Minimal residual disease comparison between Ig/TCR PCR versus NGS assays in children with Philadelphia chromosome-positive acute lymphoblastic leukemia: A report from the COG AALL1631 study.
Bibliographic record
Abstract
10023 Background: Minimal residual disease (MRD) assessment by immunoglobulin/T-cell receptor (Ig/TCR) polymerase chain reaction (PCR) is currently being used in the international pediatric Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ALL) trial EsPhALL2017/AALL1631 for risk stratification. MRD concordance has previously been demonstrated between Ig/TCR PCR and flow cytometry in Ph+ALL. We sought to assess concordance of MRD assessment between conventional Ig/TCR PCR and next-generation sequencing (NGS) assays. Methods: MRD was assessed in all pts on AALL1631 by Ig/TCR PCR at end-induction IB; those with MRD <5x10-4 were classified as standard-risk (SR) and randomized to treatment with imatinib and one of two chemotherapy regimens without hematopoietic stem cell transplant (HSCT), whereas pts with end-induction 1B MRD ≥ 5x10-4 were considered high-risk (HR) and assigned to HSCT after consolidation chemotherapy. Residual diagnostic and end-induction IB samples from consenting pts were assessed for NGS MRD by the clonoSEQ assay (Adaptive Biotechnologies) in blinded fashion and subsequently compared to Ig/TCR MRD to determine concordance as related to MRD-based HSCT recommendations ( ie, MRD ≥ 5x10-4 consistent with HR group assignment). MRD values were calculated using the kappa statistic for agreement above chance. Results: Sixty-seven pts had matched samples available for MRD assessment at end-induction 1B by both Ig/TCR PCR and NGS (Table). NGS MRD was evaluable for all 67 pts and stratified as 62 SR (<5x10-4) and 5 HR (≥5x10-4). In contrast, Ig/TCR PCR results were inevaluable for 3 pts (unsatisfactory sample quality) and indeterminate (positive, but not quantifiable) in 4 pts. Of the remaining 60 pts, 55 met SR and 5 HR criteria using Ig/TCR PCR. There was only 1 discordant case between the two methods for MRD-based HSCT recommendation among these 60 pts with a kappa statistic for agreement above chance of 0.88. Conclusions: NGS and Ig/TCR PCR assays were highly concordant in MRD assessment for risk stratification at a threshold of 5x10-4 in pediatric pts with Ph+ALL enrolled on AALL1631. Of note, the NGS assay yielded MRD results amenable for risk stratification in 100% pts compared to 89.6% for the Ig/TCR PCR methodology. These data support the use of NGS MRD testing for risk stratification in pediatric Ph+ALL.[Table: see text]
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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 | 0.012 | 0.011 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.001 | 0.001 |
| 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".