title: Prospective validation of a new method of monitoring minimal residual disease in childhood acute myelogenous leukemia.
abstract: OBJECTIVE
  This study evaluated the prognostic impact of a novel, simple, and standardized assay for monitoring minimal residual disease (MRD) in pediatric acute myelogenous leukemia (AML).
  
  
  METHODS
  The expression of seven leukemia-associated genes (WT1, PRAME, CCL23, GAGED2, MSLN, SPAG6, and ST18) was measured by TaqMan Low Density Arrays in 112 patients and 52 healthy controls. Patients were treated according to the multicenter study AML-BFM 2004. Samples were collected prospectively at standard time points. The laboratory that measured MRD was blinded to patient outcome.
  
  
  RESULTS
  Relapse-free survival (RFS) was 95% (N = 19; SE = 5%) if expression of all genes was down to normal on day 15, 63% (N = 41; SE = 8%) if expression was normalized on day 28, and 38% (N = 21; SE = 11%) in patients who still showed elevated expression on day 28. The prognostic impact of MRD remained significant (P = 0.002) when patients were stratified for the AML-BFM 2004 risk group. Multivariate analysis identified the MRD risk group and day 28 cytology as the only independent prognostic factors. Patients with a cytologic nonremission on day 28, which was confirmed by MRD, had a dismal prognosis. Only 1 out of 8 patients survived without relapse.
  
  
  CONCLUSIONS
  This novel method of monitoring MRD has a strong prognostic impact that is independent from established risk factors in childhood AML.
authors.affiliation: University of Ulm, Children's Hospital, Ulm, Germany. Daniel@Steinba.ch.
authors.forename: Daniel
authors.initials: D
authors.lastname: Steinbach
authors.affiliation: University of Frankfurt, Children's Hospital, Frankfurt, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Bader
authors.affiliation: University of Frankfurt, Children's Hospital, Frankfurt, Germany.
authors.forename: Andre
authors.initials: A
authors.lastname: Willasch
authors.affiliation: University of Ulm, Children's Hospital, Ulm, Germany.
authors.forename: Stephan
authors.initials: S
authors.lastname: Bartholomae
authors.affiliation: University of Ulm, Children's Hospital, Ulm, Germany.
authors.forename: Klaus-Michael
authors.initials: KM
authors.lastname: Debatin
authors.affiliation: Medical School Hannover, Children's Hospital, Hannover, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Zimmermann
authors.affiliation: Medical School Hannover, Children's Hospital, Hannover, Germany.
authors.forename: Ursula
authors.initials: U
authors.lastname: Creutzig
authors.affiliation: Medical School Hannover, Children's Hospital, Hannover, Germany.
authors.forename: Dirk
authors.initials: D
authors.lastname: Reinhardt
authors.affiliation: Department of Pediatrics, Jena University Hospital, Jena, Germany.
authors.forename: Bernd
authors.initials: B
authors.lastname: Gruhn
mesh_terms: D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D005260:Female; D052138:Genes, Neoplasm / Q000235:genetics*; D006801:Humans; D007223:Infant; D015470:Leukemia, Myeloid, Acute / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology*; D008297:Male; D000090204:Mesothelin; D018365:Neoplasm, Residual / Q000175:diagnosis* / Q000235:genetics*; D011379:Prognosis; D011446:Prospective Studies