Successful Outcomes of Newly Diagnosed T Lymphoblastic Lymphoma: Results From Children's Oncology Group AALL0434

Abstract

Purpose: The Children's Oncology Group (COG) protocol AALL0434 evaluated the safety and efficacy of multi-agent chemotherapy with Capizzi-based methotrexate/pegaspargase (C-MTX) in patients with newly diagnosed pediatric T-cell lymphoblastic lymphoma (T-LL) and gained preliminary data using nelarabine in high-risk patients.

Patients and methods: The trial enrolled 299 patients, age 1-31 years. High-risk (HR) patients had ≥ 1% minimal detectable disease (MDD) in the bone marrow at diagnosis or received prior steroid treatment. Induction failure was defined as failure to achieve a partial response (PR) by the end of the 4-week induction. All patients received the augmented Berlin-Frankfurt-Muenster (ABFM) C-MTX regimen. HR patients were randomly assigned to receive or not receive 6 5-day courses of nelarabine incorporated into ABFM. Patients with induction failure were nonrandomly assigned to ABFM C-MTX plus nelarabine. No patients received prophylactic cranial radiation; however, patients with CNS3 disease (CSF WBC ≥ 5/μL with blasts or cranial nerve palsies, brain/eye involvement, or hypothalamic syndrome) were ineligible.

Results: At end-induction, 98.8% of evaluable participants had at least a PR. The 4-year event-free survival (EFS) and overall survival (OS) were 84.7% ± 2.3% and 89.0% ± 2.0%. The 4-year disease-free survival (DFS) from end-induction was 85.9% ± 2.6%. There was no difference in DFS observed between the HR and standard-risk groups (P = .29) or by treatment regimen (P = .55). Disease stage, tumor response, and MDD at diagnosis did not demonstrate thresholds that resulted in differences in EFS. Nelarabine did not show an advantage for HR patients. CNS relapse occurred in only 4 patients.

Conclusion: COG AALL0434 produced excellent outcomes in one of the largest trials ever conducted for patients with newly diagnosed T-LL. The COG ABFM regimen with C-MTX provided excellent EFS and OS without cranial radiation.

Trial registration: ClinicalTrials.gov NCT00408005.

FIG 1.

CONSORT diagram. Arm A, Capizzi-based methotrexate/pegaspargase, Arm B: Capizzi-based methotrexate/pegaspargase plus nelarabine; T-LL, T-cell non-Hodgkin lymphoma.

FIG 2.

(A) Event-free survival (EFS) and overall survival (OS) curves. Four-year EFS and OS for all patients with T-cell non-Hodgkin lymphoma were 84.7% ± 2.3% and 89.0% ± 2.0% (n = 282), respectively. (B) Overall disease-free survival (DFS) from the end of induction; 4-year DFS was 85.9% ± 2.6% (n = 203).

FIG 3.

(A) Disease-free survival (DFS) for high-risk versus standard-risk groups; 4-year DFS was 85.0% ± 3.4% (n = 121) versus 87.4% ± 4.0% (n = 82; P = .2866). (B) Event-free survival (EFS) for minimal detectable disease (MDD) < 1% versus MDD ≥ 1% detected in the bone marrow at diagnosis: 4-year EFS, 82.4% ± 3.1% (n = 176) versus 89.5% ± 3.3% (n = 97; P = .3084). T-LL, T-cell non-Hodgkin lymphoma.

FIG 4.

Disease-free survival (DFS) for high-risk (HR) patients by randomly assigned arm: no nelarabine (arm A) versus nelarabine (arm B); 4-year DFS was 85.1% ± 4.8% (n = 61) versus 85.0% ± 4.9% (n = 60; P = .8338), respectively.

FIG A1.

Disease-free survival (DFS) comparison of standard-risk (SR) versus high-risk (HR) arm A versus HR arm B.

FIG A2.

Event-free survival (EFS) comparing age groups, < 10 years (n = 123), 10-16 years (n = 104), ≥ 16 years (n = 55; P = .4360).

FIG A3.

Disease-free survival (DFS) comparison of minimal detectable disease (MDD) < 1% versus ≥ 1% for the subset of high-risk (HR) patients is given below.