Chinese journal of cancer research = Chung-kuo yen cheng yen chiu · 2025
Impact of clinical characteristics and genetic profiles on outcomes of allogeneic stem cell transplantation with sorafenib maintenance in FLT3-ITD acute myeloid leukemia patients: A multi-center, retrospective study.
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Zhao Yeqian, Jiang Chuanhe, Luo Yi, Ouyang Guifang, Chen Lieguang, Yu Jian, Tan Yamin, Lai Xiaoyu, Liu Lizhen, Fu Huarui, Ye Yishan, Yang Luxin, Zhang Congxiao, Shi Jimin, Huang He, Hu Xiaoxia, Zhao Yanmin
Аннотация
OBJECTIVE: Acute myeloid leukemia (AML) patients with internal tandem duplications in the FMS-like tyrosine kinase 3 receptor gene (FLT3-ITD) receiving tyrosine kinase inhibitors maintenance after allogeneic hematopoietic stem cell transplantation (allo-HSCT) demonstrated improved survival outcomes, however, some still experienced relapse during the maintenance. This study aimed to explore risk factors which might be indicators for poor survival after allo-HSCT in this population.
METHODS: We consecutively enrolled FLT3-ITD AML patients undergoing transplantation at three centers. By integrating genetic profiles with clinical information, we assessed their impact on transplant outcomes.
RESULTS: A total of 196 patient were eligible in the analysis, among whom 14% harbored myelodysplasia-related (MR) mutations, including ASXL1, BCOR, EZH2, RUNX1, SF3B1, SRSF2, STAG2, U2AF1, and ZRSR2. Co-mutant MR was independently associated with poorer overall survival (OS) [hazard ratio (HR): 2.4, 95% confidence interval (95% CI): 1.1-5.3, P=0.030]. DNMT3A co-mutations strongly predicted adverse survival and relapse [OS: HR: 2.1, 95% CI: 1.0-4.3, P=0.045; relapse-free survival (RFS): HR: 2.2, 95% CI: 1.1-4.1, P=0.017; cumulative incidence of relapse (CIR): HR: 2.3, 95% CI: 1.1-4.8, P=0.030]. Compared to patients with negative measurable residual disease (MRD) complete remission (CR), no significant differences were observed in CR patients with positive MRD, while those without CR exhibited significantly inferior outcomes (P=0.003).
CONCLUSIONS: Patients with myelodysplasia-related gene mutations (MRmut) and/or DNMT3A mutations experienced inferior outcomes after transplantation, requiring further exploration. Furthermore, similar prognoses among CR patients highlighted the need for monitoring specific molecular residual lesions.
METHODS: We consecutively enrolled FLT3-ITD AML patients undergoing transplantation at three centers. By integrating genetic profiles with clinical information, we assessed their impact on transplant outcomes.
RESULTS: A total of 196 patient were eligible in the analysis, among whom 14% harbored myelodysplasia-related (MR) mutations, including ASXL1, BCOR, EZH2, RUNX1, SF3B1, SRSF2, STAG2, U2AF1, and ZRSR2. Co-mutant MR was independently associated with poorer overall survival (OS) [hazard ratio (HR): 2.4, 95% confidence interval (95% CI): 1.1-5.3, P=0.030]. DNMT3A co-mutations strongly predicted adverse survival and relapse [OS: HR: 2.1, 95% CI: 1.0-4.3, P=0.045; relapse-free survival (RFS): HR: 2.2, 95% CI: 1.1-4.1, P=0.017; cumulative incidence of relapse (CIR): HR: 2.3, 95% CI: 1.1-4.8, P=0.030]. Compared to patients with negative measurable residual disease (MRD) complete remission (CR), no significant differences were observed in CR patients with positive MRD, while those without CR exhibited significantly inferior outcomes (P=0.003).
CONCLUSIONS: Patients with myelodysplasia-related gene mutations (MRmut) and/or DNMT3A mutations experienced inferior outcomes after transplantation, requiring further exploration. Furthermore, similar prognoses among CR patients highlighted the need for monitoring specific molecular residual lesions.