Prognostic Factors in Adult Patients up to 60 Years with AML and Translocations of Chromosome 11q23: Individual Patient Data Based 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 , Buchner Thomas , Sauerland Cristina , Schlegelberger Brigitte , Dohner Konstanze , Dohner Hartmut , Schlenk Richard , Ganser Arnold 
Published: November 2019

Abstract
The MLL gene on chromosome 11q23 is translocated to a variety of fusion partners in about 5–10% of adults with acute myeloid leukemia (AML). The heterogeneity of these genetic aberrations hampers risk stratification of the patients. To identify prognostic parameters in AML patients up to 60 years with 11q23 aberrations, a pooled data analysis of 8 trials for the treatment of adults with AML was performed. All patients (pts) received double induction with araC and an anthracycline followed by intensive consolidation with either a high dose araC based chemotherapy or an autologous or allogeneic stem cell transplantation (alloSCT). 180 pts with 11q23 translocations were identified by cytogenetics and/or molecular techniques. 76 pts (42%) had a t(9;11), 35 (19%) a t(6;11), 17 (9%) a t(11;19), 14 (8%) a t(10;11) and 10 (6%) a t(11;17). 28 pts (16%) had other translocation partners. 77 pts (43%) had secondary chromosomal aberrations. Median age was 39 years (range 16–60). Median platelet and PB blast count was 45G/l and 7.5G/l. Median follow up is 53 months. Complete remission rate was 71%. Logistic regression identified t(9;11) (OR 2.6; 95% CI 1.2–5.9), secondary chromosomal aberrations (OR 0.4; 95% CI 0.2–0.8) and secondary leukemia (OR 0.3; 95% CI 0.1–0.6) as significant factors for induction success. Four year overall survival (OS) was 29% (95% CI 25–33%). Multivariate analysis identified presence of a t(9;11) (HR 0.6; 95% CI 0.4–0.9), platelets above the median (HR 0.6; 95% CI 0.4–0.9), secondary leukemia (HR 1.9; 95% CI 1.2–2.9) and PB blasts above the median (HR 1.9 95% CI 1.3–2.8) as significant factors for OS. Combination of these factors separated three risk groups for OS (p=0.0001): Good, pts with de novo AML, t(9;11) and PB blasts below median (4y OS 61%); intermediate, remaining pts with platelets above median (4y OS 32%); poor, remaining pts with platelets below median (4y OS 15%). Four year relapse-free survival (RFS) was 29% (95% CI 24–34%). Cox regression analysis identified the presence of a t(6;11) (HR 1.8; 95% CI 1.1–3.0) and PB blasts above the median (HR 1.7; 95% CI 1.0–2.6) as independent risk factors for RFS. By combination of these factors, three risk groups for RFS were defined: Good, pts without t(6;11) with PB blasts below median (4y RFS 63%); intermediate, pts without t(6;11) with PB blasts above median (4y RFS 23%); poor, pts with t(6;11) (4y RFS 9%). The effect of different consolidation strategies was analyzed “as treated” in CR-pts who had received at least one cycle of consolidation. In these pts, RFS was improved by an alloSCT (MRD or MUD) in first CR (p=0.04). However, this effect was restricted to the RFS-intermediate risk group (p=0.029), whereas pts in the good or poor risk group did not benefit from an alloSCT in first CR. In conclusion, the prognosis of patients with translocations of chromosome 11q23 is heterogenous. Risk stratification of these patients is feasible based on the MLL-fusion partner and clinical parameters. This prognostic model can be used as a basis for the selection of consolidation therapy.