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; W. P. 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

doi: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

C. H. Pui, D. Pei, S. C. Raimondi, E. Coustan-Smith, S. Jeha, C. Cheng, W. P. 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

Pediatrics

Research output: Contribution to journal › Article › peer-review

108 Scopus citations

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 language	English
Pages (from-to)	333-339
Number of pages	7
Journal	Leukemia
Volume	31
Issue number	2
DOIs	https://doi.org/10.1038/leu.2016.234
State	Published - 1 Feb 2017

Access to Document

10.1038/leu.2016.234

Cite this

Pui, C. H., Pei, D., Raimondi, S. C., Coustan-Smith, E., Jeha, S., Cheng, C., Bowman, W. P., 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. (2017). Clinical impact of minimal residual disease in children with different subtypes of acute lymphoblastic leukemia treated with Response-Adapted therapy. Leukemia, 31(2), 333-339. https://doi.org/10.1038/leu.2016.234

@article{65ba14b6970a43ccbeac3a069898e9d5,

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

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.",

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

note = "Funding Information: This work was supported by grants (CA21765, CA36401, and GM115279) from the National Institutes of Health and by the American Lebanese Syrian Associated Charities. Publisher Copyright: {\textcopyright} 2017 Macmillan Publishers Limited, part of Springer Nature.",

year = "2017",

month = feb,

day = "1",

doi = "10.1038/leu.2016.234",

language = "English",

volume = "31",

pages = "333--339",

journal = "Leukemia",

issn = "0887-6924",

publisher = "Nature Publishing Group",

number = "2",

}

Pui, CH, Pei, D, Raimondi, SC, Coustan-Smith, E, Jeha, S, Cheng, C, Bowman, WP, 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

TY - JOUR

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, W. P.

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.

N1 - Funding Information: This work was supported by grants (CA21765, CA36401, and GM115279) from the National Institutes of Health and by the American Lebanese Syrian Associated Charities. Publisher Copyright: © 2017 Macmillan Publishers Limited, part of Springer Nature.

PY - 2017/2/1

Y1 - 2017/2/1

N2 - 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.

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.

UR - http://www.scopus.com/inward/record.url?scp=84987600837&partnerID=8YFLogxK

U2 - 10.1038/leu.2016.234

DO - 10.1038/leu.2016.234

M3 - Article

C2 - 27560110

AN - SCOPUS:84987600837

SN - 0887-6924

VL - 31

SP - 333

EP - 339

JO - Leukemia

JF - Leukemia

IS - 2

ER -

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

Abstract

Access to Document

Other files and links

Fingerprint

Cite this