title: ETV6-RUNX1-positive childhood acute lymphoblastic leukemia: improved outcome with contemporary therapy.
abstract: ETV6-RUNX1 fusion is the most common genetic aberration in childhood acute lymphoblastic leukemia (ALL). To evaluate whether outcomes for this drug-sensitive leukemia are improved by contemporary risk-directed therapy, we studied clinical features, response and adverse events of 168 children with newly diagnosed ETV6-RUNX1-positive ALL on St Jude Total Therapy studies XIIIA (N=36), XIIIB (N=38) and XV (N=94). Results were compared with 494 ETV6-RUNX1-negative B-precursor ALL patients. ETV6-RUNX1 was associated with age 1-9 years, pre-treatment classification as low risk and lower levels of minimal residual disease (MRD) on day 19 of therapy (P<0.001). Event-free survival (EFS) or overall survival (OS) did not differ between patients with or without ETV6-RUNX1 in Total XIIIA or XIIIB. By contrast, in Total XV, patients with ETV6-RUNX1 had significantly better EFS (P=0.04; 5-year estimate, 96.8±2.4% versus 88.3±2.5%) and OS (P=0.04; 98.9±1.4% versus 93.7±1.8%) than those without ETV6-RUNX1. Within the ETV6-RUNX1 group, the only significant prognostic factor associated with higher OS was the treatment protocol Total XV (versus XIIIA or XIIIB) (P=0.01). Thus, the MRD-guided treatment schema including intensive asparaginase and high-dose methotrexate in the Total XV study produced significantly better outcomes than previous regimens and demonstrated that nearly all children with ETV6-RUNX1 ALL can be cured.
authors.affiliation: Department of Oncology, St Jude Children's Research Hospital, Memphis, TN 38105, USA. deepa.bhojwani@stjude.org
authors.forename: D
authors.initials: D
authors.lastname: Bhojwani
authors.forename: D
authors.initials: D
authors.lastname: Pei
authors.forename: J T
authors.initials: JT
authors.lastname: Sandlund
authors.forename: S
authors.initials: S
authors.lastname: Jeha
authors.forename: R C
authors.initials: RC
authors.lastname: Ribeiro
authors.forename: J E
authors.initials: JE
authors.lastname: Rubnitz
authors.forename: S C
authors.initials: SC
authors.lastname: Raimondi
authors.forename: S
authors.initials: S
authors.lastname: Shurtleff
authors.forename: M
authors.initials: M
authors.lastname: Onciu
authors.forename: C
authors.initials: C
authors.lastname: Cheng
authors.forename: E
authors.initials: E
authors.lastname: Coustan-Smith
authors.forename: W P
authors.initials: WP
authors.lastname: Bowman
authors.forename: S C
authors.initials: SC
authors.lastname: Howard
authors.forename: M L
authors.initials: ML
authors.lastname: Metzger
authors.forename: H
authors.initials: H
authors.lastname: Inaba
authors.forename: W
authors.initials: W
authors.lastname: Leung
authors.forename: W E
authors.initials: WE
authors.lastname: Evans
authors.forename: D
authors.initials: D
authors.lastname: Campana
authors.forename: M V
authors.initials: MV
authors.lastname: Relling
authors.forename: C-H
authors.initials: CH
authors.lastname: Pui
mesh_terms: D002648:Child; D002675:Child, Preschool; D050676:Core Binding Factor Alpha 2 Subunit / Q000235:genetics*; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy* / Q000378:metabolism; D011379:Prognosis; D050783:Proto-Oncogene Proteins c-ets / Q000235:genetics*; D012097:Repressor Proteins / Q000235:genetics*; D016896:Treatment Outcome; D000097764:ETS Translocation Variant 6 Protein
chemical_list: D050676:Core Binding Factor Alpha 2 Subunit; D050783:Proto-Oncogene Proteins c-ets; D012097:Repressor Proteins; D000097764:ETS Translocation Variant 6 Protein; C493728:RUNX1 protein, human