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Minimal Residual Disease

Clinical significance of flowcytometric minimal residual disease detection in pediatric acute myeloid leukemia patients treated according to the DCOG ANLL97/MRC AML12 protocol

Leukemia volume 24, pages 1599–1606 (2010)Cite this article

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Abstract

Analysis of minimal residual disease (MRD) in childhood acute myeloid leukemia (AML) may predict for clinical outcome. MRD levels were assessed by flowcytometric immunophenotyping in 94 children with AML enrolled into a single trial (United Kingdom Medical Research Council AML12 and similar Dutch Childhood Oncology Group ANLL97). An aberrant immunophenotype could be detected in 94% of patients. MRD levels after the first course of chemotherapy predicted for clinical outcome: 3-year relapse-free survival was 85%±8% (s.e.) for MRD-negative patients (MRD<0.1%), 64%±10% for MRD-low-positive patients (0.1%⩽MRD<0.5%) and only 14±9% for MRD-high-positive patients (MRD⩾0.5%; P<0.001), whereas overall survival was 95%±5%, 70%±10% and 40%±13%, respectively, (P<0.001). Multivariate analysis allowing for age, karyotype, FLT3-internal tandem duplications and white blood cell count at diagnosis showed that MRD after the first course of chemotherapy was an independent prognostic factor. Although comparison of paired diagnosis-relapse samples (n=23) showed immunophenotypic shifts in 91% of cases, this did not hamper MRD analysis. In conclusion, flowcytometric MRD detection is possible in children with AML. The level of MRD after the first course of chemotherapy provides prognostic information that may be used to guide therapy.

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Acknowledgements

We acknowledge the Leukaemia Research Fund for financial support of sample transportation (grant LRF-0041). We thank all clinicians participating in this study for providing patient material and clinical data. Members of the DCOG ANLL97 protocol committee were Siebold SN de Graaf (Chairman), Henk van den Berg, Marc Bierings, Anne van der Does-van den Berg, Gaby Kardos and Margreet van Weel-Sipman (deceased). Members of the MRC AML12 protocol committee were Brenda ES Gibson (Chairman), David Webb, Alan K Burnett, Keith Wheatley and Christine Harrison. We thank the members of the Dutch Working Party on MRD analysis in AML (R Brooimans, F Preijers, N Boeckx, A Kelder, J Slomp) for their support in evaluating the sensitivities of the LAIPs.

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Authors and Affiliations

  1. Department of Immunology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands

    V H J van der Velden, J G te Marvelde, P G Hoogeveen & J J M van Dongen

  2. Dutch Childhood Oncology Group, The Hague, The Netherlands

    A van der Sluijs-Geling, M B Bierings, S S N de Graaf & E R van Wering

  3. Department of Haematology, Royal Hospital for Sick Children, Glasgow, UK

    B E S Gibson

  4. Department of Biostatistics, Erasmus MC, Rotterdam, The Netherlands

    W C J Hop

  5. Cancer Research UK Clinical Trials Unit, University of Birmingham, Birmingham, UK

    K Wheatley

  6. Department of Pediatric Oncology, University Medical Center Utrecht, Utrecht, The Netherlands

    M B Bierings

  7. Department of Hematology, VU University Medical Center, Amsterdam, The Netherlands

    G J Schuurhuis

  8. Department of Pediatrics, University Medical Center St Radboud, Nijmegen, The Netherlands

    S S N de Graaf

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  1. V H J van der Velden
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Correspondence to V H J van der Velden.

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van der Velden, V., van der Sluijs-Geling, A., Gibson, B. et al. Clinical significance of flowcytometric minimal residual disease detection in pediatric acute myeloid leukemia patients treated according to the DCOG ANLL97/MRC AML12 protocol. Leukemia 24, 1599–1606 (2010). https://doi.org/10.1038/leu.2010.153

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