Early Thymic Precursor Found to Lack Significance in Children with T-Lymphoblastic Leukemia (T-ALL)

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The largest study of T-ALL ever conducted demonstrated “an excellent outcome” with standard four-drug induction.
The largest study of T-ALL ever conducted demonstrated “an excellent outcome” with standard four-drug induction.

SAN FRANCISCO—The largest study of T-lymphoblastic leukemia (T-ALL) ever conducted demonstrated “an excellent outcome” for patients treated with a standard four-drug induction and subsequent treatment guided by risk stratification investigators reported (Abstract 1) at the 56th American Society of Hematology (ASH) Annual Meeting and Exposition.

Additionally, the phase 3 Children's Oncology Group Study AALL0434 found the early thymic precursor (ETP) immunophenotype to lack significance, with patients with ETP having an identical outcome to those without ETP, and validated the prognostic value of end-induction minimal residual disease (MRD), said Brent L. Wood, MD, PhD, of the Departments of Laboratory Medicine and Pathology at the University of Washington in Seattle, WA.

“Treatment response is more important than subtype,” Dr. Wood added.

Between January 2007 and July 2014, the study enrolled 1,895 patients who were age 1 to 30 years. ETP status was assessed at diagnosis and MRD via flow cytometry. A total of 1,144 patients with T-ALL had complete MRD and ETP data: ETP (11.3%), Near-ETP (ETP with elevated CD5; 17%), or Not-ETP (71.6%).

Patients received the standard four-drug induction of prednisone for 28 days, vincristine weekly for 4 weeks, pegaspargase on day 4, and daunorubicin weekly for 4 weeks. Investigators measured MRD response at day 29 and stratified patients by low-, intermediate-, and high-risk of relapse (low risk <0.1% MRD, 9.3% of patients; intermediate risk <1.0% MRD, 68.2% of patients; and high risk ≥1% MRD, 19.1% of patients).

Postinduction therapy 2x2 randomization included Capizzi regimen methotrexate plus pegaspargase versus high-dose methotrexate randomization; intermediate- and high-risk patients were randomly assigned to six 5-day cycles of nelarabine or placebo and received cranial irradiation.

Patients with Not-ETP had the lowest rate of induction failure, 1.1%, compared with 7.8% with ETP and 6.7% for Near-ETP, both of which were significantly higher (P<0.0001). Despite this difference, all three groups showed “excellent” 5-year event-free survival (EFS) and overall survival (OS) rates that were not statistically different: for ETP, EFS was 87.0% and OS, 93.0%; Near-ETP was 84.4% and 91.6%, and Not-ETP, 86.9% and 92.0%, respectively.

“In all three groups, most events occurred within 12 months from diagnosis and plateaued after 2 years, although events generally occurred earlier for [patients with] ETP and Near-ETP than Not-ETP,” Dr. Wood said. “There were no relapses in ETP patients later than 12 months post-diagnosis.”

White blood cell count greater than 200,000/microliter was associated with inferior outcome in patients with non-ETP T-ALL. Day 29 MRD identified poor-risk patients, as did end of consolidation MRD greater than or equal to 0.1%. Day 8 MRD assessed in the peripheral blood “does not provide unique prognostic information,” he said.

Although the outcomes of the post-induction randomizations are still blinded, based on the results to date, T-ALL “should no longer be considered a poor-risk disease,” Dr. Wood concluded.

  1. Wood, Brent L. MD, PhD. "1 T-Lymphoblastic Leukemia (T-ALL) Shows Excellent Outcome, Lack of Significance of the Early Thymic Precursor (ETP) Immunophenotype, and Validation of the Prognostic Value of End-Induction Minimal Residual Disease (MRD) in Children's Oncology Group (COG) Study AALL0434." ASH 2014. Oral Presentation. December 7, 2014.

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