PCR vs NGS MRD discordance in Ph-positive ALL: A retrospective analysis

During the 67th American Society of Hematology (ASH) Annual Meeting and Exposition, December 6–9, 2025, Orlando, US, Nicholas Short presented results from a retrospective analysis investigating discordance between minimal residual disease (MRD) status based on next-generation sequencing (NGS) for immunoglobulin/T-cell receptor (IG/TR) vs polymerase chain reaction (PCR) for BCR::ABL1 in patients with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL). 

Key data: Among 187 patients with ≥1 sample with NGS MRD negativity and paired PCR for BCR::ABL1, 23% demonstrated NGS-negative/PCR-positive MRD discordance. Discordance occurred in 27% and 18% of patients with p190 and p210 transcript types, respectively, with PCR >0.1% and >1% occurring only in p190. Tyrosine kinase inhibitor (TKI) discontinuation in two discordant patients resulted in rapid PCR increases from 0.3% to 17.7% and from 0.03% to 28.9%. Among 80 newly diagnosed patients, those with NGS-negative/PCR-negative vs NGS-negative/PCR-positive status showed similar 3-year outcomes: relapse-free survival (RFS; 76% vs 69%; p = 0.76) and overall survival (OS; 89% vs 89%; p = 0.89).

Key learning: In patients with Ph+ ALL who achieve NGS MRD negativity, detectable PCR for BCR::ABL1 does not impact relapse or survival outcomes, regardless of PCR value. Indefinite TKI therapy may be appropriate in patients with persistent PCR for BCR::ABL1.