European LeukemiaNet 2017 risk stratification for acute myeloid leukemia: validation in a risk-adapted protocol

Abstract

The 2017 European LeukemiaNet (ELN 2017) guidelines for the diagnosis and management of acute myeloid leukemia (AML) have become fundamental guidelines to assess the prognosis and postremission therapy of patients. However, they have been retrospectively validated in few studies with patients included in different treatment protocols. We analyzed 861 patients included in the Cooperativo Para el Estudio y Tratamiento de las Leucemias Agudas y Mielodisplasias-12 risk-adapted protocol, which indicates cytarabine-based consolidation for patients allocated to the ELN 2017 favorable-risk group, whereas it recommends allogeneic stem cell transplantation (alloSCT) as a postremission strategy for the ELN 2017 intermediate- and adverse-risk groups. We retrospectively classified patients according to the ELN 2017, with 327 (48%), 109 (16%), and 245 (36%) patients allocated to the favorable-, intermediate-, and adverse-risk group, respectively. The 2- and 5-year overall survival (OS) rates were 77% and 70% for favorable-risk patients, 52% and 46% for intermediate-risk patients, and 33% and 23% for adverse-risk patients, respectively. Furthermore, we identified a subgroup of patients within the adverse group (inv(3)/t(3;3), complex karyotype, and/or TP53 mutation/17p abnormality) with a particularly poor outcome, with a 2-year OS of 15%. Our study validates the ELN 2017 risk stratification in a large cohort of patients treated with an ELN-2017 risk-adapted protocol based on alloSCT after remission for nonfavorable ELN subgroups and identifies a genetic subset with a very poor outcome that warrants investigation of novel strategies.

Graphical abstract

Figure 1.

Distribution of patients with AML included in the study within the ELN 2017 risk categories. *Patients allocated to this category have been identified by NPM1 and FLT3-ITD mutational status. **Patients with ASXL1 mutation without RUNX1 mutation. ***Patients with TP53 mutation or abn(17p) without complex karyotype.

Figure 2.

Treatment disposition of patients according to responses and outcomes of patients of each ELN 2017 risk category.

Figure 3.

Univariate and multivariate analysis for CR, OS, and EFS. OR, odds ratio; HR, hazard ratio; CI, confidence interval.

Figure 4.

Outcome (OS, EFS, CIR) of the entire cohort and in each ELN risk category: (A) OS and EFS of the entire cohort. (B) OS according to ELN 2017 risk category. (C) EFS according to ELN 2017 risk category. (D-F) CIR and death without relapse of patients allocated in the ELN 2017 favorable (D), intermediate (E), and adverse (F) risk category. Pairwise comparison of OS, EFS, and CI has been adjusted with the Bonferroni method.

Figure 5.

Outcome after alloSCT according to ELN 2017 risk category. (A) OS after alloSCT according to the ELN 2017 risk categories. (B) EFS after alloSCT according to the ELN 2017 risk categories. (C-E) CI of relapse and death without relapse of patients allocated in the ELN 2017 favorable (C), intermediate (D), and adverse (E) risk category. Pairwise comparison of OS, EFS, and CIR has been adjusted with the Bonferroni method. Starting time for the analysis is the date of alloSCT.

Figure 6.

Outcome according to ELN risk category dividing the adverse risk category in two different subgroups, ELN Adv− and the very adverse risk/ELN Adv+. (A) OS and (B) EFS of the ELN 2017 risk groups stratifying the ELN 2017 adverse risk patients in the 2 proposed groups (ELN Adv− and very adverse risk/ELN Adv+). Pairwise comparison of OS and EFS has been adjusted with the Bonferroni method. Outcome after alloSCT in both ELN Adv subgroups in terms of OS (C) and CIR and NRM (D).