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Early thymic precursor immunophenotype does not affect T-cell ALL outcomes
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SAN FRANCISCO — Children with T-cell acute lymphoblastic leukemia achieved favorable 5-year EFS and OS outcomes regardless of whether they expressed the early thymic precursor immunophenotype, according to results of a phase 3 study presented at the ASH Annual Meeting and Exposition.
The presence of minimal residual disease in the bone marrow at day 29 after induction therapy or at the end of consolidation therapy were both associated with a poorer outcome; however, minimal residual disease in the peripheral blood at day 8 did not provide additional prognostic utility, results also showed.
“We can say that T-cell ALL, treated with the therapy used on [this study], has an excellent outcome,” Brent L. Wood, MD, PhD, of the departments of laboratory medicine and pathology at the University of Washington, said during his presentation in the plenary session. “T-cell ALL, at least in the pediatric population, should no longer be considered a poor-risk disease.”
Wood and colleagues evaluated data from 1,144 children with T-cell ALL to confirm whether the early thymic precursor (ETP) immunophenotype was associated with poor outcomes.
A majority of the patients did not have an ETP-like immunophenotype (n=819; 71.6%) — or were “not-ETP” — whereas 130 patients (11.3%) had the ETP immunophenotype. Researchers classified the other 195 patients (17%) as “near-ETP” because they met ETP criteria except for elevated CD5.
All patients received a standard four-drug induction regimen including prednisone.
After day 29, patients underwent risk stratification based in part on bone marrow minimal residual disease levels ˂0.1% (low risk), ˂1% (intermediate risk) and ˃1% (high risk).
Fewer patients (18.6%) with the ETP immunophenotype had minimal residual disease levels ˂0.01% at day 29 compared with patients who were near-ETP (35.2%) or not-ETP (69.5%).
Induction failure — defined as ˃25% blasts by morphology at the end of induction therapy — also occurred in more patients with the ETP (7.8%) or near-ETP (6.7%) immunophenotype compared with patients who were not-ETP (1.1%; P˂.0001).
Researchers then randomly assigned patients with intermediate- or high-risk disease to therapy with or without six 5-day courses of therapy with nelarabine (Arranon, GlaxoSmithKline) during delayed intensification and maintenance therapy. Intermediate- and high-risk patients all underwent cranial irradiation according to their degree of central nervous system involvement (CNS 1 or CNS 2 disease, 1,200 centigray [cGy]; CNS 3 disease, 1,800 cGy).
All patients were also randomly assigned to interim maintenance with Capizzi methotrexate plus pegasparaginase or high-dose methotrexate.
An analysis from the randomizations is ongoing as researchers wait for the data to mature, Wood said.
Overall, patients had favorable 4-year EFS rates whether they had the ETP (82.9%), near-ETP (84.7%) or not-ETP (86.9%) immunophenotype. Four-year OS rates also were similar among patients who were ETP (91%), near-ETP (92.6%) and not-ETP (91.5%).
“Despite the differences in minimal residual disease and induction failure, the 5-year EFS and OS were essentially the same between these groups,” Wood said during a press briefing. “After the first 1 to 2 years, there were essentially no events on this trial, and no difference at all between any of the ETP subsets. The poor ETP status that had been previously prescribed to this disease appears to have been eradicated by the therapy used on this trial.”
More patients who were near-ETP or not-ETP had baseline white blood cell counts ˃200,000/mcL than patients with ETP (30% vs. 9.6%; P˂.0001). White blood cell counts ˃200,000/mcL were associated with inferior EFS and OS outcomes for patients who were near-ETP (P=.0003), and inferior EFS outcomes for patients who were not-ETP (P=.012).
Patients in the overall cohort with minimal residual disease ˃.01% had a poorer EFS (76.3% vs. 89%; P=.0001) and OS (86.6% vs. 93.8%; P=.0008). This association persisted in patients who were not-ETP for both EFS (76.6% vs. 90.8%; P=.0001) and OS (84.3% vs. 94%; P=.0064) and for patients who were near-ETP for EFS (80.2% vs. 94%; P=.0073). The presence of minimal residual disease >0.1% at the end of consolidation was associated with a very poor outcome in all three groups of patients.
Minimal residual disease ˃.01% in the peripheral blood at day 8 was associated with inferior EFS (80.3% vs. 92%; P=.017) but not OS. This information also lost significance when researchers focused on patients with day-29 minimal residual disease ˂.01%.
“T-cell ALL treated with the regimen that we used has an excellent outcome, and there really was no difference in outcome that we were able to identify between the ETP subsets,” Wood said. “The study also demonstrates the utility of post therapeutic monitoring using minimal residual disease detection that was able to stratify patients in terms of risk at both the end of induction at day 29, as well as at the end of consolidation.”
For more information:
Wood BL. Abstract #1. Presented at: ASH Annual Meeting and Exposition; Dec. 6-9, 2014; San Francisco.
Disclosure: The researchers report no relevant financial disclosures.
– by Alexandra Todak