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.
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.
Ehlers
Stephanie
S
Department of Pediatric Hematology and Oncology, Medical School Hannover, Hannover, Germany. ehlers.stephanie@mh-hannover.de
Herbst
Christin
C
Zimmermann
Martin
M
Scharn
Nicole
N
Germeshausen
Manuela
M
von Neuhoff
Nils
N
Zwaan
Christian Michel
CM
Reinhardt
Katarina
K
Hollink
Iris H
IH
Klusmann
Jan-Henning
JH
Lehrnbecher
Thomas
T
Roettgers
Silja
S
Stary
Jan
J
Dworzak
Michael
M
Welte
Karl
K
Creutzig
Ursula
U
Reinhardt
Dirk
D
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
D020033:Protein Isoforms; D016188:Receptors, Granulocyte Colony-Stimulating Factor; D016179:Granulocyte Colony-Stimulating Factor