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MRD in Pediatric ALL

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Pediatric Acute Lymphoblastic Leukemia
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Abstract

Even after microscopic remission after induction therapy, however, in this more than billions of leukemic cells potentially are supposed to escape this microscopic detection. In recent years, technological progress has enabled us to detect residual leukemic cells, which cannot be detected only by means of conventional assessment using microscopic morphology. These residual cells in microscopic remission are “minimal residual diseases (MRD)”. PCR and flow cytometry (FCM) are two major methods to detect MRD, and these methods had several advantages/disadvantages. PCR-MRD can detect as low as 0.001% of residual leukemic cells, while the sensitivity of FCM-MRD is 0.01%. On the other hand, FCM-MRD has advantages in terms of simple preparation methods, short duration to obtain results, cheaper cost, and broad applicability. Irrespective of MRD detection methods, time points to be assessed, and threshold, potent impacts on prognosis have been confirmed by numerous clinical studies. MRD assessment is essential to stratify patients according to relapse risk.

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References

  1. Kato M, Manabe A. Treatment and biology of pediatric acute lymphoblastic leukemia. Pediatr Int. 2018;60:4–12.

    Article  Google Scholar 

  2. van Dongen JJ, Seriu T, Panzer-Grumayer ER, et al. Prognostic value of minimal residual disease in acute lymphoblastic leukaemia in childhood. Lancet. 1998;352:1731–8.

    Article  Google Scholar 

  3. Pui CH, Pei D, Raimondi SC, et al. Clinical impact of minimal residual disease in children with different subtypes of acute lymphoblastic leukemia treated with response-adapted therapy. Leukemia. 2017;31:333–9.

    Article  Google Scholar 

  4. Pongers-Willemse MJ, Verhagen OJ, Tibbe GJ, et al. Real-time quantitative PCR for the detection of minimal residual disease in acute lymphoblastic leukemia using junctional region specific TaqMan probes. Leukemia. 1998;12:2006–14.

    Article  CAS  Google Scholar 

  5. Bruggemann M, Droese J, Bolz I, et al. Improved assessment of minimal residual disease in B cell malignancies using fluorogenic consensus probes for real-time quantitative PCR. Leukemia. 2000;14:1419–25.

    Article  CAS  Google Scholar 

  6. van der Velden VH, Cazzaniga G, Schrauder A, et al. Analysis of minimal residual disease by Ig/TCR gene rearrangements: guidelines for interpretation of real-time quantitative PCR data. Leukemia. 2007;21:604–11.

    Article  Google Scholar 

  7. van Dongen JJ, van der Velden VH, Bruggemann M, Orfao A. Minimal residual disease diagnostics in acute lymphoblastic leukemia: need for sensitive, fast, and standardized technologies. Blood. 2015;125:3996–4009.

    Article  Google Scholar 

  8. Campana D, Coustan-Smith E. Measurements of treatment response in childhood acute leukemia. Korean J Hematol. 2012;47:245–54.

    Article  Google Scholar 

  9. Theunissen P, Mejstrikova E, Sedek L, et al. Standardized flow cytometry for highly sensitive MRD measurements in B-cell acute lymphoblastic leukemia. Blood. 2017;129:347–57.

    Article  CAS  Google Scholar 

  10. Kalina T, Flores-Montero J, van der Velden VH, et al. EuroFlow standardization of flow cytometer instrument settings and immunophenotyping protocols. Leukemia. 2012;26:1986–2010.

    Article  CAS  Google Scholar 

  11. Campana D, Coustan-Smith E. Detection of minimal residual disease in acute leukemia by flow cytometry. Cytometry. 1999;38:139–52.

    Article  CAS  Google Scholar 

  12. Conter V, Bartram CR, Valsecchi MG, et al. Molecular response to treatment redefines all prognostic factors in children and adolescents with B-cell precursor acute lymphoblastic leukemia: results in 3184 patients of the AIEOP-BFM ALL 2000 study. Blood. 2010;115:3206–14.

    Article  CAS  Google Scholar 

  13. Schrappe M, Valsecchi MG, Bartram CR, et al. Late MRD response determines relapse risk overall and in subsets of childhood T-cell ALL: results of the AIEOP-BFM-ALL 2000 study. Blood. 2011;118:2077–84.

    Article  CAS  Google Scholar 

  14. Pieters R, de Groot-Kruseman H, Van der Velden V, et al. Successful therapy reduction and intensification for childhood acute lymphoblastic Leukemia based on minimal residual disease monitoring: study ALL10 from the Dutch childhood oncology group. J Clin Oncol. 2016;34:2591–601.

    Article  Google Scholar 

  15. Coustan-Smith E, Behm FG, Sanchez J, et al. Immunological detection of minimal residual disease in children with acute lymphoblastic leukaemia. Lancet. 1998;351:550–4.

    Article  CAS  Google Scholar 

  16. Berry DA, Zhou S, Higley H, et al. Association of Minimal Residual Disease with Clinical Outcome in Pediatric and adult acute lymphoblastic Leukemia: a meta-analysis. JAMA Oncol. 2017;3:e170580.

    Article  Google Scholar 

  17. Eckert C, Henze G, Seeger K, et al. Use of allogeneic hematopoietic stem-cell transplantation based on minimal residual disease response improves outcomes for children with relapsed acute lymphoblastic leukemia in the intermediate-risk group. J Clin Oncol. 2013;31:2736–42.

    Article  Google Scholar 

  18. Cave H, van der Werff ten Bosch J, Suciu S, et al. Clinical significance of minimal residual disease in childhood acute lymphoblastic leukemia. European Organization for Research and Treatment of Cancer—childhood Leukemia cooperative group. N Engl J Med. 1998;339:591–8.

    Article  CAS  Google Scholar 

  19. Van der Velden VH, Corral L, Valsecchi MG, et al. Prognostic significance of minimal residual disease in infants with acute lymphoblastic leukemia treated within the Interfant-99 protocol. Leukemia. 2009;23:1073–9.

    Article  Google Scholar 

  20. Mullighan CG, Jeha S, Pei D, et al. Outcome of children with hypodiploid ALL treated with risk-directed therapy based on MRD levels. Blood. 2015;126:2896–9.

    Article  Google Scholar 

  21. Pui CH, Rebora P, Schrappe M, et al. Outcome of children with Hypodiploid acute lymphoblastic Leukemia: a retrospective multinational study. J Clin Oncol. 2019;37:770–9.

    Article  CAS  Google Scholar 

  22. McNeer JL, Devidas M, Dai Y, et al. Hematopoietic stem-cell transplantation does not improve the poor outcome of children with hypodiploid acute lymphoblastic Leukemia: a report from Children's oncology group. J Clin Oncol. 2019;37:780–9.

    Article  CAS  Google Scholar 

  23. Roberts KG, Pei D, Campana D, et al. Outcomes of children with BCR-ABL1-like acute lymphoblastic leukemia treated with risk-directed therapy based on the levels of minimal residual disease. J Clin Oncol. 2014;32:3012–20.

    Article  CAS  Google Scholar 

  24. Jain N, Roberts KG, Jabbour E, et al. Ph-like acute lymphoblastic leukemia: a high-risk subtype in adults. Blood. 2017;129:572–81.

    Article  CAS  Google Scholar 

  25. Vora A, Goulden N, Mitchell C, et al. Augmented post-remission therapy for a minimal residual disease-defined high-risk subgroup of children and young people with clinical standard-risk and intermediate-risk acute lymphoblastic leukaemia (UKALL 2003): a randomised controlled trial. Lancet Oncol. 2014;15:809–18.

    Article  Google Scholar 

  26. Vora A, Goulden N, Wade R, et al. Treatment reduction for children and young adults with low-risk acute lymphoblastic leukaemia defined by minimal residual disease (UKALL 2003): a randomised controlled trial. Lancet Oncol. 2013;14:199–209.

    Article  CAS  Google Scholar 

  27. Faham M, Zheng J, Moorhead M, et al. Deep-sequencing approach for minimal residual disease detection in acute lymphoblastic leukemia. Blood. 2012;120:5173–80.

    Article  CAS  Google Scholar 

  28. Ladetto M, Bruggemann M, Monitillo L, et al. Next-generation sequencing and real-time quantitative PCR for minimal residual disease detection in B-cell disorders. Leukemia. 2014;28:1299–307.

    Article  CAS  Google Scholar 

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Correspondence to Motohiro Kato .

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Kato, M. (2020). MRD in Pediatric ALL. In: Kato, M. (eds) Pediatric Acute Lymphoblastic Leukemia. Springer, Singapore. https://doi.org/10.1007/978-981-15-0548-5_5

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  • DOI: https://doi.org/10.1007/978-981-15-0548-5_5

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  • Publisher Name: Springer, Singapore

  • Print ISBN: 978-981-15-0547-8

  • Online ISBN: 978-981-15-0548-5

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