Clinical impact of minimal residual disease in children with different subtypes of acute lymphoblastic leukemia treated with Response-Adapted therapy

C. H. Pui, D. Pei, S. C. Raimondi, E. Coustan-Smith, S. Jeha, C. Cheng, Paul Bowman, J. T. Sandlund, R. C. Ribeiro, J. E. Rubnitz, H. Inaba, T. A. Gruber, W. H. Leung, J. J. Yang, J. R. Downing, W. E. Evans, M. V. Relling, D. Campana

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Abstract

To determine the clinical significance of minimal residual disease (MRD) in patients with prognostically relevant subtypes of childhood acute lymphoblastic leukemia (ALL), we analyzed data from 488 patients treated in St Jude Total Therapy Study XV with treatment intensity based mainly on MRD levels measured during remission induction. MRD levels on day 19 predicted treatment outcome for patients with hyperdiploid >50 ALL, National Cancer Institute (NCI) standard-risk B-ALL or T-cell ALL, while MRD levels on day 46 were prognostic for patients with NCI standard-risk or high-risk B-ALL. Patients with t(12;21)/(ETV6-RUNX1) or hyperdiploidy >50 ALL had the best prognosis; those with a negative MRD on day 19 had a particularly low risk of relapse: 1.9% and 3.8%, respectively. Patients with NCI high-risk B-ALL or T-cell ALL had an inferior outcome; even with undetectable MRD on day 46, cumulative risk of relapse was 12.7% and 15.5%, respectively. Among patients with NCI standard-risk B-ALL, the outcome was intermediate overall but was poor if MRD was ≥1% on day 19 or MRD was detectable at any level on day 46. Our results indicate that the clinical impact of MRD on treatment outcome in childhood ALL varies considerably according to leukemia subtype and time of measurement.

Original languageEnglish
Pages (from-to)333-339
Number of pages7
JournalLeukemia
Volume31
Issue number2
DOIs
StatePublished - 1 Feb 2017

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Residual Neoplasm
Precursor Cell Lymphoblastic Leukemia-Lymphoma
National Cancer Institute (U.S.)
Biphenotypic Acute Leukemia
Polyploidy
Therapeutics
Remission Induction
Recurrence
Leukemia

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Pui, C. H. ; Pei, D. ; Raimondi, S. C. ; Coustan-Smith, E. ; Jeha, S. ; Cheng, C. ; Bowman, Paul ; Sandlund, J. T. ; Ribeiro, R. C. ; Rubnitz, J. E. ; Inaba, H. ; Gruber, T. A. ; Leung, W. H. ; Yang, J. J. ; Downing, J. R. ; Evans, W. E. ; Relling, M. V. ; Campana, D. / Clinical impact of minimal residual disease in children with different subtypes of acute lymphoblastic leukemia treated with Response-Adapted therapy. In: Leukemia. 2017 ; Vol. 31, No. 2. pp. 333-339.
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abstract = "To determine the clinical significance of minimal residual disease (MRD) in patients with prognostically relevant subtypes of childhood acute lymphoblastic leukemia (ALL), we analyzed data from 488 patients treated in St Jude Total Therapy Study XV with treatment intensity based mainly on MRD levels measured during remission induction. MRD levels on day 19 predicted treatment outcome for patients with hyperdiploid >50 ALL, National Cancer Institute (NCI) standard-risk B-ALL or T-cell ALL, while MRD levels on day 46 were prognostic for patients with NCI standard-risk or high-risk B-ALL. Patients with t(12;21)/(ETV6-RUNX1) or hyperdiploidy >50 ALL had the best prognosis; those with a negative MRD on day 19 had a particularly low risk of relapse: 1.9{\%} and 3.8{\%}, respectively. Patients with NCI high-risk B-ALL or T-cell ALL had an inferior outcome; even with undetectable MRD on day 46, cumulative risk of relapse was 12.7{\%} and 15.5{\%}, respectively. Among patients with NCI standard-risk B-ALL, the outcome was intermediate overall but was poor if MRD was ≥1{\%} on day 19 or MRD was detectable at any level on day 46. Our results indicate that the clinical impact of MRD on treatment outcome in childhood ALL varies considerably according to leukemia subtype and time of measurement.",
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Pui, CH, Pei, D, Raimondi, SC, Coustan-Smith, E, Jeha, S, Cheng, C, Bowman, P, Sandlund, JT, Ribeiro, RC, Rubnitz, JE, Inaba, H, Gruber, TA, Leung, WH, Yang, JJ, Downing, JR, Evans, WE, Relling, MV & Campana, D 2017, 'Clinical impact of minimal residual disease in children with different subtypes of acute lymphoblastic leukemia treated with Response-Adapted therapy', Leukemia, vol. 31, no. 2, pp. 333-339. https://doi.org/10.1038/leu.2016.234

Clinical impact of minimal residual disease in children with different subtypes of acute lymphoblastic leukemia treated with Response-Adapted therapy. / Pui, C. H.; Pei, D.; Raimondi, S. C.; Coustan-Smith, E.; Jeha, S.; Cheng, C.; Bowman, Paul; Sandlund, J. T.; Ribeiro, R. C.; Rubnitz, J. E.; Inaba, H.; Gruber, T. A.; Leung, W. H.; Yang, J. J.; Downing, J. R.; Evans, W. E.; Relling, M. V.; Campana, D.

In: Leukemia, Vol. 31, No. 2, 01.02.2017, p. 333-339.

Research output: Contribution to journalArticleResearchpeer-review

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T1 - Clinical impact of minimal residual disease in children with different subtypes of acute lymphoblastic leukemia treated with Response-Adapted therapy

AU - Pui, C. H.

AU - Pei, D.

AU - Raimondi, S. C.

AU - Coustan-Smith, E.

AU - Jeha, S.

AU - Cheng, C.

AU - Bowman, Paul

AU - Sandlund, J. T.

AU - Ribeiro, R. C.

AU - Rubnitz, J. E.

AU - Inaba, H.

AU - Gruber, T. A.

AU - Leung, W. H.

AU - Yang, J. J.

AU - Downing, J. R.

AU - Evans, W. E.

AU - Relling, M. V.

AU - Campana, D.

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AB - To determine the clinical significance of minimal residual disease (MRD) in patients with prognostically relevant subtypes of childhood acute lymphoblastic leukemia (ALL), we analyzed data from 488 patients treated in St Jude Total Therapy Study XV with treatment intensity based mainly on MRD levels measured during remission induction. MRD levels on day 19 predicted treatment outcome for patients with hyperdiploid >50 ALL, National Cancer Institute (NCI) standard-risk B-ALL or T-cell ALL, while MRD levels on day 46 were prognostic for patients with NCI standard-risk or high-risk B-ALL. Patients with t(12;21)/(ETV6-RUNX1) or hyperdiploidy >50 ALL had the best prognosis; those with a negative MRD on day 19 had a particularly low risk of relapse: 1.9% and 3.8%, respectively. Patients with NCI high-risk B-ALL or T-cell ALL had an inferior outcome; even with undetectable MRD on day 46, cumulative risk of relapse was 12.7% and 15.5%, respectively. Among patients with NCI standard-risk B-ALL, the outcome was intermediate overall but was poor if MRD was ≥1% on day 19 or MRD was detectable at any level on day 46. Our results indicate that the clinical impact of MRD on treatment outcome in childhood ALL varies considerably according to leukemia subtype and time of measurement.

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