Prognostic significance of ETP phenotype and minimal residual disease in T-ALL: a Children’s Oncology Group study

•Children with T-ALL treated in the COG AALL0434 had excellent EFS and OS independent of the ETP status.•Persistent leukemia after induction was a strong predictor of inferior outcome in patients with non-ETP T-ALL. [Display omitted] The early thymic precursor (ETP) immunophenotype was previously re...

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Published inBlood Vol. 142; no. 24; pp. 2069 - 2078
Main Authors Wood, Brent L., Devidas, Meenakshi, Summers, Ryan J., Chen, Zhiguo, Asselin, Barbara, Rabin, Karen R., Zweidler-McKay, Patrick A., Winick, Naomi J., Borowitz, Michael J., Carroll, William L., Raetz, Elizabeth A., Loh, Mignon L., Hunger, Stephen P., Dunsmore, Kimberly P., Teachey, David T., Winter, Stuart S.
Format Journal Article
LanguageEnglish
Published United States Elsevier Inc 14.12.2023
The American Society of Hematology
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Summary:•Children with T-ALL treated in the COG AALL0434 had excellent EFS and OS independent of the ETP status.•Persistent leukemia after induction was a strong predictor of inferior outcome in patients with non-ETP T-ALL. [Display omitted] The early thymic precursor (ETP) immunophenotype was previously reported to confer poor outcome in T-cell acute lymphoblastic leukemia (T-ALL). Between 2009 and 2014, 1256 newly diagnosed children and young adults enrolled in Children’s Oncology Group (COG) AALL0434 were assessed for ETP status and minimal residual disease (MRD) using flow cytometry at a central reference laboratory. The subject phenotypes were categorized as ETP (n = 145; 11.5%), near-ETP (n = 209; 16.7%), or non-ETP (n = 902; 71.8%). Despite higher rates of induction failure for ETP (6.2%) and near-ETP (6.2%) than non-ETP (1.2%; P < .0001), all 3 groups showed excellent 5-year event-free survival (EFS) and overall survival (OS): ETP (80.4% ± 3.9% and 86.8 ± 3.4%, respectively), near-ETP (81.1% ± 3.3% and 89.6% ± 2.6%, respectively), and non-ETP (85.3% ± 1.4% and 90.0% ± 1.2%, respectively; P = .1679 and P = .3297, respectively). There was no difference in EFS or OS for subjects with a day-29 MRD <0.01% vs 0.01% to 0.1%. However, day-29 MRD ≥0.1% was associated with inferior EFS and OS for patients with near-ETP and non-ETP, but not for those with ETP. For subjects with day-29 MRD ≥1%, end-consolidation MRD ≥0.01% was a striking predictor of inferior EFS (80.9% ± 4.1% vs 52.4% ± 8.1%, respectively; P = .0001). When considered as a single variable, subjects with all 3 T-ALL phenotypes had similar outcomes and subjects with persistent postinduction disease had inferior outcomes, regardless of their ETP phenotype. This clinical trial was registered at AALL0434 as #NCT00408005.
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ISSN:0006-4971
1528-0020
DOI:10.1182/blood.2023020678