Flow-cytometric vs. -morphologic assessment of remission in childhood acute lymphoblastic leukemia

a report from the Children’s Oncology Group (COG)

Sumit Gupta, Meenakshi Devidas, Mignon L. Loh, Elizabeth A. Raetz, Si Chen, Cindy Wang, Patrick A Brown, Andrew J. Carroll, Nyla A. Heerema, Julie M. Gastier-Foster, Kimberly P. Dunsmore, Eric C. Larsen, Kelly W. Maloney, Leonard A. Mattano, Stuart S. Winter, Naomi J. Winick, William L. Carroll, Stephen P. Hunger, Michael J Borowitz, Brent L. Wood

Research output: Contribution to journalArticle

Abstract

Minimal residual disease (MRD) after initial therapy is integral to risk stratification in B-precursor 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 age 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. Overall, 19.8% of patients with M2/M3 morphology 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.

Original languageEnglish (US)
Pages (from-to)1-10
Number of pages10
JournalLeukemia
DOIs
StateAccepted/In press - Feb 23 2018

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Residual Neoplasm
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Precursor T-Cell Lymphoblastic Leukemia-Lymphoma
Flow Cytometry
Disease-Free Survival
Bone Marrow

ASJC Scopus subject areas

  • Hematology
  • Cancer Research
  • Anesthesiology and Pain Medicine

Cite this

Flow-cytometric vs. -morphologic assessment of remission in childhood acute lymphoblastic leukemia : a report from the Children’s Oncology Group (COG). / Gupta, Sumit; Devidas, Meenakshi; Loh, Mignon L.; Raetz, Elizabeth A.; Chen, Si; Wang, Cindy; Brown, Patrick A; Carroll, Andrew J.; Heerema, Nyla A.; Gastier-Foster, Julie M.; Dunsmore, Kimberly P.; Larsen, Eric C.; Maloney, Kelly W.; Mattano, Leonard A.; Winter, Stuart S.; Winick, Naomi J.; Carroll, William L.; Hunger, Stephen P.; Borowitz, Michael J; Wood, Brent L.

In: Leukemia, 23.02.2018, p. 1-10.

Research output: Contribution to journalArticle

Gupta, S, Devidas, M, Loh, ML, Raetz, EA, Chen, S, Wang, C, Brown, PA, Carroll, AJ, Heerema, NA, Gastier-Foster, JM, Dunsmore, KP, Larsen, EC, Maloney, KW, Mattano, LA, Winter, SS, Winick, NJ, Carroll, WL, Hunger, SP, Borowitz, MJ & Wood, BL 2018, 'Flow-cytometric vs. -morphologic assessment of remission in childhood acute lymphoblastic leukemia: a report from the Children’s Oncology Group (COG)', Leukemia, pp. 1-10. https://doi.org/10.1038/s41375-018-0039-7
Gupta, Sumit ; Devidas, Meenakshi ; Loh, Mignon L. ; Raetz, Elizabeth A. ; Chen, Si ; Wang, Cindy ; Brown, Patrick A ; Carroll, Andrew J. ; Heerema, Nyla A. ; Gastier-Foster, Julie M. ; Dunsmore, Kimberly P. ; Larsen, Eric C. ; Maloney, Kelly W. ; Mattano, Leonard A. ; Winter, Stuart S. ; Winick, Naomi J. ; Carroll, William L. ; Hunger, Stephen P. ; Borowitz, Michael J ; Wood, Brent L. / Flow-cytometric vs. -morphologic assessment of remission in childhood acute lymphoblastic leukemia : a report from the Children’s Oncology Group (COG). In: Leukemia. 2018 ; pp. 1-10.
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abstract = "Minimal residual disease (MRD) after initial therapy is integral to risk stratification in B-precursor 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 age 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. Overall, 19.8{\%} of patients with M2/M3 morphology 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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T2 - a report from the Children’s Oncology Group (COG)

AU - Gupta, Sumit

AU - Devidas, Meenakshi

AU - Loh, Mignon L.

AU - Raetz, Elizabeth A.

AU - Chen, Si

AU - Wang, Cindy

AU - Brown, Patrick A

AU - Carroll, Andrew J.

AU - Heerema, Nyla A.

AU - Gastier-Foster, Julie M.

AU - Dunsmore, Kimberly P.

AU - Larsen, Eric C.

AU - Maloney, Kelly W.

AU - Mattano, Leonard A.

AU - Winter, Stuart S.

AU - Winick, Naomi J.

AU - Carroll, William L.

AU - Hunger, Stephen P.

AU - Borowitz, Michael J

AU - Wood, Brent L.

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