ASH 2014: T-Cell Acute Lymphoblastic Leukemia Outcomes Excellent, Even for 'Poor-Risk' Group
Outcomes in children with T-cell acute lymphoblastic leukemia (ALL), which has traditionally been considered a poor-prognosis cancer, are better than expected, even for the early thymic precursor (ETP) phenotype, according to investigators from the Children’s Oncology Group (COG) who presented their findings at the Plenary Session of the 56th American Society of Hematology (ASH) Annual Meeting and Exposition (Abstract 1).
“We looked at the overall outcomes among children with and without this form of T-cell ALL and noticed that those with the more aggressive subtypes had the same outcomes as other children with T-cell ALL, despite having a higher incidence of residual disease early after therapy,” said Brent Wood, MD, PhD, of the University of Washington in Seattle.
“T-cell ALL should no longer be considered a poor-risk disease,” he said, based on findings from the largest study ever conducted in this malignancy.
COC AALL0434 Details
Results of previous studies have been mixed regarding the prognostic significance of ETP. “The question has remained,” Dr. Wood said, “should we modify treatment for ETP?”
The phase III COG AALL0434 study addressed this issue in a study of 1,144 children and young adults who had ETP status assessed at diagnosis and who received contemporary therapy. Patients were treated with a standard four-drug induction; postinduction they were randomly assigned to Capizzi methotrexate plus pegaspargase (Oncaspar) vs high-dose methotrexate, then further randomly assigned to nelarabine (Arranon) or no nelarabine. Those with intermediate- and high-risk disease also received cranial irradiation. The relative benefit of these different treatments was not reported at this time.
The researchers determined that 11.3% of patients had the “ETP” phenotype, 17.0% had a “near ETP” phenotype, and 71.6% were “not ETP.”
Minimal Residual Disease
Patients were assessed for the presence of minimal residual disease by flow cytometry on day 8 and day 29 of treatment, which is informative regarding their risk for progression. Minimal residual disease status (< .01%) was found to be different among ETP (18.6%), near-ETP (35.2%) and not-ETP (69.5%) patients. The ETP and near-ETP subsets most commonly fit a high-risk profile. Initial induction treatment was more likely to fail in these groups; rates of induction failure were 7.8%, 6.7%, and 1.1%, respectively.
“However, while minimal residual disease status and induction failure differed, the 5-year event-free and overall survival rates were similar among the groups,” Dr. Wood reported. “Poor ETP status appears to have been eradicated by the therapy used in this trial.”
These “excellent” outcomes were a 5-year event-free survival rate of approximately 85% and overall survival rate of 92% for all subsets. Most events occurred within 12 months of diagnosis and plateaued after 2 years, although events generally occurred earlier for ETP and near-ETP patients than for not-ETP patients.
The study confirmed the utility of minimal residual disease risk stratification. Day 29 minimal residual disease < .01% was predictive of the best overall survival, and peripheral blood assessment on day 8 did not add prognostic information. Patients with minimal residual disease > 1% in the bone marrow had the worse outcomes, Dr. Wood reported.
“At the end of consolidation treatment, many patients who were minimal residual disease–positive early on became minimal residual disease–negative,” he added.
Dr. Wood also said the findings suggest that measuring treatment response by minimal residual disease “is more closely associated with outcomes than pretreatment characteristics, such as ETP subtype.”
The study authors reported no potential conflicts of interest.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
