Ultrasensitive Ngs Mrd Assessment in Ph+ All: Prognostic Impact and Correlation With Rt-Pcr for BCR::ABL1

Authors

Nicholas J Short
Elias Jabbour
Walid Macaron
Farhad Ravandi
Nitin Jain
Rashmi Kanagal-Shamanna
Keyur P Patel
Sanam Loghavi
Fadi G Haddad
Musa Yilmaz
Ghayas C Issa
Partow Kebriaei
Steven M Kornblau
Sarah Pelletier
Wilmer Flores
Jairo Matthews
Rebecca Garris
Hagop Kantarjian

Publication Date

8-1-2023

Journal

American Journal of Hematology

DOI

10.1002/ajh.26949

PMID

37183966

Abstract

Reverse transcription polymerase chain reaction (RT-PCR) for BCR::ABL1 is the most common and widely accepted method of measurable residual disease (MRD) assessment in Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL); however, RT-PCR may not be an optimal measure of MRD in many cases of Ph+ ALL. We evaluated the clinical impact of a highly sensitive next-generation sequencing (NGS) MRD assay (sensitivity of 10-6 ) and its correlation with RT-PCR for BCR::ABL1 in patients with Ph+ ALL. Overall, 32% of patients had a discordance between MRD assessment by RT-PCR and NGS, and 31% of patients who achieved NGS MRD negativity were PCR+ at the same timepoint. Among eight patients with long-term detectable BCR::ABL1 by PCR, six were PCR+/NGS-. These patients generally had stable PCR levels that persisted despite therapeutic interventions, and none subsequently relapsed; in contrast, patients who were PCR+/NGS+ had more variable PCR values that responded to therapeutic intervention. In a separate cohort of prospectively collected clinical samples, 11 of 65 patients (17%) with Ph+ ALL who achieved NGS MRD negativity had detectable BCR::ABL1 by PCR, and none of these patients relapsed. Relapse-free survival and overall survival were similar in patients who were PCR+/NGS- and PCR-/NGS-, suggesting that PCR for BCR::ABL1 did not provide additional prognostic information in patients who achieved NGS MRD negativity. NGS-based assessment of MRD is prognostic in Ph+ ALL and identifies patients with low-level detectable BCR::ABL1 who are unlikely to relapse nor to benefit from therapeutic interventions.

Keywords

Humans, Fusion Proteins, bcr-abl, Prognosis, Reverse Transcriptase Polymerase Chain Reaction, Precursor Cell Lymphoblastic Leukemia-Lymphoma, Neoplasm, Residual, High-Throughput Nucleotide Sequencing, Recurrence

Published Open-Access

yes

Recommended Citation

Short, Nicholas J; Jabbour, Elias; Macaron, Walid; et al., "Ultrasensitive Ngs Mrd Assessment in Ph+ All: Prognostic Impact and Correlation With Rt-Pcr for BCR::ABL1" (2023). Faculty, Staff and Student Publications. 4640.
https://digitalcommons.library.tmc.edu/uthgsbs_docs/4640