Abstract

Aberrations of the MLL gene on chromosome 11q23 occur in about 5–10% of adult patients with acute myeloid leukemia (AML). Most commonly, fusion of the MLL gene to the genes AF9 on chromosome 9 or AF6 on chromosome 6 are found resulting in the translocation t(9;11) and t(6;11), respectively. The remaining patients with aberrations of chromosome 11q23 constitute a heterogeneous group with numerous fusion partners. This genetic heterogeneity hampers risk stratification of these patients. Accordingly, AML patients with 11q23 aberrations have varyingly been stratified as intermediate or high risk patients by different study groups. To analyze the impact of different 11q23 aberrations on the prognosis of AML patients up to 60 years, a pooled data analysis of 5 consecutive studies for the treatment of adult AML patients was performed. All patients received double induction treatment with araC and an anthracycline followed by an intensive consolidation with either a high dose araC based chemotherapy regimen or an autologous or allogeneic stem cell transplantation. In total, 137 patients with 11q23 aberrations were identified by cytogenetics and/or molecular techniques. 51 patients (37%) had a t(9;11), 19 patients (14%) a t(6;11), 8 patients (6%) a t(11;19), 6 patients (4%) a t(11;17) and 5 patients (4%) a t(10;11). 48 patients (35%) hold other fusion partners or deletions of 11q23. For further evaluation, patients harbouring other 11q23 aberrations than t(9;11) and t(6;11) were grouped together. Median age of all patients was 39 years (range 16–60). Overall complete remission rate was 75% with no significant difference between the groups (82% for t(9;11), 74% for t(6;11) and 70% for others). Altogether, 9% of the patients had treatment failure and 8% died during induction. Relapse-free survival (RFS) and overall survival (OS) at 5 years for the entire group was 34% and 28%, respectively. RFS and OS of the t(6;11) group was 0% and 11% respectively and thus was significantly inferior to patients with t(9;11) (RFS: 48%, OS: 33%) and patients with other 11q23 aberrations (RFS: 32%, OS: 28%). Within the t(9;11) group there was no difference in RFS or OS between patients who had a t(9;11) as a sole aberration (n=35) and patients with additional aberrations (n=16). Moreover, in t(9;11) no difference in RFS was observed between treatment with high dose araC, autologous or allogeneic stem cell transplantation as late consolidation. In conclusion, these data demonstrate that prognosis of patients with 11q23 is heterogeneous. Patients with t(9;11) have a relatively good outcome independent of the consolidation therapy used. In contrast, the prognosis of patients with t(6;11) is extremely poor. Therefore, patients with t(6;11) should be regarded as high risk and alternative treatment strategies for this subgroup are required.

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