Comparative analysis of different approaches to measure treatment response in acute myeloid leukemia

Hiroto Inaba, Elaine Coustan-Smith, Xueyuan Cao, Stanley B. Pounds, Sheila A. Shurtleff, Kathleen Y. Wang, Susana C. Raimondi, Mihaela Onciu, Jeffrey Jacobsen, Raul C. Ribeiro, Gary V. Dahl, W. Paul Bowman, Jeffrey W. Taub, Barbara Degar, Wing Leung, James R. Downing, Ching Hon Pui, Jeffrey E. Rubnitz, Dario Campana

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Abstract

Purpose: In acute myeloid leukemia (AML), initial treatment response by morphologic analysis of bone marrow predicts long-term outcome. Response can now be assessed by minimal residual disease (MRD) monitoring with flow cytometry or polymerase chain reaction (PCR). We determined the relation among the results of these approaches and their prognostic value. Patients and Methods: In the multicenter AML02 study, follow-up bone marrow samples from 203 children and adolescents with newly diagnosed AML were examined by flow cytometry (n = 1,514), morphology (n = 1,382), and PCR amplification of fusion transcripts (n = 508). Results were correlated with treatment outcome. Results: Among 1,215 samples with less than 5% leukemic myeloblasts by morphology, 100 (8.2%) were MRD positive (≥ 0.1%) by flow cytometry, whereas 96 (57.5%) of the 167 samples with ≥ 5% blasts were MRD negative. Virtually all (308 of 311; 99.0%) MRD-negative samples by PCR were also MRD negative by flow cytometry. However, only 19 (9.6%) of the 197 PCR-positive samples were flow cytometry positive, with analyses of AML1-ETO and CBFβ-MYH11 accounting for most discrepancies, whereas eight of 13 MLL-positive samples had detectable MRD by flow cytometry. MRD by flow cytometry after induction 1 or 2 predicted lower event-free survival and higher relapse rate (P < .001) and was an independent prognostic factor in a multivariable analysis; prediction was not improved by morphologic information or molecular findings. Conclusion: In childhood AML, morphologic assessment of treatment response has limited value if MRD is measured by flow cytometry. MLL fusion transcripts can provide prognostic information in some patients, whereas monitoring of AML1-ETO and CBFβ-MYH11 transcripts is largely uninformative.

Original languageEnglish (US)
Pages (from-to)3625-3632
Number of pages8
JournalJournal of Clinical Oncology
Volume30
Issue number29
DOIs
StatePublished - Oct 10 2012

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Residual Neoplasm
Acute Myeloid Leukemia
Flow Cytometry
Polymerase Chain Reaction
Therapeutics
Bone Marrow
Granulocyte Precursor Cells
Physiologic Monitoring
Multicenter Studies
Disease-Free Survival
Recurrence

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

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Inaba, H., Coustan-Smith, E., Cao, X., Pounds, S. B., Shurtleff, S. A., Wang, K. Y., ... Campana, D. (2012). Comparative analysis of different approaches to measure treatment response in acute myeloid leukemia. Journal of Clinical Oncology, 30(29), 3625-3632. https://doi.org/10.1200/JCO.2011.41.5323

Comparative analysis of different approaches to measure treatment response in acute myeloid leukemia. / Inaba, Hiroto; Coustan-Smith, Elaine; Cao, Xueyuan; Pounds, Stanley B.; Shurtleff, Sheila A.; Wang, Kathleen Y.; Raimondi, Susana C.; Onciu, Mihaela; Jacobsen, Jeffrey; Ribeiro, Raul C.; Dahl, Gary V.; Bowman, W. Paul; Taub, Jeffrey W.; Degar, Barbara; Leung, Wing; Downing, James R.; Pui, Ching Hon; Rubnitz, Jeffrey E.; Campana, Dario.

In: Journal of Clinical Oncology, Vol. 30, No. 29, 10.10.2012, p. 3625-3632.

Research output: Contribution to journalArticle

Inaba, H, Coustan-Smith, E, Cao, X, Pounds, SB, Shurtleff, SA, Wang, KY, Raimondi, SC, Onciu, M, Jacobsen, J, Ribeiro, RC, Dahl, GV, Bowman, WP, Taub, JW, Degar, B, Leung, W, Downing, JR, Pui, CH, Rubnitz, JE & Campana, D 2012, 'Comparative analysis of different approaches to measure treatment response in acute myeloid leukemia', Journal of Clinical Oncology, vol. 30, no. 29, pp. 3625-3632. https://doi.org/10.1200/JCO.2011.41.5323
Inaba, Hiroto ; Coustan-Smith, Elaine ; Cao, Xueyuan ; Pounds, Stanley B. ; Shurtleff, Sheila A. ; Wang, Kathleen Y. ; Raimondi, Susana C. ; Onciu, Mihaela ; Jacobsen, Jeffrey ; Ribeiro, Raul C. ; Dahl, Gary V. ; Bowman, W. Paul ; Taub, Jeffrey W. ; Degar, Barbara ; Leung, Wing ; Downing, James R. ; Pui, Ching Hon ; Rubnitz, Jeffrey E. ; Campana, Dario. / Comparative analysis of different approaches to measure treatment response in acute myeloid leukemia. In: Journal of Clinical Oncology. 2012 ; Vol. 30, No. 29. pp. 3625-3632.
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abstract = "Purpose: In acute myeloid leukemia (AML), initial treatment response by morphologic analysis of bone marrow predicts long-term outcome. Response can now be assessed by minimal residual disease (MRD) monitoring with flow cytometry or polymerase chain reaction (PCR). We determined the relation among the results of these approaches and their prognostic value. Patients and Methods: In the multicenter AML02 study, follow-up bone marrow samples from 203 children and adolescents with newly diagnosed AML were examined by flow cytometry (n = 1,514), morphology (n = 1,382), and PCR amplification of fusion transcripts (n = 508). Results were correlated with treatment outcome. Results: Among 1,215 samples with less than 5{\%} leukemic myeloblasts by morphology, 100 (8.2{\%}) were MRD positive (≥ 0.1{\%}) by flow cytometry, whereas 96 (57.5{\%}) of the 167 samples with ≥ 5{\%} blasts were MRD negative. Virtually all (308 of 311; 99.0{\%}) MRD-negative samples by PCR were also MRD negative by flow cytometry. However, only 19 (9.6{\%}) of the 197 PCR-positive samples were flow cytometry positive, with analyses of AML1-ETO and CBFβ-MYH11 accounting for most discrepancies, whereas eight of 13 MLL-positive samples had detectable MRD by flow cytometry. MRD by flow cytometry after induction 1 or 2 predicted lower event-free survival and higher relapse rate (P < .001) and was an independent prognostic factor in a multivariable analysis; prediction was not improved by morphologic information or molecular findings. Conclusion: In childhood AML, morphologic assessment of treatment response has limited value if MRD is measured by flow cytometry. MLL fusion transcripts can provide prognostic information in some patients, whereas monitoring of AML1-ETO and CBFβ-MYH11 transcripts is largely uninformative.",
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T1 - Comparative analysis of different approaches to measure treatment response in acute myeloid leukemia

AU - Inaba, Hiroto

AU - Coustan-Smith, Elaine

AU - Cao, Xueyuan

AU - Pounds, Stanley B.

AU - Shurtleff, Sheila A.

AU - Wang, Kathleen Y.

AU - Raimondi, Susana C.

AU - Onciu, Mihaela

AU - Jacobsen, Jeffrey

AU - Ribeiro, Raul C.

AU - Dahl, Gary V.

AU - Bowman, W. Paul

AU - Taub, Jeffrey W.

AU - Degar, Barbara

AU - Leung, Wing

AU - Downing, James R.

AU - Pui, Ching Hon

AU - Rubnitz, Jeffrey E.

AU - Campana, Dario

PY - 2012/10/10

Y1 - 2012/10/10

N2 - Purpose: In acute myeloid leukemia (AML), initial treatment response by morphologic analysis of bone marrow predicts long-term outcome. Response can now be assessed by minimal residual disease (MRD) monitoring with flow cytometry or polymerase chain reaction (PCR). We determined the relation among the results of these approaches and their prognostic value. Patients and Methods: In the multicenter AML02 study, follow-up bone marrow samples from 203 children and adolescents with newly diagnosed AML were examined by flow cytometry (n = 1,514), morphology (n = 1,382), and PCR amplification of fusion transcripts (n = 508). Results were correlated with treatment outcome. Results: Among 1,215 samples with less than 5% leukemic myeloblasts by morphology, 100 (8.2%) were MRD positive (≥ 0.1%) by flow cytometry, whereas 96 (57.5%) of the 167 samples with ≥ 5% blasts were MRD negative. Virtually all (308 of 311; 99.0%) MRD-negative samples by PCR were also MRD negative by flow cytometry. However, only 19 (9.6%) of the 197 PCR-positive samples were flow cytometry positive, with analyses of AML1-ETO and CBFβ-MYH11 accounting for most discrepancies, whereas eight of 13 MLL-positive samples had detectable MRD by flow cytometry. MRD by flow cytometry after induction 1 or 2 predicted lower event-free survival and higher relapse rate (P < .001) and was an independent prognostic factor in a multivariable analysis; prediction was not improved by morphologic information or molecular findings. Conclusion: In childhood AML, morphologic assessment of treatment response has limited value if MRD is measured by flow cytometry. MLL fusion transcripts can provide prognostic information in some patients, whereas monitoring of AML1-ETO and CBFβ-MYH11 transcripts is largely uninformative.

AB - Purpose: In acute myeloid leukemia (AML), initial treatment response by morphologic analysis of bone marrow predicts long-term outcome. Response can now be assessed by minimal residual disease (MRD) monitoring with flow cytometry or polymerase chain reaction (PCR). We determined the relation among the results of these approaches and their prognostic value. Patients and Methods: In the multicenter AML02 study, follow-up bone marrow samples from 203 children and adolescents with newly diagnosed AML were examined by flow cytometry (n = 1,514), morphology (n = 1,382), and PCR amplification of fusion transcripts (n = 508). Results were correlated with treatment outcome. Results: Among 1,215 samples with less than 5% leukemic myeloblasts by morphology, 100 (8.2%) were MRD positive (≥ 0.1%) by flow cytometry, whereas 96 (57.5%) of the 167 samples with ≥ 5% blasts were MRD negative. Virtually all (308 of 311; 99.0%) MRD-negative samples by PCR were also MRD negative by flow cytometry. However, only 19 (9.6%) of the 197 PCR-positive samples were flow cytometry positive, with analyses of AML1-ETO and CBFβ-MYH11 accounting for most discrepancies, whereas eight of 13 MLL-positive samples had detectable MRD by flow cytometry. MRD by flow cytometry after induction 1 or 2 predicted lower event-free survival and higher relapse rate (P < .001) and was an independent prognostic factor in a multivariable analysis; prediction was not improved by morphologic information or molecular findings. Conclusion: In childhood AML, morphologic assessment of treatment response has limited value if MRD is measured by flow cytometry. MLL fusion transcripts can provide prognostic information in some patients, whereas monitoring of AML1-ETO and CBFβ-MYH11 transcripts is largely uninformative.

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