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

The Children's Cancer Group (CCG) found that children with moderate risk ac ute lymphoblastic leukemia (ALL) had an improved 5-year event-free survival (EFS) rate when treated with therapy that included a doubled delayed inten sification (DDI) vs a single DI (SDI) phase. Because of increased toxicity with DDI, it is important to determine whether subgroups of children with A LL 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 impa ct of TEL-AML1 status and ploidy on treatment outcome in a cohort of 75 chi ldren with standard risk ALL treated at our institution between 1983 and 19 93 with SDI therapy. TEL-AML1 fusion was present in 19/43 (44%) evaluable c ases. Fifteen of 56 (27%) evaluable cases were classified as hyperdiploid b ased on a modal chromosome number of greater than or equal to 51 and/or a D NA index of greater than or equal to 1.16. The 7-year EFS was 81% for the 1 9 TEL-AML1-positive patients vs 54% for the 24 TEL-AML1-negative patients ( P = 0.0264). In multivariate analyses, TEL-AML1-positive status was associa ted with a superior EFS (P = 0.02) even when the intial white blood count w as included in the model. Overall survival (OS) at 7 years for TEL-AML1-pos itive 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 treatm ent intensification on specific biologically defined subgroups of children with ALL.