Grouping of Genetic Risk By the European Leukemia Net Classification Predicts Overall Survival and Relapse Incidence in Patients with Acute Myeloid Leukemia Undergoing Allogeneic Stem Cell Transplantation

Introduction: In acute myeloid leukemia (AML) genetic risk factors are among the strongest predictors for overall outcome. Recently, the European Leukemia Net (ELN) proposed a revised classification based on the presence or absence of specific cytogenetic and/or molecular aberrations. Here, we evaluated the prognostic significance of this system in patients with AML undergoing allogeneic stem cell transplantation (alloSCT).

Patients and Methods: A total of 363 patients transplanted at our center between 2004 and 2014 was retrospectively evaluated. According to the ELN classification genetic risk was favorable (N=51), intermediate-1 (N=120), intermediate-2 (N=98), or adverse (N=94). Remission status at the time of alloSCT was first complete remission (CR1) (N=204), CR>1 (N=61), or refractory (N=98). In 107 patients standard myeloablative conditioning (MAC) was used, whereas reduced intensity conditioning (RIC) was applied in 256 patients. Grafts were from either related (N=103) or unrelated (matched: N=191, mismatched: N=69) donors. The median age was 52 (range: 18-75) years.

Results: For the surviving patients the median follow-up was 30 (range: 3-129) months. Whereas in the subgroup of patients aged ≥60 years (N=98) no significant differences in disease-free survival (DFS) or cumulative incidence of relapse (CI-R) between the 4 ELN subgroups were found, the ELN classification was highly predictive for in the subgroups aged <60 years. Patients with an adverse risk karyotype had significantly lower DFS as compared to patients with a favorable or an intermediate risk profile, i.e. 30% versus 56% for favorable, 52% for intermediate-1, or 59% for intermediate-2 (p=0.0064). Correspondingly, the CI-R was highest in patients with an adverse risk profile, i.e. 53% at 5 years. In turn, patients with favorable, intermediate-1, or intermediate-2 risk disease had a CI-R of 15%, 40%, or 21% (p<0.001). In the intermediate-1 subgroup, adverse outcome, i.e. relapse, was predominant in the group of FLT3-ITD positive patients, whereas the CI-R in patients lacking a FLT3-ITD was similar to what was observed in the intermediate-2 subgroup.

Conclusions:  Taken together, our data suggest that the ELN classification of genetic risk is suitable for predicting relapse and overall survival of patients with AML aged <60 years undergoing alloSCT. The adverse outcome of patients in the intermediate-2 subgroup may be related to presence of a FLT3-ITD. Therefore, further efforts are needed to improve the clinical results in this particular group.