Complexities of Measurable Residual Disease Assays in Acute Lymphoblastic Leukemia: A Guide for the Practicing Clinician.

Abstract

Background: Assessment of measurable residual disease (MRD) assessment is an internal component of prognostication and management of acute lymphoblastic leukemia (ALL). A range of assays - differing in sensitivity, complexity, and clinical application - are available. As these technologies advance, clinicians face new challenges in selecting and interpreting MRD tests.

Summary: MRD testing is essential for risk stratification and treatment guidance in pediatric and adult ALL. Key assay platforms include multiparameter flow cytometry, quantitative PCR, and next-generation sequencing (NGS) for clonal B- or T-cell receptor rearrangements. NGS MRD offers superior detection depth, especially in post-hematopoietic cell transplantation, and post-CAR T-cell therapy. In Philadelphia chromosome-positive ALL, persistent BCR::ABL1 may represent non-leukemic clones, warranting the use of lineage-specific assays. While bone marrow remains the standard MRD source, assessment of MRD in blood and cerebrospinal fluid are gaining support in select contexts. MRD assessment in T-cell ALL remains complex due to antigen heterogeneity and infrequent clonal targets.

Key messages: This review provides a practical overview of MRD testing in ALL, comparing available technologies and highlighting clinical implications of assay selection, sensitivity, and sample type.