Poor prognostic implications of myelodysplasia-related mutations in both older and younger patients with de novo AML

Abstract

A set of myelodysplasia-related (MDS-R) gene mutations are incorporated into the 2022 European LeukemiaNet risk classification as adverse genetic factors for acute myeloid leukemia (AML) based on their poor prognostic impact on older patients. The impact of these mutations on younger patients (age < 60 years) remains elusive. In the study of 1213 patients with de novo non-M3 AML, we identified MDS-R mutations in 32.7% of the total cohort, 44.9% of older patients and 23.4% of younger patients. The patients with MDS-R mutations had a significantly lower complete remission rate in both younger and older age groups. With a median follow-up of 9.2 years, the MDS-R group experienced shorter overall survival (P = 0.034 for older and 0.035 for younger patients) and event-free survival (P = 0.004 for older and 0.042 for younger patients). Furthermore, patients with MDS-R mutations more frequently harbored measurable residual disease that was detectable using next generation sequencing at morphological CR than those without MDS-R mutations. Allogeneic hematopoietic stem cell transplantation (allo-HSCT) might ameliorate the negative impact of MDS-R mutations. In summary, AML patients with MDS-R mutations have significantly poorer outcomes regardless of age. More intensive treatment, such as allo-HSCT and/or novel therapies, is warranted for AML patients with MDS-R mutations.

An Ensemble Model for Acute Myeloid Leukemia Risk Stratification Recommendations by Combining Machine Learning with Clinical Guidelines

“…33 Moreover, myelodysplasia-related mutations like SRSF2 indicate poor outcomes across all age groups, underscoring the need for intensive treatment. 34 Another earlier research highlighted the prognostic importance of favorable karyotypes inv (16) in AML. 31 The analysis of HSCT effectiveness across different risk levels offers novel perspectives on treatment effects.…”

Applicability of 2022 classifications of acute myeloid leukemia in the real-world setting

“…Our data confirm the reports from a previous study that patients with a single MDS-related gene mutation have a better OS than those with >1 alteration. 32 Thus, one could speculate whether having a single MDS-related gene and a NK is sufficient to decide upon treatment intensification, as suggested in a recent ELN 2022 validation study. 33 Future efforts focusing on the relation between the new prognostication system and various treatments (especially hematopoietic stem cell transplantation) are warranted.…”

Annotation-Free Deep Learning for Predicting Gene Mutations from Whole Slide Images of Acute Myeloid Leukemia

“…1a). The gene mutation status was determined using TruSight myeloid panel on the HiSeq platform (Illumina, San Diego, CA) [25], which were annotated as 1 (indicating the presence of pathogenic or likely pathogenic mutations) or 0 (indicating the absence of pathogenic or likely pathogenic mutations). In our cohort, a total of 34 genes were frequently found to be mutated, and in this study, we listed the mutation frequencies of more than 10% and selected the top two highest frequent mutations as the targets (Table 1).…”