General AML

The prognostic impact of KIT mutations in pediatric patients with CBF-AML – A Chinese study

KIT mutations are associated with adverse outcomes in adult patients with Core-Binding Factor Acute Myeloid Leukemia (CBF-AML).1 However, the prognostic significance of KIT mutations in pediatric CBF-AML patients is not yet elucidated, hence the rationale for this study.

 Xi Chen from the Children’s Hospital of Chongqing Medical University, Chongqing, China and colleagues investigated the clinical significance of KIT mutations in pediatric CBF-AML patients. The results of their study were published ahead of print in Leukemia & Lymphoma on 9th August 2017.2

Bone Marrow (BM) samples from 212 de novo AML patients (median age = 7 years) who were treated at the Children’s Hospital of Chongqing Medical University in Chongqing between 2007 and 2015 were analyzed in this study. 30% of patients were found to have CBF-AML (n = 50, median age = 7 years) either with (n = 15) or without (n = 35) KIT mutations.

The key results of the study were:
  • KIT mutations in CBF-AML patients (n = 15) were clustered in exon 8 (4/15), exon 11 (3/15) and exon 17 (8/15)
  • 5-year Overall Survival (OS) in CBF-AML patients with KIT Wild Type (WT) and exon 11 (n = 31) and KIT mutation on exon 8 or 17 (n = 10); 73.0 ±5% vs 30.0 ±14.5%, P = 0.007
  • 5-year Event Free Survival (EFS) in CBF-AML patients with KIT WT and exon 11 and KIT mutation on exon 8 or 17; 73.0 ±5% vs 30.0±14.5%; P = 0.003
  • KIT mutations in exon 8 and 17 were independent factors for adverse OS (HR = 3.77, P = 0.021) and EFS (HR = 3.45, P = 0.03)

The study found a correlation between KIT mutations and poor outcomes in pediatric CBF-AML patients.

The authors concluded their study by highlighting that “KIT exons 8 and 17 mutations are independent indicators for inferior prognosis in pediatric CBF-AML”.  They further suggested that a study with a larger CBF-AML cohort should be conducted in order to validate the findings of their study.

Abstract

The prevalence and clinical relevance of KIT mutations in childhood core-binding factor (CBF) acute myeloid leukemia (AML) have not been well characterized. In this study, a total of 212 children with de novo AML were enrolled from a Chinese population and 50 (23.5%) of the patients were deemed CBF-AML. KIT mutations were identified in 30% of the CBF-AML cohort. The KIT mutations were clustered in exon 17 and exon 8, and KIT mutations in exons 8 and 17 were correlated with a shorter overall survival (OS) (5-year OS: 30.0 ± 14.5% vs. 73.0 ± 8.5%, p = .007) and event-free survival (EFS) (5-year EFS: 30.0 ± 14.5% vs. 73.0 ± 8.5%, p = .003). Multivariate analysis revealed KIT mutations as an independent risk factor in CBF-AML. Our results suggest that KIT mutations are a molecular marker for an inferior prognosis in pediatric CBF-AML.

References
  1. Allen C.et al. The importance of relative mutant level for evaluating impact on outcome of KIT, FLT3 and CBL mutations in core-binding factor acute myeloid leukemia. Leukemia. 2013 Sep; 27(9): 1891–901. DOI: 10.1038/leu.2013.186. Epub 2013 Jun 20.
  2. Chen X. et al. KIT mutations correlate with adverse survival in children with core-binding factor acute myeloid leukemia. Leuk Lymohoma. 2017 Aug 9: 1–8. DOI: 10.1080/10428194.2017.1361025. [Epub ahead of print].