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 post-remission 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 CETLAM-12 risk-adapted protocol, which indicates cytarabine-based consolidation for patients allocated to the ELN 2017 favorable-risk group, while it recommends allogeneic stem cell transplantation as a post-remission 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) 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 non-favorable ELN subgroups, and identifies a genetic subset with a very poor outcome which warrants investigation of novel strategies.

Pre-transplant gene profiling characterization by next-generation DNA sequencing might predict relapse occurrence after hematopoietic stem cell transplantation in patients affected by AML

“…Patients in the adverse risk group reported the highest cumulative incidence of relapse (37%) and the worse overall survival (54%) and disease-free survival (45%) at 2 years. On the other hand, they found no associations between ELN risk stratification and TRM ( 43 , 45 ), which we also saw in our cohort of patients.…”

“…It has been previously reported that AML relapse occurrence after transplant is linked to an adverse ELN genetic risk as compared to the favorable one ( 43 ). Moreover, the lack of a 1CR status before conditioning increases the risk of relapse after HSCT.…”

Clinical Efficacies of FLT3 Inhibitors in Patients with Acute Myeloid Leukemia

“…A low AR (low FLT3-ITD) is correlated with favorable risk in the intermediate-risk group with coincident nucleophosmin 1 (NPM1) mutation [ 10 ]. The associations are reflected in the 2017 European LeukemiaNet (ELN) risk stratification of AML [ 16 ]. Meanwhile, FLT3-TKD mutations mean point mutations within the receptor’s activation loop stabilizing and activating the kinase conformation.…”

Clinical efficacy of azacytidine and venetoclax and prognostic impact of Tim-3 and galectin-9 in acute myeloid leukemia and high-risk myelodysplastic syndromes: A single-center real-life experience

“…Diagnosis is based on identification of at least 20% myeloblasts in the bone marrow (BM) or peripheral blood (PB) according to 2016 World Health Organization (WHO) guidelines, except for AML with specific cytogenetic abnormalities or nucleophosmin 1 ( NPM1 ) mutated leukemias (Giudice V et, 2021; Heuser M et al, 2020 ; Khoury JD et al, 2022 ). AML risk evaluation is based on the European LeukemiaNet (ELN) guidelines defining three risk categories: favorable, intermediate, and adverse ( Bataller A et al, 2022 ). In particular, combination of certain somatic mutations (e.g., biallelic mutation of CEBPA, NPM1, FLT3-ITD, or TP53 ) and chromosomal alterations (including t(8; 21), inv(16), or alterations involving chromosome 7) can predict AML prognosis ( Bataller A et al, 2022 ; Fu W, et al, 2022 ).…”