Recently, mutations in the CEBPA gene, encoding CCAAT/enhancer binding protein alpha have been identified in 10 to 15% of patients with acute myeloid leukemia (AML) exhibiting a normal karyotype and mutant CEBPA was shown to predict favorable outcome. However, the impact of different postremission strategies such as high-dose cytarabine based chemotherapy (chemo), autologous (auto-SCT) or allogeneic stem cell transplantation (allo-SCT) in subgroups defined by these molecular markers is under discussion. Therefore, we initiated a pooled data analysis on patients exhibiting a normal karyotype at diagnosis treated within the prospective treatment trials AML-2/95, AML-1/99, AMLHD93 and AMLHD98A.

All patients (age 16–60 years) received two cycles of induction therapy with standard dose cytarabine combined with etoposide and idarubicin. After a first consolidation therapy, patients were assigned to an allo-SCT if an HLA-identical sibling donor was available in all four trials. In the AML-2/95 and AMLHD93 trials all other patients were assigned to chemo whereas in the AML-1/99 and AMLHD98A trials patients were randomised between auto-SCT and chemo. All patients were analyzed for CEBPA-mutations in the N-terminal transactivation domains and the C-terminal basic region-leucine zipper domain by direct sequencing of genomic DNA.

Between 1993 and 2004 a total of n=872 patients exhibiting a normal karyotype had been registered. Actually in 413 patients results of CEBPA analyses are available and 54 (13%) exhibited a mutation (46% N-terminal, 15% C-terminal, 39% N- and C-terminal). Response to induction therapy was 85% (46/54) and 74% (259/352) in the CEBPA mutated group and the CEBPA wild-type group, respectively. RFS and OS were 59% and 38% (p=0.01) as well as 66% and 41% (p=0.002) in the CEBPA mutated group and the CEBPA wild-type group, respectively after a median follow-up of 42 months. The distribution of postremission therapy of the 46 patients in the CEBPA mutated group was n=22 Chemo, n=13 allo-tpl, n=9 auto-tpl, n=2 allo-tpl from a matched unrelated donor. Analysis based on the availability of a matched related donor revealed a significant better RFS (p=0.03) and OS (p=0.03) for patients with an matched related donor.

Conclusion: Although AML patients with normal karyotype and a CEBPA mutation comprises a group with favorable prognosis allogeneic transplantation from an HLA-matched family donor seems to improve long term outcome. Confirmation of these preliminary data on a larger series of patients are necessary to improve a risk-adapted decision on postremission strategies.

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