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

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...

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Main Authors: Yulia S. Korkina, Timur T. Valiev, Natalia A. Batmanova, Mikhail V. Kiselevskiy, Irina Z. Shubina, Kirill I. Kirgizov, Svetlana R. Varfolomeeva
Format: Article
Language:English
Published: MDPI AG 2025-06-01
Series:Children
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Online Access:https://www.mdpi.com/2227-9067/12/7/860
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author Yulia S. Korkina
Timur T. Valiev
Natalia A. Batmanova
Mikhail V. Kiselevskiy
Irina Z. Shubina
Kirill I. Kirgizov
Svetlana R. Varfolomeeva
author_facet Yulia S. Korkina
Timur T. Valiev
Natalia A. Batmanova
Mikhail V. Kiselevskiy
Irina Z. Shubina
Kirill I. Kirgizov
Svetlana R. Varfolomeeva
author_sort Yulia S. Korkina
collection DOAJ
description 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<sup>−4</sup> 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.
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spelling doaj-art-de4cfde7e971499ba869dbf28f76e2702025-08-20T03:32:31ZengMDPI AGChildren2227-90672025-06-0112786010.3390/children12070860False-Positive and False-Negative MRD Results in Children with Acute Lymphoblastic Leukemia: Navigating Between Scylla and Charybdis (Brief Review and Clinical Experience)Yulia S. Korkina0Timur T. Valiev1Natalia A. Batmanova2Mikhail V. Kiselevskiy3Irina Z. Shubina4Kirill I. Kirgizov5Svetlana R. Varfolomeeva6Research Institute of Pediatric Oncology and Hematology, FSBI “N.N. Blokhin National Medical Research Center of Oncology” of the Ministry of Health of Russia, Kashirskoye Sh.23, Moscow 115522, RussiaResearch Institute of Pediatric Oncology and Hematology, FSBI “N.N. Blokhin National Medical Research Center of Oncology” of the Ministry of Health of Russia, Kashirskoye Sh.23, Moscow 115522, RussiaResearch Institute of Pediatric Oncology and Hematology, FSBI “N.N. Blokhin National Medical Research Center of Oncology” of the Ministry of Health of Russia, Kashirskoye Sh.23, Moscow 115522, RussiaResearch Institute of Experimental Diagnostics and Therapy of Tumors, FSBI “N.N. Blokhin National Medical Research Center of Oncology” of the Ministry of Health of Russia, Kashirskoye Sh.24, Moscow 115522, RussiaResearch Institute of Experimental Diagnostics and Therapy of Tumors, FSBI “N.N. Blokhin National Medical Research Center of Oncology” of the Ministry of Health of Russia, Kashirskoye Sh.24, Moscow 115522, RussiaResearch Institute of Pediatric Oncology and Hematology, FSBI “N.N. Blokhin National Medical Research Center of Oncology” of the Ministry of Health of Russia, Kashirskoye Sh.23, Moscow 115522, RussiaResearch Institute of Pediatric Oncology and Hematology, FSBI “N.N. Blokhin National Medical Research Center of Oncology” of the Ministry of Health of Russia, Kashirskoye Sh.23, Moscow 115522, RussiaBackground/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<sup>−4</sup> 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.https://www.mdpi.com/2227-9067/12/7/860minimal residual diseasefalse-positive MRDfalse-negative MRDflow cytometryacute lymphoblastic leukemiachildren
spellingShingle Yulia S. Korkina
Timur T. Valiev
Natalia A. Batmanova
Mikhail V. Kiselevskiy
Irina Z. Shubina
Kirill I. Kirgizov
Svetlana R. Varfolomeeva
False-Positive and False-Negative MRD Results in Children with Acute Lymphoblastic Leukemia: Navigating Between Scylla and Charybdis (Brief Review and Clinical Experience)
Children
minimal residual disease
false-positive MRD
false-negative MRD
flow cytometry
acute lymphoblastic leukemia
children
title False-Positive and False-Negative MRD Results in Children with Acute Lymphoblastic Leukemia: Navigating Between Scylla and Charybdis (Brief Review and Clinical Experience)
title_full False-Positive and False-Negative MRD Results in Children with Acute Lymphoblastic Leukemia: Navigating Between Scylla and Charybdis (Brief Review and Clinical Experience)
title_fullStr False-Positive and False-Negative MRD Results in Children with Acute Lymphoblastic Leukemia: Navigating Between Scylla and Charybdis (Brief Review and Clinical Experience)
title_full_unstemmed False-Positive and False-Negative MRD Results in Children with Acute Lymphoblastic Leukemia: Navigating Between Scylla and Charybdis (Brief Review and Clinical Experience)
title_short False-Positive and False-Negative MRD Results in Children with Acute Lymphoblastic Leukemia: Navigating Between Scylla and Charybdis (Brief Review and Clinical Experience)
title_sort false positive and false negative mrd results in children with acute lymphoblastic leukemia navigating between scylla and charybdis brief review and clinical experience
topic minimal residual disease
false-positive MRD
false-negative MRD
flow cytometry
acute lymphoblastic leukemia
children
url https://www.mdpi.com/2227-9067/12/7/860
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