Prognostic Impact of t(1;19) in Pediatric B-Cell Acute Lymphoblastic Leukemia (B-ALL) Patients Treated on Contemporary Children's Oncology Group (COG) Protocols
Bibliographic record
Abstract
Background Translocation t(1;19)(q23;p13.3) resulting in the TCF3::PBX1 fusion is a recurrent cytogenetic alteration in 5-7% of B-cell acute lymphoblastic leukemia (B-ALL) that occurs more frequently in Black children. Historically, t(1;19) was associated with inferior outcomes with higher rates of central nervous system (CNS) relapse; contemporary prognostic impact is unclear. We assessed t(1;19) outcomes with modern Children's Oncology Group (COG) therapy. Methods From 2010 to 2019, children and young adults with newly diagnosed B-ALL enrolled on standard risk (SR)(AALL0932; NCT01190930) or high risk (HR) (AALL1131; NCT02883049) protocols based on initial white blood cell count (WBC), age, extramedullary disease status, cytogenetic subtype, day 8 peripheral blood and end of induction (EOI) bone marrow flow cytometric minimal residual disease (MRD). Cytogenetic alterations were classified as favorable (ETV6::RUNX1 or double trisomies of chromosomes 4 and 10), unfavorable (iAMP21, KMT2A rearrangement, hypodiploidy) or neutral (all others). The t(1;19), detected by metaphase karyotyping and confirmed by central review, was considered a neutral cytogenetic lesion not impacting risk stratification. Patients 1-10 years of age with WBC <50,000/uL without unfavorable cytogenetics, CNS3 or testicular disease and EOI marrow MRD <0.01% were treated on AALL0932 while NCI HR (age ≥10 years and/or WBC ≥50,000/uL) and any patients with unfavorable cytogenetics, EOI MRD ≥0.01% and/or CNS3 or testicular leukemia or steroid pretreatment were treated on AALL1131. Patients with Down syndrome or Philadelphia chromosome-positive B-ALL were excluded from this analysis. Results Among 6417 patients 1-31 years, 270 (4.2%) had t(1;19) by karyotype, including 90 (33%) and 180 (67%) with a balanced and unbalanced translocation, respectively. The t(1;19) was associated with age ≥ 10 years, female sex, WBC ≥ 50,000/µL, CNS2/3 disease, Black race or Hispanic ethnicity, and Day 29 MRD < 0.01%. The 5-year (yr) disease-free (DFS) and overall survival (OS) for all patients with and without t(1;19) were not significantly different (DFS 92.1% ± 1.8% vs 91.2% ± 0.4%, P =0.39; OS 95.1% ± 1.4% vs 96.4% ± 0.3%, P=0.46) and there were no significant differences between balanced or unbalanced translocations (DFS 91.0% ± 3.2% vs 92.6% ± 2.1%, P = 0.61; OS 94.4% ± 2.6% vs 95.5% ± 1.7%, P=0.69). When separately analyzing 5-yr DFS and OS among NCI SR and NCI HR patients with and without t(1;19), there were similarly no significant differences [NCI SR: DFS 96.8% ± 1.6% vs. 94.0% ± 0.4%, P=0.11 and OS 97.6% ± 1.4%, vs. 98.3% ± 0.2%, P=0.78; NCI HR: DFS 87.7% ± 3.0% vs. 83.4% ± 1.0%, P=0.14 and OS 92.8%±2.3% vs. 90.9% ± 0.8%, P=0.35]. When compared to other patients with neutral cytogenetics, patients with t(1;19) had improved 5-yr DFS and similar OS (DFS 92.1% ± 1.8% vs 87.2% ± 0.7%, P = 0.01; OS 95.1% ± 1.4% vs 94.6% ± 0.5%, P = 0.853). Notably, NCI SR patients with t(1;19) fared as well as those with favorable cytogenetics (DFS 96.8% ± 1.6% vs 95.9% ± 0.4%, P = 0.34, OS 97.6% ± 1.4% vs 98.9% ± 0.2%, P = 0.37). Relapses occurred in 16 (5.9%) patients with t(1;19) compared to 480 (7.8%) without t(1;19) with a similar percentage of isolated CNS relapses (1.9% vs 1.7%), respectively. In a multivariable Cox regression model adjusted for other disease related variables, t(1;19) was significantly associated with decreased risk vs. unfavorable cytogenetics (hazard ratio 0.25, 95% CI: 0.15-0.41, P <.001) and other neutral cytogenetics (hazard ratio 0.62, 95% CI: 0.40-0.97, P = 0.04); and was not statistically significantly different than favorable cytogenetics outcomes (hazard ratio 1.27, 95% CI: 0.79-1.98, P = 0.33). Conclusions With contemporary therapy, t(1;19) did not confer an inferior prognosis overall. Notably, patients with t(1;19) had improved DFS and OS compared to those with other neutral cytogenetics and, among the NCI SR group, fared as well as those with favorable cytogenetics. T(1;19) did not confer an increase in CNS relapse. Our data support that patients with t(1;19) do not need therapy intensification when treated on contemporary risk-directed COG regimens.
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 machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.002 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 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 source (direct Gemma or distilled Codex), 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".