Abstract
BackgroundThe aim of this study was to analyze the long-term survival of AML patients with CEBPA mutations.Patients and methodsWe investigated 88 AML patients with a median age of 61 years and (1) cytogenetically normal AML (CN-AML), (2) monoallelic (moCEBPA) or biallelic (biCEBPA) CEBPA mutation, and (3) intensive induction treatment. 60/88 patients have been described previously with a shorter follow-up.ResultsMedian follow-up time was 9.8 years (95% CI: 9.4-10.1 years) compared to 3.2 and 5.2 years in our former analyses. Patients with biCEBPA mutations survived significantly longer compared to those with moCEBPA (median overall survival (OS) 9.6 years vs. 1.7 years, p = 0.008). Patients ≤ 60 years and biCEBPA mutations showed a favorable prognosis with a 10-year OS rate of 81%.Both, bi- and moCEBPA-mutated groups had a low early death (d60) rate of 7% and 9%, respectively. Complete remission (CR) rates for biCEBPA- and moCEBPA-mutated patients were 82% vs. 70% (p = 0.17). biCEBPA-mutated patients showed a longer relapse free survival (RFS) (median RFS 9.4 years vs. 1.5 years, p = 0.021) and a lower cumulative incidence of relapse (CIR) compared to moCEBPA-mutated patients. These differences in OS and RFS were confirmed after adjustment for known clinical and molecular prognostic factors.ConclusionsIn this long-term observation we confirmed the favorable prognostic outcome of patients with biCEBPA mutations compared to moCEBPA-mutated CN-AML. The high probability of OS (81%) in younger patients is helpful to guide intensity of postremission therapy.Electronic supplementary materialThe online version of this article (doi:10.1186/s13045-014-0055-7) contains supplementary material, which is available to authorized users.
Highlights
The aim of this study was to analyze the long-term survival of AML patients with CEBPA mutations
Patients In this analysis we included all cytogenetically normal (CN) AML patients with a monoallelic or a biallelic CEBPA mutation treated within the two large multicenter AML Cooperative group clinical studies, the AMLCG99 trial [NCT00266136] and the AMLCG2008 trial [NCT01382147; EUDRACT2007-003103-12] or in analogy to clinical studies in our university hospital
Comparison of moCEBPA- vs. biCEBPA-mutated patients with respect to clinical and molecular parameters Analyses were performed in 88 patients with cytogenetically normal AML (CN-AML) and a mutation of CEBPA
Summary
The aim of this study was to analyze the long-term survival of AML patients with CEBPA mutations. The gene encoding for the CCAAT/enhancer binding protein-α (CEBPA) is located on chromosome 19 band q13.11. It was first full-length cloned in 1997 [2]. The CEBPA protein is 42 kDa of size. It is expressed in myelomonocytic cells and upregulated in granulocytic differentiation acting as a myeloid transcription factor. C-terminal mutations occur mainly in the basic Zipper (bZIP) domain of CEBPA, and impair its function to homodimerize and heterodimerize with other proteins as well as its DNA binding [4]. Mutations of CEBPA have been shown to be associated with CN-AML where they occur with frequencies of 8 -18% [6,7,8,9,10] and with the French-American-British (FAB) subtypes M1 and M2 [11]
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