T-lymphoblastic leukemia (T-ALL) should no longer be considered a poor-risk disease in the pediatric population, according to data presented at ASH.
SAN FRANCISCO-T-lymphoblastic leukemia (T-ALL) should no longer be considered a poor-risk disease in the pediatric population, according to data presented by Brent L. Wood, MD, PhD, of the University of Washington, Seattle, during the plenary session of the 2014 American Society of Hematology (ASH) Annual Meeting.
Wood presented results of the Children’s Oncology Group AALL0434 trial that indicated that all patients with T-ALL in the trial had excellent outcomes, even those with early thymic precursor (ETP) immunophenotype, a protein signature of T-ALL previously associated with poor outcomes.
In fact, study results found that although patients with ETP T-ALL had a higher incidence of residual disease early after therapy, overall outcomes revealed that children with or without ETP had similar overall survival.
AALL0434 was a phase III study of patients aged 1 to 30 years with T-ALL. All patients underwent standard four-drug induction with prednisone, VCR, pegaspargase, and daunorubicin. Response was assessed at day 29 and the researchers then randomly assigned patients classified as intermediate- or high-risk to Capizzi methotrexate plus pegaspargase or high-dose methotrexate with or without nelarabine. Minimal residual disease (MRD) was assessed by flow cytometry in peripheral blood of day 8 and bone marrow on day 29.
The study included 1,144 patients, all of whom were categorized as ETP (n = 130), near ETP (n = 195), or not-ETP (n = 819) using flow cytometry.
At induction end, patients classified as ETP (7.8%) or near-ETP (6.7%) had significantly higher rates of induction failure compared with the not-ETP patients (1.1%; P < .0001). In addition, there were lower rates of MRD less than 0.01% in patients with ETP (18.6%) and near ETP (35.2%) than not-ETP (69.5%). Despite that difference, survival outcomes were similar between the groups.
The 5-year event-free survival was 87% for ETP patients, 84.4% for near-ETP, and 86.9% for not-ETP patients. Rates of 5-year overall survival were also similar between the three groups (93% vs 91.6% vs 92%).
“Day 8 blast clearance from the peripheral blood was associated with better outcomes, as well as with the achievement of negative MRD status at the end of induction, but does not identify a poor-risk subset among those who achieve a negative MRD status,” Wood said.
In addition, although white count at presentation has been said not to be a risk factor associated with T-ALL, results from this study indicate that a white count of greater than or equal to 200,000 was associated with an inferior outcome in comparison to patients whose white count was below 200,000.
“This was particularly a feature of the near ETP and not-ETP subtypes where about 30% of the patients showed this high white count and was not really a feature of the ETP subtype,” Wood said.