Prognostic Significance of ETP Phenotype and Minimal Residual Disease in T-ALL: A Children's Oncology Group Study.

The early thymic precursor (ETP) immunophenotype was previously reported to confer poor outcome in T-cell acute lymphoblastic leukemia (T-ALL), requiring prospective confirmation using contemporary risk-adjusted therapy. Between 2009 and 2014, 1,256 newly-diagnosed children and young adults enrolled on COG AALL0434 were assessed for ETP status and minimal residual disease (MRD) using flow cytometry at a central reference laboratory. Subjects were categorized as ETP (n=145; 11.5%), Near-ETP (n=209; 16.7%) or Not-ETP (n=902, 71.8%). Despite higher rates of induction failure for ETP (6.2%) and Near-ETP (6.2%) than Not-ETP (1.2%) (P<0.0001), all 3 groups showed excellent 5-year event-free survival (EFS) and overall survival (OS): ETP (80.4±3.9%; 86.8±3.4%), Near-ETP (81.1±3.3%; 89.6±2.6%) and Not-ETP (85.3±1.4%; 90.0±1.2%) (P=0.1679; P=0.3297). There was no difference in EFS or OS for subjects with day 29 MRD <0.01% vs. 0.01%-0.1%. However, Day 29 MRD ≥0.1% was associated with inferior EFS and OS for patients with Near-ETP and Not-ETP, but not for those with ETP. Subjects with near-ETP and Not-ETP and a presenting WBC ≥200,000/microliter had inferior EFS and OS, but not for 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%; P=0.0001). When considered as a single variable, subjects with all three T-ALL phenotypes had similar outcomes, and subjects with persistent post-induction disease had inferior outcomes regardless of their ETP phenotype. Although ETP status alone is not an independent predictor of outcome, future studies may provide additional insights into the mechanistic basis of resistant disease in stem-like T-ALL. Clinical trial is registered at AALL0434 (NCT00408005).