The effect of haploidentical hematopoietic stem cell transplantation on comutations based on next‐generation sequencing in adult acute myeloid leukemia patients with the FLT3‐ITD mutation

Abstract

According to the 2022 European LeukemiaNet, all acute myeloid leukemia (AML) cases with FLT3‐ITD mutations are now categorized as intermediate risk irrespective of the FLT3‐ITD allelic ratio or concurrent presence of NPM1 mutation. However, whether other next‐generation sequencing (NGS) comutation genes can add layers to FLT3‐ITD and whether the poor outcomes of FLT3‐ITD comutations can be overcome by haploidentical hematopoietic stem cell transplantation (haplo‐HSCT) are unclear. This study aimed to investigate which comutations based on NGS at diagnosis affect the clinical prognosis of de novo AML patients with FLT3‐ITD mutations and the effect of haplo‐HSCT on comutations. We analyzed 95 de novo AML patients with FLT3‐ITD mutations from January 2018 to August 2021 based on the NGS 99‐gene platform. Forty‐one other types of molecular mutations were detected. The most common cooccurring mutations were NPM1 (n = 43, 45.3%) and DNMT3A (n = 21, 22.1%). NPM1 mutation did not affect the clinical outcomes. Acute myeloid leukemia patients with FLT3‐ITD and DNMT3A comutations had significantly worse 3‐year Disease‐free survival (DFS) (49.5% vs. 69.3%, P = 0.01) and Overall survival (OS) rates (61.1% vs. 69.8%, P = 0.54) than those without DNMT3A mutations, and survival was significantly more favorable after haplo‐HSCT than that after chemotherapy (3‐year DFS, 85.7% vs. 30.8%, P = 0.006; 3‐year OS, 85.7% vs. 43.1%, p = 0.08). In multivariate analysis, DNMT3A mutation was a risk factor for DFS, while haplo‐HSCT was a protective factor. In conclusion, DNMT3A mutation might be a poor prognostic factor in adult AML patients with FLT3‐ITD mutations, and haplo‐HSCT could overcome the poor prognosis of DNMT3A comutation.