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Do CSF3R Mutations Affect Prognosis for Children With Favorable-Risk AML?

By: Joseph Fanelli
Posted: Monday, August 17, 2020

For children with acute myeloid leukemia (AML), colony stimulating factor 3 receptor (CSF3R) mutations may further stratify pediatric patients with favorable-risk disease, according to a letter presented in the journal Blood. Soheil Meshinchi, MD, PhD, of the Fred Hutchinson Cancer Research Center, Seattle, and colleagues found that patients with co-occurring t(8;21) translocation experienced positive outcomes. In contrast, patients with CEBPA mutations experienced “very poor” outcomes with high rates of relapse when treated with chemotherapy alone.

CEBPA mutations should not be considered favorable risk based solely on [the] presence of a CEBPA mutation or an initial good response to therapy,” the authors concluded.

For this study, 2,150 patients from two children’s oncology group phase III trials—AAML0531 and AAML1031—were deemed eligible with comprehensive clinical and karyotype information. The patients’ mutational status was determined by next generation sequencing, and CEBPA mutation status was determined by fragment length analysis and Sanger sequencing.

The authors identified 35 patients (1.6%) with CSF3R mutations, with mutations occurring mostly in the proximal region of the transmembrane domain or in the cytoplasmic domain as truncating events. The T618I mutation was the most commonly detected; it was observed in nearly half of patients. In addition, an overwhelming majority (89%) of patients with CSF3R mutations demonstrated co-occurring t(8;21) fusion or CEBPA mutations.

For the 31 patients with CSF3R mutations with CEBPA or t(8'21) variants, the event-free survival rate was 61±18%. However, when stratified based on co-occurring CEBPA or t(8;21), patients with dual CSF3R and CEBPA mutations had an event-free survival rate of 25±25%, compared with 83±18% for those with CSF3R and t(8;21) mutations. Despite significantly higher response rates and inferior event-free survival, patients with CSF3R and CEBPA mutations had an overall survival rate of 73±28%, whereas those with CSF3R and t(8;21) mutations had an overall survival rate of 100±0%.

Disclosure: The authors have conflicts of interest to report.

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