title: FLT3 mutation status is a predictor of early death in pediatric acute promyelocytic leukemia: a report from the Children's Oncology Group.
abstract: BACKGROUND
  FLT3 mutations (FLT3/Mut) are prevalent in de novo AML and are associated with early relapse. The prevalence and prognostic significance of FLT3/Mut have not been well defined in childhood acute promyelocytic leukemia (APL).
  
  
  METHODS
  Diagnostic specimens from 104 pediatric APL patients were screened for FLT3/Mut (FLT3/ITD or FLT3/ALM). FLT3/Mut status was correlated with disease characteristics and clinical outcome for patients treated on CALGB C9710 (n = 50).
  
  
  RESULTS
  Forty-two of the 104 patients (40%) had either FLT3/ITD (n = 28, 27%) or FLT3/ALM (n = 15, 14%). Median diagnostic WBC count was 23,400 cells/µl vs. 3,600 cells/µl for those with and without FLT3/Mut (P < 0.001), and similar results for the cohort of 50 patients treated on C9710 (P < 0.001). In patients treated on C9710, presence of a FLT3 mutation was highly correlated with diagnostic WBC count >10,000 (P = 0.004), microgranular variant histology (P = 0.035), and a lower remission rate (P = 0.009). In patients who received ATRA (C9710 or CCG-2911, n = 8), those with FLT3/Mut had an induction death rate of 30% (7/23) compared to 3% (1/35) in FLT3/WT patients (P = 0.005). In patients with high WBC counts (>10,000), those with FLT3/Mut had a significantly higher risk of induction death versus FLT3/WT patients (47% vs. 0%, P = 0.05). FLT3/Mut was not associated with adverse outcome in those who survived induction therapy.
  
  
  CONCLUSIONS
  FLT3/Mut are prevalent in pediatric APL and are associated with high WBC count and increased induction death. This study provides further evidence for testing APL patients for FLT3/Mut and the potential role for FLT3 inhibitors in this disease.
authors.affiliation: Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA. mkutny@peds.uab.edu
authors.forename: Matthew A
authors.initials: MA
authors.lastname: Kutny
authors.forename: Barry K
authors.initials: BK
authors.lastname: Moser
authors.forename: Kristina
authors.initials: K
authors.lastname: Laumann
authors.forename: James H
authors.initials: JH
authors.lastname: Feusner
authors.forename: Alan
authors.initials: A
authors.lastname: Gamis
authors.forename: John
authors.initials: J
authors.lastname: Gregory
authors.forename: Richard A
authors.initials: RA
authors.lastname: Larson
authors.forename: Bayard L
authors.initials: BL
authors.lastname: Powell
authors.forename: Wendy
authors.initials: W
authors.lastname: Stock
authors.forename: Cheryl L
authors.initials: CL
authors.lastname: Willman
authors.forename: William G
authors.initials: WG
authors.lastname: Woods
authors.forename: Soheil
authors.initials: S
authors.lastname: Meshinchi
mesh_terms: D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007223:Infant; D015473:Leukemia, Promyelocytic, Acute / Q000097:blood / Q000235:genetics* / Q000401:mortality / Q000628:therapy; D007958:Leukocyte Count; D008297:Male; D009154:Mutation; D011379:Prognosis; D015996:Survival Rate; D055815:Young Adult; D051941:fms-Like Tyrosine Kinase 3 / Q000235:genetics*
chemical_list: C497970:FLT3 protein, human; D051941:fms-Like Tyrosine Kinase 3