Children with T-cell acute lymphoblastic leukemia (T-ALL) have excellent outcomes after treatment with AALL0434, a standard 4-drug induction therapy. End-induction minimal residual disease (MRD) was more important in predicting treatment response than the early thymic precursor (ETP) immunophenotype, according to the results from the Combination Chemotherapy in Treating Young Patients With Newly Diagnosed T-Cell Acute Lymphoblastic Leukemia or T-Cell Lymphoblastic Lymphoma [NCT00408005] trial presented by Brent L. Wood, MD, PhD, University of Washington, Seattle, Washington, USA.

The phase 3 trial enrolled 1895 patients (aged 1 to 30 years) with T-ALL. The prognostic impact of MRD was measured by 8- and 9-color flow cytometry in the peripheral blood at day 8 and in bone marrow at end of induction (day 29), and end of consolidation was compared with prognostic ability of ETP status assessed at diagnosis. AALL0434 therapy consisted of prednisone for 28 days, vincristine weekly for 4 weeks, pegaspargase on day 4, and daunorubicin weekly for 4 weeks. An initial subset of cases confirmed that near ETP meets ETP criteria except for elevated CD5 B-cells.

An initial subset of thymocytes, ETP, retains stem-cell-like features, as reviewed by Coustan-Smith and colleagues [Lancet Oncol. 2009], who helped to define criteria for standardization in the AALL0434 study. The presence of ETP cells in patients with T-ALL confers a poor prognosis with use of standard intensive chemotherapy. Thus, early recognition is believed essential for the development of an effective clinical management strategy.

In the AALL0434 study, ETP, near ETP, and not ETP were noted in 11.3%, 17.0%, and 71.6% of patients, respectively. At day 29, MRD < 0.01% was significantly more evident in the group without ETP compared with those with ETP or near ETP (P < .0001). Induction failure, defined as > 35% blasts by morphology in bone marrow at day 29, was proportionally more evident in the group with ETP (45.5%) and near ETP (48.1%) compared with not ETP (11.2%). However, percentage outcomes for 4-year event-free survival (EFS) and overall survival (OS) were similar regardless of the subtype (Table 1).

MRD is an important predictor of relapse in children with T-ALL. An MRD day 29 risk < 0.1% was considered low risk, < 1.0% intermediate, and ≥ 1.0% high. An MRD D29 < 0.01% to < 10.0% was associated with a higher probability of EFS and OS compared with an MRD D29 ≥ 10%. EFS and OS were similar regardless of the ETP subtype.

Patients with MRD ≥ 0.1% at the end of consolidation fared poorly (P < .0001) compared with those with MRD < 0.1%. Early (day 8) blast clearance from peripheral blood was associated with significantly better outcomes (P < .02). However, it did not identify poor risk among the < 0.01% MRD D29 subset. In addition, a white blood cell count ≥ 200 000 was associated with worse outcome with near ETP (P = .003) and not ETP (P = .012), whereas frequency was low with ETP. Off-protocol therapy events at the end of induction and during consolidation appeared similar among the subtypes. No preferential attrition (15% to 20% on Children’s Oncology Group ALL trials) by MRD stratification at the end of induction was seen among ETP subtypes.