Prospective Analysis of TEL Gene Rearrangements in Childhood Acute Lymphoblastic Leukemia: A Children's Oncology Group Study

Author:

Rubnitz Jeffrey E.1,Wichlan David1,Devidas Meenakshi1,Shuster Jonathan1,Linda Stephen B.1,Kurtzberg Joanne1,Bell Beverly1,Hunger Stephen P.1,Chauvenet Allen1,Pui Ching-Hon1,Camitta Bruce1,Pullen Jeanette1

Affiliation:

1. From the Department of Oncology, St Jude Children's Research Hospital, Memphis, TN; Statistics and Data Center, Children's Oncology Group & University of Florida, Gainesville, FL; Pediatric Hematology/Oncology, Duke University, Durham, NC; Pediatric Hematology/Oncology, Medical College of Georgia, Augusta, GA; Pediatric Hematology-Oncology, University of Florida, Gainesville, FL; Department of Pediatrics, West Virginia University, Charleston, WV; Department of Pediatric Hematology-Oncology, Midwest...

Abstract

Purpose To prospectively determine the prognostic significance of the TEL-AML1 fusion in children with acute lymphoblastic leukemia (ALL). Patients and Methods TEL gene status was determined for 926 patients with B-precursor ALL enrolled on the Pediatric Oncology Group ALinC 16 trials and patients were observed for a median time of 8 years. Results Rearrangements of the TEL gene were detected in 244 patients (26%). The estimated 5-year event-free survival rate (± SE) for patients with TEL rearrangements was 86% ± 2%, compared with 72% ± 2% for those with germline TEL (P < .0001). TEL rearrangements were associated with a superior outcome among patients with standard-risk ALL, high-risk ALL, and rapid early responses to therapy. In a multivariate analysis that included risk group, sex, and day 15 marrow status, TEL status was an independent predictor of outcome (P = .0002). Conclusion We conclude that TEL gene status should be incorporated into risk classification schemes and suggest that patients who have standard-risk features, the TEL-AML1 fusion, and rapid early responses to therapy, should be treated with antimetabolite-based therapy designed to maintain their high cure rates and avoid late effects.

Publisher

American Society of Clinical Oncology (ASCO)

Subject

Cancer Research,Oncology

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