1.
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
Tang, F., Zhao, X., Ruan, G., Jiang, Q., Jiang, H., Xu, L., Wang, Y., Zhang, X., Liu, K., Huang, X.
Hematological oncology. 2023
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.
2.
Impact of pre-transplantation minimal residual disease determined by multiparameter flow cytometry on the outcome of AML patients with FLT3-ITD after allogeneic stem cell transplantation
Zhao, X., Wang, Z., Ruan, G., Liu, Y., Wang, Y., Zhang, X., Xu, L., Huang, X., Chang, Y.
Annals of hematology. 2018
Abstract
In this study, using multiparameter flow cytometry (FCM), we investigate the impact of minimal residual disease prior to transplantation (pre-MRD) on the transplant outcomes of AML patients with fms-related tyrosine kinase 3 (FLT3)-internal tandem duplication (ITD) mutation. A total of 20 patients who received HLA-matched sibling donor transplantation (MSDT) and 63 patients who received unmanipulated haploidentical hematopoietic stem cell transplantation (haplo-HSCT) were enrolled. Patients were classified into four groups based on the status of pre-FCM: group 1 with positive pre-FCM before MSDT, group 2 with negative pre-FCM before MSDT, group 3 with positive pre-FCM before haplo-HSCT, and group 4 with positive pre-FCM before haplo-HSCT. The results showed that patients in group 1 had the highest cumulative incidence of relapse (2-year CIR, 75.0%), the lowest leukemia-free survival (2-year LFS, 33.3%), and the overall survival (2-year OS, 25.0%) among all four groups. The other three groups of patients had comparable CIR (2-year CIR: group 2 vs. 3 vs. 4, 12.5% vs. 31.3% vs. 22.2%, P > 0.05) and LFS (2-year LFS: group 2 vs. 3 vs. 4, 87.5% vs. 62.5% vs. 66.5%, P > 0.05). Multivariate analysis indicated that disease status (> CR) and pre-MRD were associated with a higher CIR and a lower LFS when patients were classified by pre-MRD and transplant type. Our results suggested that AML patients with FLT3-ITD were able to be separated into high-risk and low-risk relapse groups based on pre-MRD, as determined by multiparameter FCM. Haplo-HSCT might overcome the negative impact of pre-MRD on patient outcomes compared to MSDT. These results require further investigation in prospective study with large numbers of cases.