title: TEL-AML1 fusion identifies a subset of children with standard risk acute lymphoblastic leukemia who have an excellent prognosis when treated with therapy that includes a single delayed intensification.
abstract: The Children's Cancer Group (CCG) found that children with moderate risk acute lymphoblastic leukemia (ALL) had an improved 5-year event-free survival (EFS) rate when treated with therapy that included a doubled delayed intensification (DDI) vs a single DI (SDI) phase. Because of increased toxicity with DDI, it is important to determine whether subgroups of children with ALL can be identified who have excellent outcomes with SDI therapy. TEL-AML1 fusion and hyperdiploid DNA content are present in the leukemic blasts of significant proportions of children with ALL and have been associated with an excellent prognosis. In this study, we retrospectively examined the impact of TEL-AML1 status and ploidy on treatment outcome in a cohort of 75 children with standard risk ALL treated at our institution between 1983 and 1993 with SDI therapy. TEL-AML1 fusion was present in 19/43 (44%) evaluable cases. Fifteen of 56 (27%) evaluable cases were classified as hyperdiploid based on a modal chromosome number of >/=51 and/or a DNA index of >/=1.16. The 7-year EFS was 81% for the 19 TEL-AML1-positive patients vs 54% for the 24 TEL-AML1-negative patients (P = 0.0264). In multivariate analyses, TEL-AML1-positive status was associated with a superior EFS (P = 0.02) even when the intial white blood count was included in the model. Overall survival (OS) at 7 years for TEL-AML1-positive patients was 100% vs 83% for TEL-AML1-negative patients (P = 0.0677). There were no differences in 7-year EFS or OS based on ploidy comparisons. These results underscore the need to examine closely the effects of treatment intensification on specific biologically defined subgroups of children with ALL.
authors.affiliation: Department of Pediatrics, University of Colorado School of Medicine, USA.
authors.forename: K
authors.initials: K
authors.lastname: Maloney
authors.forename: L
authors.initials: L
authors.lastname: McGavran
authors.forename: J
authors.initials: J
authors.lastname: Murphy
authors.forename: L
authors.initials: L
authors.lastname: Odom
authors.forename: L
authors.initials: L
authors.lastname: Stork
authors.forename: Q
authors.initials: Q
authors.lastname: Wei
authors.forename: S
authors.initials: S
authors.lastname: Hunger
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D001772:Blood Cell Count; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D050676:Core Binding Factor Alpha 2 Subunit; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007223:Infant; D015999:Multivariate Analysis; D009363:Neoplasm Proteins / Q000235:genetics*; D015514:Oncogene Proteins, Fusion; D011003:Ploidies; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000175:diagnosis* / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality; D011379:Prognosis; D012189:Retrospective Studies; D012307:Risk Factors; D015996:Survival Rate; D016896:Treatment Outcome; D000097764:ETS Translocation Variant 6 Protein
chemical_list: D000970:Antineoplastic Agents; D050676:Core Binding Factor Alpha 2 Subunit; D009363:Neoplasm Proteins; D015514:Oncogene Proteins, Fusion; C102421:TEL-AML1 fusion protein; D000097764:ETS Translocation Variant 6 Protein