Biology-Driven Classification of Childhood Acute Lymphoblastic Leukemia: A Combined Analysis of Prognostic Markers from the Pediatric Oncology Group (POG) and Children’s Cancer Group (CCG).
Bibliographic record
Abstract
Abstract Risk adapted therapy, tailoring treatment to the likelihood of relapse, has constituted a significant advance in the treatment of childhood ALL. The recent merger of the POG and CCG provided an opportunity to reassess previous approaches and to develop a new biology driven classification system based on data from both legacy groups. All children (age 12 months to 21.99 years) with newly diagnosed B-precursor (ALL), consecutively enrolled on CCG (December 1988 to August 1995, N = 3056) and POG (January 1986 to November 1999, N = 6800) protocols, were evaluated for the impact of numerous clinical and laboratory variables on event free survival at 5 and 8 years in each group separately, thereby superseding differences in treatment approaches. Infants and patients with a T- cell phenotype were excluded from the analyses. Very high risk was defined as the group for which myeloablative therapy might be indicated with an anticipated 5 year EFS <45%, while a reduction in therapy could be justified for the lowest risk patients with a >85% 5 year EFS. Patients identified as being at very high risk for relapse had hypodiploidy (<45 chromosomes) (CCG 34.8%, POG 46.5% - 5 year EFS), induction failure (CCG 11.3% 5 year EFS) or t(9;22) or BCR/ABL (POG 27.5%, CCG 29.6% 5 year EFS). Patients identified as low risk for relapse were NCI standard risk patients with either t(12;21) (TEL-AML1) (CCG 86%, POG 85% 5 year EFS) or all three trisomies of 4, 10, and 17 (CCG 91.5%, POG 89.3% 5 year EFS). Certain NCI high risk patients were identified as having a higher risk for relapse but did not fall into the VHR category: t(4;11)(POG 49.9%, CCG 50.0% 5 year EFS),CNS3 (CCG 59.3%, POG 67.8% 5 year EFS) and slow early response (SER) defined by M2/3 at day 14 (Standard risk 66% SER versus 84% and for high risk ALL 63% SER versus 75%). Other potential VHR factors that require confirmation included, slow early responder t(4;11) (CCG 11.1% 5 year EFS) and monosomy 7 (CCG 44%, POG 66.6% 5 year EFS). A balanced t(1;19) had only a minor unfavorable effect on EFS. The COG has identified a risk classification system that builds on the previous NCI risk classification system for childhood ALL, incorporating the cytogenetic and molecular genetic features of the blasts, as well as rapidity of clinical response. The division of B-precursor ALL patients into low risk (18%), standard risk (49%), high risk (30%) and very high risk (3%) groups will : 1) identify those patients for whom therapy might be reduced without sacrificing overall cure rates, 2) determine those patients who will require intensified therapy and 3) suggest underlying biological pathways that mediate cure or treatment failure.
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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 | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.002 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 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".