Case-control study suggests a favorable impact of TEL rearrangement in patients with B-lineage acute lymphoblastic leukemia treated with antimetabolite-based therapy : A Pediatric Oncology Group study

• Published in: Blood 1997-02, Vol.89 (4), p.1143-1146
• Main Authors: RUBNITZ, J. E, SHUSTER, J. J, LAND, V. J, LINK, M. P, PULLEN, D. J, CAMITTA, B. M, PUI, C.-H, DOWNING, J. R, BEHM, F. G
• Format: Article
• Language: English
• Subjects: Antimetabolites, Antineoplastic - therapeutic use; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Asparaginase - administration & dosage; Biological and medical sciences; Biomarkers, Tumor - genetics; Blotting, Southern; Burkitt Lymphoma - drug therapy; Burkitt Lymphoma - genetics; Burkitt Lymphoma - mortality; Case-Control Studies; Child; Chromosomes, Human, Pair 12 - genetics; Chromosomes, Human, Pair 12 - ultrastructure; Chromosomes, Human, Pair 21 - genetics; Chromosomes, Human, Pair 21 - ultrastructure; Core Binding Factor Alpha 2 Subunit; Cytarabine - administration & dosage; DNA, Neoplasm - genetics; Female; Hematologic and hematopoietic diseases; Humans; Hydrocortisone - administration & dosage; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; Male; Medical sciences; Mercaptopurine - administration & dosage; Methotrexate - administration & dosage; Neoplasm Proteins - genetics; Oncogene Proteins, Fusion; Prednisone - administration & dosage; Prognosis; Remission Induction; Retrospective Studies; Single-Blind Method; Translocation, Genetic; Treatment Outcome; Vincristine - administration & dosage
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood.v89.4.1143

TEL gene rearrangement is the most common genetic lesion in pediatric acute lymphoblastic leukemia (ALL), occurring in about 25% of B-lineage cases. We previously showed that, among patients treated on St Jude protocols, TEL rearrangement independently conferred an excellent prognosis. To extend these results to patients treated with antimetabolite-based therapy, we performed Southern blot analysis to determine the TEL gene status of 104 cases of B-lineage ALL treated on Pediatric Oncology Group 8602, matched on age, gender, and leukocyte count. There were 52 failures among the 77 patients with germline TEL, compared with only 8 failures among 27 patients in the rearranged group. Based on a two-sided logistic regression analysis, stratified for age (subdivided at 10 years), leukocyte count (subdivided at 50,000), and gender, the estimated odds of failing by 4 years in the germline TEL group is 5.4 times that of the rearranged TEL group, with 95% confidence from 1.9 to 15.6, two-sided P = .0009. Thus, the presence of a rearranged TEL gene is also associated with an improved survival among patients treated with antimetabolite-based therapy. Our results indicate that all newly diagnosed ALL patients should be screened for TEL gene rearrangements and suggest that these patients are candidates for less intensive therapy.