title: Favorable outcome in 20-year follow-up of children with very-low-risk ALL and minimal standard therapy, with special reference to TEL-AML1 fusion.
abstract: BACKGROUND
  As the treatment results of childhood ALL have improved, avoidance of late effects has become increasingly important. Identification of favorable prognostic factors helps to achieve this goal.
  
  
  METHODS
  We studied the prognostic value of TEL-AML1 fusion and a risk factor composed of age, white blood cell count (WBC), lymphomatous features, and hemoglobin level (Hb). We also compared outcome between two cohorts; cohort 1 (n=100) diagnosed 1975-1981, and cohort 2 (n=102) 1989-1991. Both cohorts were retrospectively divided in two groups: very-low-risk (WBC <10 x 10(9)/L, age 2 to <10 years, no lymphomatous features, Hb <90 g/L), and non-low-risk (=the remainder). We performed fluorescent in situ hybridization (FISH) of TEL-AML1 fusion of the marrow samples obtained at diagnosis.
  
  
  RESULTS
  The median follow-up is 20 years in cohort 1, and 8 years in cohort 2. In both cohorts, the very-low-risk category comprised one-fourth of the children. TEL-AML1 fusion was more frequent in the very-low-risk (35%) than in the non-low-risk group (17%) (P=0.03). The 8-year event-free survival (EFS) of children with the fusion was better than of those without, 74 vs. 54% (P=0.040). The 8-year EFS in the very-low-risk group was 76% in cohort 1, and 79% in cohort 2 (n.s.). In the non-low-risk groups, EFS was 39 vs. 64% (P=0.02), respectively.
  
  
  CONCLUSIONS
  Our data support the reported association of TEL-AML1 fusion with a favorable outcome although the risk group had a greater impact. These very-long-term follow-up data also indicate that children with very-low-risk ALL (slow disease) had a favorable outcome already in the late 1970s, and may be over treated with the contemporary ALL protocols.
authors.affiliation: Hospital for Children and Adolescents, Helsinki University Central Hospital, Helsinki, Finland. jukka.kanerva@hus.fi
authors.forename: Jukka
authors.initials: J
authors.lastname: Kanerva
authors.forename: Ulla M
authors.initials: UM
authors.lastname: Saarinen-Pihkala
authors.forename: Tarja
authors.initials: T
authors.lastname: Niini
authors.forename: Pekka
authors.initials: P
authors.lastname: Riikonen
authors.forename: Merja
authors.initials: M
authors.lastname: Möttönen
authors.forename: Anne
authors.initials: A
authors.lastname: Mäkipernaa
authors.forename: Toivo T
authors.initials: TT
authors.lastname: Salmi
authors.forename: Kim
authors.initials: K
authors.lastname: Vettenranta
authors.forename: Sakari
authors.initials: S
authors.lastname: Knuutila
mesh_terms: D000293:Adolescent; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D050676:Core Binding Factor Alpha 2 Subunit; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007223:Infant; D008297:Male; D015514:Oncogene Proteins, Fusion / Q000235:genetics*; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000175:diagnosis* / Q000188:drug therapy* / Q000235:genetics; D011379:Prognosis; D012074:Remission Induction; 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; D015514:Oncogene Proteins, Fusion; C102421:TEL-AML1 fusion protein; D000097764:ETS Translocation Variant 6 Protein