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

Abstract

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.

Graphical abstract

Figure 1.

CONSORT diagram of participant allocation. alloHSCT, allogeneic hematopoietic stem-cell transplantation; MRD, minimal residual disease; T-ALL, T-cell acute lymphoblastic leukemia; T-NHL, T-cell non-Hodgkin lymphoma.

Figure 2.

EFS, OS, and cumulative incidence of relapse (CIR) as per ETP status. (A) Five-year EFS rates were 80.4% ± 3.9% for ETP, 81.1% ± 3.3% for near-ETP, and 85.3% ± 1.4% for non-ETP (P = .1679). (B) Five-year OS rates were 86.8% ± 3.4% for ETP, 89.6% ± 2.6% for near-ETP, and 90.0% ± 1.2% for non-ETP (P = .3297). (C) Five-year CIR rates were 6.7% ± 2.2% for ETP, 10.1% ± 2.1% for near-ETP, and 8.8% ± 1.0% for non-ETP (P = .5411). (D) Five-year cumulative incidence of remission death rates were 5.3% ± 2.0% for ETP, 1.0% ± 0.7% for near-ETP, and 3.2% ± 0.6% for non-ETP (P = .0959).

Figure 3.

EFS and OS based on the MRD status at the EOI. (A) Five-year EFS was 73.1% ± 2.3% for patients with EOI MRD ≥0.1% and 90.6% ± 1.1% for patients with an EOI MRD <0.1% (P < .0001). (B) Five-year OS was 84.3% ± 1.9% for patients with an EOI MRD ≥0.1% and 93.4% ± 1.0% for patients with EOI MRD <0.1% (P < .0001).

Figure 4.

CIR based on MRD status at EOI in patients with ETP, near-ETP, and non-ETP. (A) Five-year CIR rates for patients with ETP were 6.3% ± 2.7% for MRD <0.1% and 11.0% ± 3.0% for MRD ≥0.1%. (P = .9328). (B) Five-year CIR rates for patients with near-ETP were 6.3% ± 2.7% for MRD <0.1% and 11.0% ± 3.0% for MRD ≥0.1%. (P = .2749). (C) Five-year CIR rates for patients with non-ETP were 5.4% ± 0.9% for MRD <0.1% and 20.5% ± 2.9% for MRD ≥0.1%. (P < .0001).

Figure 5.

Disease-free survival (DFS) rates based on EOC MRD in patients with ETP, near-ETP, and non-ETP with a day-29 MRD ≥1%. Five-year DFS for (A) total cohort: 69.6% ± 8.6% for patients with EOC MRD ≥0.01% and 88.7% ± 3.4% for patients with EOC MRD <0.01% (P = .0055); (B) ETP: 88.9% ± 10.5% for EOC MRD ≥0.01% and 90.4% ± 7.2% for EOC MRD <0.01% (P = .7642); (C) near-ETP: 75.0% ± 15.3% for EOC MRD ≥0.01% and 78.6% ± 10.5% for EOC MRD <0.01% (P = .7406); and (D) non-ETP: 58.2% ± 18.8% for EOC MRD ≥0.01% and 89.3% ± 5.0% for EOC MRD <0.01% (P = .0042).