False-Positive and False-Negative MRD Results in Children with Acute Lymphoblastic Leukemia: Navigating Between Scylla and Charybdis (Brief Review and Clinical Experience)

TL;DR

This paper discusses challenges in detecting minimal residual disease in childhood leukemia, balancing accurate diagnosis with avoiding unnecessary treatments.

Contribution

The paper highlights the clinical implications of false-positive and false-negative MRD results and proposes a balanced approach for accurate detection.

Findings

Flow cytometry achieves high sensitivity for MRD detection but still faces false results.

Combining genomic methods with flow cytometry can improve MRD evaluation accuracy.

Excessive sensitivity may lead to detecting clinically insignificant disease traces and unnecessary treatment escalation.

Abstract

Background/Objectives: Acute lymphoblastic leukemia (ALL) is the most common malignant disease in children. Contemporary antitumor treatment protocols provide long-term survival rates in over 90% of patients with ALL. High effectiveness of the treatment has been achieved as a result of chemotherapy optimization, use of targeted drugs, up-to-date genetic information, and detection of minimal residual disease (MRD). Current highly sensitive methods for MRD detection have advantages and disadvantages, and the challenge is to distinguish between false-positive and false-negative tests. Methods: A comprehensive search through MEDLINE, PubMed, Scopus, and ScienceDirect using the MRD-related keywords was performed, and included a final set of 72 academic articles. Results: At present, flow cytometry for MRD detection provides the necessary sensitivity of 10−4 and allows for reliable prediction of ALL dynamics and effective therapeutic strategies. However, even multicolor flow cytometry (MFC) cannot avoid cases of false-positive or false-negative results. Highly sensitive and productive genomic methods in addition to MFC may enhance the accuracy of MRD evaluation. On the other hand, overwhelming efforts to reach the highest sensitivity of the detection methods may lead to the detection of clinically insignificant manifestations of minimal residual disease and, subsequently, to unjustified escalation of antitumor therapy. Conclusions: The necessary ground for an adequate sensitivity of the MRD detection methods could ensure the fine line between false-positive and false-negative MRD results in patients with childhood ALL to develop an appropriate therapeutic strategy.