Presence of Residual Disease Detected by Multidimensional Flow Cytometry Identifies Patients with AML At High Risk of Relapse – a Report From the Children's Oncology Group,
Bibliographic record
Abstract
Abstract Abstract 3545 We previously demonstrated that presence of post induction residual disease detected by multidimensional flow cytometry (MDF) was associated with higher relapse risk and worse survival in a cohort of 225 children treated on AAML03p1. In this study we used a similar methodology in examining the post induction marrow specimens in patients treated on the COG AML phase III trial AAML0531. This study randomized 1022 children and young adults without Down Syndrome (DS) to an MRC based chemotherapy backbone with or without Gemtuzumab Ozogamicin (GO) in the first and fourth course of therapy. Of the 1022 eligible patients, 784 patients consented to participate in the correlative biology study and submitted marrow specimens by the end of first course for evaluation of disease status by MDF. Of these 784 marrow specimens, residual disease (RD) defined as ≥0.1% blasts by MDF was identified in 240 patients (31%). Prevalence of RD in patients in morphologic CR was 20% vs. 63% in those who failed to achieve a morphologic CR (37% of those who were not in morphologic CR had no RD by MDF). Presence of RD varied by risk groups, where those with favorable risk features (CBF AML) had an RD prevalence of 14%, high risk patients (-7, -5/del5q, high risk FLT3/ITD, course 1 blasts >15%) had an RD prevalence of 68% and the intermediate risk patients had an RD prevalence of 27%. Patients with RD who were in morphologic CR or PR at the end of the first course had disease-free survival (DFS) at 3 years of 34% vs. 60% in those without RD (p<0.0001). Corresponding overall survival (OS) at 3 years was 54% and 76% in those with and without RD, respectively (p<0.0001). We further evaluated the ability of post induction RD to predict outcome in specific risk categories. Of the 180 patients considered favorable risk by cytogenetic features who were in morphologic CR or PR at end of first course, 23 had RD by MDF (13%). Presence of RD in this favorable risk cohort was not associated with worse disease-free survival (DFS, p=0.54). Similar lack of prognostic significance was observed in patients considered high risk (p=0.38). In contrast to high and low risk patients, in 435 patients with no known risk features (intermediate risk) 118 patients had RD detected by MDF (27%). DFS at 3 years from end of first course in patients with RD was 33% vs. 55% for those without RD (p<0.0001). Corresponding OS at 3 years for those with and without RD was 51% and 70%, respectively (p<0.001). This study demonstrates the significance of early response to chemotherapy as measured by MDF in predicting clinical outcome in childhood AML. It also demonstrates that the presence of RD may not be predictive of outcome in those with high or low risk features. Multi-dimensional flow cytometry has been incorporated into the current COG phase III AML trial. Disclosures: Smith: Eisai: ; Archimedes Pharma: Membership on an entity's Board of Directors or advisory committees; Pfizer, Inc.: Membership on an entity's Board of Directors or advisory committees; Seattle Genetics:.
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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 | 0.001 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 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".