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Relationship between subtype-specific minimal residual disease level and long-term prognosis in children with acute lymphoblastic leukemia

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Abstract

Minimal residual disease (MRD) based risk stratification criteria for specific genetic subtypes remained unclear in childhood acute lymphoblastic leukemia (ALL). Among 723 children with newly diagnosed ALL treated with the Chinese Children Leukemia Group CCLG-2008 protocol, MRD was assessed at time point 1 (TP1, at the end of induction) and TP2 (before consolidation treatment) and the MRD levels significantly differed in patients with different fusion genes or immunophenotypes (P all < 0.001). Moreover, the prognostic impact of MRD varied by distinct molecular subtypes. We stratified patients in each molecular subtype into two MRD groups based on the results. For patients carrying BCR::ABL1 or KMT2A rearrangements, we classified patients with MRD < 10–2 at both TP1 and TP2 as the low MRD group and the others as the high MRD group. ETV6::RUNX1+ patients with TP1 MRD < 10–3 and TP2 MRD-negative were classified as the low MRD group and the others as the high MRD group. For T-ALL, We defined children with TP1 MRD ≥ 10–3 as the high MRD group and the others as the low MRD group. The 10-year relapse-free survival of low MRD group was significantly better than that of high MRD group. We verified the prognostic impact of the subtype-specific MRD-based stratification in patients treated with the BCH-ALL2003 protocol. In conclusion, the subtype-specific MRD risk stratification may contribute to the precise treatment of childhood ALL.

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No datasets were generated or analysed during the current study.

References

  1. Malard F, Mohty M (2020) Acute lymphoblastic leukaemia. Lancet 395(10230):1146–1162

    Article  PubMed  CAS  Google Scholar 

  2. Hunger SP, Mullighan CG (2015) Acute lymphoblastic leukemia in children. N Engl J Med 373(16):1541–1552

    Article  PubMed  CAS  Google Scholar 

  3. Bhojwani D, Pui CH (2013) Relapsed childhood acute lymphoblastic leukaemia. Lancet Oncol 14(6):e205–e217

    Article  PubMed  Google Scholar 

  4. Jia MZ et al (2023) Tracing back of relapse clones by Ig/TCR gene rearrangements reveals complex patterns of recurrence in pediatric acute lymphoblastic leukemia. Int J Lab Hematol 45(5):717–725

    Article  PubMed  Google Scholar 

  5. Zhao XS et al (2012) Monitoring MRD with flow cytometry: an effective method to predict relapse for ALL patients after allogeneic hematopoietic stem cell transplantation. Ann Hematol 91(2):183–192

    Article  PubMed  CAS  Google Scholar 

  6. Ravandi F et al (2016) Minimal residual disease assessed by multi-parameter flow cytometry is highly prognostic in adult patients with acute lymphoblastic leukaemia. Br J Haematol 172(3):392–400

    Article  PubMed  CAS  Google Scholar 

  7. O’Connor D et al (2018) Genotype-specific minimal residual disease interpretation improves stratification in pediatric acute lymphoblastic leukemia. J Clin Oncol 36(1):34–43

    Article  PubMed  CAS  Google Scholar 

  8. Pui CH et al (2017) Clinical impact of minimal residual disease in children with different subtypes of acute lymphoblastic leukemia treated with response-adapted therapy. Leukemia 31(2):333–339

    Article  PubMed  Google Scholar 

  9. Gao C et al (2012) Clinical features, early treatment responses, and outcomes of pediatric acute lymphoblastic leukemia in China with or without specific fusion transcripts: a single institutional study of 1,004 patients. Am J Hematol 87(11):1022–1027

    Article  PubMed  Google Scholar 

  10. Cui L et al (2018) Outcome of children with newly diagnosed acute lymphoblastic leukemia treated with CCLG-ALL 2008: the first nation-wide prospective multicenter study in China. Am J Hematol 93(7):913–920

    Article  PubMed  Google Scholar 

  11. Cui L et al (2010) Combined analysis of minimal residual disease at two time points and its value for risk stratification in childhood B-lineage acute lymphoblastic leukemia. Leuk Res 34(10):1314–1319

    Article  PubMed  Google Scholar 

  12. van der Velden VH et al (2007) Analysis of minimal residual disease by Ig/TCR gene rearrangements: guidelines for interpretation of real-time quantitative PCR data. Leukemia 21(4):604–611

    Article  PubMed  Google Scholar 

  13. Vidriales MB et al (2003) Minimal residual disease monitoring by flow cytometry. Best Pract Res Clin Haematol 16(4):599–612

    Article  PubMed  Google Scholar 

  14. Tran TH et al (2022) Whole-transcriptome analysis in acute lymphoblastic leukemia: a report from the DFCI ALL Consortium Protocol 16–001. Blood Adv 6(4):1329–1341

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  15. Tran TH, Hunger SP (2022) The genomic landscape of pediatric acute lymphoblastic leukemia and precision medicine opportunities. Semin Cancer Biol 84:144–152

    Article  PubMed  CAS  Google Scholar 

  16. Li JF et al (2018) Transcriptional landscape of B cell precursor acute lymphoblastic leukemia based on an international study of 1,223 cases. Proc Natl Acad Sci U S A 115(50):E11711-e11720

    Article  ADS  PubMed  PubMed Central  CAS  Google Scholar 

  17. Cui L et al (2021) Combined analysis of IKZF1 deletions and CRLF2 expression on prognostic impact in pediatric B-cell precursor acute lymphoblastic leukemia. Leuk Lymphoma 62(2):410–418

    Article  PubMed  CAS  Google Scholar 

  18. Druker BJ (2002) Perspectives on the development of a molecularly targeted agent. Cancer Cell 1(1):31–36

    Article  PubMed  CAS  Google Scholar 

  19. Schrappe M et al (2011) Late MRD response determines relapse risk overall and in subsets of childhood T-cell ALL: results of the AIEOP-BFM-ALL 2000 study. Blood 118(8):2077–2084

    Article  PubMed  CAS  Google Scholar 

  20. Faham M et al (2012) Deep-sequencing approach for minimal residual disease detection in acute lymphoblastic leukemia. Blood 120(26):5173–5180

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  21. Sala Torra O et al (2017) Next-generation sequencing in adult B cell acute lymphoblastic leukemia patients. Biol Blood Marrow Transplant 23(4):691–696

    Article  PubMed  CAS  Google Scholar 

Download references

Funding

This work was supported by the National Natural Science Foundation of China, No. 81970135, No. 81870114, the Beijing Natural Science Foundation of China, No. 7202044, the New Sunshine Charity Foundation, China, No. 2017002, Funding for Reform and Development of Beijing Municipal Health Commission.

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Authors and Affiliations

  1. Hematologic Diseases Laboratory, Beijing Pediatric Research Institute, Beijing Children’s Hospital, Capital Medical University, National Center for Children’s Health, Beijing, China

    Xiao-Tong Huang, Chao Gao, Tian-Lin Xue, Zi-Jing Zhao, Lei Cui & Zhi-Gang Li

  2. National Key Discipline of Pediatrics, Capital Medical University, Beijing, China

    Xiao-Tong Huang, Chan-Juan Wang, Chao Gao, Tian-Lin Xue, Zi-Jing Zhao, Tian-You Wang, Min-Yuan Wu, Lei Cui, Rui-Dong Zhang & Zhi-Gang Li

  3. Beijing Key Laboratory of Pediatric Hematology-Oncology, Hematology Center, Beijing Children’s Hospital, National Center for Children’s Health, Capital Medical University, Beijing, China

    Xiao-Tong Huang, Chan-Juan Wang, Chao Gao, Tian-Lin Xue, Zi-Jing Zhao, Tian-You Wang, Min-Yuan Wu, Lei Cui, Rui-Dong Zhang & Zhi-Gang Li

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  1. Xiao-Tong Huang
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  2. Chan-Juan Wang
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  3. Chao Gao
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  8. Lei Cui
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  9. Rui-Dong Zhang
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  10. Zhi-Gang Li
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Contributions

HXT analyzed the data and wrote the original draft. WCJ and ZZJ collected the clinical data. GC and XTL performed the experiments. WTY, WMY and ZRD made clinical contributions. LZG , CL and ZRD designed the research and revised the paper. All authors were involved in the final approval of the paper.

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Correspondence to Lei Cui, Rui-Dong Zhang or Zhi-Gang Li.

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Huang, XT., Wang, CJ., Gao, C. et al. Relationship between subtype-specific minimal residual disease level and long-term prognosis in children with acute lymphoblastic leukemia. Ann Hematol (2024). https://doi.org/10.1007/s00277-024-05687-y

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