Comparison of immunoglobulin high-throughput sequencing MRD in bone marrow and peripheral blood in pediatric B-ALL: A report from the Children's Oncology Group AALL1731.

Pediatric Oncology
DOI: 10.1200/jco.2024.42.16_suppl.10014 Publication Date: 2024-06-03T19:38:10Z
ABSTRACT
10014 Background: Minimal (measurable) residual disease (MRD) at end of induction (EOI) therapy is a strong predictor outcome in pediatric B-ALL. Currently, EOI MRD assessed bone marrow (BM). We hypothesized that the highly sensitive assay, high-throughput sequencing (HTS) immunoglobulin loci, can effectively monitor peripheral blood (PB) and may provide less invasive way to track response. Methods: conducted HTS on paired BM PB samples from 808 NCI standard risk (SR) B-ALL patients enrolled Children’s Oncology Group study AALL1731 (NCT03914625). determined correlation between via Spearman’s rank correlations. calculated BM/PB ratio compared these by subgroup using Kruskal-Wallis tests. defined subgroups cytogenetics (cyto) ( ETV6::RUNX1, double trisomies chromosome 4 10 (DT), Unfavorable (hypodiploidy, iAMP21, or KMT2A-rearranged), Neutral (lacking DT, unfavorable)), group (SR-average (AVG) SR-High). Flow cytometry-defined was < 0.01% for all SR-AVG (N = 623) ≥0.01% selected SR-High 185). Results: There with an overall coefficient 0.75 (P 0.001). Correlation similar cytogenetics: 0.69 63; P 0.001), 147; Neutral, 0.74 580; Unfavorable, 0.66(N 18; 0.003). For groups, 0.67 (p 0.001) SR-High, 0.64 Of 591 detectable MRD, 474 (80.2%), undetectable 94 (15.9%) indeterminate (no leukemic cell detected 500,000 total cells sample) 23 (3.9%). Among 182 175 (96.2%) had MRD. Disease burden higher than significantly (median 16.5 vs 2.6, The median also varied those cyto having highest (15.3 6.3 3.8 3.1 Neutral; 0.013). Conclusions: This largest analysis date. show across cytogenetic groups. among suggesting tropism. Importantly, nearly flow ≥0.01%, threshold warranting intensification. However, most Thus, useful adjunct screening clinical management patients. Defining stratification will require outcome.
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