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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Acknowledgements
This work was supported by grants (CA21765, CA36401, and GM115279) from the National Institutes of Health and by the American Lebanese Syrian Associated Charities.
Author contributions
C-HP and DC designed the study, reviewed and interpreted data and wrote the paper; C-HP, SJ, WPB, JTS, RCR, JER, HI, TAG and WHL enrolled patients and revised the manuscript; DP and CC provided statistical expertize, analyses and data interpretation; SCR performed genetic analyses and EC-S minimal residual disease determination. All authors made substantial contributions to the concept, design and conduct of the clinical trial, were involved in the writing and critical revision of the manuscript, and gave final approval of the revision to be submitted.
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Pui, CH., Pei, D., Raimondi, S. et al. Clinical impact of minimal residual disease in children with different subtypes of acute lymphoblastic leukemia treated with Response-Adapted therapy. Leukemia 31, 333–339 (2017). https://doi.org/10.1038/leu.2016.234
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DOI: https://doi.org/10.1038/leu.2016.234
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