Flow cytometric minimal residual disease measurement accounting for cytogenetics in children with non-high-risk acute lymphoblastic leukemia treated according to the ALL-MB 2008 protocol

Cancer Med. 2024 Apr;13(8):e7172. doi: 10.1002/cam4.7172.

Abstract

Background: Quantitative measurement of minimal residual disease (MRD) is the "gold standard" for estimating the response to therapy in childhood B-cell precursor acute lymphoblastic leukemia (BCP-ALL). Nevertheless, the speed of the MRD response differs for different cytogenetic subgroups. Here we present results of MRD measurement in children with BCP-ALL, in terms of genetic subgroups with relation to clinically defined risk groups.

Methods: A total of 485 children with non-high-risk BCP-ALL with available cytogenetic data and MRD studied at the end-of-induction (EOI) by multicolor flow cytometry (MFC) were included. All patients were treated with standard-risk (SR) of intermediate-risk (ImR) regimens of "ALL-MB 2008" reduced-intensity protocol.

Results and discussion: Among all study group patients, 203 were found to have low-risk cytogenetics (ETV6::RUNX1 or high hyperdiploidy), while remaining 282 children were classified in intermediate cytogenetic risk group. For the patients with favorable and intermediate risk cytogenetics, the most significant thresholds for MFC-MRD values were different: 0.03% and 0.04% respectively. Nevertheless, the most meaningful thresholds were different for clinically defined SR and ImR groups. For the SR group, irrespective to presence/absence of favorable genetic lesions, MFC-MRD threshold of 0.1% was the most clinically valuable, although for ImR group the most informative thresholds were different in patients from low-(0.03%) and intermediate (0.01%) cytogenetic risk groups.

Conclusion: Our data show that combining clinical risk factors with MFC-MRD measurement is the most useful tool for risk group stratification of children with BCP-ALL in the reduced-intensity protocols. However, this algorithm can be supplemented with cytogenetic data for part of the ImR group.

Keywords: acute lymphoblastic leukemia; flow cytometry; genetic risk groups; minimal residual disease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Child
  • Child, Preschool
  • Core Binding Factor Alpha 2 Subunit / genetics
  • Cytogenetic Analysis / methods
  • Female
  • Flow Cytometry* / methods
  • Humans
  • Infant
  • Male
  • Neoplasm, Residual* / genetics
  • Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / diagnosis
  • Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / drug therapy
  • Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / genetics
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / drug therapy
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / genetics

Substances

  • Core Binding Factor Alpha 2 Subunit