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

PURPOSE:

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.

PATIENTS AND 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).

CONCLUSION:

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: Stephanie Ehlers, Christin Herbst, Martin Zimmermann, Nicole Scharn, Manuela Germeshausen, Nils von Neuhoff, Christian Michel Zwaan, Katarina Reinhardt, Iris H Hollink, Jan-Henning Klusmann, Thomas Lehrnbecher, Silja Roettgers, Jan Stary, Michael Dworzak, Karl Welte, Ursula Creutzig, Dirk Reinhardt
• Journal: Journal of clinical oncology : official journal of the American Society of Clinical Oncology (J Clin Oncol) Vol. 28 Issue 15 Pg. 2591-7 (May 20 2010) ISSN: 1527-7755 [Electronic] United States
• PMID: 20406937 (Publication Type: Clinical Trial, Phase III, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Protein Isoforms
• Receptors, Granulocyte Colony-Stimulating Factor
• Granulocyte Colony-Stimulating Factor

Topics

• Adolescent
• Child
• Child, Preschool
• Female
• Flow Cytometry
• Granulocyte Colony-Stimulating Factor (therapeutic use)
• Humans
• Incidence
• Leukemia, Myeloid, Acute (drug therapy, genetics, metabolism)
• Male
• Prospective Studies
• Protein Isoforms
• Receptors, Granulocyte Colony-Stimulating Factor (biosynthesis, genetics)
• Recurrence
• Treatment Outcome