Outcome prediction by the 2022 European LeukemiaNet genetic-risk classification for adults with acute myeloid leukemia: an Alliance study

Abstract

Recently, the European LeukemiaNet (ELN) revised its genetic-risk classification of acute myeloid leukemia (AML). We categorized 1637 adults with AML treated with cytarabine/anthracycline regimens according to the 2022 and 2017 ELN classifications. Compared with the 2017 ELN classification, 2022 favorable group decreased from 40% to 35% and adverse group increased from 37% to 41% of patients. The 2022 genetic-risk groups seemed to accurately reflect treatment outcomes in all patients and patients aged <60 years, but in patients aged ≥60 years, relapse rates, disease-free (DFS) and overall (OS) survival were not significantly different between intermediate and adverse groups. In younger African-American patients, DFS and OS did not differ between intermediate-risk and adverse-risk patients nor did DFS between favorable and intermediate groups. In Hispanic patients, DFS and OS did not differ between favorable and intermediate groups. Outcome prediction abilities of 2022 and 2017 ELN classifications were similar. Among favorable-risk patients, myelodysplasia-related mutations did not affect patients with CEBPAbZIP mutations or core-binding factor AML, but changed risk assignment of NPM1-mutated/FLT3-ITD-negative patients to intermediate. NPM1-mutated patients with adverse-risk cytogenetic abnormalities were closer prognostically to the intermediate than adverse group. Our analyses both confirm and challenge prognostic significance of some of the newly added markers.

Stellae-123 gene expression signature improved risk stratification in Taiwanese acute myeloid leukemia patients

“…Nevertheless, it is noteworthy that one-fifth of the patients in our cohort exhibited myelodysplasia-related gene mutations or cytogenetic abnormalities (Table S1 ), thereby partially representing the currently defined "myelodysplasia-related" AML population. Additionally, our cohort is characterized by a higher proportion of ELN favorable-risk patients, resembling a miniature version of our previously published cohort 40 , yet distinct from others 41 , 42 , which could partially lead to a relatively lower HSCT rate. Thus, while the incorporation of age and the Stellae-123 models can complement ELN-risk assessment in our cohort, the broader applicability of our findings necessitates further validation.…”

Circular RNAs: pivotal role in the leukemogenesis and novel indicators for the diagnosis and prognosis of acute myeloid leukemia

“…Although the latest edition of this genetic-risk classification of AML seemed to accurately reflect the individual patient's treatment outcomes in patients aged <60 years, in older patients, relapse rate, disease-free (DFS) and overall (OS) survival were not significantly different between intermediate and adverse groups (12). Most AML patients still lack actionable targets for successful targeting and long-term survival remains low (5-year OS 28.7%) (13).…”

The relevance of the hematopoietic niche for therapy resistance in acute myeloid leukemia

“…Despite recent diagnostic and therapeutic advances, the prognosis of acute myeloid leukemia (AML) remains poor 1 . While often an initial therapy response can be achieved, relapses occur frequently and the disease becomes more difficult to treat.…”