Monitoring measurable residual disease in paediatric acute lymphoblastic leukaemia using immunoglobulin gene clonality based on next-generation sequencing
  • Ahn, Won Kee
  • Yu, Kyunghee
  • Kim, Hongkyung
  • Lee, Seung-Tae
  • Choi, Jong Rak
  • 외 4명
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초록

Background: Assessment of measurable residual disease (MRD) is an essential prognostic tool for B-lymphoblastic leukaemia (B-ALL). In this study, we evaluated the utility of next-generation sequencing (NGS)–based MRD assessment in real-world clinical practice. Method: The study included 93 paediatric patients with B-ALL treated at our institution between January 2017 and June 2022. Clonality for IGH or IGK rearrangements was identified in most bone marrow samples (91/93, 97.8%) obtained at diagnosis. Results: In 421 monitoring samples, concordance was 74.8% between NGS and multiparameter flow cytometry and 70.7% between NGS and reverse transcription-PCR. Elevated quantities of clones of IGH alone (P < 0.001; hazard ratio [HR], 22.2; 95% confidence interval [CI], 7.1–69.1), IGK alone (P = 0.011; HR, 5.8; 95% CI, 1.5–22.5), and IGH or IGK (P < 0.001; HR, 7.2; 95% CI, 2.6–20.0) were associated with an increased risk of relapse. Detection of new clone(s) in NGS was also associated with inferior relapse-free survival (P < 0.001; HR, 18.1; 95% CI, 3.0–108.6). Multivariable analysis confirmed age at diagnosis, BCR::ABL1-like mutation, TCF3::PBX1 mutation, and increased quantity of IGH or IGK clones during monitoring as unfavourable factors. Conclusion: In conclusion, this study highlights the usefulness of NGS-based MRD as a routine assessment tool for prognostication of paediatric patients with B-ALL. © The Author(s) 2024.

키워드

Acute lymphoblastic leukaemiaImmunoglobulin heavy chain genesImmunoglobulin kappa light chain genesMeasurable residual diseaseNext-generation sequencingRISK STRATIFICATIONPROGNOSTIC-FACTORSYOUNG-ADULTSAIEOP-BFMT-CELLCHILDHOODRELAPSECHILDRENADOLESCENTSDIAGNOSIS
제목
Monitoring measurable residual disease in paediatric acute lymphoblastic leukaemia using immunoglobulin gene clonality based on next-generation sequencing
저자
Ahn, Won KeeYu, KyungheeKim, HongkyungLee, Seung-TaeChoi, Jong RakHan, Jung WooLyu, Chuhl JooHahn, SeungminShin, Saeam
DOI
10.1186/s12935-024-03404-3
발행일
2024-06
유형
Article
저널명
Cancer Cell International
24
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