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A recurrent immunophenotype at diagnosis independently identifies high-risk pediatric acute myeloid leukemia: a report from Children’s Oncology Group

Leukemia volume 30, pages 2077–2080 (2016)Cite this article

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Risk stratification of therapy for pediatric acute myeloid leukemia (AML) has been a focus of clinical protocol design to maximize treatment for high-risk groups while reducing therapeutic intensity for lower-risk groups. Molecular and cytogenetic markers have been used to define risk groups before therapy; however, 20% of pediatric cases lack all known markers1 and ~60% of cases lack markers that stratify outcome.2, 3 The detection of measurable residual disease (MRD) by multidimensional flow cytometry (MDF) in the remaining ‘standard risk’ group has permitted the stratification of patients who lack genetic abnormalities linked to therapy outcomes.4 However, discrimination between good and poor-risk groups based on the immunophenotype at diagnosis has not been sufficiently robust to routinely stratify patients. Previous reports have largely focused on the relationship between outcome and the expression of a single antigen.5 Multidimensional immunophenotypes have been reported,6, 7, 8 but none clearly identify risk cohorts.

By combining the quantitative expression of multiple antigens, not just their presence or absence, we have identified a previously uncharacterized multidimensional immunophenotype in a cohort of pediatric patients from Children’s Oncology Group (COG) clinical trial AAML0531. We sought to determine the clinical, biological and outcome characteristics of patients with this phenotype.

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Acknowledgements

We would like to thank the patients and families for participating in AAML0531. Particularly we would like to thank the family of the index patient for the permission to name the adverse prognostic phenotype RAM. Documentation of informed consent is on record with the Children’s Oncology Group and with HematoLogics Inc. This work was supported by grants U10CA098543 (Chair’s grant), U10CA098413 (the Statistical Center Grant), U10CA180886 (National Clinical Trials Network Operations Center Grant), U10CA180899 (National Clinical Trials Network Statistics and Data Center) and U10CA180886 (Biomarker, Imaging and Quality of Life Studies Funding Program). The trial was registered at www.clinicaltrials.gov as NCT00372593.

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Author notes

  1. S Meshinchi and M R Loken: These authors contributed equally to this work.

Authors and Affiliations

  1. HematoLogics, Inc, Seattle, WA, USA

    L Eidenschink Brodersen, A J Menssen, L Pardo, A P Voigt & M R Loken

  2. Children's Oncology Group, Monrovia, CA, USA

    T A Alonzo, R B Gerbing, A S Gamis & S Meshinchi

  3. University of Southern California, Los Angeles, CA, USA

    T A Alonzo

  4. Nationwide Children’s Hospital, Columbus, OH, USA

    S B Kahwash

  5. University of Minnesota Medical Center, Minneapolis, MN, USA

    B Hirsch

  6. St. Jude’s Children’s Research Hospital, Memphis, TN, USA

    S Raimondi

  7. Children’s Mercy Hospitals & Clinics, Kansas City, MO, USA

    A S Gamis

  8. Fred Hutchinson Cancer Research Center, Seattle, WA, USA

    S Meshinchi

Authors
  1. L Eidenschink Brodersen
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  2. T A Alonzo
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  3. A J Menssen
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  4. R B Gerbing
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  5. L Pardo
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  6. A P Voigt
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  7. S B Kahwash
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  8. B Hirsch
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  9. S Raimondi
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  10. A S Gamis
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  11. S Meshinchi
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  12. M R Loken
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Corresponding author

Correspondence to L Eidenschink Brodersen.

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Competing interests

LEB, AJM, LP, APV and MRL are employed by Hematologics, Inc. MRL is an equity owner of Hematologics, Inc.

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Supplementary Information accompanies this paper on the Leukemia website

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Eidenschink Brodersen, L., Alonzo, T., Menssen, A. et al. A recurrent immunophenotype at diagnosis independently identifies high-risk pediatric acute myeloid leukemia: a report from Children’s Oncology Group. Leukemia 30, 2077–2080 (2016). https://doi.org/10.1038/leu.2016.119

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