title: Excellent prognosis of late relapses of ETV6/RUNX1-positive childhood acute lymphoblastic leukemia: lessons from the FRALLE 93 protocol.
abstract: BACKGROUND
  The prognosis of patients with relapses of ETV6/RUNX1-positive acute lymphoblastic leukemia remains to be evaluated, particularly with regards to the frequency of late relapses. We performed a long-term, follow-up retrospective study to address the outcome of patients with ETV6/RUNX1-positive leukemia relapses.
  
  
  METHODS
  Among the 713 children tested for ETV6/RUNX1 enrolled into the FRALLE 93 protocol, 43 ETV6/RUNX1-positive patients relapsed (19.4%). Most were initially stratified in the low or intermediate risk groups. The median follow-up after relapse was 54.2 months. All but three received second-line salvage therapy and 16 underwent allogeneic transplantation.
  
  
  RESULTS
  ETV6/RUNX1 had a strong effect on overall survival after relapse (3-year survival= 64.7% for positive cases versus 46.5% for negative cases) (P=0.007). The 5-year cumulative incidence of relapse was 19.4% and testes were more frequently involved in ETV6/RUNX1-positive relapses (P=0.04). In 81.4% of cases the relapses were late, early combined or isolated extramedullary relapses. The 5-year survival rate of patients with ETV6-RUNX1-positive acute lymphoblastic leukemia relapses reached 80.8% when the relapse occurred after 36 months (versus 31.2% when the relapse occurred earlier). In univariate analysis, female gender was associated with a poor survival, whereas site of relapse, age at diagnosis, leukocytosis and consolidation strategy had no effect. In multivariate analysis, only the duration of first remission remained associated with outcome.
  
  
  CONCLUSIONS
  We found an excellent outcome for patients with ETV6/RUNX1-positive leukemia relapses that occurred more than 36 months after diagnosis. The duration of first complete remission may, therefore, be a guide to define the treatment strategy for patients with relapsed ETV6/RUNX1- positive leukemia.
authors.affiliation: Department of Pediatric Hematology/Oncology, University Hospital of Rennes, France. virginie.gandemer@chu-rennes.fr
authors.forename: Virginie
authors.initials: V
authors.lastname: Gandemer
authors.forename: Sylvie
authors.initials: S
authors.lastname: Chevret
authors.forename: Arnaud
authors.initials: A
authors.lastname: Petit
authors.forename: Christiane
authors.initials: C
authors.lastname: Vermylen
authors.forename: Thierry
authors.initials: T
authors.lastname: Leblanc
authors.forename: Gérard
authors.initials: G
authors.lastname: Michel
authors.forename: Claudine
authors.initials: C
authors.lastname: Schmitt
authors.forename: Odile
authors.initials: O
authors.lastname: Lejars
authors.forename: Pascale
authors.initials: P
authors.lastname: Schneider
authors.forename: François
authors.initials: F
authors.lastname: Demeocq
authors.forename: Brigitte
authors.initials: B
authors.lastname: Bader-Meunier
authors.forename: Françoise
authors.initials: F
authors.lastname: Bernaudin
authors.forename: Yves
authors.initials: Y
authors.lastname: Perel
authors.forename: Marie-Françoise
authors.initials: MF
authors.lastname: Auclerc
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Cayuela
authors.forename: Guy
authors.initials: G
authors.lastname: Leverger
authors.forename: André
authors.initials: A
authors.lastname: Baruchel
mesh_terms: D000293:Adolescent; D000328:Adult; D018943:Anthracyclines / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D001215:Asparaginase / Q000008:administration & dosage; D002648:Child; D002675:Child, Preschool; D050676:Core Binding Factor Alpha 2 Subunit; D003348:Cortisone / Q000008:administration & dosage; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D008297:Male; D015514:Oncogene Proteins, Fusion; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000401:mortality* / Q000628:therapy*; D012008:Recurrence; D012189:Retrospective Studies; D012307:Risk Factors; D015996:Survival Rate; D014184:Transplantation, Homologous; D014750:Vincristine / Q000008:administration & dosage; D000097764:ETS Translocation Variant 6 Protein
chemical_list: D018943:Anthracyclines; D001215:Asparaginase; D050676:Core Binding Factor Alpha 2 Subunit; D003348:Cortisone; D015514:Oncogene Proteins, Fusion; D014750:Vincristine; C102421:TEL-AML1 fusion protein; D000097764:ETS Translocation Variant 6 Protein