title: Granulocyte colony-stimulating factor (G-CSF) treatment of childhood acute myeloid leukemias that overexpress the differentiation-defective G-CSF receptor isoform IV is associated with a higher incidence of relapse.
abstract: OBJECTIVE
  This prospective, multicenter Acute Myeloid Leukemia Berlin-Frankfurt-Muenster (AML-BFM) 98 study randomly tested the ability of granulocyte colony-stimulating factor (G-CSF) to reduce infectious complications and to improve outcomes in children and adolescents with acute myeloid leukemia (AML). However, a trend toward an increased incidence of relapses in the standard-risk (SR) group after G-CSF treatment was observed.
  
  
  METHODS
  Of 154 SR patients in the AML-BFM 98 cohort, 50 patients were tested for G-CSF receptor (G-CSFR) RNA isoform I and IV expression, G-CSFR cell surface expression, and acquired mutations in the G-CSFR gene.
  
  
  RESULTS
  In patients randomly assigned to receive G-CSF after induction, 16 patients overexpressing the G-CSFR isoform IV showed an increased 5-year cumulative incidence of relapse (50% +/- 13%) compared with 14 patients with low-level isoform IV expression (14% +/- 10%; log-rank P = .04). The level of G-CSFR isoform IV had no significant effect in patients not receiving G-CSF (P = .19). Multivariate analyses of the G-CSF-treated subgroup, including the parameters G-CSFR isoform IV overexpression, sex, and favorable cytogenetics as covariables, revealed the prognostic relevance of G-CSFR isoform IV overexpression for 5-year event-free survival (P = .031) and the 5-year cumulative incidence of relapse (P = .049).
  
  
  CONCLUSIONS
  Our results demonstrate that children and adolescents with AMLs that overexpress the differentiation-defective G-CSFR isoform IV respond to G-CSF administration after induction, but with a significantly higher incidence of relapse.
authors.affiliation: Department of Pediatric Hematology and Oncology, Medical School Hannover, Hannover, Germany. ehlers.stephanie@mh-hannover.de
authors.forename: Stephanie
authors.initials: S
authors.lastname: Ehlers
authors.forename: Christin
authors.initials: C
authors.lastname: Herbst
authors.forename: Martin
authors.initials: M
authors.lastname: Zimmermann
authors.forename: Nicole
authors.initials: N
authors.lastname: Scharn
authors.forename: Manuela
authors.initials: M
authors.lastname: Germeshausen
authors.forename: Nils
authors.initials: N
authors.lastname: von Neuhoff
authors.forename: Christian Michel
authors.initials: CM
authors.lastname: Zwaan
authors.forename: Katarina
authors.initials: K
authors.lastname: Reinhardt
authors.forename: Iris H
authors.initials: IH
authors.lastname: Hollink
authors.forename: Jan-Henning
authors.initials: JH
authors.lastname: Klusmann
authors.forename: Thomas
authors.initials: T
authors.lastname: Lehrnbecher
authors.forename: Silja
authors.initials: S
authors.lastname: Roettgers
authors.forename: Jan
authors.initials: J
authors.lastname: Stary
authors.forename: Michael
authors.initials: M
authors.lastname: Dworzak
authors.forename: Karl
authors.initials: K
authors.lastname: Welte
authors.forename: Ursula
authors.initials: U
authors.lastname: Creutzig
authors.forename: Dirk
authors.initials: D
authors.lastname: Reinhardt
mesh_terms: D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D005260:Female; D005434:Flow Cytometry; D016179:Granulocyte Colony-Stimulating Factor / Q000627:therapeutic use*; D006801:Humans; D015994:Incidence; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D008297:Male; D011446:Prospective Studies; D020033:Protein Isoforms; D016188:Receptors, Granulocyte Colony-Stimulating Factor / Q000096:biosynthesis* / Q000235:genetics; D012008:Recurrence; D016896:Treatment Outcome
chemical_list: D020033:Protein Isoforms; D016188:Receptors, Granulocyte Colony-Stimulating Factor; D016179:Granulocyte Colony-Stimulating Factor