Article Report

This is an unedited manuscript that has been accepted for publication. Nature Research are providing this early version of the manuscript as a service to our customers. The manuscript will undergo copyediting, typesetting and a proof review before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers apply.

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



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.

  • Subscribe to Leukemia for full access:



Additional access options:

Already a subscriber?  Log in  now or  Register  for online access.

Author information

Author notes

    • S Gupta
    •  & M Devidas

    Co-first authors.

    • M Borowitz
    •  & B L Wood

    Co-senior authors.


  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


  1. Search for S Gupta in:

  2. Search for M Devidas in:

  3. Search for M L Loh in:

  4. Search for E A Raetz in:

  5. Search for S Chen in:

  6. Search for C Wang in:

  7. Search for P Brown in:

  8. Search for A J Carroll in:

  9. Search for N A Heerema in:

  10. Search for J M Gastier-Foster in:

  11. Search for K P Dunsmore in:

  12. Search for E C Larsen in:

  13. Search for K W Maloney in:

  14. Search for L A Mattano in:

  15. Search for S S Winter in:

  16. Search for N J Winick in:

  17. Search for W L Carroll in:

  18. Search for S P Hunger in:

  19. Search for M Borowitz in:

  20. Search for B L Wood in:

Corresponding author

Correspondence to S Gupta.