Document Type

Article

Publication Date

10-2-2024

Identifier

DOI: 10.3390/ijms251910619; PMCID: PMC11477226

Abstract

Assessment of minimal residual disease (MRD) is the most powerful predictor of outcome in B-type acute lymphoblastic leukemia (B-ALL). MRD, defined as the presence of leukemic cells in the blood or bone marrow, is used for the evaluation of therapy efficacy. We report on a microfluidic-based MRD (MF-MRD) assay that allows for frequent evaluation of blood for the presence of circulating leukemia cells (CLCs). The microfluidic chip affinity selects B-lineage cells, including CLCs using anti-CD19 antibodies poised on the wall of the microfluidic chip. Affinity-selected cells are released from the capture surface and can be subjected to immunophenotyping to enumerate the CLCs, perform fluorescence in situ hybridization (FISH), and/or molecular analysis of the CLCs' mRNA/gDNA. During longitudinal testing of 20 patients throughout induction and consolidation therapy, the MF-MRD performed 116 tests, while only 41 were completed with multiparameter flow cytometry (MFC-MRD) using a bone marrow aspirate, as standard-of-care. Overall, 57% MF-MRD tests were MRD(+) as defined by CLC numbers exceeding a threshold of 5 × 10-4%, which was determined to be the limit of quantitation. Above a threshold of 0.01%, MFC-MRD was positive in 34% of patients. The MF offered the advantage of the opportunity for efficiently processing small volumes of blood (2 mL), which is important in the care of pediatric patients, especially infants. The minimally invasive means of blood collection are of high value when treating patients whose MRD is typically tested using an invasive bone marrow biopsy. MF-MRD detection can be useful for stratification of patients into risk groups and monitoring of patient well-being after completion of treatment for early recognition of potential impending disease recurrence.

Journal Title

Int J Mol Sci

Volume

25

Issue

19

MeSH Keywords

Humans; Neoplasm, Residual; Child; Child, Preschool; Female; Male; Precursor B-Cell Lymphoblastic Leukemia-Lymphoma; Adolescent; Infant; B-Lymphocytes; Flow Cytometry; Immunophenotyping; Neoplastic Cells, Circulating; In Situ Hybridization, Fluorescence; Microfluidics; Antigens, CD19

Keywords

B-type acute lymphoblastic leukemia; affinity isolation; microfluidics; minimal residual disease; pediatric patients

Comments

Grants and funding

This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).

Publisher's Link: https://www.mdpi.com/1422-0067/25/19/10619

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