 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.004 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 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".