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

Jeffrey E. Rubnitz, David Wichlan, Meenakshi Devidas, Jonathan Shuster, Stephen B. Linda, Joanne Kurtzberg, Beverly Bell, Stephen P. Hunger, Allen Chauvenet, Ching-Hon Pui, Bruce Camitta, Jeanette Pullen

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 Children's Cancer Center, Milwaukee, WI; and the Department of Pediatric Hematology-Oncology, University of Mississippi, Jackson, MS

Corresponding author: Jeffrey E. Rubnitz, MD, PhD, Department of Oncology, Mail Stop 260, St Jude Children's Research Hospital, 332 N Lauderdale St, Memphis, TN 38105-2794; e-mail: jeffrey.rubnitz{at}stjude.org

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.

Supported in part by the St Jude Children's Research Hospital Cancer Center support grant P30 CA-21765; the Pediatric Oncology Group (POG) grant CA 30969; the POG Statistical Office grant U10 CA-29139; the Children's Oncology Group (COG) grant CA 98543; grant R21 CA-73983 from the National Institutes of Health; and by the American Lebanese Syrian Associated Charities. A complete listing of grant support for research conducted by Children's Cancer Group and POG before initiation of the COG grant in 2003 is available online at: http://www.childrensoncologygroup.org/admin/grantinfo.htm.

Authors’ disclosures of potential conflicts of interest and author contributions are found at the end of this article.