Prognosis of Adult Patients ≤60 Years with AML and Aberrations of Chromosome 11q23: Pooled Data Analysis of the German AML-Intergroup.
Authors: Krauter Jürgen , Wagner Katharina , Schäfer Irina , Marschalek Rolf , Meyer Claus , Heil Gerhard , Schaich Markus Andreas , Ehninger Gerhard , Niederwieser Dietger W. , Krahl Rainer , Dohner Konstanze , Dohner Hartmut , Schlenk Richard , Ganser Arnold 
Published: October 2019

Abstract
Aberrations of the MLL gene on chromosome 11q23 occur in about 5–10% of adult patients with acute myeloid leukemia (AML). Most frequently, the MLL gene is fused to the genes AF9 on chromosome 9 or AF6 on chromosome 6 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 heterogeneity hampers risk stratification of the patients. Accordingly, AML patients with 11q23 aberrations have varyingly been stratified as intermediate or high risk patients by different study groups. To analyze the prognostic impact of different 11q23 aberrations in AML patients up to 60 years, a pooled data analysis of 6 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, 150 patients with 11q23 aberrations were identified by cytogenetics and/or molecular techniques. 53 patients (35%) had a t(9;11), 27 patients (18%) a t(6;11), 10 patients (7%) a t(11;19), 8 patients (5%) a t(11;17) and 6 patients (4%) a t(10;11). 46 patients (31%) had other fusion partners or deletions of 11q23. Median age of all patients was 39 years (range 16–60). Overall complete remission rate was 73% with no significant difference between the groups (79% for t(9;11), 74% for t(6;11) and 66% for others). Altogether, 9% of the patients had treatment failure and 7% died during induction. Relapse-free survival (RFS) and overall survival (OS) at 5 years for the entire group was 24% and 26%, respectively. RFS and OS of the t(6;11) group was 6% and 13% and thus was significantly inferior to patients with t(9;11) (RFS: 48%, OS: 31%) and patients with other 11q23 translocations (RFS: 20%, OS: 18%) or 11q23 deletions (RFS: 38%, OS: 33%). 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=36) and patients with additional aberrations (n=17) and between patients with de novo or secondary AML. 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. Regarding other translocations of 11q23, there was no difference in RFS and OS between patients with t(11;17), t(11;19), t(10;11) and patients with various other fusion partners. In conclusion, these data demonstrate that the prognosis of patients with 11q23 is heterogeneous. Patients with t(9;11) who enter CR 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.