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Flow cytometric vs morphologic assessment of remission in childhood acute lymphoblastic leukemia: A report from the Children’s Oncology Group (COG)

Abstract

Minimal residual disease (MRD) after initial therapy is integral to risk stratification in B- and T-precursor acute lymphoblastic leukemia (B-ALL, T-ALL). Although MRD determines depth of remission, remission remains defined by morphology. We determined the outcomes of children with discordant assessments of remission by morphology vs flow cytometry using patients aged 1−30.99 years enrolled on Children’s Oncology Group ALL trials who underwent bone marrow assessment at the end of induction (N=9350). Morphologic response was assessed locally as M1 (<5% lymphoblasts; remission), M2 (5−25%) or M3 (>25%). MRD was centrally measured by flow cytometry. Of the patients with M2/M3 morphology, 19.8% had MRD <5%. M1 with MRD 5% was less common in B-ALL (0.9%) than T-ALL (6.9%; P<0.0001). In B-ALL, M1/MRD 5% was associated with superior 5-year event-free survival (EFS) than M2/MRD 5% (59.1±6.5% vs 39.1±7.9%; P=0.009), but was inferior to M1/MRD <5% (87.1±0.4%; P<0.0001). MRD levels were higher in M2/MRD 5% than M1/MRD 5% patients. In T-ALL, EFS was not significantly different between M1/MRD 5% and M2/MRD 5%. Patients with morphologic remission but MRD 5% have outcomes similar to those who fail to achieve morphological remission, and significantly inferior to those with M1 marrows and concordant MRD, suggesting that flow cytometry should augment the definition of remission in ALL.

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Author information

Author notes

    • S Gupta
    •  & M Devidas

    Co-first authors.

    • M Borowitz
    •  & B L Wood

    Co-senior authors.

Affiliations

  1. Division of Haematology/Oncology, The Hospital for Sick Children, Toronto, Ontario, Canada

    • S Gupta
  2. Department of Biostatistics, University of Florida, Gainesville, FL, USA

    • M Devidas
    • , S Chen
    •  & C Wang
  3. University of California at San Francisco, San Francisco, CA, USA

    • M L Loh
  4. Primary Children’s Hospital, Salt Lake City, UT, USA

    • E A Raetz
  5. Johns Hopkins University/Sidney Kimmel Cancer Center, Baltimore, MD, USA

    • P Brown
  6. Children's Hospital of Alabama, Birmingham, AL, USA

    • A J Carroll
    •  & S P Hunger
  7. The Ohio State University, Columbus, OH, USA

    • N A Heerema
  8. Nationwide Children’s Hospital, Columbus, OH, USA

    • J M Gastier-Foster
  9. University of Virginia Cancer Center, Charlottesville, VA, USA

    • K P Dunsmore
  10. Maine Children's Cancer Program, Scarborough, ME, USA

    • E C Larsen
  11. Children's Hospital Colorado, Aurora, CO, USA

    • K W Maloney
  12. HARP Pharma Consulting, Mystic, CT, USA

    • L A Mattano
  13. University of New Mexico Cancer Center, Albuquerque, NM, USA

    • S S Winter
  14. University of Texas Southwestern/Simmons Cancer Center-Dallas, Dallas, TX, USA

    • N J Winick
  15. Laura and Isaac Perlmutter Cancer Center, New York, NY, USA

    • W L Carroll
  16. Children's Hospital of Philadelphia, Philadelphia, PA, USA

    • M Borowitz
  17. Seattle Children's Hospital, Seattle, WA, USA

    • B L Wood

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Corresponding author

Correspondence to S Gupta.

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DOI

https://doi.org/10.1038/leu.2017.341